Hydrocephalus

Hydrocephalus is a condition in which there is an abnormal accumulation of cerebrospinal

fluid (CSF) within the brain.This typically causes increased pressure inside the skull. Older
people may have headaches, double vision, poor balance, urinary incontinence, personality
changes, or mental impairment. In babies there may be a rapid increase in head size. Other
symptoms may include vomiting, sleepiness, seizures, and downward pointing of the eyes
Hydrocephalus can occur due to birth defects or be acquired later in life. Associated birth defects
include neural tube defects and those that result in aqueductal stenosis .Other causes
include meningitis, brain tumors, traumatic brain injury, intraventricular hemorrhage,
and subarachnoid hemorrhage. There are four types of hydrocephalus: communicating, non-
communicating, ex-vacuo, and normal pressure. Diagnosis is typically by examination
and medical imaging.]
Hydrocephalus is typically treated by the surgical placement of a shunt system. A procedure
called a third ventriculostomy may be an option in a few people. Complications from shunts may
include overdrainage, underdrainage, mechanical failure, infection, or obstruction. This may
require replacement. Outcomes are variable; however, many live normal lives. Without treatment
death may occur
About one to two per 1,000 newborns have hydrocephalus. Rates in the developing world may
be more. Normal pressure hydrocephalus is estimated to affect about 5 per 100,000 people with
rates increasing with age Description of hydrocephalus by Hippocrates date back more than
2000 years The word "hydrocephalus" is from Greek hydro-, meaning 'water', and kephalos,
meaning

Signs and symptoms

Illustration showing different effects of hydrocephalus on the brain and cranium.

The clinical presentation of hydrocephalus varies with chronicity. Acute dilatation of the
ventricular system is more likely to manifest with the nonspecific signs and symptoms of
increased intracranial pressure. By contrast chronic dilatation (especially in the elderly
population) may have a more insidious onset presenting, for instance, with Hakim's triad (Adams
triad).
Symptoms of increased intracranial pressure may
include headaches, vomiting, nausea, papilledema, sleepiness or coma. Elevated intracranial
pressure may result in uncal and/or cerebellar tonsill herniation, with resulting life-
threatening brain stem compression.
Hakim's triad of gait instability, urinary incontinence and dementia is a relatively typical
manifestation of the distinct entity normal pressure hydrocephalus (NPH). Focal neurological
deficits may also occur, such as abducens nerve palsy and vertical gaze palsy (Parinaud
syndrome due to compression of the quadrigeminal plate, where the neural centers coordinating
the conjugated vertical eye movement are located). The symptoms depend on the cause of the
blockage, the person's age, and how much brain tissue has been damaged by the swelling.
In infants with hydrocephalus, CSF builds up in the central nervous system, causing
the fontanelle (soft spot) to bulge and the head to be larger than expected. Early symptoms may
also include:

 Eyes that appear to gaze downward;

 Irritability;
 Seizures;
 Separated sutures;
 Sleepiness;
 Vomiting.
Symptoms that may occur in older children can include:

 Brief, shrill, high-pitched cry;

 Changes in personality, memory, or the ability to reason or think;
 Changes in facial appearance and eye spacing;
 Crossed eyes or uncontrolled eye movements;
 Difficulty feeding;
 Excessive sleepiness;
 Headache;
 Irritability, poor temper control;
 Loss of bladder control (urinary incontinence);
 Loss of coordination and trouble walking;
 Muscle spasticity (spasm);
 Slow growth (child 0–5 years);
 Slow or restricted movement;
 Vomiting .
Because hydrocephalus can injure the brain, thought and behavior may be adversely
affected. Learning disabilities including short-term memory loss are common among those with
hydrocephalus, who tend to score better on verbal IQ than on performance IQ, which is thought
to reflect the distribution of nerve damage to the brain. However the severity of hydrocephalus
can differ considerably between individuals and some are of average or above-average
intelligence. Someone with hydrocephalus may have motion and visual problems, problems with
coordination, or may be clumsy. They may reach puberty earlier than the average child
(see precocious puberty). About one in four develops epilepsy.

Cause
Congenital

One year old girl with hydrocephalus showing "sunset eyes", before shunt surgery.
Congenital hydrocephalus is present in the infant prior to birth, meaning the fetus developed
hydrocephalus in utero during fetal development. The most common cause of congenital
hydrocephlaus is aqueductal stenosis. Aqueductal stenosis occurs when the narrow passage
between the third and fourth ventricles in the brain is blocked or too narrow to allow sufficient
cerebral spinal fluid to drain. Fluid accumulates in the upper ventricles, causing hydrocephalus.
Other causes of congenital hydrocephalus include neural tube defects, arachnoid cysts, Dandy-
Walker syndrome, and Arnold-Chiari malformation.
The cranial bones fuse by the end of the third year of life. For head enlargement to occur,
hydrocephalus must occur before then. The causes are usually genetic but can also be acquired
and usually occur within the first few months of life, which include 1) intraventricular matrix
hemorrhages in premature infants, 2) infections, 3) type II Arnold-Chiari malformation, 4)
aqueduct atresia and stenosis, and 5) Dandy-Walker malformation.
In newborns and toddlers with hydrocephalus, the head circumference is enlarged rapidly and
soon surpasses the 97th percentile. Since the skull bones have not yet firmly joined together,
bulging, firm anterior and posterior fontanelles may be present even when the patient is in an
upright position.
The infant exhibits fretfulness, poor feeding, and frequent vomiting. As the hydrocephalus
progresses, torpor sets in, and the infant shows lack of interest in his surroundings. Later on, the
upper eyelids become retracted and the eyes are turned downwards ("sunset eyes") (due to
hydrocephalic pressure on the mesencephalic tegmentum and paralysis of upward gaze).
Movements become weak and the arms may become tremulous. Papilledema is absent but there
may be reduction of vision. The head becomes so enlarged that the child may eventually be
bedridden.
About 80-90% of fetuses or newborn infants with spina bifida—often associated
with meningocele or myelomeningocele — develop hydrocephalus

Acquired
This condition is acquired as a consequence of CNS infections, meningitis, brain tumors, head
trauma, intracranial hemorrhage (subarachnoid or intraparenchymal) and is usually extremely
painful.

Type
The cause of hydrocephalus is not known with certainty and is probably multifactorial. It may be
caused by impaired cerebrospinal fluid (CSF) flow, reabsorption, or excessive CSF production.

 Obstruction to CSF flow hinders the free passage of cerebrospinal fluid through the
ventricular system and subarachnoid space (e.g., stenosis of the cerebral aqueduct or
obstruction of the interventricular foramina) secondary
to tumors, hemorrhages, infections or congenital malformations) and can cause increases in
central nervous system pressure.
 Hydrocephalus can also be caused by overproduction of cerebrospinal fluid (relative
obstruction) (e.g., Choroid plexus papilloma, villous hypertrophy).
 Bilateral ureteric obstruction is a rare, but reported, cause of hydrocephalus.
Based on its underlying mechanisms, hydrocephalus can be classified into communicating and
non-communicating (obstructive). Both forms can be either congenital or acquired.

Communicating
Communicating hydrocephalus, also known as non-obstructive hydrocephalus, is caused by
impaired cerebrospinal fluid reabsorption in the absence of any CSF-flow obstruction between
the ventricles and subarachnoid space. It has been theorized that this is due to functional
impairment of the arachnoidal granulations (also called arachnoid granulations or Pacchioni's
granulations), which are located along the superior sagittal sinus and is the site of cerebrospinal
fluid reabsorption back into the venous system. Various neurologic conditions may result in
communicating hydrocephalus, including subarachnoid/intraventricular
hemorrhage, meningitis and congenital absence of arachnoid villi. Scarring and fibrosis of
the subarachnoid space following infectious, inflammatory, or hemorrhagic events can also
prevent resorption of CSF, causing diffuse ventricular dilatation.

Non-communicating
Non-communicating hydrocephalus, or obstructive hydrocephalus, is caused by a CSF-flow
obstruction.

 Foramen of Monro obstruction may lead to dilation of one or, if large enough (e.g., in colloid
cyst), both lateral ventricles.
 The aqueduct of Sylvius, normally narrow to begin with, may be obstructed by a number of
genetically or acquired lesions (e.g., atresia, ependymitis, hemorrhage, tumor) and lead to
dilation of both lateral ventricles as well as the third ventricle.
 Fourth ventricle obstruction will lead to dilatation of the aqueduct as well as the lateral and
third ventricles (e.g., Chiari malformation).
 The foramina of Luschka and foramen of Magendie may be obstructed due to congenital
malformation (e.g., Dandy-Walker malformation).
Other

Hydrocephalus ex vacuo from vascular dementia as seen on MRI

 Normal pressure hydrocephalus (NPH) is a particular form of communicating hydrocephalus,

characterized by enlarged cerebral ventricles, with only intermittently elevated cerebrospinal
fluid pressure. The diagnosis of NPH can be established only with the help of continuous
intraventricular pressure recordings (over 24 hours or even longer), since more often than
not instant measurements yield normal pressure values. Dynamic compliance studies may
be also helpful. Altered compliance (elasticity) of the ventricular walls, as well as
increased viscosity of the cerebrospinal fluid, may play a role in the pathogenesis of normal
pressure hydrocephalus.
 Hydrocephalus ex vacuo also refers to an enlargement of cerebral ventricles and
subarachnoid spaces, and is usually due to brain atrophy (as it occurs in dementias), post-
traumatic brain injuries and even in some psychiatric disorders, such as schizophrenia As
opposed to hydrocephalus, this is a compensatory enlargement of the CSF-spaces in
response to brain parenchyma loss - it is not the result of increased CSF pressure.

Mechanism
Spontaneous intracerebral and intraventricular hemorrhage with hydrocephalus shown on CT scan

Hydrocephalus is usually due to blockage of cerebrospinal fluid (CSF) outflow in the ventricles or
in the subarachnoid space over the brain. In a person without hydrocephalus, CSF continuously
circulates through the brain, its ventricles and the spinal cord and is continuously drained away
into the circulatory system. Alternatively, the condition may result from an overproduction of the
CSF, from a congenital malformation blocking normal drainage of the fluid, or from complications
of head injuries or infections
Compression of the brain by the accumulating fluid eventually may cause neurological symptoms
such as convulsions, intellectual disability and epileptic seizures. These signs occur sooner in
adults, whose skulls are no longer able to expand to accommodate the increasing fluid volume
within. Fetuses, infants, and young children with hydrocephalus typically have an abnormally
large head, excluding the face, because the pressure of the fluid causes the individual skull
bones — which have yet to fuse — to bulge outward at their juncture points. Another medical
sign, in infants, is a characteristic fixed downward gaze with whites of the eyes showing above
the iris, as though the infant were trying to examine its own lower eyelids
The elevated intracranial pressure may cause compression of the brain, leading to brain damage
and other complications. Conditions among affected individuals vary widely.
If the foramina of the fourth ventricle or the cerebral aqueduct are blocked, cerebrospinal fluid
(CSF) can accumulate within the ventricles. This condition is called internal hydrocephalus and it
results in increased CSF pressure. The production of CSF continues, even when the passages
that normally allow it to exit the brain are blocked. Consequently, fluid builds inside the brain,
causing pressure that dilates the ventricles and compresses the nervous tissue. Compression of
the nervous tissue usually results in irreversible brain damage. If the skull bones are not
completely ossified when the hydrocephalus occurs, the pressure may also severely enlarge the
head. The cerebral aqueduct may be blocked at the time of birth or may become blocked later in
life because of a tumor growing in the brainstem.

Treatment

Baby recovering from shunt surgery

Hydrocephalus can be successfully treated by placing a drainage tube (shunt) between the brain
ventricles and abdominal cavity. There is some risk of infection being introduced into the brain
through these shunts, however, and the shunts must be replaced as the person grows. A
subarachnoid hemorrhage may block the return of CSF to the circulation.
This should be distinguished from external hydrocephalus. This is a condition generally seen in
infants and involving enlarged fluid spaces or subarachnoid spaces around the outside of the
brain. This is generally a benign condition that resolves spontaneously by 2 years of age.
(Greenberg, Handbook of Neurosurgery, 5th Edition, pg 174). Imaging studies and a good
medical history can help to differentiate external hydrocephalus from subdural hemorrhages or
symptomatic chronic extra-axial fluid collections which are accompanied
by vomiting, headaches and seizures.
Hydrocephalus treatment is surgical, creating a way for the excess fluid to drain away. In the
short term, an external ventricular drain (EVD), also known as an extraventricular drain or
ventriculostomy, provides relief for urgent/emergent care. In the long term, some patients will
need any of various types of cerebral shunt. It involves the placement of a ventricular catheter (a
tube made of silastic) into the cerebral ventricles to bypass the flow
obstruction/malfunctioning arachnoidal granulations and drain the excess fluid into other body
cavities, from where it can be resorbed. Most shunts drain the fluid into the peritoneal
cavity (ventriculo-peritoneal shunt), but alternative sites include the right atrium (ventriculo-atrial
shunt), pleural cavity (ventriculo-pleural shunt), and gallbladder. A shunt system can also be
placed in the lumbar space of the spine and have the CSF redirected to the peritoneal
cavity (Lumbar-peritoneal shunt). An alternative treatment for obstructive hydrocephalus in
selected patients is the endoscopic third ventriculostomy (ETV), whereby a surgically created
opening in the floor of the third ventricle allows the CSF to flow directly to the basal cisterns,
thereby shortcutting any obstruction, as in aqueductal stenosis. This may or may not be
appropriate based on individual anatomy. For infants, ETV is sometimes combined with choroid
plexus cauterization, which reduces the amount of cerebrospinal fluid produced by the brain. The
technique, known as ETV/CPC was pioneered in Uganda by neurosurgeon Ben Warf and is now
in use in several U.S. hospitals.

Shunt complication
Examples of possible complications include shunt malfunction, shunt failure, and shunt infection,
along with infection of the shunt tract following surgery (the most common reason for shunt
failure is infection of the shunt tract). Although a shunt generally works well, it may stop working if
it disconnects, becomes blocked (clogged), infected, or it is outgrown. If this happens the
cerebrospinal fluid will begin to accumulate again and a number of physical symptoms will
develop (headaches, nausea, vomiting, photophobia/light sensitivity), some extremely serious,
like seizures. The shunt failure rate is also relatively high (of the 40,000 surgeries performed
annually to treat hydrocephalus, only 30% are a patient's first surgery) and it is not uncommon
for patients to have multiple shunt revisions within their lifetime.
Another complication can occur when CSF drains more rapidly than it is produced by the choroid
plexus, causing symptoms - listlessness, severe headaches, irritability, light sensitivity,
auditory hyperesthesia (sound
sensitivity), nausea, vomiting, dizziness, vertigo, migraines, seizures, a change in
personality, weakness in the arms or legs, strabismus, and double vision - to appear when the
patient is vertical. If the patient lies down, the symptoms usually vanish quickly. A CT scan may
or may not show any change in ventricle size, particularly if the patient has a history of slit-like
ventricles. Difficulty in diagnosing overdrainage can make treatment of this complication
particularly frustrating for patients and their families. Resistance to
traditional analgesic pharmacological therapy may also be a sign of shunt
overdrainage or failure.
The diagnosis of cerebrospinal fluid buildup is complex and requires specialist expertise.
Diagnosis of the particular complication usually depends on when the symptoms appear - that is,
whether symptoms occur when the patient is upright or in a prone position, with the head at
roughly the same level as the feet.
Developing countries
Because the shunt systems are too expensive for most people in developing countries, such
people often die without getting a shunt. Worse, the rate of revision in shunt systems adds to the
cost of shunting many times. Looking at this point, a study compares shunt systems and
highlights the role of low-cost shunt systems in most of the developing countries It compares the
Chhabra shunt system to shunt systems from developed countries.

History

Skull of a hydrocephalic child (1800s)

References to hydrocephalic skulls can be found in ancient Egyptian medical literature from 2500
BC to 500 AD. Hydrocephalus was described more clearly by the
ancient Greek physician Hippocrates in the 4th century BC, while a more accurate description
was later given by the Roman physician Galen in the 2nd century AD.
The first clinical description of an operative procedure for hydrocephalus appears in the Al-
Tasrif (1000 AD) by the Arab surgeon, Abulcasis, who clearly described the evacuation of
superficial intracranial fluid in hydrocephalic children. He described it in his chapter on
neurosurgical disease, describing infantile hydrocephalus as being caused by mechanical
compression. He wrote
"The skull of a newborn baby is often full of liquid, either because the matron has compressed it
excessively or for other, unknown reasons. The volume of the skull then increases daily, so that
the bones of the skull fail to close. In this case, we must open the middle of the skull in three
places, make the liquid flow out, then close the wound and tighten the skull with a bandage."
Historical specimen of an infant with severe hydrocephalus, probably untreated

In 1881, a few years after the landmark study of Retzius and Key, Carl Wernicke pioneered
sterile ventricular puncture and external drainage of cerebrospinal fluid for the treatment of
hydrocephalus It remained an intractable condition until the 20th century, when shunts and
other neurosurgical treatment modalities were developed.
It is a lesser-known medical condition; relatively little research is conducted to improve treatment,
and there is still no cure. In developing countries, the condition often goes untreated at birth.
Before birth, the condition is difficult to diagnose, and there is limited access to medical
treatment. However, when head swelling is prominent, children are taken at great expense for
treatment. By then, brain tissue is undeveloped and neurosurgery is rare and difficult. Children
more commonly live with undeveloped brain tissue and consequential intellectual disability.

Society and culture

Awareness campaign

Hydrocephalus awareness ribbon

September was designated National Hydrocephalus Awareness Month in July 2009 by the U.S.
Congress in HR373. The Resolution campaign is due in part to the Advocacy work of the
Pediatric Hydrocephalus Foundation, Inc. Prior to July 2009, there was no Awareness month for
this condition. Many of the hydrocephalus organizations within the United States use various
ribbon designs as a part of their awareness and fundraising activities.
Exceptional case
Main article: Dandy-Walker syndrome
One exceptional case of hydrocephalus was a man whose brain shrank to a thin sheet of tissue,
due to buildup of cerebrospinal fluid in his skull. As a child, the man had a shunt, but it was
removed when he was 14. In July 2007, at age 44, he went to a hospital due to mild weakness in
his left leg. When doctors learned of the man's medical history, they performed a computed
tomography (CT) scan and magnetic resonance imaging (MRI) scan, and were astonished to see
"massive enlargement" of the lateral ventricles in the skull. Dr. Lionel Feuillet of Hôpital de la
Timone in Marseille said, "The images were most unusual... the brain was virtually
absent. Intelligence tests showed the patient had an IQ of 75, below the average score of 100.
This would be considered "borderline intellectual functioning", just above what would be officially
considered mentally challenged.
The patient was a married father of two children, and worked as a civil servant, leading an at
least superficially normal life, despite having enlarged ventricles with a decreased volume of
brain tissue. "What I find amazing to this day is how the brain can deal with something which you
think should not be compatible with life", commented Dr. Max Muenke, a pediatric brain defect
specialist at the National Human Genome Research Institute. "If something happens very slowly
over quite some time, maybe over decades, the different parts of the brain take up functions that
would normally be done by the part that is pushed to the side

Notable cases
 Author Sherman Alexie, born with the condition, wrote about it in his semi-autobiographical
junior fiction novel The Absolutely True Diary of a Part-Time Indian.
 Prince William, Duke of Gloucester probably contracted meningitis at birth which resulted in
this condition.
 Poliomyelitis
From Wikipedia, the free encyclopedia

"Polio" redirects here. For the virus, see Poliovirus.

Not to be confused with poliosis, a condition of the hair being or becoming white or grey.

Poliomyelitis

Synonyms Polio, infantile paralysis

 A man with a smaller right leg due to poliomyelitis

Specialty Neurology, infectious disease

Symptoms Muscle weakness resulting in an inability to

move

Complications Post-polio syndrome

Usual onset Few hours to days

Causes Poliovirus spread by faecal-oral route

Diagnostic method Finding the virus in the feces or antibodies in

the blood

Prevention Polio vaccine

 Treatment Supportive care

Frequency 42 people (2016)

Poliomyelitis, often called polio or infantile paralysis, is an infectious disease caused by

the poliovirus. In about 0.5% of cases there is muscle weakness resulting in an inability to
move. This can occur over a few hours to a few days. The weakness most often involves the legs
but may less commonly involve the muscles of the head, neck and diaphragm. Many but not all
people fully recover. In those with muscle weakness about 2% to 5% of children and 15% to 30%
of adults die.[1]Another 25% of people have minor symptoms such as fever and a sore throat and
up to 5% have headache, neck stiffness and pains in the arms and legs.[1][3] These people are
usually back to normal within one or two weeks. In up to 70% of infections there are no
symptoms.[1] Years after recovery post-polio syndrome may occur, with a slow development of
muscle weakness similar to that which the person had during the initial infection.[2]
Poliovirus is usually spread from person to person through infected fecal matter entering the
mouth.[1] It may also be spread by food or water containing human feces and less commonly from
infected saliva.[1][3] Those who are infected may spread the disease for up to six weeks even if no
symptoms are present. The disease may be diagnosed by finding the virus in the feces or
detecting antibodies against it in the blood. The disease only occurs naturally in humans.[1]
The disease is preventable with the polio vaccine; however, a number of doses are required for it
to be effective.[3] The US Centers for Disease Control and Prevention recommends polio
vaccination boosters for travelers and those who live in countries where the disease is
occurring.[4] Once infected there is no specific treatment.[3] In 2016, polio affected 42 people, while
there were about 350,000 cases in 1988.[3][5] In 2014 the disease was only spreading between
people in Afghanistan, Nigeria, and Pakistan.[3] In 2015 Nigeria had stopped the spread of wild
poliovirus but it reoccurred in 2016.[6][7]
Poliomyelitis has existed for thousands of years, with depictions of the disease in ancient art. The
disease was first recognized as a distinct condition by Michael Underwood in 1789[1] and the
virus that causes it was first identified in 1908 by Karl Landsteiner.[8] Major outbreaks started to
occur in the late 19th century in Europe and the United States.[1] In the 20th century it became
one of the most worrying childhood diseases in these areas.[9] The first polio vaccine was
developed in the 1950s by Jonas Salk.[10] It is hoped that vaccination efforts and early detection
of cases will result in global eradication of the disease by 2018.[11]

Contents
[hide]

 1Signs and symptoms

 2Cause
o 2.1Transmission
 3Pathophysiology
o 3.1Paralytic polio
 4Diagnosis
 5Prevention
o 5.1Passive immunization
o 5.2Vaccine
 6Treatment
 7Prognosis
o 7.1Recovery
o 7.2Complications
 o 7.3Post-polio syndrome
 8Epidemiology
o 8.1Emergency declaration
o 8.2Americas
o 8.3Western Pacific
o 8.4Europe
o 8.5South-East Asia
o 8.6Syria
o 8.7Africa
o 8.8Afghanistan and Pakistan
 9History
o 9.1Etymology
 10Research
 11References
 12Further reading
 13External links

Signs and symptoms

Outcomes of poliovirus infection

Outcome Proportion of cases[1]

No symptoms 72%

Minor illness 24%

Nonparalytic aseptic
1–5%
meningitis

Paralytic poliomyelitis 0.1–0.5%

— Spinal polio 79% of paralytic cases

— Bulbospinal polio 19% of paralytic cases

— Bulbar polio 2% of paralytic cases

The term "poliomyelitis" is used to identify the disease caused by any of the three serotypes of
poliovirus. Two basic patterns of polio infection are described: a minor illness which does not
involve the central nervous system (CNS), sometimes called abortive poliomyelitis, and a major
illness involving the CNS, which may be paralytic or nonparalytic.[12] In most people with a normal
immune system, a poliovirus infection is asymptomatic. Rarely, the infection produces minor
symptoms; these may include upper respiratory tract infection (sore throat and
fever), gastrointestinal disturbances (nausea, vomiting, abdominal pain, constipation or, rarely,
diarrhea), and influenza-like illness.[1]
The virus enters the central nervous system in about 1% of infections. Most patients with CNS
involvement develop nonparalytic aseptic meningitis, with symptoms of headache, neck, back,
abdominal and extremity pain, fever, vomiting, lethargy, and irritability.[13][14] About one to five in
1000 cases progress to paralytic disease, in which the muscles become weak, floppy and poorly
controlled, and, finally, completely paralyzed; this condition is known as acute flaccid
paralysis.[15] Depending on the site of paralysis, paralytic poliomyelitis is classified as
spinal, bulbar, or bulbospinal. Encephalitis, an infection of the brain tissue itself, can occur in rare
cases, and is usually restricted to infants. It is characterized by confusion, changes in mental
status, headaches, fever, and, less commonly, seizures and spastic paralysis.[16]

Cause
Main article: Poliovirus

A TEM micrograph of poliovirus

Poliomyelitis is caused by infection with a member of the genus Enterovirus known

as poliovirus (PV). This group of RNA viruses colonize the gastrointestinal tract[17] — specifically
the oropharynx and the intestine. The incubation time (to the first signs and symptoms) ranges
from three to 35 days, with a more common span of six to 20 days.[1] PV infects and causes
disease in humans alone.[18] Its structure is very simple, composed of a single (+)
sense RNA genome enclosed in a protein shell called a capsid.[18] In addition to protecting the
virus’s genetic material, the capsid proteins enable poliovirus to infect certain types of cells.
Three serotypes of poliovirus have been identified—poliovirus type 1 (PV1), type 2 (PV2), and
type 3 (PV3)—each with a slightly different capsid protein.[19] All three are extremely virulent and
produce the same disease symptoms.[18] PV1 is the most commonly encountered form, and the
one most closely associated with paralysis.[20]
Individuals who are exposed to the virus, either through infection or by immunization with polio
vaccine, develop immunity. In immune individuals, IgA antibodies against poliovirus are present
in the tonsils and gastrointestinal tract, and are able to block virus
replication; IgG and IgM antibodies against PV can prevent the spread of the virus to motor
neurons of the central nervous system.[21] Infection or vaccination with one serotype of poliovirus
does not provide immunity against the other serotypes, and full immunity requires exposure to
each serotype.[21]
A rare condition with a similar presentation, nonpoliovirus poliomyelitis, may result from infections
with nonpoliovirus enteroviruses.[22]
Transmission
Poliomyelitis is highly contagious via the fecal-oral (intestinal source) and the oral-oral
(oropharyngeal source) routes.[21] In endemic areas, wild polioviruses can infect virtually the
entire human population.[23] It is seasonal in temperate climates, with peak transmission occurring
in summer and autumn.[21] These seasonal differences are far less pronounced
in tropical areas.[23] The time between first exposure and first symptoms, known as the incubation
period, is usually 6 to 20 days, with a maximum range of 3 to 35 days.[24] Virus particles are
excreted in the feces for several weeks following initial infection.[24] The disease
is transmitted primarily via the fecal-oral route, by ingesting contaminated food or water. It is
occasionally transmitted via the oral-oral route,[20] a mode especially visible in areas with good
sanitation and hygiene.[21] Polio is most infectious between 7 and 10 days before and after the
appearance of symptoms, but transmission is possible as long as the virus remains in the saliva
or feces.[20]
Factors that increase the risk of polio infection or affect the severity of the disease
include immune deficiency,[25] malnutrition,[26] physical activity immediately following the onset of
paralysis,[27] skeletal muscle injury due to injection of vaccines or therapeutic
agents,[28] and pregnancy.[29] Although the virus can cross the maternal-fetal barrier during
pregnancy, the fetus does not appear to be affected by either maternal infection or polio
vaccination.[30] Maternal antibodies also cross the placenta, providing passive immunity that
protects the infant from polio infection during the first few months of life.[31]
As a precaution against infection, public swimming pools were often closed in affected areas
during poliomyelitis epidemics.

Pathophysiology

A blockage of the lumbar anterior spinal cord artery due to polio (PV3)

Poliovirus enters the body through the mouth, infecting the first cells with which it comes in
contact — the pharynx and intestinal mucosa. It gains entry by binding to an immunoglobulin-
like receptor, known as the poliovirus receptor or CD155, on the cell membrane.[32] The virus then
hijacks the host cell's own machinery, and begins to replicate. Poliovirus divides within
gastrointestinal cells for about a week, from where it spreads to the tonsils (specifically
the follicular dendritic cells residing within the tonsilar germinal centers), the intestinal lymphoid
tissue including the M cells of Peyer's patches, and the deep cervical and mesenteric lymph
nodes, where it multiplies abundantly. The virus is subsequently absorbed into the
bloodstream.[33]
Known as viremia, the presence of a virus in the bloodstream enables it to be widely distributed
throughout the body. Poliovirus can survive and multiply within the blood and lymphatics for long
periods of time, sometimes as long as 17 weeks.[34] In a small percentage of cases, it can spread
and replicate in other sites, such as brown fat, the reticuloendothelial tissues, and muscle.[35] This
sustained replication causes a major viremia, and leads to the development of minor influenza-
like symptoms. Rarely, this may progress and the virus may invade the central nervous system,
provoking a local inflammatory response. In most cases, this causes a self-limiting inflammation
of the meninges, the layers of tissue surrounding the brain, which is known as nonparalytic
aseptic meningitis.[13] Penetration of the CNS provides no known benefit to the virus, and is quite
possibly an incidental deviation of a normal gastrointestinal infection.[36] The mechanisms by
which poliovirus spreads to the CNS are poorly understood, but it appears to be primarily a
chance event—largely independent of the age, gender, or socioeconomic position of the
individual.[36]
Paralytic polio

Denervation of skeletal muscle tissue secondary to poliovirus infection can lead to paralysis.

In around 1% of infections, poliovirus spreads along certain nerve fiber pathways, preferentially
replicating in and destroying motor neurons within the spinal cord, brain stem, or motor cortex.
This leads to the development of paralytic poliomyelitis, the various forms of which (spinal,
bulbar, and bulbospinal) vary only with the amount of neuronal damage and inflammation that
occurs, and the region of the CNS affected.
The destruction of neuronal cells produces lesions within the spinal ganglia; these may also
occur in the reticular formation, vestibular nuclei, cerebellar vermis, and deep cerebellar
nuclei.[36] Inflammation associated with nerve cell destruction often alters the color and
appearance of the gray matter in the spinal column, causing it to appear reddish and
swollen.[13] Other destructive changes associated with paralytic disease occur in
the forebrain region, specifically the hypothalamus and thalamus.[36] The molecular mechanisms
by which poliovirus causes paralytic disease are poorly understood.
Early symptoms of paralytic polio include high fever, headache, stiffness in the back and neck,
asymmetrical weakness of various muscles, sensitivity to touch, difficulty swallowing, muscle
pain, loss of superficial and deep reflexes, paresthesia (pins and needles), irritability,
constipation, or difficulty urinating. Paralysis generally develops one to ten days after early
symptoms begin, progresses for two to three days, and is usually complete by the time the fever
breaks.[37]
The likelihood of developing paralytic polio increases with age, as does the extent of paralysis. In
children, nonparalytic meningitis is the most likely consequence of CNS involvement, and
paralysis occurs in only one in 1000 cases. In adults, paralysis occurs in one in 75 cases.[38] In
children under five years of age, paralysis of one leg is most common; in adults, extensive
paralysis of the chest and abdomen also affecting all four limbs—quadriplegia—is more
likely.[39] Paralysis rates also vary depending on the serotype of the infecting poliovirus; the
highest rates of paralysis (one in 200) are associated with poliovirus type 1, the lowest rates (one
in 2,000) are associated with type 2.[40]
Spinal polio
The location of motor neurons in the anterior horn cells of the spinal column

Spinal polio, the most common form of paralytic poliomyelitis, results from viral invasion of the
motor neurons of the anterior horn cells, or the ventral (front) grey matter section in the spinal
column, which are responsible for movement of the muscles, including those of the trunk, limbs,
and the intercostal muscles.[15] Virus invasion causes inflammation of the nerve cells, leading to
damage or destruction of motor neuron ganglia. When spinal neurons die, Wallerian
degeneration takes place, leading to weakness of those muscles formerly innervated by the now-
dead neurons.[41] With the destruction of nerve cells, the muscles no longer receive signals from
the brain or spinal cord; without nerve stimulation, the muscles atrophy, becoming weak, floppy
and poorly controlled, and finally completely paralyzed.[15]Maximum paralysis progresses rapidly
(two to four days), and usually involves fever and muscle pain. Deep tendon reflexes are also
affected, and are typically absent or diminished; sensation (the ability to feel) in the paralyzed
limbs, however, is not affected.[42]
The extent of spinal paralysis depends on the region of the cord affected, which may
be cervical, thoracic, or lumbar.[43] The virus may affect muscles on both sides of the body, but
more often the paralysis is asymmetrical.[33] Any limb or combination of limbs may be affected—
one leg, one arm, or both legs and both arms. Paralysis is often more severe proximally (where
the limb joins the body) than distally (the fingertips and toes).[33]
Bulbar polio

The location and anatomy of the bulbar region (in orange)

Making up about 2% of cases of paralytic polio, bulbar polio occurs when poliovirus invades and
destroys nerves within the bulbar region of the brain stem.[1] The bulbar region is a white
matter pathway that connects the cerebral cortex to the brain stem. The destruction of these
nerves weakens the muscles supplied by the cranial nerves, producing symptoms
of encephalitis, and causes difficulty breathing, speaking and swallowing.[14] Critical nerves
affected are the glossopharyngeal nerve (which partially controls swallowing and functions in the
throat, tongue movement, and taste), the vagus nerve (which sends signals to the heart,
intestines, and lungs), and the accessory nerve (which controls upper neck movement). Due to
the effect on swallowing, secretions of mucus may build up in the airway, causing
suffocation.[37] Other signs and symptoms include facial weakness (caused by destruction of
the trigeminal nerve and facial nerve, which innervate the cheeks, tear ducts, gums, and muscles
of the face, among other structures), double vision, difficulty in chewing, and
abnormal respiratory rate, depth, and rhythm (which may lead to respiratory arrest). Pulmonary
edema and shock are also possible and may be fatal.[43]
Bulbospinal polio
Approximately 19% of all paralytic polio cases have both bulbar and spinal symptoms; this
subtype is called respiratory or bulbospinal polio.[1] Here, the virus affects the upper part of the
cervical spinal cord (cervical vertebrae C3 through C5), and paralysis of the diaphragm occurs.
The critical nerves affected are the phrenic nerve (which drives the diaphragm to inflate
the lungs) and those that drive the muscles needed for swallowing. By destroying these nerves,
this form of polio affects breathing, making it difficult or impossible for the patient to breathe
without the support of a ventilator. It can lead to paralysis of the arms and legs and may also
affect swallowing and heart functions.[44]

Diagnosis
Paralytic poliomyelitis may be clinically suspected in individuals experiencing acute onset of
flaccid paralysis in one or more limbs with decreased or absent tendon reflexes in the affected
limbs that cannot be attributed to another apparent cause, and without sensory
or cognitive loss.[45]
A laboratory diagnosis is usually made based on recovery of poliovirus from a stool sample or a
swab of the pharynx. Antibodies to poliovirus can be diagnostic, and are generally detected in the
blood of infected patients early in the course of infection.[1] Analysis of the patient's cerebrospinal
fluid (CSF), which is collected by a lumbar puncture ("spinal tap"), reveals an increased number
of white blood cells (primarily lymphocytes) and a mildly elevated protein level. Detection of virus
in the CSF is diagnostic of paralytic polio, but rarely occurs.[1]
If poliovirus is isolated from a patient experiencing acute flaccid paralysis, it is further tested
through oligonucleotide mapping (genetic fingerprinting), or more recently by PCR amplification,
to determine whether it is "wild type" (that is, the virus encountered in nature) or "vaccine type"
(derived from a strain of poliovirus used to produce polio vaccine).[46]It is important to determine
the source of the virus because for each reported case of paralytic polio caused by wild
poliovirus, an estimated 200 to 3,000 other contagious asymptomatic carriers exist.[47]

Prevention
Passive immunization
In 1950, William Hammon at the University of Pittsburgh purified the gamma globulin component
of the blood plasma of polio survivors.[48] Hammon proposed the gamma globulin, which
contained antibodies to poliovirus, could be used to halt poliovirus infection, prevent disease, and
reduce the severity of disease in other patients who had contracted polio. The results of a
large clinical trial were promising; the gamma globulin was shown to be about 80% effective in
preventing the development of paralytic poliomyelitis.[49] It was also shown to reduce the severity
of the disease in patients who developed polio.[48] Due to the limited supply of blood plasma
gamma globulin was later deemed impractical for widespread use and the medical community
focused on the development of a polio vaccine.[50]
Vaccine
Main article: Polio vaccine
A child receiving an oral polio vaccine

Two types of vaccine are used throughout the world to combat polio. Both types induce immunity
to polio, efficiently blocking person-to-person transmission of wild poliovirus, thereby protecting
both individual vaccine recipients and the wider community (so-called herd immunity).[51]
The first candidate polio vaccine, based on one serotype of a live but attenuated (weakened)
virus, was developed by the virologist Hilary Koprowski. Koprowski's prototype vaccine was
given to an eight-year-old boy on 27 February 1950.[52] Koprowski continued to work on the
vaccine throughout the 1950s, leading to large-scale trials in the then Belgian Congo and the
vaccination of seven million children in Poland against serotypes PV1 and PV3 between 1958
and 1960.[53]
The second inactivated virus vaccine was developed in 1952 by Jonas Salk at the University of
Pittsburgh, and announced to the world on 12 April 1955.[54] The Salk vaccine, or inactivated
poliovirus vaccine (IPV), is based on poliovirus grown in a type of monkey kidney tissue
culture (vero cell line), which is chemically inactivated with formalin.[21] After two doses of IPV
(given by injection), 90% or more of individuals develop protective antibody to all
three serotypes of poliovirus, and at least 99% are immune to poliovirus following three doses.[1]
Subsequently, Albert Sabin developed another live, oral polio vaccine (OPV). It was produced by
the repeated passage of the virus through nonhuman cells at
subphysiological temperatures.[55] The attenuated poliovirus in the Sabin vaccine replicates very
efficiently in the gut, the primary site of wild poliovirus infection and replication, but the vaccine
strain is unable to replicate efficiently within nervous system tissue.[56] A single dose of Sabin's
oral polio vaccine produces immunity to all three poliovirus serotypes in about 50% of recipients.
Three doses of live-attenuated OPV produce protective antibody to all three poliovirus types in
more than 95% of recipients.[1] Human trials of Sabin's vaccine began in 1957,[57] and in 1958 it
was selected, in competition with the live vaccines of Koprowski and other researchers, by the
US National Institutes of Health.[53] Licensed in 1962,[57] it rapidly became the only polio vaccine
used worldwide.[53]
Because OPV is inexpensive, easy to administer, and produces excellent immunity in the
intestine (which helps prevent infection with wild virus in areas where it is endemic), it has been
the vaccine of choice for controlling poliomyelitis in many countries.[58] On very rare occasions
(about one case per 750,000 vaccine recipients), the attenuated virus in OPV reverts into a form
that can paralyze.[24] Most industrialized countries have switched to IPV, which cannot revert,
either as the sole vaccine against poliomyelitis or in combination with oral polio vaccine.[59]

Treatment
There is no cure for polio. The focus of modern treatment has been on providing relief of
symptoms, speeding recovery and preventing complications. Supportive measures
include antibiotics to prevent infections in weakened muscles, analgesics for pain, moderate
exercise and a nutritious diet.[60] Treatment of polio often requires long-term rehabilitation,
including occupational therapy, physical therapy, braces, corrective shoes and, in some
cases, orthopedic surgery.[43]
Portable ventilators may be required to support breathing. Historically, a noninvasive, negative-
pressure ventilator, more commonly called an iron lung, was used to artificially maintain
respiration during an acute polio infection until a person could breathe independently (generally
about one to two weeks). Today, many polio survivors with permanent respiratory paralysis use
modern jacket-type negative-pressure ventilators worn over the chest and abdomen.[61]
Other historical treatments for polio include hydrotherapy, electrotherapy, massage and passive
motion exercises, and surgical treatments, such as tendon lengthening and nerve grafting.[15]

Prognosis

A child with a deformity of her right leg due to polio

Patients with abortive polio infections recover completely. In those who develop only aseptic
meningitis, the symptoms can be expected to persist for two to ten days, followed by complete
recovery.[62] In cases of spinal polio, if the affected nerve cells are completely destroyed, paralysis
will be permanent; cells that are not destroyed, but lose function temporarily, may recover within
four to six weeks after onset.[62]Half the patients with spinal polio recover fully; one-quarter
recover with mild disability, and the remaining quarter are left with severe disability.[63] The degree
of both acute paralysis and residual paralysis is likely to be proportional to the degree of viremia,
and inversely proportional to the degree of immunity.[36] Spinal polio is rarely fatal.[37]
Without respiratory support, consequences of poliomyelitis with respiratory involvement
include suffocation or pneumonia from aspiration of secretions.[61] Overall, 5–10% of patients with
paralytic polio die due to the paralysis of muscles used for breathing. The case fatality rate (CFR)
varies by age: 2–5% of children and up to 15–30% of adults die.[1] Bulbar polio often causes
death if respiratory support is not provided;[44] with support, its CFR ranges from 25 to 75%,
depending on the age of the patient.[1][64] When intermittent positive pressure ventilation is
available, the fatalities can be reduced to 15%.[65]
Recovery
Many cases of poliomyelitis result in only temporary paralysis.[15] Nerve impulses return to the
formerly paralyzed muscle within a month, and recovery is usually complete in six to eight
months.[62] The neurophysiological processes involved in recovery following acute paralytic
poliomyelitis are quite effective; muscles are able to retain normal strength even if half the
original motor neurons have been lost.[66]Paralysis remaining after one year is likely to be
permanent, although modest recoveries of muscle strength are possible 12 to 18 months after
infection.[62]
One mechanism involved in recovery is nerve terminal sprouting, in which remaining brainstem
and spinal cord motor neurons develop new branches, or axonal sprouts.[67]These sprouts
can reinnervate orphaned muscle fibers that have been denervated by acute polio
infection,[68] restoring the fibers' capacity to contract and improving strength.[69]Terminal sprouting
may generate a few significantly enlarged motor neurons doing work previously performed by as
many as four or five units:[38] a single motor neuron that once controlled 200 muscle cells might
control 800 to 1000 cells. Other mechanisms that occur during the rehabilitation phase, and
contribute to muscle strength restoration, include myofiber hypertrophy—enlargement of muscle
fibers through exercise and activity—and transformation of type II muscle fibers to type I muscle
fibers.[68][70]
In addition to these physiological processes, the body possesses a number of compensatory
mechanisms to maintain function in the presence of residual paralysis. These include the use of
weaker muscles at a higher than usual intensity relative to the muscle's maximal capacity,
enhancing athletic development of previously little-used muscles, and using ligaments for
stability, which enables greater mobility.[70]
Complications
Residual complications of paralytic polio often occur following the initial recovery
process.[14] Muscle paresis and paralysis can sometimes result in skeletal deformities, tightening
of the joints and movement disability. Once the muscles in the limb become flaccid, they may
interfere with the function of other muscles. A typical manifestation of this problem is equinus
foot (similar to club foot). This deformity develops when the muscles that pull the toes downward
are working, but those that pull it upward are not, and the foot naturally tends to drop toward the
ground. If the problem is left untreated, the Achilles tendons at the back of the foot retract and
the foot cannot take on a normal position. Polio victims that develop equinus foot cannot walk
properly because they cannot put their heel on the ground. A similar situation can develop if the
arms become paralyzed.[71] In some cases the growth of an affected leg is slowed by polio, while
the other leg continues to grow normally. The result is that one leg is shorter than the other and
the person limps and leans to one side, in turn leading to deformities of the spine (such
as scoliosis).[71] Osteoporosis and increased likelihood of bone fractures may occur. An
intervention to prevent or lessen length disparity can be to perform an epiphysiodesis on the
distal femoral and proximal tibial/fibular condyles, so that limb's growth is artificially stunted, and
by the time of epiphyseal (growth) plate closure, the legs are more equal in length. Alternatively,
a person can be fitted with custom made footwear which corrects the difference in leg lengths.
Other surgery to re-balance muscular agonist/antagonist imbalances may also be helpful.
Extended use of braces or wheelchairs may cause compression neuropathy, as well as a loss of
proper function of the veins in the legs, due to pooling of blood in paralyzed lower
limbs.[44][72] Complications from prolonged immobility involving
the lungs, kidneys and heart include pulmonary edema, aspiration pneumonia, urinary tract
infections, kidney stones, paralytic ileus, myocarditis and corpulmonale.[44][72]
Post-polio syndrome
Main article: Post-polio syndrome
Between 25% and 50% of individuals who have recovered from paralytic polio in childhood can
develop additional symptoms decades after recovering from the acute infection,[73]notably new
muscle weakness and extreme fatigue. This condition is known as post-polio syndrome (PPS) or
post-polio sequelae.[74] The symptoms of PPS are thought to involve a failure of the
oversized motor units created during the recovery phase of the paralytic
disease.[75][76] Contributing factors that increase the risk of PPS include aging with loss of neuron
units, the presence of a permanent residual impairment after recovery from the acute illness, and
both overuse and disuse of neurons. PPS is a slow, progressive disease, and there is no specific
treatment for it.[74] Post-polio syndrome is not an infectious process, and persons experiencing
the syndrome do not shed poliovirus.[1]

Epidemiology
Reported polio cases in 2016[3][5]

Circulating
Wild vaccine- Transmission
Country Type(s)
cases derived status
cases

WPV1
Pakistan 20 1 endemic
cVDPV2

Afghanistan 13 0 endemic WPV1

WPV1
Nigeria 4 1 endemic
cVDPV2

Laos 0 3 cVDPV only cVDPV1

Total 37 5

See also: Poliomyelitis eradication

Following the widespread use of poliovirus vaccine in the mid-1950s, the incidence of
poliomyelitis declined dramatically in many industrialized countries. A global effort
to eradicate polio began in 1988, led by the World Health Organization, UNICEF, and The Rotary
Foundation.[77] These efforts have reduced the number of annual diagnosed cases by 99.9%;
from an estimated 350,000 cases in 1988 to a low of 483 cases in 2001, after which it remained
at a level of about 1,000 - 2000 cases per year for a number of years.[78][79] In 2015, cases
decreased to 98 and further decreased in 2016 to 37 wild cases and 5 circulating vaccine-
derived cases.[80][81] Polio is one of only two diseases currently the subject of a global eradication
program, the other being Guinea worm disease.[82] So far, the only diseases completely
eradicated by humankind are smallpox, declared so, in 1980,[83][84] and rinderpest, likewise, in
2011.[85] A number of eradication milestones have already been reached, and several regions of
the world have been certified polio-free.
A concern is the presence of circulating vaccine-derived polioviruses (cVDPV). The OPV is not
perfect: while the genetic characteristics are carefully balanced to maximize efficacy and
minimize virulence, it is possible for the OPV to mutate. As a result, persons given the OPV can
acquire acute or chronic infections; or can transmit (circulate) mutated OPV to other people. It is
likely that cVDPV cases will exceed wild cases in the near future, making it desirable to
discontinue use of the OPV as soon as safely possible.[86]
Emergency declaration
In April 2012, the World Health Assembly declared the completion of polio eradication a
programmatic emergency for global public health.[87]
Americas
The Americas were declared polio-free in 1994.[88]
Western Pacific
In 2000 polio was declared to have been officially eliminated in 37 Western Pacific countries,
including China and Australia.[89][90]
Despite eradication ten years prior, an outbreak was confirmed in China in September 2011
involving a strain prevalent in neighboring Pakistan.[91]
Europe
Europe was declared polio-free in 2002.[92] On 1 September 2015, WHO confirmed 2 cases of
circulating vaccine-derived poliovirus type 1 in Ukraine.[93]
South-East Asia
The last case of polio in the region was in India in January 2011.[94] Since January 2011, there
have been no reported cases of the wild polio infections in India, and in February 2012 the
country was taken off the WHO list of polio endemic countries. It was reported that if there are no
cases of wild polio in the country for two more years, it would be declared as a polio-free
country.[95][96]
On 27 March 2014 the WHO announced the eradication of poliomyelitis in the South-East Asia
Region, which includes eleven countries: Bangladesh, Bhutan, North
Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste.[97] With
the addition of this region, 80 per cent of the world population lives in polio-free regions.[97]
Syria
In 2015, polio was believed to remain naturally spreading in only two
countries, Pakistan and Afghanistan,[97][98][99][100] although it continued to cause epidemics in other
nearby countries due to hidden or reestablished transmission.[101]
In Syria difficulties in executing immunization programs in the ongoing civil war led to a return of
polio, probably in 2012,[102] acknowledged by the WHO in 2013.[103][104] 15 cases were confirmed
among children in Syria between October and November 2013 in DeirEzzor. Later, two more
cases, each one in rural Damascus and Aleppo, were identified. It was the first outbreak in Syria
since 1999. Doctors and international public health agencies report more than 90 cases of polio
in Syria, with fears of contagion in rebel areas from lack of sanitation and safe-water
services.[105] In May 2014, the World Health Organization declared polio's renewed spread
a world health emergency.[106][107]
A vaccination campaign in Syria operated literally under fire and led to the deaths of several
vaccinators,[108] but returned vaccination coverage to pre-war levels.[109] No new cases have been
reported since January 2014; vaccination continues, and Iraq is also being closely
monitored.[110][111]
Africa
In 2003 in northern Nigeria—a country which at that time was considered provisionally polio
free—a fatwa was issued declaring that the polio vaccine was designed to render children
sterile.[112] Subsequently, polio reappeared in Nigeria and spread from there to several other
countries. In 2013, nine health workers administering polio vaccine were targeted and killed by
gunmen on motorcycles in Kano, but this was the first[113] and last attack.[114] Local traditional and
religious leaders and polio survivors worked to revive the campaign,[115] and Nigeria has not had a
polio case since July 24, 2014. In September 2015, Nigeria was removed from the polio-endemic
list.[116] In 2016 two cases recurred.[7]
In 2013 the Center for Disease Control received reports of 183 cases of polio in Somalia, 14
in Kenya and 8 cases in the Somali Region of Ethiopia,[117] but Africa had no confirmed cases of
wild poliovirus (WPV) in 2015.[98] A case of circulating vaccine-derived poliovirus (cVDPV) type 2
was detected in Siguiri in Guinea's Kankan region, in August 2014.[118] In September 2015, a case
of cVDPV in Mali was confirmed by the WHO.[118]
Afghanistan and Pakistan
This is the last remaining region with wild polio cases. Both major sides of the Afghan civil war
support polio vaccination[119] and polio rates are declining rapidly in Afghanistan, with 19 cases in
2015[98][115] and 13 in 2016.[120]
In Pakistan there were 53 cases in 2015, the highest number for any country,[98][115] and 20 in
2016.[120] Vaccination in Pakistan is hindered by conflict and organizational problems. The
militant Pakistani Taliban claims vaccination is a Western plot to sterilise local children.[121] 66
vaccinators were killed in 2013 and 2014.[122][123] Cases have dropped by 70% in 2015; reasons
include Dh440 million support from the United Arab Emirates to vaccinate more than ten million
children,[123][124] changes in the military situation, and arrests of some of those who attacked polio
workers.[121][125]

History
See also: History of poliomyelitis, Timeline of poliomyelitis, and List of poliomyelitis survivors

An Egyptian stele thought to represent a polio victim, 18th Dynasty (1403–1365 BC)

The effects of polio have been known since prehistory; Egyptian paintings and carvings depict
otherwise healthy people with withered limbs, and children walking with canes at a young
age.[126] The first clinical description was provided by the English physician Michael Underwood in
1789, where he refers to polio as "a debility of the lower extremities".[127] The work of
physicians Jakob Heine in 1840 and Karl Oskar Medin in 1890 led to it being known as Heine–
Medin disease.[128] The disease was later called infantile paralysis, based on its propensity to
affect children.
Before the 20th century, polio infections were rarely seen in infants before six months of age,
most cases occurring in children six months to four years of age. Poorer sanitation of the time
resulted in a constant exposure to the virus, which enhanced a natural immunity within the
population. In developed countries during the late 19th and early 20th centuries, improvements
were made in community sanitation, including better sewage disposal and clean water supplies.
These changes drastically increased the proportion of children and adults at risk of paralytic polio
infection, by reducing childhood exposure and immunity to the disease.[129]
Small localized paralytic polio epidemics began to appear in Europe and the United States
around 1900.[130] Outbreaks reached pandemic proportions in Europe, North America, Australia,
and New Zealand during the first half of the 20th century. By 1950 the peak age incidence of
paralytic poliomyelitis in the United States had shifted from infants to children aged five to nine
years, when the risk of paralysis is greater; about one-third of the cases were reported in persons
over 15 years of age.[131] Accordingly, the rate of paralysis and death due to polio infection also
increased during this time.[130] In the United States, the 1952 polio epidemic became the worst
outbreak in the nation's history. Of nearly 58,000 cases reported that year 3,145 died and 21,269
were left with mild to disabling paralysis.[132] Intensive care medicine has its origin in the fight
against polio.[133] Most hospitals in the 1950s had limited access to iron lungs for patients unable
to breathe without mechanical assistance. Respiratory centers designed to assist the most
severe polio patients, first established in 1952 at the Blegdam Hospital
of Copenhagen by Danish anesthesiologist Bjørn Ibsen, were the harbingers of
subsequent intensive care units (ICU). (A year later, Ibsen would establish the world's first
dedicated ICU.)[134]
The polio epidemics not only altered the lives of those who survived them, but also brought
profound cultural changes, spurring grassroots fund-raising campaigns that would revolutionize
medical philanthropy, and giving rise to the modern field of rehabilitation therapy. As one of the
largest disabled groups in the world, polio survivors also helped to advance the modern disability
rights movement through campaigns for the social and civil rights of the disabled. The World
Health Organization estimates that there are 10 to 20 million polio survivors worldwide.[135] In
1977 there were 254,000 persons living in the United States who had been paralyzed by
polio.[136] According to doctors and local polio support groups, some 40,000 polio survivors with
varying degrees of paralysis live in Germany, 30,000 in Japan, 24,000 in France, 16,000 in
Australia, 12,000 in Canada and 12,000 in the United Kingdom.[135] Many notable individuals have
survived polio and often credit the prolonged immobility and residual paralysis associated with
polio as a driving force in their lives and careers.[137]
The disease was very well publicized during the polio epidemics of the 1950s, with extensive
media coverage of any scientific advancements that might lead to a cure. Thus, the scientists
working on polio became some of the most famous of the century. Fifteen scientists and two
laymen who made important contributions to the knowledge and treatment of poliomyelitis are
honored by the Polio Hall of Fame, which was dedicated in 1957 at the Roosevelt Warm Springs
Institute for Rehabilitation in Warm Springs, Georgia, US. In 2008 four organizations (Rotary
International, the World Health Organization, the U.S. Centers for Disease Control and UNICEF)
were added to the Hall of Fame.[138][139]
World Polio Day (24 October) was established by Rotary International to commemorate the birth
of Jonas Salk, who led the first team to develop a vaccine against poliomyelitis. Use of this
inactivated poliovirus vaccine and subsequent widespread use of the oral poliovirus vaccine
developed by Albert Sabin led to establishment of the Global Polio Eradication Initiative (GPEI) in
1988. Since then, GPEI has reduced polio worldwide by 99%.[140]
Etymology
The term derives from the Ancient Greek poliós (πολιός), meaning
"grey", myelós (µυελός “marrow”), referring to the grey matter of the spinal cord, and the suffix -
itis, which denotes inflammation.,[13] i.e., inflammation of the spinal cord’s grey matter, although a
severe infection can extend into the brainstem and even higher structures, resulting
in polioencephalitis, producing a lack of ability to breathe that requires mechanical assistance
such as an iron lung.
Research
The Poliovirus Antivirals Initiative was launched in 2007 with the aim of developing antiviral
medications for polio, but while several promising candidates were identified, none have
progressed beyond Phase II clinical trials.[141][142]
 Poliomyelitis
From Wikipedia, the free encyclopedia

"Polio" redirects here. For the virus, see Poliovirus.

Not to be confused with poliosis, a condition of the hair being or becoming white or grey.

Poliomyelitis

Synonyms Polio, infantile paralysis

A man with a smaller right leg due to poliomyelitis

 /ˌpoʊlioʊˌmaɪəˈlaɪtɪs/
Pronunciation

Specialty Neurology, infectious disease

Symptoms Muscle weakness resulting in an inability to

move[1]
 Complications Post-polio syndrome[2]

Usual onset Few hours to days[1][3]

Causes Poliovirus spread by faecal[1]

Diagnostic method Finding the virus in the feces or antibodies in

the blood[1]

Prevention Polio vaccine[3]

Treatment Supportive care[3]

Frequency 42 people (2016)[3]

[edit on Wikidata]

Poliomyelitis, often called polio or infantile paralysis, is an infectious disease caused by

the poliovirus. In about 0.5% of cases there is muscle weakness resulting in an inability to
move.[1] This can occur over a few hours to a few days.[1][3] The weakness most often involves the
legs but may less commonly involve the muscles of the head, neck and diaphragm. Many but not
all people fully recover. In those with muscle weakness about 2% to 5% of children and 15% to
30% of adults die.[1]Another 25% of people have minor symptoms such as fever and a sore throat
and up to 5% have headache, neck stiffness and pains in the arms and legs.[1][3] These people
are usually back to normal within one or two weeks. In up to 70% of infections there are no
symptoms.[1] Years after recovery post-polio syndrome may occur, with a slow development of
muscle weakness similar to that which the person had during the initial infection.[2]
Poliovirus is usually spread from person to person through infected fecal matter entering the
mouth.[1] It may also be spread by food or water containing human feces and less commonly from
infected saliva.[1][3] Those who are infected may spread the disease for up to six weeks even if no
symptoms are present. The disease may be diagnosed by finding the virus in the feces or
detecting antibodies against it in the blood. The disease only occurs naturally in humans.[1]
The disease is preventable with the polio vaccine; however, a number of doses are required for it
to be effective.[3] The US Centers for Disease Control and Prevention recommends polio
vaccination boosters for travelers and those who live in countries where the disease is
occurring.[4] Once infected there is no specific treatment.[3] In 2016, polio affected 42 people, while
there were about 350,000 cases in 1988.[3][5] In 2014 the disease was only spreading between
people in Afghanistan, Nigeria, and Pakistan.[3] In 2015 Nigeria had stopped the spread of wild
poliovirus but it reoccurred in 2016.[6][7]
Poliomyelitis has existed for thousands of years, with depictions of the disease in ancient art. The
disease was first recognized as a distinct condition by Michael Underwood in 1789[1] and the
virus that causes it was first identified in 1908 by Karl Landsteiner.[8] Major outbreaks started to
occur in the late 19th century in Europe and the United States.[1] In the 20th century it became
one of the most worrying childhood diseases in these areas.[9] The first polio vaccine was
developed in the 1950s by Jonas Salk.[10] It is hoped that vaccination efforts and early detection
of cases will result in global eradication of the disease by 2018.[11]

Contents
[hide]
 1Signs and symptoms
 2Cause
o 2.1Transmission
 3Pathophysiology
o 3.1Paralytic polio
 4Diagnosis
 5Prevention
o 5.1Passive immunization
o 5.2Vaccine
 6Treatment
 7Prognosis
o 7.1Recovery
o 7.2Complications
o 7.3Post-polio syndrome
 8Epidemiology
o 8.1Emergency declaration
o 8.2Americas
o 8.3Western Pacific
o 8.4Europe
o 8.5South-East Asia
o 8.6Syria
o 8.7Africa
o 8.8Afghanistan and Pakistan
 9History
o 9.1Etymology
 10Research
 11References
 12Further reading
 13External links

Signs and symptoms

Outcomes of poliovirus infection

Outcome Proportion of cases[1]

No symptoms 72%

Minor illness 24%

Nonparalytic aseptic
1–5%
meningitis

Paralytic poliomyelitis 0.1–0.5%

 — Spinal polio 79% of paralytic cases

— Bulbospinal polio 19% of paralytic cases

— Bulbar polio 2% of paralytic cases

The term "poliomyelitis" is used to identify the disease caused by any of the three serotypes of
poliovirus. Two basic patterns of polio infection are described: a minor illness which does not
involve the central nervous system (CNS), sometimes called abortive poliomyelitis, and a major
illness involving the CNS, which may be paralytic or nonparalytic.[12] In most people with a normal
immune system, a poliovirus infection is asymptomatic. Rarely, the infection produces minor
symptoms; these may include upper respiratory tract infection (sore throat and
fever), gastrointestinal disturbances (nausea, vomiting, abdominal pain, constipation or, rarely,
diarrhea), and influenza-like illness.[1]
The virus enters the central nervous system in about 1% of infections. Most patients with CNS
involvement develop nonparalytic aseptic meningitis, with symptoms of headache, neck, back,
abdominal and extremity pain, fever, vomiting, lethargy, and irritability.[13][14] About one to five in
1000 cases progress to paralytic disease, in which the muscles become weak, floppy and poorly
controlled, and, finally, completely paralyzed; this condition is known as acute flaccid
paralysis.[15] Depending on the site of paralysis, paralytic poliomyelitis is classified as
spinal, bulbar, or bulbospinal. Encephalitis, an infection of the brain tissue itself, can occur in rare
cases, and is usually restricted to infants. It is characterized by confusion, changes in mental
status, headaches, fever, and, less commonly, seizures and spastic paralysis.[16]

Cause
Main article: Poliovirus

A TEM micrograph of poliovirus

Poliomyelitis is caused by infection with a member of the genus Enterovirus known

as poliovirus (PV). This group of RNA viruses colonize the gastrointestinal tract[17] — specifically
the oropharynx and the intestine. The incubation time (to the first signs and symptoms) ranges
from three to 35 days, with a more common span of six to 20 days.[1] PV infects and causes
disease in humans alone.[18] Its structure is very simple, composed of a single (+)
sense RNA genome enclosed in a protein shell called a capsid.[18] In addition to protecting the
virus’s genetic material, the capsid proteins enable poliovirus to infect certain types of cells.
Three serotypes of poliovirus have been identified—poliovirus type 1 (PV1), type 2 (PV2), and
type 3 (PV3)—each with a slightly different capsid protein.[19] All three are extremely virulent and
produce the same disease symptoms.[18] PV1 is the most commonly encountered form, and the
one most closely associated with paralysis.[20]
Individuals who are exposed to the virus, either through infection or by immunization with polio
vaccine, develop immunity. In immune individuals, IgA antibodies against poliovirus are present
in the tonsils and gastrointestinal tract, and are able to block virus
replication; IgG and IgM antibodies against PV can prevent the spread of the virus to motor
neurons of the central nervous system.[21] Infection or vaccination with one serotype of poliovirus
does not provide immunity against the other serotypes, and full immunity requires exposure to
each serotype.[21]
A rare condition with a similar presentation, nonpoliovirus poliomyelitis, may result from infections
with nonpoliovirus enteroviruses.[22]
Transmission
Poliomyelitis is highly contagious via the fecal-oral (intestinal source) and the oral-oral
(oropharyngeal source) routes.[21] In endemic areas, wild polioviruses can infect virtually the
entire human population.[23] It is seasonal in temperate climates, with peak transmission occurring
in summer and autumn.[21] These seasonal differences are far less pronounced
in tropical areas.[23] The time between first exposure and first symptoms, known as the incubation
period, is usually 6 to 20 days, with a maximum range of 3 to 35 days.[24] Virus particles are
excreted in the feces for several weeks following initial infection.[24] The disease
is transmitted primarily via the fecal-oral route, by ingesting contaminated food or water. It is
occasionally transmitted via the oral-oral route,[20] a mode especially visible in areas with good
sanitation and hygiene.[21] Polio is most infectious between 7 and 10 days before and after the
appearance of symptoms, but transmission is possible as long as the virus remains in the saliva
or feces.[20]
Factors that increase the risk of polio infection or affect the severity of the disease
include immune deficiency,[25] malnutrition,[26] physical activity immediately following the onset of
paralysis,[27] skeletal muscle injury due to injection of vaccines or therapeutic
agents,[28] and pregnancy.[29] Although the virus can cross the maternal-fetal barrier during
pregnancy, the fetus does not appear to be affected by either maternal infection or polio
vaccination.[30] Maternal antibodies also cross the placenta, providing passive immunity that
protects the infant from polio infection during the first few months of life.[31]
As a precaution against infection, public swimming pools were often closed in affected areas
during poliomyelitis epidemics.

Pathophysiology

A blockage of the lumbar anterior spinal cord artery due to polio (PV3)
Poliovirus enters the body through the mouth, infecting the first cells with which it comes in
contact — the pharynx and intestinal mucosa. It gains entry by binding to an immunoglobulin-
like receptor, known as the poliovirus receptor or CD155, on the cell membrane.[32] The virus then
hijacks the host cell's own machinery, and begins to replicate. Poliovirus divides within
gastrointestinal cells for about a week, from where it spreads to the tonsils (specifically
the follicular dendritic cells residing within the tonsilar germinal centers), the intestinal lymphoid
tissue including the M cells of Peyer's patches, and the deep cervical and mesenteric lymph
nodes, where it multiplies abundantly. The virus is subsequently absorbed into the
bloodstream.[33]
Known as viremia, the presence of a virus in the bloodstream enables it to be widely distributed
throughout the body. Poliovirus can survive and multiply within the blood and lymphatics for long
periods of time, sometimes as long as 17 weeks.[34] In a small percentage of cases, it can spread
and replicate in other sites, such as brown fat, the reticuloendothelial tissues, and muscle.[35] This
sustained replication causes a major viremia, and leads to the development of minor influenza-
like symptoms. Rarely, this may progress and the virus may invade the central nervous system,
provoking a local inflammatory response. In most cases, this causes a self-limiting inflammation
of the meninges, the layers of tissue surrounding the brain, which is known as nonparalytic
aseptic meningitis.[13] Penetration of the CNS provides no known benefit to the virus, and is quite
possibly an incidental deviation of a normal gastrointestinal infection.[36] The mechanisms by
which poliovirus spreads to the CNS are poorly understood, but it appears to be primarily a
chance event—largely independent of the age, gender, or socioeconomic position of the
individual.[36]
Paralytic polio

Denervation of skeletal muscle tissue secondary to poliovirus infection can lead to paralysis.

In around 1% of infections, poliovirus spreads along certain nerve fiber pathways, preferentially
replicating in and destroying motor neurons within the spinal cord, brain stem, or motor cortex.
This leads to the development of paralytic poliomyelitis, the various forms of which (spinal,
bulbar, and bulbospinal) vary only with the amount of neuronal damage and inflammation that
occurs, and the region of the CNS affected.
The destruction of neuronal cells produces lesions within the spinal ganglia; these may also
occur in the reticular formation, vestibular nuclei, cerebellar vermis, and deep cerebellar
nuclei.[36] Inflammation associated with nerve cell destruction often alters the color and
appearance of the gray matter in the spinal column, causing it to appear reddish and
swollen.[13] Other destructive changes associated with paralytic disease occur in
the forebrain region, specifically the hypothalamus and thalamus.[36] The molecular mechanisms
by which poliovirus causes paralytic disease are poorly understood.
Early symptoms of paralytic polio include high fever, headache, stiffness in the back and neck,
asymmetrical weakness of various muscles, sensitivity to touch, difficulty swallowing, muscle
pain, loss of superficial and deep reflexes, paresthesia (pins and needles), irritability,
constipation, or difficulty urinating. Paralysis generally develops one to ten days after early
symptoms begin, progresses for two to three days, and is usually complete by the time the fever
breaks.[37]
The likelihood of developing paralytic polio increases with age, as does the extent of paralysis. In
children, nonparalytic meningitis is the most likely consequence of CNS involvement, and
paralysis occurs in only one in 1000 cases. In adults, paralysis occurs in one in 75 cases.[38] In
children under five years of age, paralysis of one leg is most common; in adults, extensive
paralysis of the chest and abdomen also affecting all four limbs—quadriplegia—is more
likely.[39] Paralysis rates also vary depending on the serotype of the infecting poliovirus; the
highest rates of paralysis (one in 200) are associated with poliovirus type 1, the lowest rates (one
in 2,000) are associated with type 2.[40]
Spinal polio

The location of motor neurons in the anterior horn cells of the spinal column

Spinal polio, the most common form of paralytic poliomyelitis, results from viral invasion of the
motor neurons of the anterior horn cells, or the ventral (front) grey matter section in the spinal
column, which are responsible for movement of the muscles, including those of the trunk, limbs,
and the intercostal muscles.[15] Virus invasion causes inflammation of the nerve cells, leading to
damage or destruction of motor neuron ganglia. When spinal neurons die, Wallerian
degeneration takes place, leading to weakness of those muscles formerly innervated by the now-
dead neurons.[41] With the destruction of nerve cells, the muscles no longer receive signals from
the brain or spinal cord; without nerve stimulation, the muscles atrophy, becoming weak, floppy
and poorly controlled, and finally completely paralyzed.[15]Maximum paralysis progresses rapidly
(two to four days), and usually involves fever and muscle pain. Deep tendon reflexes are also
affected, and are typically absent or diminished; sensation (the ability to feel) in the paralyzed
limbs, however, is not affected.[42]
The extent of spinal paralysis depends on the region of the cord affected, which may
be cervical, thoracic, or lumbar.[43] The virus may affect muscles on both sides of the body, but
more often the paralysis is asymmetrical.[33] Any limb or combination of limbs may be affected—
one leg, one arm, or both legs and both arms. Paralysis is often more severe proximally (where
the limb joins the body) than distally (the fingertips and toes).[33]
Bulbar polio

The location and anatomy of the bulbar region (in orange)

Making up about 2% of cases of paralytic polio, bulbar polio occurs when poliovirus invades and
destroys nerves within the bulbar region of the brain stem.[1] The bulbar region is a white
matter pathway that connects the cerebral cortex to the brain stem. The destruction of these
nerves weakens the muscles supplied by the cranial nerves, producing symptoms
of encephalitis, and causes difficulty breathing, speaking and swallowing.[14] Critical nerves
affected are the glossopharyngeal nerve (which partially controls swallowing and functions in the
throat, tongue movement, and taste), the vagus nerve (which sends signals to the heart,
intestines, and lungs), and the accessory nerve (which controls upper neck movement). Due to
the effect on swallowing, secretions of mucus may build up in the airway, causing
suffocation.[37] Other signs and symptoms include facial weakness (caused by destruction of
the trigeminal nerve and facial nerve, which innervate the cheeks, tear ducts, gums, and muscles
of the face, among other structures), double vision, difficulty in chewing, and
abnormal respiratory rate, depth, and rhythm (which may lead to respiratory arrest). Pulmonary
edema and shock are also possible and may be fatal.[43]
Bulbospinal polio
Approximately 19% of all paralytic polio cases have both bulbar and spinal symptoms; this
subtype is called respiratory or bulbospinal polio.[1] Here, the virus affects the upper part of the
cervical spinal cord (cervical vertebrae C3 through C5), and paralysis of the diaphragm occurs.
The critical nerves affected are the phrenic nerve (which drives the diaphragm to inflate
the lungs) and those that drive the muscles needed for swallowing. By destroying these nerves,
this form of polio affects breathing, making it difficult or impossible for the patient to breathe
without the support of a ventilator. It can lead to paralysis of the arms and legs and may also
affect swallowing and heart functions.[44]

Diagnosis
Paralytic poliomyelitis may be clinically suspected in individuals experiencing acute onset of
flaccid paralysis in one or more limbs with decreased or absent tendon reflexes in the affected
limbs that cannot be attributed to another apparent cause, and without sensory
or cognitive loss.[45]
A laboratory diagnosis is usually made based on recovery of poliovirus from a stool sample or a
swab of the pharynx. Antibodies to poliovirus can be diagnostic, and are generally detected in the
blood of infected patients early in the course of infection.[1] Analysis of the patient's cerebrospinal
fluid (CSF), which is collected by a lumbar puncture ("spinal tap"), reveals an increased number
of white blood cells (primarily lymphocytes) and a mildly elevated protein level. Detection of virus
in the CSF is diagnostic of paralytic polio, but rarely occurs.[1]
If poliovirus is isolated from a patient experiencing acute flaccid paralysis, it is further tested
through oligonucleotide mapping (genetic fingerprinting), or more recently by PCR amplification,
to determine whether it is "wild type" (that is, the virus encountered in nature) or "vaccine type"
(derived from a strain of poliovirus used to produce polio vaccine).[46]It is important to determine
the source of the virus because for each reported case of paralytic polio caused by wild
poliovirus, an estimated 200 to 3,000 other contagious asymptomatic carriers exist.[47]

Prevention
Passive immunization
In 1950, William Hammon at the University of Pittsburgh purified the gamma globulin component
of the blood plasma of polio survivors.[48] Hammon proposed the gamma globulin, which
contained antibodies to poliovirus, could be used to halt poliovirus infection, prevent disease, and
reduce the severity of disease in other patients who had contracted polio. The results of a
large clinical trial were promising; the gamma globulin was shown to be about 80% effective in
preventing the development of paralytic poliomyelitis.[49] It was also shown to reduce the severity
of the disease in patients who developed polio.[48] Due to the limited supply of blood plasma
gamma globulin was later deemed impractical for widespread use and the medical community
focused on the development of a polio vaccine.[50]
Vaccine
Main article: Polio vaccine

A child receiving an oral polio vaccine

Two types of vaccine are used throughout the world to combat polio. Both types induce immunity
to polio, efficiently blocking person-to-person transmission of wild poliovirus, thereby protecting
both individual vaccine recipients and the wider community (so-called herd immunity).[51]
The first candidate polio vaccine, based on one serotype of a live but attenuated (weakened)
virus, was developed by the virologist Hilary Koprowski. Koprowski's prototype vaccine was
given to an eight-year-old boy on 27 February 1950.[52] Koprowski continued to work on the
vaccine throughout the 1950s, leading to large-scale trials in the then Belgian Congo and the
vaccination of seven million children in Poland against serotypes PV1 and PV3 between 1958
and 1960.[53]
The second inactivated virus vaccine was developed in 1952 by Jonas Salk at the University of
Pittsburgh, and announced to the world on 12 April 1955.[54] The Salk vaccine, or inactivated
poliovirus vaccine (IPV), is based on poliovirus grown in a type of monkey kidney tissue
culture (vero cell line), which is chemically inactivated with formalin.[21] After two doses of IPV
(given by injection), 90% or more of individuals develop protective antibody to all
three serotypes of poliovirus, and at least 99% are immune to poliovirus following three doses.[1]
Subsequently, Albert Sabin developed another live, oral polio vaccine (OPV). It was produced by
the repeated passage of the virus through nonhuman cells at
subphysiological temperatures.[55] The attenuated poliovirus in the Sabin vaccine replicates very
efficiently in the gut, the primary site of wild poliovirus infection and replication, but the vaccine
strain is unable to replicate efficiently within nervous system tissue.[56] A single dose of Sabin's
oral polio vaccine produces immunity to all three poliovirus serotypes in about 50% of recipients.
Three doses of live-attenuated OPV produce protective antibody to all three poliovirus types in
more than 95% of recipients.[1] Human trials of Sabin's vaccine began in 1957,[57] and in 1958 it
was selected, in competition with the live vaccines of Koprowski and other researchers, by the
US National Institutes of Health.[53] Licensed in 1962,[57] it rapidly became the only polio vaccine
used worldwide.[53]
Because OPV is inexpensive, easy to administer, and produces excellent immunity in the
intestine (which helps prevent infection with wild virus in areas where it is endemic), it has been
the vaccine of choice for controlling poliomyelitis in many countries.[58] On very rare occasions
(about one case per 750,000 vaccine recipients), the attenuated virus in OPV reverts into a form
that can paralyze.[24] Most industrialized countries have switched to IPV, which cannot revert,
either as the sole vaccine against poliomyelitis or in combination with oral polio vaccine.[59]

Treatment
There is no cure for polio. The focus of modern treatment has been on providing relief of
symptoms, speeding recovery and preventing complications. Supportive measures
include antibiotics to prevent infections in weakened muscles, analgesics for pain, moderate
exercise and a nutritious diet.[60] Treatment of polio often requires long-term rehabilitation,
including occupational therapy, physical therapy, braces, corrective shoes and, in some
cases, orthopedic surgery.[43]
Portable ventilators may be required to support breathing. Historically, a noninvasive, negative-
pressure ventilator, more commonly called an iron lung, was used to artificially maintain
respiration during an acute polio infection until a person could breathe independently (generally
about one to two weeks). Today, many polio survivors with permanent respiratory paralysis use
modern jacket-type negative-pressure ventilators worn over the chest and abdomen.[61]
Other historical treatments for polio include hydrotherapy, electrotherapy, massage and passive
motion exercises, and surgical treatments, such as tendon lengthening and nerve grafting.[15]

Prognosis

A child with a deformity of her right leg due to polio

Patients with abortive polio infections recover completely. In those who develop only aseptic
meningitis, the symptoms can be expected to persist for two to ten days, followed by complete
recovery.[62] In cases of spinal polio, if the affected nerve cells are completely destroyed, paralysis
will be permanent; cells that are not destroyed, but lose function temporarily, may recover within
four to six weeks after onset.[62]Half the patients with spinal polio recover fully; one-quarter
recover with mild disability, and the remaining quarter are left with severe disability.[63] The degree
of both acute paralysis and residual paralysis is likely to be proportional to the degree of viremia,
and inversely proportional to the degree of immunity.[36] Spinal polio is rarely fatal.[37]
Without respiratory support, consequences of poliomyelitis with respiratory involvement
include suffocation or pneumonia from aspiration of secretions.[61] Overall, 5–10% of patients with
paralytic polio die due to the paralysis of muscles used for breathing. The case fatality rate (CFR)
varies by age: 2–5% of children and up to 15–30% of adults die.[1] Bulbar polio often causes
death if respiratory support is not provided;[44] with support, its CFR ranges from 25 to 75%,
depending on the age of the patient.[1][64] When intermittent positive pressure ventilation is
available, the fatalities can be reduced to 15%.[65]
Recovery
Many cases of poliomyelitis result in only temporary paralysis.[15] Nerve impulses return to the
formerly paralyzed muscle within a month, and recovery is usually complete in six to eight
months.[62] The neurophysiological processes involved in recovery following acute paralytic
poliomyelitis are quite effective; muscles are able to retain normal strength even if half the
original motor neurons have been lost.[66]Paralysis remaining after one year is likely to be
permanent, although modest recoveries of muscle strength are possible 12 to 18 months after
infection.[62]
One mechanism involved in recovery is nerve terminal sprouting, in which remaining brainstem
and spinal cord motor neurons develop new branches, or axonal sprouts.[67]These sprouts
can reinnervate orphaned muscle fibers that have been denervated by acute polio
infection,[68] restoring the fibers' capacity to contract and improving strength.[69]Terminal sprouting
may generate a few significantly enlarged motor neurons doing work previously performed by as
many as four or five units:[38] a single motor neuron that once controlled 200 muscle cells might
control 800 to 1000 cells. Other mechanisms that occur during the rehabilitation phase, and
contribute to muscle strength restoration, include myofiber hypertrophy—enlargement of muscle
fibers through exercise and activity—and transformation of type II muscle fibers to type I muscle
fibers.[68][70]
In addition to these physiological processes, the body possesses a number of compensatory
mechanisms to maintain function in the presence of residual paralysis. These include the use of
weaker muscles at a higher than usual intensity relative to the muscle's maximal capacity,
enhancing athletic development of previously little-used muscles, and using ligaments for
stability, which enables greater mobility.[70]
Complications
Residual complications of paralytic polio often occur following the initial recovery
process.[14] Muscle paresis and paralysis can sometimes result in skeletal deformities, tightening
of the joints and movement disability. Once the muscles in the limb become flaccid, they may
interfere with the function of other muscles. A typical manifestation of this problem is equinus
foot (similar to club foot). This deformity develops when the muscles that pull the toes downward
are working, but those that pull it upward are not, and the foot naturally tends to drop toward the
ground. If the problem is left untreated, the Achilles tendons at the back of the foot retract and
the foot cannot take on a normal position. Polio victims that develop equinus foot cannot walk
properly because they cannot put their heel on the ground. A similar situation can develop if the
arms become paralyzed.[71] In some cases the growth of an affected leg is slowed by polio, while
the other leg continues to grow normally. The result is that one leg is shorter than the other and
the person limps and leans to one side, in turn leading to deformities of the spine (such
as scoliosis).[71] Osteoporosis and increased likelihood of bone fractures may occur. An
intervention to prevent or lessen length disparity can be to perform an epiphysiodesis on the
distal femoral and proximal tibial/fibular condyles, so that limb's growth is artificially stunted, and
by the time of epiphyseal (growth) plate closure, the legs are more equal in length. Alternatively,
a person can be fitted with custom made footwear which corrects the difference in leg lengths.
Other surgery to re-balance muscular agonist/antagonist imbalances may also be helpful.
Extended use of braces or wheelchairs may cause compression neuropathy, as well as a loss of
proper function of the veins in the legs, due to pooling of blood in paralyzed lower
limbs.[44][72] Complications from prolonged immobility involving
the lungs, kidneys and heart include pulmonary edema, aspiration pneumonia, urinary tract
infections, kidney stones, paralytic ileus, myocarditis and corpulmonale.[44][72]
Post-polio syndrome
Main article: Post-polio syndrome
Between 25% and 50% of individuals who have recovered from paralytic polio in childhood can
develop additional symptoms decades after recovering from the acute infection,[73]notably new
muscle weakness and extreme fatigue. This condition is known as post-polio syndrome (PPS) or
post-polio sequelae.[74] The symptoms of PPS are thought to involve a failure of the
oversized motor units created during the recovery phase of the paralytic
disease.[75][76] Contributing factors that increase the risk of PPS include aging with loss of neuron
units, the presence of a permanent residual impairment after recovery from the acute illness, and
both overuse and disuse of neurons. PPS is a slow, progressive disease, and there is no specific
treatment for it.[74] Post-polio syndrome is not an infectious process, and persons experiencing
the syndrome do not shed poliovirus.[1]

Epidemiology
Reported polio cases in 2016[3][5]

Circulating
Wild vaccine- Transmission
Country Type(s)
cases derived status
cases

WPV1
Pakistan 20 1 endemic
cVDPV2

Afghanistan 13 0 endemic WPV1

WPV1
Nigeria 4 1 endemic
cVDPV2

Laos 0 3 cVDPV only cVDPV1

Total 37 5

See also: Poliomyelitis eradication

Following the widespread use of poliovirus vaccine in the mid-1950s, the incidence of
poliomyelitis declined dramatically in many industrialized countries. A global effort
to eradicate polio began in 1988, led by the World Health Organization, UNICEF, and The Rotary
Foundation.[77] These efforts have reduced the number of annual diagnosed cases by 99.9%;
from an estimated 350,000 cases in 1988 to a low of 483 cases in 2001, after which it remained
at a level of about 1,000 - 2000 cases per year for a number of years.[78][79] In 2015, cases
decreased to 98 and further decreased in 2016 to 37 wild cases and 5 circulating vaccine-
derived cases.[80][81] Polio is one of only two diseases currently the subject of a global eradication
program, the other being Guinea worm disease.[82] So far, the only diseases completely
eradicated by humankind are smallpox, declared so, in 1980,[83][84] and rinderpest, likewise, in
2011.[85] A number of eradication milestones have already been reached, and several regions of
the world have been certified polio-free.
A concern is the presence of circulating vaccine-derived polioviruses (cVDPV). The OPV is not
perfect: while the genetic characteristics are carefully balanced to maximize efficacy and
minimize virulence, it is possible for the OPV to mutate. As a result, persons given the OPV can
acquire acute or chronic infections; or can transmit (circulate) mutated OPV to other people. It is
likely that cVDPV cases will exceed wild cases in the near future, making it desirable to
discontinue use of the OPV as soon as safely possible.[86]
Emergency declaration
In April 2012, the World Health Assembly declared the completion of polio eradication a
programmatic emergency for global public health.[87]
Americas
The Americas were declared polio-free in 1994.[88]
Western Pacific
In 2000 polio was declared to have been officially eliminated in 37 Western Pacific countries,
including China and Australia.[89][90]
Despite eradication ten years prior, an outbreak was confirmed in China in September 2011
involving a strain prevalent in neighboring Pakistan.[91]
Europe
Europe was declared polio-free in 2002.[92] On 1 September 2015, WHO confirmed 2 cases of
circulating vaccine-derived poliovirus type 1 in Ukraine.[93]
South-East Asia
The last case of polio in the region was in India in January 2011.[94] Since January 2011, there
have been no reported cases of the wild polio infections in India, and in February 2012 the
country was taken off the WHO list of polio endemic countries. It was reported that if there are no
cases of wild polio in the country for two more years, it would be declared as a polio-free
country.[95][96]
On 27 March 2014 the WHO announced the eradication of poliomyelitis in the South-East Asia
Region, which includes eleven countries: Bangladesh, Bhutan, North
Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste.[97] With
the addition of this region, 80 per cent of the world population lives in polio-free regions.[97]
Syria
In 2015, polio was believed to remain naturally spreading in only two
countries, Pakistan and Afghanistan,[97][98][99][100] although it continued to cause epidemics in other
nearby countries due to hidden or reestablished transmission.[101]
In Syria difficulties in executing immunization programs in the ongoing civil war led to a return of
polio, probably in 2012,[102] acknowledged by the WHO in 2013.[103][104] 15 cases were confirmed
among children in Syria between October and November 2013 in DeirEzzor. Later, two more
cases, each one in rural Damascus and Aleppo, were identified. It was the first outbreak in Syria
since 1999. Doctors and international public health agencies report more than 90 cases of polio
in Syria, with fears of contagion in rebel areas from lack of sanitation and safe-water
services.[105] In May 2014, the World Health Organization declared polio's renewed spread
a world health emergency.[106][107]
A vaccination campaign in Syria operated literally under fire and led to the deaths of several
vaccinators,[108] but returned vaccination coverage to pre-war levels.[109] No new cases have been
reported since January 2014; vaccination continues, and Iraq is also being closely
monitored.[110][111]
Africa
In 2003 in northern Nigeria—a country which at that time was considered provisionally polio
free—a fatwa was issued declaring that the polio vaccine was designed to render children
sterile.[112] Subsequently, polio reappeared in Nigeria and spread from there to several other
countries. In 2013, nine health workers administering polio vaccine were targeted and killed by
gunmen on motorcycles in Kano, but this was the first[113] and last attack.[114] Local traditional and
religious leaders and polio survivors worked to revive the campaign,[115] and Nigeria has not had a
polio case since July 24, 2014. In September 2015, Nigeria was removed from the polio-endemic
list.[116] In 2016 two cases recurred.[7]
In 2013 the Center for Disease Control received reports of 183 cases of polio in Somalia, 14
in Kenya and 8 cases in the Somali Region of Ethiopia,[117] but Africa had no confirmed cases of
wild poliovirus (WPV) in 2015.[98] A case of circulating vaccine-derived poliovirus (cVDPV) type 2
was detected in Siguiri in Guinea's Kankan region, in August 2014.[118] In September 2015, a case
of cVDPV in Mali was confirmed by the WHO.[118]
Afghanistan and Pakistan
This is the last remaining region with wild polio cases. Both major sides of the Afghan civil war
support polio vaccination[119] and polio rates are declining rapidly in Afghanistan, with 19 cases in
2015[98][115] and 13 in 2016.[120]
In Pakistan there were 53 cases in 2015, the highest number for any country,[98][115] and 20 in
2016.[120] Vaccination in Pakistan is hindered by conflict and organizational problems. The
militant Pakistani Taliban claims vaccination is a Western plot to sterilise local children.[121] 66
vaccinators were killed in 2013 and 2014.[122][123] Cases have dropped by 70% in 2015; reasons
include Dh440 million support from the United Arab Emirates to vaccinate more than ten million
children,[123][124] changes in the military situation, and arrests of some of those who attacked polio
workers.[121][125]

History
See also: History of poliomyelitis, Timeline of poliomyelitis, and List of poliomyelitis survivors

An Egyptian stele thought to represent a polio victim, 18th Dynasty (1403–1365 BC)

The effects of polio have been known since prehistory; Egyptian paintings and carvings depict
otherwise healthy people with withered limbs, and children walking with canes at a young
age.[126] The first clinical description was provided by the English physician Michael Underwood in
1789, where he refers to polio as "a debility of the lower extremities".[127] The work of
physicians Jakob Heine in 1840 and Karl Oskar Medin in 1890 led to it being known as Heine–
Medin disease.[128] The disease was later called infantile paralysis, based on its propensity to
affect children.
Before the 20th century, polio infections were rarely seen in infants before six months of age,
most cases occurring in children six months to four years of age. Poorer sanitation of the time
resulted in a constant exposure to the virus, which enhanced a natural immunity within the
population. In developed countries during the late 19th and early 20th centuries, improvements
were made in community sanitation, including better sewage disposal and clean water supplies.
These changes drastically increased the proportion of children and adults at risk of paralytic polio
infection, by reducing childhood exposure and immunity to the disease.[129]
Small localized paralytic polio epidemics began to appear in Europe and the United States
around 1900.[130] Outbreaks reached pandemic proportions in Europe, North America, Australia,
and New Zealand during the first half of the 20th century. By 1950 the peak age incidence of
paralytic poliomyelitis in the United States had shifted from infants to children aged five to nine
years, when the risk of paralysis is greater; about one-third of the cases were reported in persons
over 15 years of age.[131] Accordingly, the rate of paralysis and death due to polio infection also
increased during this time.[130] In the United States, the 1952 polio epidemic became the worst
outbreak in the nation's history. Of nearly 58,000 cases reported that year 3,145 died and 21,269
were left with mild to disabling paralysis.[132] Intensive care medicine has its origin in the fight
against polio.[133] Most hospitals in the 1950s had limited access to iron lungs for patients unable
to breathe without mechanical assistance. Respiratory centers designed to assist the most
severe polio patients, first established in 1952 at the Blegdam Hospital
of Copenhagen by Danish anesthesiologist Bjørn Ibsen, were the harbingers of
subsequent intensive care units (ICU). (A year later, Ibsen would establish the world's first
dedicated ICU.)[134]
The polio epidemics not only altered the lives of those who survived them, but also brought
profound cultural changes, spurring grassroots fund-raising campaigns that would revolutionize
medical philanthropy, and giving rise to the modern field of rehabilitation therapy. As one of the
largest disabled groups in the world, polio survivors also helped to advance the modern disability
rights movement through campaigns for the social and civil rights of the disabled. The World
Health Organization estimates that there are 10 to 20 million polio survivors worldwide.[135] In
1977 there were 254,000 persons living in the United States who had been paralyzed by
polio.[136] According to doctors and local polio support groups, some 40,000 polio survivors with
varying degrees of paralysis live in Germany, 30,000 in Japan, 24,000 in France, 16,000 in
Australia, 12,000 in Canada and 12,000 in the United Kingdom.[135] Many notable individuals have
survived polio and often credit the prolonged immobility and residual paralysis associated with
polio as a driving force in their lives and careers.[137]
The disease was very well publicized during the polio epidemics of the 1950s, with extensive
media coverage of any scientific advancements that might lead to a cure. Thus, the scientists
working on polio became some of the most famous of the century. Fifteen scientists and two
laymen who made important contributions to the knowledge and treatment of poliomyelitis are
honored by the Polio Hall of Fame, which was dedicated in 1957 at the Roosevelt Warm Springs
Institute for Rehabilitation in Warm Springs, Georgia, US. In 2008 four organizations (Rotary
International, the World Health Organization, the U.S. Centers for Disease Control and UNICEF)
were added to the Hall of Fame.[138][139]
World Polio Day (24 October) was established by Rotary International to commemorate the birth
of Jonas Salk, who led the first team to develop a vaccine against poliomyelitis. Use of this
inactivated poliovirus vaccine and subsequent widespread use of the oral poliovirus vaccine
developed by Albert Sabin led to establishment of the Global Polio Eradication Initiative (GPEI) in
1988. Since then, GPEI has reduced polio worldwide by 99%.[140]
Etymology
The term derives from the Ancient Greek poliós (πολιός), meaning
"grey", myelós (µυελός “marrow”), referring to the grey matter of the spinal cord, and the suffix -
itis, which denotes inflammation.,[13] i.e., inflammation of the spinal cord’s grey matter, although a
severe infection can extend into the brainstem and even higher structures, resulting
in polioencephalitis, producing a lack of ability to breathe that requires mechanical assistance
such as an iron lung.

Research
The Poliovirus Antivirals Initiative was launched in 2007 with the aim of developing antiviral
medications for polio, but while several promising candidates were identified, none have
progressed beyond Phase II clinical trials.[141][142]
 Epilepsy
From Wikipedia, the free encyclopedia

"Epilepsia" and "Epileptic" redirect here. For the journal, see Epilepsia (journal). For the novel,
see Epileptic (graphic novel).

Epilepsy

Synonyms seizure disorder

Generalized 3 Hz spike-and-wave discharges on an

electroencephalogram

Specialty Neurology

Symptoms Periods of vigorous shaking, nearly undetectable

spells[1]

Duration Long term[1]

Causes Unknown, brain injury, stroke, brain tumors,

infections of the brain, birth defects[1][2][3]
 Diagnostic Electroencephalogram, ruling out other possible

method causes[4]

Similar Fainting, alcohol withdrawal, electrolyte problems[4]

conditions

Treatment Medication, surgery, neurostimulation, dietary

changes[5][6]

Prognosis Controllable in 70%[7]

Frequency 39 million / 0.5% (2015)[8]

Deaths 125,000 (2015)[9]

[edit on Wikidata]

Epilepsy is a group of neurological disorders characterized by epileptic seizures.[10][11] Epileptic

seizures are episodes that can vary from brief and nearly undetectable to long periods of
vigorous shaking.[1] These episodes can result in physical injuries including occasionally broken
bones.[1] In epilepsy, seizures tend to recur and as a rule, have no immediate underlying
cause.[10] Isolated seizures that are provoked by a specific cause such as poisoning are not
deemed to represent epilepsy.[12]People with epilepsy in some areas of the world
experience stigma due to the condition.[1]
The cause of most cases of epilepsy is unknown.[1] Some cases occur as the result of brain
injury, stroke, brain tumors, infections of the brain, and birth defects, through a process known
as epileptogenesis.[1][2][3] Known genetic mutations are directly linked to a small proportion of
cases.[4][13] Epileptic seizures are the result of excessive and abnormal nerve cell activity in
the cortex of the brain.[12] The diagnosis involves ruling out other conditions that might cause
similar symptoms such as fainting and determining if another cause of seizures is present such
as alcohol withdrawal or electrolyte problems. This may be partly done by imaging the brain and
performing blood tests. Epilepsy can often be confirmed with an electroencephalogram (EEG),
but a normal test does not rule out the condition.[4]
Epilepsy that occurs as a result of other issues may be preventable.[1] Seizures are controllable
with medication in about 70% of cases.[7] Inexpensive options are often available.[1] In those
whose seizures do not respond to medication, then surgery, neurostimulation, or dietary changes
may be considered.[5][6] Not all cases of epilepsy are lifelong, and many people improve to the
point that treatment is no longer needed.[1]
As of 2015 about 39 million people have epilepsy.[8] Nearly 80% of cases occur in the developing
world.[1] In 2015 it resulted in 125,000 deaths up from 112,000 deaths in 1990.[9][14] Epilepsy is
more common in older people.[15][16] In the developed world, onset of new cases occurs most
frequently in babies and the elderly.[17] In the developing world onset is more common in older
children and young adults, due to differences in the frequency of the underlying causes.[18] About
5–10% of people will have an unprovoked seizure by the age of 80,[19] and the chance of
experiencing a second seizure is between 40 and 50%.[20] In many areas of the world those with
epilepsy either have restrictions placed on their ability to drive or are not permitted to drive until
 they are free of seizures for a specific length of time.[21] The word epilepsy is
from Ancient Greek: ἐπιλαμβάνειν "to seize, possess, or afflict".[22]

Video explanation

Contents
[hide]

 1Signs and symptoms

o 1.1Seizures
o 1.2Postictal
o 1.3Psychosocial
 2Causes
o 2.1Genetics
o 2.2Acquired
 3Mechanism
o 3.1Epilepsy
o 3.2Seizures
 4Diagnosis
o 4.1Definition
o 4.2Classification
o 4.3Syndromes
o 4.4Tests
o 4.5Differential diagnosis
 5Prevention
 6Management
o 6.1First aid
o 6.2Medications
o 6.3Surgery
o 6.4Diet
o 6.5Other
o 6.6Alternative medicine
 7Prognosis
o 7.1Mortality
 8Epidemiology
 9History
 10Society and culture
o 10.1Stigma
o 10.2Economics
o 10.3Vehicles
o 10.4Support organizations
 11Research
 12Other animals
 13References
 14Further reading
 15External links

Signs and symptoms[edit]

An instructional video about epileptic seizures

A still image of a generalized seizure

A bite to the tip of the tongue due to a seizure

Epilepsy is characterized by a long-term risk of recurrent seizures.[23] These seizures may present
in several ways depending on the part of the brain involved and the person's age.[23][24]
Seizures[edit]
Main article: Epileptic seizure
The most common type (60%) of seizures are convulsive.[24] Of these, one-third begin
as generalized seizures from the start, affecting both hemispheres of the brain.[24] Two-thirds
begin as focal seizures (which affect one hemisphere of the brain) which may then progress
to generalized seizures.[24] The remaining 40% of seizures are non-convulsive. An example of this
type is the absence seizure, which presents as a decreased level of consciousness and usually
lasts about 10 seconds.[2][25]
Focal seizures are often preceded by certain experiences, known as auras.[26] They include
sensory (visual, hearing, or smell), psychic, autonomic, and motor phenomena.[2] Jerking activity
may start in a specific muscle group and spread to surrounding muscle groups in which case it is
known as a Jacksonian march.[27] Automatisms may occur, which are non-consciously-generated
activities and mostly simple repetitive movements like smacking of the lips or more complex
activities such as attempts to pick up something.[27]
There are six main types of generalized seizures: tonic-clonic, tonic, clonic, myoclonic, absence,
and atonic seizures.[28]They all involve loss of consciousness and typically happen without
warning.
Tonic-clonic seizures occur with a contraction of the limbs followed by their extension along with
arching of the back which lasts 10–30 seconds (the tonic phase). A cry may be heard due to
contraction of the chest muscles, followed by a shaking of the limbs in unison (clonic phase).
Tonic seizures produce constant contractions of the muscles. A person often turns blue as
breathing is stopped. In clonic seizures there is shaking of the limbs in unison. After the shaking
has stopped it may take 10–30 minutes for the person to return to normal; this period is called
the "postictal state" or "postictal phase." Loss of bowel or bladder control may occur during a
seizure.[29] The tongue may be bitten at either the tip or on the sides during a seizure.[30] In tonic-
clonic seizure, bites to the sides are more common.[30] Tongue bites are also relatively common
in psychogenic non-epileptic seizures.[30]
Myoclonic seizures involve spasms of muscles in either a few areas or all over.[31] Absence
seizures can be subtle with only a slight turn of the head or eye blinking.[2] The person does not
fall over and returns to normal right after it ends.[2] Atonic seizures involve the loss of muscle
activity for greater than one second.[27] This typically occurs on both sides of the body.[27]
About 6% of those with epilepsy have seizures that are often triggered by specific events and are
known as reflex seizures.[32] Those with reflex epilepsy have seizures that are only triggered by
specific stimuli.[33] Common triggers include flashing lights and sudden noises.[32] In certain types
of epilepsy, seizures happen more often during sleep,[34] and in other types they occur almost
only when sleeping.[35]
Postictal[edit]
After the active portion of a seizure (the ictal state) there is typically a period of recovery during
which there is confusion, referred to as the postictal period before a normal level of
consciousness returns.[26] It usually lasts 3 to 15 minutes[36] but may last for hours.[37] Other
common symptoms include feeling tired, headache, difficulty speaking, and abnormal
behavior.[37] Psychosis after a seizure is relatively common, occurring in 6–10% of
people.[38] Often people do not remember what happened during this time.[37] Localized weakness,
known as Todd's paralysis, may also occur after a focal seizure. When it occurs it typically lasts
for seconds to minutes but may rarely last for a day or two.[39]
Psychosocial[edit]
Epilepsy can have adverse effects on social and psychological well-being.[24] These effects may
include social isolation, stigmatization, or disability.[24] They may result in lower educational
achievement and worse employment outcomes.[24]Learning disabilities are common in those with
the condition, and especially among children with epilepsy.[24] The stigma of epilepsy can also
affect the families of those with the disorder.[29]
Certain disorders occur more often in people with epilepsy, depending partly on the epilepsy
syndrome present. These include depression, anxiety, obsessive–compulsive
disorder (OCD),[40] and migraine.[41] Attention deficit hyperactivity disorder affects three to five
times more children with epilepsy than children without the condition.[42] ADHD and epilepsy have
significant consequences on a child's behavioral, learning, and social development.[43] Epilepsy is
also more common in children with autism.[44]

Causes[edit]
See also: Causes of seizures

Epilepsy can have both genetic and acquired causes, with interaction of these factors in many
cases.[45] Established acquired causes include serious brain trauma, stroke, tumours and
problems in the brain as a result of a previous infection.[45] In about 60% of cases the cause is
unknown.[24][29] Epilepsies caused by genetic, congenital, or developmental conditions are more
common among younger people, while brain tumors and strokes are more likely in older
people.[24]
Seizures may also occur as a consequence of other health problems;[28] if they occur right around
a specific cause, such as a stroke, head injury, toxic ingestion or metabolic problem, they are
known as acute symptomatic seizures and are in the broader classification of seizure-related
disorders rather than epilepsy itself.[46][47]
Genetics[edit]
Genetics is believed to be involved in the majority of cases, either directly or indirectly.[13] Some
epilepsies are due to a single gene defect (1–2%); most are due to the interaction of multiple
genes and environmental factors.[13] Each of the single gene defects is rare, with more than 200
in all described.[48] Most genes involved affect ion channels, either directly or indirectly.[45] These
include genes for ion channels themselves, enzymes, GABA, and G protein-coupled receptors.[31]
In identical twins, if one is affected there is a 50–60% chance that the other will also be
affected.[13] In non-identical twins the risk is 15%.[13] These risks are greater in those with
generalized rather than focal seizures.[13] If both twins are affected, most of the time they have the
same epileptic syndrome (70–90%).[13] Other close relatives of a person with epilepsy have a risk
five times that of the general population.[49] Between 1 and 10% of those with Down
syndrome and 90% of those with Angelman syndrome have epilepsy.[49]
Acquired[edit]
Epilepsy may occur as a result of a number of other conditions including tumors, strokes, head
trauma, previous infections of the central nervous system, genetic abnormalities, and as a result
of brain damage around the time of birth.[28][29] Of those with brain tumors, almost 30% have
epilepsy, making them the cause of about 4% of cases.[49] The risk is greatest for tumors in the
temporal lobe and those that grow slowly.[49] Other mass lesions such as cerebral cavernous
malformations and arteriovenous malformations have risks as high as 40–60%.[49] Of those who
have had a stroke, 2–4% develop epilepsy.[49] In the United Kingdom strokes account for 15% of
cases and it is believed to be the cause in 30% of the elderly.[24][49] Between 6 and 20% of
epilepsy is believed to be due to head trauma.[49] Mild brain injury increases the risk about two-
fold while severe brain injury increases the risk seven-fold.[49] In those who have experienced a
high-powered gunshot wound to the head, the risk is about 50%.[49]
Some evidence links epilepsy and coeliac disease and non-celiac gluten sensitivity, while other
evidence does not. There appears to be a specific syndrome which includes coeliac disease,
epilepsy and calcifications in the brain.[50][51] A 2012 review estimates that between 1% and 6% of
people with epilepsy have CD while 1% of the general population has the condition.[51]
The risk of epilepsy following meningitis is less than 10%; that disease more commonly causes
seizures during the infection itself.[49] In herpes simplex encephalitis the risk of a seizure is around
50%[49] with a high risk of epilepsy following (up to 25%).[52][53] Infection with the pork tapeworm,
which can result in neurocysticercosis, is the cause of up to half of epilepsy cases in areas of the
world where the parasite is common.[49] Epilepsy may also occur after other brain infections such
as cerebral malaria, toxoplasmosis, and toxocariasis.[49] Chronic alcohol use increases the risk of
epilepsy: those who drink six units of alcohol per day have a two and a half fold increase in
risk.[49] Other risks include Alzheimer's disease, multiple sclerosis, tuberous sclerosis,
and autoimmune encephalitis.[49] Getting vaccinated does not increase the risk of
epilepsy.[49] Malnutrition is a risk factor seen mostly in the developing world, although it is unclear
however if it is a direct cause or an association.[18] People with cerebral palsy have an increased
risk of epilepsy, with half of people with spastic quadriplegia and spastic hemiplegia having the
disease.[54]

Mechanism[edit]
Normally brain electrical activity is non-synchronous.[2] Its activity is regulated by various factors
both within the neuron and the cellular environment. Factors within the neuron include the type,
number and distribution of ion channels, changes to receptors and changes of gene
expression.[55] Factors around the neuron include ion concentrations, synaptic plasticity and
regulation of transmitter breakdown by glial cells.[55][56]
Epilepsy[edit]
The exact mechanism of epilepsy is unknown,[57] but a little is known about its cellular and
network mechanisms. However, it is unknown under which circumstances the brain shifts into the
activity of a seizure with its excessive synchronization.[58][59]
In epilepsy, the resistance of excitatory neurons to fire during this period is decreased.[2] This
may occur due to changes in ion channels or inhibitory neurons not functioning properly.[2] This
then results in a specific area from which seizures may develop, known as a "seizure
focus".[2] Another mechanism of epilepsy may be the up-regulation of excitatory circuits or down-
regulation of inhibitory circuits following an injury to the brain.[2][3] These secondary epilepsies
occur through processes known as epileptogenesis.[2][3]Failure of the blood–brain barrier may also
be a causal mechanism as it would allow substances in the blood to enter the brain.[60]
Seizures[edit]
There is evidence that epileptic seizures are usually not a random event. Seizures are often
brought on by factors such as stress, alcohol abuse, flickering light, or a lack of sleep, among
others. The term seizure threshold is used to indicate the amount of stimulus necessary to bring
about a seizure. Seizure threshold is lowered in epilepsy.[58]
In epileptic seizures a group of neurons begin firing in an abnormal, excessive,[24] and
synchronized manner.[2] This results in a wave of depolarization known as a paroxysmal
depolarizing shift.[61] Normally, after an excitatory neuron fires it becomes more resistant to firing
for a period of time.[2] This is due in part to the effect of inhibitory neurons, electrical changes
within the excitatory neuron, and the negative effects of adenosine.[2]
Focal seizures begin in one hemisphere of the brain while generalized seizures begin in both
hemispheres.[28] Some types of seizures may change brain structure, while others appear to have
little effect.[62] Gliosis, neuronal loss, and atrophy of specific areas of the brain are linked to
epilepsy but it is unclear if epilepsy causes these changes or if these changes result in
epilepsy.[62]

Diagnosis[edit]

An EEG can aid in locating the focus of the epileptic seizure.

The diagnosis of epilepsy is typically made based on observation of the seizure onset and the
underlying cause.[24] An electroencephalogram (EEG) to look for abnormal patterns of brain
waves and neuroimaging (CT scan or MRI) to look at the structure of the brain are also usually
part of the workup.[24] While figuring out a specific epileptic syndrome is often attempted, it is not
always possible.[24] Video and EEG monitoring may be useful in difficult cases.[63]
Definition[edit]
Epilepsy is a disorder of the brain defined by any of the following conditions:[11]

1. At least two unprovoked (or reflex) seizures occurring greater than 24 hours apart
2. One unprovoked (or reflex) seizure and a probability of further seizures similar to the
general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the
next 10 years
3. Diagnosis of an epilepsy syndrome

Furthermore, epilepsy is considered to be resolved for individuals who had an age-

dependent epilepsy syndrome but are now past that age or those who have remained
seizure-free for the last 10 years, with no seizure medicines for the last 5 years.[11]
This 2014 definition of the International League Against Epilepsy[11] is a clarification of the
ILAE 2005 conceptual definition, according to which epilepsy is "a disorder of the brain
characterized by an enduring predisposition to generate epileptic seizures and by the
neurobiologic, cognitive, psychological, and social consequences of this condition. The
definition of epilepsy requires the occurrence of at least one epileptic seizure."[64][65]
It is, therefore, possible to outgrow epilepsy or to undergo treatment that causes epilepsy to
be resolved, but with no guarantee that it will not return. In the definition, epilepsy is now
called a disease, rather than a disorder. This was a decision of the executive committee of
the ILAE, taken because the word "disorder," while perhaps having less stigma than does
"disease," also does not express the degree of seriousness that epilepsy deserves.[11]
The definition is practical in nature and is designed for clinical use. In particular, it aims to
clarify when an "enduring predisposition" according to the 2005 conceptual definition is
present. Researchers, statistically-minded epidemiologists, and other specialized groups
may choose to use the older definition or a definition of their own devising. The ILAE
considers doing so is perfectly allowable, so long as it is clear what definition is being
used.[11]
Classification[edit]
In contrast to the classification of seizures which focuses on what happens during a seizure,
the classification of epilepsies focuses on the underlying causes. When a person is admitted
to hospital after an epileptic seizure the diagnostic workup results preferably in the seizure
itself being classified (e.g. tonic-clonic) and in the underlying disease being identified
(e.g. hippocampal sclerosis).[63] The name of the diagnosis finally made depends on the
available diagnostic results and the applied definitions and classifications (of seizures and
epilepsies) and its respective terminology.
The International League Against Epilepsy (ILAE) provided a classification of the epilepsies
and epileptic syndromes in 1989 as follows:[66]

1. Localization-related epilepsies and syndromes

1. Unknown cause (e.g. benign childhood epilepsy with centrotemporal spikes)
2. Symptomatic/cryptogenic (e.g. temporal lobe epilepsy)
2. Generalized
1. Unknown cause (e.g. childhood absence epilepsy)
2. Cryptogenic or symptomatic (e.g. Lennox-Gastaut syndrome)
3. Symptomatic (e.g. early infantile epileptic encephalopathy with burst
suppression)
3. Epilepsies and syndromes undetermined whether focal or generalized
1. With both generalized and focal seizures (e.g. epilepsy with continuous spike-
waves during slow wave sleep)
4. Special syndromes (with situation-related seizures)[66]

This classification was widely accepted but has also been criticized mainly because the
underlying causes of epilepsy (which are a major determinant of clinical course and
prognosis) were not covered in detail.[67] In 2010 the ILAE Commission for Classification
of the Epilepsies addressed this issue and divided epilepsies into three categories
(genetic, structural/metabolic, unknown cause)[68] that were refined in their 2011
recommendation into four categories and a number of subcategories reflecting recent
technologic and scientific advances.[69]

1. Unknown cause (mostly genetic or presumed genetic origin)

1. Pure epilepsies due to single gene disorders
2. Pure epilepsies with complex inheritance
2. Symptomatic (associated with gross anatomic or pathologic abnormalities)
1. Mostly genetic or developmental causation
1. Childhood epilepsy syndromes
2. Progressive myoclonic epilepsies
3. Neurocutaneous syndromes
4. Other neurologic single gene disorders
5. Disorders of chromosome function
6. Developmental anomalies of cerebral structure
 2. Mostly acquired causes
1. Hippocampal sclerosis
2. Perinatal and infantile causes
3. Cerebral trauma, tumor or infection
4. Cerebrovascular disorders
5. Cerebral immunologic disorders
6. Degenerative and other neurologic conditions
3. Provoked (a specific systemic or environmental factor is the predominant cause of the
seizures)
1. Provoking factors
2. Reflex epilepsies
4. Crytogenic (presumed symptomatic nature in which the cause has not been identified)[69]

Syndromes[edit]
Main article: Epilepsy syndromes
Cases of epilepsy may be organized into epilepsy syndromes by the specific
features that are present. These features include the age that seizure begin, the
seizure types, EEG findings, among others. Identifying an epilepsy syndrome is
useful as it helps determine the underlying causes as well as what anti-seizure
medication should be tried.[28][70]
The ability to categorize a case of epilepsy into a specific syndrome occurs more
often with children since the onset of seizures is commonly early.[47] Less serious
examples are benign rolandic epilepsy (2.8 per 100,000), childhood absence
epilepsy (0.8 per 100,000) and juvenile myoclonic epilepsy (0.7 per
100,000).[47] Severe syndromes with diffuse brain dysfunction caused, at least partly,
by some aspect of epilepsy, are also referred to as epileptic encephalopathies.
These are associated with frequent seizures that are resistant to treatment and
severe cognitive dysfunction, for instance Lennox–Gastaut syndrome and West
syndrome.[71] Genetics is believed to play an important role in epilepsies by a number
of mechanisms. Simple and complex modes of inheritance have been identified for
some of them. However, extensive screening have failed to identify many
single gene variants of large effect.[72] More recent exome and genome sequencing
studies have begun to reveal a number of de novo gene mutations that are
responsible for some epileptic encephalopathies,
including CHD2 and SYNGAP1[73][74][75] and DNM1, GABBR2, FASN and RYR3.[76]
Syndromes in which causes are not clearly identified are difficult to match with
categories of the current classification of epilepsy. Categorization for these cases
was made somewhat arbitrarily.[69] The idiopathic (unknown cause) category of the
2011 classification includes syndromes in which the general clinical features and/or
age specificity strongly point to a presumed genetic cause.[69] Some childhood
epilepsy syndromes are included in the unknown cause category in which the cause
is presumed genetic, for instance benign rolandic epilepsy. Others are included
in symptomatic despite a presumed genetic cause (in at least in some cases), for
instance Lennox-Gastaut syndrome.[69]Clinical syndromes in which epilepsy is not
the main feature (e.g. Angelman syndrome) were categorized symptomatic but it
was argued to include these within the category idiopathic.[69] Classification of
epilepsies and particularly of epilepsy syndromes will change with advances in
research.
Tests[edit]
An electroencephalogram (EEG) can assist in showing brain activity suggestive of
an increased risk of seizures. It is only recommended for those who are likely to
have had an epileptic seizure on the basis of symptoms. In the diagnosis of epilepsy,
electroencephalography may help distinguish the type of seizure or syndrome
present. In children it is typically only needed after a second seizure. It cannot be
used to rule out the diagnosis and may be falsely positive in those without the
disease. In certain situations it may be useful to perform the EEG while the affected
individual is sleeping or sleep deprived.[63]
Diagnostic imaging by CT scan and MRI is recommended after a first non-febrile
seizure to detect structural problems in and around the brain.[63] MRI is generally a
better imaging test except when bleeding is suspected, for which CT is more
sensitive and more easily available.[19] If someone attends the emergency room with
a seizure but returns to normal quickly, imaging tests may be done at a later
point.[19] If a person has a previous diagnosis of epilepsy with previous imaging,
repeating the imaging is usually not needed even if there are subsequent seizures.[63]
For adults, the testing of electrolyte, blood glucose and calcium levels is important to
rule out problems with these as causes.[63] An electrocardiogram can rule out
problems with the rhythm of the heart.[63] A lumbar puncture may be useful to
diagnose a central nervous system infection but is not routinely needed.[19] In
children additional tests may be required such as urine biochemistry and blood
testing looking for metabolic disorders.[63][77]
A high blood prolactin level within the first 20 minutes following a seizure may be
useful to help confirm an epileptic seizure as opposed to psychogenic non-epileptic
seizure.[78][79] Serum prolactin level is less useful for detecting focal seizures.[80] If it is
normal an epileptic seizure is still possible[79] and a serum prolactin does not
separate epileptic seizures from syncope.[81] It is not recommended as a routine part
of the diagnosis of epilepsy.[63]
Differential diagnosis[edit]
Diagnosis of epilepsy can be difficult. A number of other conditions may present very
similar signs and symptoms to seizures,
including syncope, hyperventilation, migraines, narcolepsy, panic
attacks and psychogenic non-epileptic seizures (PNES).[82][83] In particular
a syncope can be accompanied by a short episode of convulsions.[84] Nocturnal
frontal lobe epilepsy, often misdiagnosed as nightmares, was considered to be
a parasomnia but later identified to be an epilepsy syndrome.[85] Attacks of the
movement disorder paroxysmal dyskinesia may be taken for epileptic
seizures.[86] The cause of a drop attack can be, among many others, an atonic
seizure.[83]
Children may have behaviors that are easily mistaken for epileptic seizures but are
not. These include breath-holding spells, bed wetting, night terrors, tics and shudder
attacks.[83] Gastroesophageal reflux may cause arching of the back and twisting of
the head to the side in infants, which may be mistaken for tonic-clonic seizures.[83]
Misdiagnosis is frequent (occurring in about 5 to 30% of cases).[24] Different studies
showed that in many cases seizure-like attacks in apparent treatment-resistant
epilepsy have a cardiovascular cause.[84][87] Approximately 20% of the people seen at
epilepsy clinics have PNES[19] and of those who have PNES about 10% also have
epilepsy;[88] separating the two based on the seizure episode alone without further
testing is often difficult.[88]

Prevention[edit]
While many cases are not preventable, efforts to reduce head injuries, provide good
care around the time of birth, and reduce environmental parasites such as the pork
tapeworm may be effective.[29] Efforts in one part of Central America to decrease
rates of pork tapeworm resulted in a 50% decrease in new cases of epilepsy.[18]
Management[edit]
Epilepsy is usually treated with daily medication once a second seizure has
occurred,[24][63] but for those at high risk, medication may be started after the first
seizure.[63] In drug-resistant cases different management options may be looked at
including a special diet, the implantation of a neurostimulator, or neurosurgery.
First aid[edit]
Rolling a person with an active tonic-clonic seizure onto their side and into
the recovery position helps prevent fluids from getting into the lungs.[89] Putting
fingers, a bite block or tongue depressor in the mouth is not recommended as it
might make the person vomit or result in the rescuer being bitten.[26][89] Efforts should
be taken to prevent further self-injury.[26] Spinal precautions are generally not
needed.[89]
If a seizure lasts longer than 5 minutes or if there are more than two seizures in an
hour without a return to a normal level of consciousness between them, it is
considered a medical emergency known as status epilepticus.[63][90] This may
require medical help to keep the airway open and protected;[63] a nasopharyngeal
airway may be useful for this.[89] At home the recommended initial medication for
seizure of a long duration is midazolam placed in the mouth.[91] Diazepam may also
be used rectally.[91] In hospital, intravenous lorazepam is preferred.[63] If two doses
of benzodiazepines are not effective, other medications such as phenytoin are
recommended.[63] Convulsive status epilepticus that does not respond to initial
treatment typically requires admission to the intensive care unit and treatment with
stronger agents such as thiopentone or propofol.[63]
Medications[edit]

Anticonvulsants

The mainstay treatment of epilepsy is anticonvulsant medications, possibly for the

person's entire life.[24] The choice of anticonvulsant is based on seizure type, epilepsy
syndrome, other medications used, other health problems, and the person's age and
lifestyle.[91] A single medication is recommended initially;[92] if this is not effective,
switching to a single other medication is recommended.[63] Two medications at once
is recommended only if a single medication does not work.[63] In about half, the first
agent is effective; a second single agent helps in about 13% and a third or two
agents at the same time may help an additional 4%.[93] About 30% of people continue
to have seizures despite anticonvulsant treatment.[7]
There are a number of medications
available. Phenytoin, carbamazepine and valproate appear to be equally effective in
both focal and generalized seizures.[94][needs update][95][needs update] Controlled
release carbamazepine appears to work as well as immediate release
carbamazepine, and may have fewer side effects.[96][needs update] In the United Kingdom,
carbamazepine or lamotrigine are recommended as first-line treatment for focal
seizures, with levetiracetam and valproate as second-line due to issues of cost and
side effects.[63] Valproate is recommended first-line for generalized seizures with
lamotrigine being second-line.[63] In those with absence seizures, ethosuximide or
valproate are recommended; valproate is particularly effective in myoclonic seizures
and tonic or atonic seizures.[63] If seizures are well-controlled on a particular
treatment, it is not usually necessary to routinely check the medication levels in the
blood.[63]
The least expensive anticonvulsant is phenobarbital at around $5 USD a
year.[18] The World Health Organization gives it a first-line recommendation in the
developing world and it is commonly used there.[97][98] Access however may be
difficult as some countries label it as a controlled drug.[18]
Adverse effects from medications are reported in 10 to 90% of people, depending on
how and from whom the data is collected.[99] Most adverse effects are dose-related
and mild.[99] Some examples include mood changes, sleepiness, or an unsteadiness
in gait.[99] Certain medications have side effects that are not related to dose such as
rashes, liver toxicity, or suppression of the bone marrow.[99] Up to a quarter of people
stop treatment due to adverse effects.[99] Some medications are associated with birth
defects when used in pregnancy.[63] Many of the common used medications, such as
valproate, phenytoin, carbamazepine, phenobarbitol, and gabapentin have been
reported to cause increased risk of birth defects,[100] especially when used during
the first trimester.[101] Despite this, treatment is often continued once effective,
because the risk of untreated epilepsy is believed to be greater than the risk of the
medications.[101] Among the antiepileptic medications, levetiracetam and lamotrigine
seem to carry the lowest risk of causing birth defects.[100]
Slowly stopping medications may be reasonable in some people who do not have a
seizure for two to four years; however, around a third of people have a recurrence,
most often during the first six months.[63][102] Stopping is possible in about 70% of
children and 60% of adults.[29]
Surgery[edit]
Epilepsy surgery may be an option for people with focal seizures that remain a
problem despite other treatments.[103] These other treatments include at least a trial
of two or three medications.[104] The goal of surgery is total control of seizures[105] and
this may be achieved in 60–70% of cases.[104] Common procedures include cutting
out the hippocampus via an anterior temporal lobe resection, removal of tumors, and
removing parts of the neocortex.[104] Some procedures such as a corpus
callosotomy are attempted in an effort to decrease the number of seizures rather
than cure the condition.[104] Following surgery, medications may be slowly withdrawn
in many cases.[104]
Neurostimulation may be another option in those who are not candidates for
surgery.[63] Three types have been shown to be effective in those who do not
respond to medications: vagus nerve stimulation, anterior thalamic stimulation,
and closed-loop responsive stimulation.[5]
Diet[edit]
A ketogenic diet (high-fat, low-carbohydrate, adequate-protein) appears to decrease
the number of seizures and eliminate seizures in some.[6] It is a reasonable option in
those who have epilepsy that is not improved with medications and for whom
surgery is not an option.[6] About 10% stay on the diet for a few years due to issues
of effectiveness and tolerability.[106] Side effects include stomach and intestinal
problems in 30%, and there are long term concerns of heart disease.[106] Less radical
diets are easier to tolerate and may be effective.[6] It is unclear why this diet
works.[107] Exercise has been proposed as possibly useful for preventing
seizures[108] with some data to support this claim.[109]
In people with coeliac disease or non-celiac gluten sensitivity and occipital
calcifications, a gluten-free diet may decrease the frequency of seizures.[51]
Other[edit]
Avoidance therapy consists of minimizing or eliminating triggers. For example, in
those who are sensitive to light, using a small television, avoiding video games, or
wearing dark glasses may be useful.[110] Operant-based biofeedback based on the
EEG waves has some support in those who do not respond to
medications.[111] Psychological methods should not, however, be used to replace
medications.[63] Some dogs, commonly referred to as seizure dogs, may help during
or after a seizure.[112][113] It is not clear if dogs have the ability to predict seizures
before they occur.[114]
Alternative medicine[edit]
Alternative medicine, including acupuncture,[115] psychological
interventions,[116] routine vitamins,[117] and yoga,[118] have no reliable evidence to
support their use in epilepsy. There is not enough evidence to support the use
of cannabis.[119][120] Melatonin, as of 2016, is insufficiently supported by
evidence.[121] The trials were of poor methodological quality and it was not possible to
draw any definitive conclusions.[121][needs update]

Prognosis[edit]

Deaths due to epilepsy per million persons in 2012

0–7

8–10

11–13

14–17

18–21

22–28
 29–37

38–67

68–100

101–232

Epilepsy cannot usually be cured, but medication can control seizures effectively in
about 70% of cases.[7] Of those with generalized seizures, more than 80% can be
well controlled with medications while this is true in only 50% of people with focal
seizures.[5] One predictor of long-term outcome is the number of seizures that occur
in the first six months.[24] Other factors increasing the risk of a poor outcome include
little response to the initial treatment, generalized seizures, a family history of
epilepsy, psychiatric problems, and waves on the EEG representing generalized
epileptiform activity.[122] In the developing world, 75% of people are either untreated
or not appropriately treated.[29] In Africa, 90% do not get treatment.[29]This is partly
related to appropriate medications not being available or being too expensive.[29]
Mortality[edit]
People with epilepsy are at an increased risk of death.[123] This increase is between
1.6 and 4.1 fold greater than that of the general population[124] and is often related to:
the underlying cause of the seizures, status epilepticus, suicide, trauma, and sudden
unexpected death in epilepsy (SUDEP).[123] Death from status epilepticus is primarily
due to an underlying problem rather than missing doses of medications.[123] The risk
of suicide is increased between two and six times in those with epilepsy.[125][126] The
cause of this is unclear.[125] SUDEP appears to be partly related to the frequency of
generalized tonic-clonicseizures[127] and accounts for about 15% of epilepsy related
deaths.[122] It is unclear how to decrease its risk.[127] The greatest increase in mortality
from epilepsy is among the elderly.[124] Those with epilepsy due to an unknown cause
have little increased risk.[124] In the United Kingdom, it is estimated that 40–60% of
deaths are possibly preventable.[24] In the developing world, many deaths are due to
untreated epilepsy leading to falls or status epilepticus.[18]

Epidemiology[edit]
Epilepsy is one of the most common serious neurological disorders[128] affecting
about 39 million people as of 2015.[8] It affects 1% of the population by age 20 and
3% of the population by age 75.[16] It is more common in males than females with the
overall difference being small.[18][47] Most of those with the disorder (80%) are in
the developing world.[29]
The estimated prevalence of active epilepsy (as of 2012) is in the range 3–10 per
1,000, with active epilepsy defined as someone with epilepsy who has had a least
one unprovoked seizure in the last five years.[47][129] Epilepsy begins each year in 40–
70 per 100,000 in developed countries and 80–140 per 100,000 in developing
countries.[29]Poverty is a risk and includes both being from a poor country and being
poor relative to others within one's country.[18] In the developed world epilepsy most
commonly starts either in the young or in the old.[18] In the developing world its onset
is more common in older children and young adults due to the higher rates of trauma
and infectious diseases.[18] In developed countries the number of cases a year has
decreased in children and increased among the elderly between the 1970s and
2003.[129] This has been attributed partly to better survival following strokes in the
elderly.[47]

History[edit]
See also: On the Sacred Disease

Hippocrates, 17th century engraving by Peter Paul Rubens of an antique bust.

The oldest medical records show that epilepsy has been affecting people at least
since the beginning of recorded history.[130] Throughout ancient history, the disease
was thought to be a spiritual condition.[130] The world's oldest description of an
epileptic seizure comes from a text in Akkadian (a language used in
ancient Mesopotamia) and was written around 2000 BC.[22] The person described in
the text was diagnosed as being under the influence of a Moon god, and underwent
an exorcism.[22] Epileptic seizures are listed in the Code of Hammurabi (c. 1790 BC)
as reason for which a purchased slave may be returned for a refund,[22] and
the Edwin Smith Papyrus (c. 1700 BC) describes cases of individuals with epileptic
convulsions.[22]
The oldest known detailed record of the disease itself is in the Sakikku,
a Babylonian cuneiform medical text from 1067–1046 BC.[130] This text gives signs
and symptoms, details treatment and likely outcomes,[22] and describes many
features of the different seizure types.[130] As the Babylonians had no biomedical
understanding of the nature of disease, they attributed the seizures to possession by
evil spirits and called for treating the condition through spiritual means.[130] Around
900 BC, PunarvasuAtreya described epilepsy as loss of consciousness;[131] this
definition was carried forward into the Ayurvedic text of Charaka Samhita (about 400
BC).[132]
The ancient Greeks had contradictory views of the disease. They thought of epilepsy
as a form of spiritual possession, but also associated the condition with genius and
the divine. One of the names they gave to it was the sacred disease (ἠ
ἱερὰνόσος).[22][133] Epilepsy appears within Greek mythology: it is associated with the
Moon goddesses Selene and Artemis, who afflicted those who upset them. The
Greeks thought that important figures such as Julius Caesar and Hercules had the
disease.[22] The notable exception to this divine and spiritual view was that of the
school of Hippocrates. In the fifth century BC, Hippocrates rejected the idea that the
disease was caused by spirits. In his landmark work On the Sacred Disease, he
proposed that epilepsy was not divine in origin and instead was a medically treatable
problem originating in the brain.[22][130]He accused those of attributing a sacred cause
to the disease of spreading ignorance through a belief in superstitious
magic.[22] Hippocrates proposed that heredity was important as a cause, described
worse outcomes if the disease presents at an early age, and made note of the
physical characteristics as well as the social shame associated with it.[22] Instead of
referring to it as the sacred disease, he used the term great disease, giving rise to
the modern term grand mal, used for tonic–clonic seizures.[22] Despite his work
detailing the physical origins of the disease, his view was not accepted at the
time.[130] Evil spirits continued to be blamed until at least the 17th century.[130]
In Ancient Rome people did not eat or drink with the same pottery as that used by
someone who was affected.[134] People of the time would spit on their chest believing
that this would keep the problem from affected them.[134] According to Apuleius and
other ancient physicians, in order detect epilepsy it was common to light a piece
of gagates, whose smoke would trigger the seizure.[135] Occasionally a
spinning potter's wheel was used, perhaps a reference to photosensitive epilepsy.[136]
In most cultures, persons with epilepsy have been stigmatized, shunned, or even
imprisoned; in the Salpêtrière, the birthplace of modern neurology, Jean-Martin
Charcot found people with epilepsy side-by-side with the mentally ill, those with
chronic syphilis, and the criminally insane.[137] In ancient Rome, epilepsy was known
as the morbuscomitialis ('disease of the assembly hall') and was seen as a curse
from the gods. In northern Italy, epilepsy was once traditionally known as Saint
Valentine's malady.[138]
In the mid-1800s, the first effective anti-seizure medication, bromide, was
introduced.[99] The first modern treatment, phenobarbital, was developed in 1912,
with phenytoin coming into use in 1938.[139]

Society and culture[edit]

See also: List of people with epilepsy

Stigma[edit]
Stigma is commonly experienced, around the world, by those with epilepsy.[140] It can
affect people economically, socially and culturally.[140] In India and China, epilepsy
may be used as justification to deny marriage.[29] People in some areas still believe
those with epilepsy to be cursed.[18] In Tanzania, as in other parts of Africa, epilepsy
is associated with possession by evil spirits, witchcraft, or poisoning and is believed
by many to be contagious,[137] for which there is no evidence.[18] Before 1970 the
United Kingdom had laws which prevented people with epilepsy from
marrying.[29] The stigma may result in some people with epilepsy denying that they
have ever had seizures.[47]
Economics[edit]
Seizures result in direct economic costs of about one billion dollars in the United
States.[19] Epilepsy resulted in economic costs in Europe of around 15.5 billion Euros
in 2004.[24]In India epilepsy is estimated to result in costs of 1.7 billion USD or 0.5%
of the GDP.[29] It is the cause of about 1% of emergency department visits (2% for
emergency departments for children) in the United States.[141]
Vehicles[edit]
See also: Epilepsy and driving
Those with epilepsy are at about twice the risk of being involved in a motor vehicular
collision and thus in many areas of the world are not allowed to drive or only able to
drive if certain conditions are met.[21] In some places physicians are required by law
to report if a person has had a seizure to the licensing body while in others the
requirement is only that they encourage the person in question to report it
themselves.[21] Countries that require physician reporting include Sweden, Austria,
Denmark and Spain.[21] Countries that require the individual to report include the UK
and New Zealand and the physician may report if they believe the individual has not
already.[21] In Canada, the United States and Australia the requirements around
reporting vary by province or state.[21] If seizures are well controlled most feel
allowing driving is reasonable.[142] The amount of time a person must be free from
seizures before they can drive varies by country.[142] Many countries require one to
three years without seizures.[142] In the United States the time needed without a
seizure is determined by each state and is between three months and one year.[142]
Those with epilepsy or seizures are typically denied a pilot license.[143] In Canada if
an individual has had no more than one seizure, they may be considered after five
years for a limited license if all other testing is normal.[144] Those with febrile seizures
and drug related seizures may also be considered.[144] In the United States,
the Federal Aviation Administration does not allow those with epilepsy to get a
commercial pilot license.[145] Rarely, exceptions can be made for persons who have
had an isolated seizure or febrile seizures and have remained free of seizures into
adulthood without medication.[146] In the United Kingdom, a full national private pilot
license requires the same standards as a professional driver's license.[147] This
requires a period of ten years without seizures while off medications.[148] Those who
do not meet this requirement may acquire a restricted license if free from seizures
for five years.[147]
Support organizations[edit]
There are organizations that provide support for people and families affected by
epilepsy. The Out of the Shadows campaign, a joint effort by the World Health
Organization, the International League Against Epilepsy and the International
Bureau for Epilepsy, provides help internationally.[29] The Joint Epilepsy Council
serves the UK and Ireland.[63] In the United States, the Epilepsy Foundation is a
national organization that works to increase the acceptance of those with the
disease, their ability to function in society and to promote research for a cure.[149] The
Epilepsy Foundation, some hospitals, and some individuals also run support groups
in the United States.[150]

Research[edit]
Seizure prediction refers to attempts to forecast epileptic seizures based on the EEG
before they occur.[151] As of 2011, no effective mechanism to predict seizures has
been developed.[151] Kindling, where repeated exposures to events that could cause
seizures eventually causes seizures more easily, has been used to create animal
models of epilepsy.[152]
Gene therapy is being studied in some types of epilepsy.[153] Medications that alter
immune function, such as intravenous immunoglobulins, are poorly supported by
evidence.[154]Noninvasive stereotactic radiosurgery is, as of 2012, being compared to
standard surgery for certain types of epilepsy.[155]
Common locations for the start of seizures and neural networks have been found to
be affected in the majority of epilepsy.[156] Efforts to figure out how epilepsy occurs is
working to take into account the different regions of the brain and the timing of their
activity.[157]
Other animals[edit]
Main article: Epilepsy in animals
Epilepsy occurs in a number of other animals including dogs and cats and is the
most common brain disorder in dogs.[158] It is typically treated with anticonvulsants
such as phenobarbital or bromide in dogs and phenobarbital in cats.[159] Imepitoin is
also used in dogs.[160] While generalized seizures in horses are fairly easy to
diagnose, it may be more difficult in non-generalized seizures and EEGs may be
useful.[161]
 Tetanus
From Wikipedia, the free encyclopedia

This article is about the disease. For the physiological use of the term, see tetanic contraction.

Tetanus

Muscle spasms (specifically opisthotonos) in a person with tetanus.

Painting by Sir Charles Bell, 1809.

Specialty Infectious disease

Symptoms Muscle spasms, fever, headache[1]

Usual onset 3–21 days following exposure[1]

Duration Months[1]

Causes Clostridium tetani[1]

Risk factors Break in the skin[2]

Diagnostic method Based on symptoms[1]

Prevention Tetanus vaccine[1]

Treatment Tetanus immune globulin, muscle

relaxants, mechanical ventilation[1][3]
 Frequency 209,000 (2015)[4]

Deaths 56,700 (2015)[5]

[edit on Wikidata]

Tetanus, also known as lockjaw, is an infection characterized by muscle spasms. In the most
common type, the spasms begin in the jaw and then progress to the rest of the body. These
spasms usually last a few minutes each time and occur frequently for three to four
weeks.[1] Spasms may be so severe that bone fractures may occur.[6] Other symptoms may
include fever, sweating, headache, trouble swallowing, high blood pressure, and a fast heart
rate.[1][6] Onset of symptoms is typically three to twenty-one days following infection. It may take
months to recover. About 10% of those infected die.[1]
Tetanus is caused by an infection with the bacterium Clostridium tetani,[1] which is commonly
found in soil, saliva, dust, and manure.[2] The bacteria generally enter through a break in the skin
such as a cut or puncture wound by a contaminated object.[2] They produce toxins that interfere
with muscle contractions, resulting in the typical symptoms.[3] Diagnosis is based on the
presenting signs and symptoms. The disease does not spread between people.[1]
Infection can be prevented by proper immunization with the tetanus vaccine. In those who have a
significant wound and less than three doses of the vaccine both immunization and tetanus
immune globulin are recommended. The wound should be cleaned and any dead tissue should
be removed. In those who are infected tetanus immune globulin or, if it is not
available, intravenous immunoglobulin (IVIG) is used.[1] Muscle relaxants may be used to control
spasms. Mechanical ventilation may be required if a person's breathing is affected.[3]
Tetanus occurs in all parts of the world but is most frequent in hot and wet climates where the
soil contains a lot of organic matter.[1] In 2015 there were about 209,000 infections and about
59,000 deaths.[4][5] This is down from 356,000 deaths in 1990.[7] Description of the disease
by Hippocrates exists from at least as far back as the 5th century BC. The cause of the disease
was determined in 1884 by Antonio Carle and Giorgio Rattone at the University of Turin, with a
vaccine being developed in 1924.[1]

Contents
[hide]

 1Signs and symptoms

o 1.1Incubation period
o 1.2Generalized tetanus
o 1.3Neonatal tetanus
o 1.4Local tetanus
o 1.5Cephalic tetanus
 2Cause
 3Pathophysiology
 4Diagnosis
 5Prevention
o 5.1Post-exposure prophylaxis
 6Treatment
o 6.1Mild tetanus
o 6.2Severe tetanus
 7Epidemiology
 8History
 o 8.1Etymology
 9See also
 10References
 11External links

Signs and symptoms[edit]

Tetanus often begins with mild spasms in the jaw muscles—also known as lockjaw or trismus.
The spasms can also affect the facial muscles resulting in an appearance called risussardonicus.
Chest, neck, back, abdominal muscles, and buttocks may be affected. Back muscle spasms
often cause arching, called opisthotonos. Sometimes the spasms affect muscles that help with
breathing, which can lead to breathing problems.[8]
Prolonged muscular action causes sudden, powerful, and painful contractions of muscle groups,
which is called "tetany". These episodes can cause fractures and muscle tears. Other symptoms
include drooling, excessive sweating, fever, hand or foot spasms, irritability, difficulty
swallowing, suffocation, heart attack, breathing problems, irregular heartbeat, and uncontrolled
urination or defecation.[citation needed]
Even with treatment, about 10% of people who contract tetanus die.[8] The mortality rate is higher
in unvaccinated people and people over 60 years of age.[8]
Incubation period[edit]
The incubation period of tetanus may be up to several months, but is usually about ten
days.[9][10] In general, the farther the injury site is from the central nervous system, the longer the
incubation period. The shorter the incubation period, the more severe the symptoms.[11] In
neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7
days. On the basis of clinical findings, four different forms of tetanus have been described.[8]
Generalized tetanus[edit]
Generalized tetanus is the most common type of tetanus, representing about 80% of cases. The
generalized form usually presents with a descending pattern. The first sign is trismus, or lockjaw,
and the facial spasms called risussardonicus, followed by stiffness of the neck, difficulty in
swallowing, and rigidity of pectoral and calf muscles. Other symptoms include elevated
temperature, sweating, elevated blood pressure, and episodic rapid heart rate. Spasms may
occur frequently and last for several minutes with the body shaped into a characteristic form
called opisthotonos. Spasms continue for up to four weeks, and complete recovery may take
months.[citation needed] Sympathetic overactivity (SOA) is common in severe tetanus and manifests as
labile hypertension, tachycardia, dysrhythmia, peripheral vasculature constriction, profuse
sweating, fever, increased carbon dioxide output, increased catecholamine excretion and late
development of hypotension. Death can occur within four days.
Neonatal tetanus[edit]
Main article: Neonatal tetanus

Neonatal tetanus is a form of generalized tetanus that occurs in newborns, usually those born to
mothers who themselves have not been vaccinated. If the mother has been vaccinated against
tetanus, the infants acquire passive immunity and are thus protected.[12] It usually occurs through
infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile
instrument. As of 1998 neonatal tetanus was common in many developing countries and was
responsible for about 14% (215,000) of all neonatal deaths.[13] In 2010 the worldwide death toll
was 58,000 newborns. As the result of a public health campaign, the death toll from neonatal
tetanus was reduced by 90% between 1990 and 2010, and by 2013 the disease had been largely
eliminated from all but 25 countries.[14] Neonatal tetanus is rare in developed countries.
Local tetanus[edit]
Local tetanus is an uncommon form of the disease, in which patients have persistent contraction
of muscles in the same anatomic area as the injury. The contractions may persist for many
weeks before gradually subsiding. Local tetanus is generally milder; only about 1% of cases are
fatal, but it may precede the onset of generalized tetanus.[citation needed]
Cephalic tetanus[edit]
Cephalic tetanus is the rarest form of the disease (0.9–3% of cases)[15] and is limited to muscles
and nerves in the head.[16] It usually occurs after trauma to the head area, including skull
fracture,[17] laceration,[17] eye injury,[16] dental extraction,[18] and otitis media,[19] but it has been
observed from injuries to other parts of the body.[20] Paralysis of the facial nerve is most
frequently implicated, which may cause lockjaw, facial palsy, or ptosis, but other cranial nerves
can also be affected.[18][21] Cephalic tetanus may progress to a more generalized form of the
disease.[15][21] Due to its rarity, clinicians may be unfamiliar with the clinical presentation and may
not suspect tetanus as the illness.[16] Treatment can be complicated as symptoms may be
concurrent with the initial injury that caused the infection.[17] Cephalic tetanus is more likely than
other forms of tetanus to be fatal, with the progression to generalized tetanus carrying a 15–30%
case fatality rate.[15][17][21]

Cause[edit]

Clostridium tetani is strongly durable due to its endospores. Pictured is the bacterium alone, with a spore
being produced, and the spore alone.

Tetanus is caused by the tetanus bacterium Clostridium tetani.[22] Tetanus is often associated
with rust, especially rusty nails. Although rust itself does not cause tetanus, objects that
accumulate rust are often found outdoors or in places that harbour anaerobic bacteria.
Additionally, the rough surface of rusty metal provides a prime habitat for C. tetani endospores to
reside in (due to its high surface area), while a nail affords a means to puncture skin and deliver
endospores deep within the body at the site of the wound.[23]
An endospore is a non-metabolizing survival structure that begins to metabolize and cause
infection once in an adequate environment. Because C. tetani is an anaerobic bacterium, it and
its endospores thrive in environments that lack oxygen. Hence, stepping on a nail (rusty or not)
may result in a tetanus infection, as the low-oxygen (anaerobic) environment is caused by the
oxidization of the same object that causes a puncture wound, delivering endospores to a suitable
environment for growth.[24] The bite of a dog can transmit tetanus.[25]
Tetanus is an international health problem, as C. tetani spores are ubiquitous. The disease
occurs almost exclusively in persons unvaccinated or inadequately immunized.[26] It is more
common in hot, damp climates with soil rich in organic matter. This is particularly true
with manure-treated soils, as the spores are widely distributed in the intestines and feces of
many animals such as horses, sheep, cattle, dogs, cats, rats, guinea pigs, and
chickens.[8] Spores can be introduced into the body through puncture wounds. In agricultural
areas, a significant number of human adults may harbor the organism. The spores can also be
found on skin surfaces and in contaminated heroin.[8] Heroin users, particularly those that inject
the drug subcutaneously, appear to be at high risk of contracting tetanus.[8] Rarely, tetanus can
be contracted through surgical procedures, intramuscular injections, compound fractures, and
dental infections.[27]

Pathophysiology[edit]
Tetanus affects skeletal muscle, a type of striated muscle used in voluntary movement. The other
type of striated muscle, cardiac, or heart muscle, cannot be tetanized because of its intrinsic
electrical properties.
The tetanus toxin initially binds to peripheral nerve terminals. It is transported within the axon and
across synaptic junctions until it reaches the central nervous system. There it becomes rapidly
fixed to gangliosides at the presynaptic inhibitory motor nerve endings, and is taken up into the
axon by endocytosis. The effect of the toxin is to block the release of
inhibitory neurotransmitters glycine and gamma-aminobutyric acid (GABA) across the synaptic
cleft, which is required to check the nervous impulse. If nervous impulses cannot be checked by
normal inhibitory mechanisms, the generalized muscular spasms characteristic of tetanus are
produced. The toxin appears to act by selective cleavage of a protein component of synaptic
vesicles, synaptobrevin II, and this prevents the release of neurotransmitters by the cells.[citation
needed]

Diagnosis[edit]
There are currently no blood tests for diagnosing tetanus. The diagnosis is based on the
presentation of tetanus symptoms and does not depend upon isolation of the bacterium, which is
recovered from the wound in only 30% of cases and can be isolated from patients without
tetanus. Laboratory identification of C. tetani can be demonstrated only by production of
tetanospasmin in mice.[8] Having recently experienced head trauma may indicate cephalic
tetanus if no other diagnosis has been made.
The "spatula test" is a clinical test for tetanus that involves touching the posterior pharyngeal wall
with a soft-tipped instrument and observing the effect. A positive test result is the involuntary
contraction of the jaw (biting down on the "spatula") and a negative test result would normally be
a gag reflex attempting to expel the foreign object. A short report in The American Journal of
Tropical Medicine and Hygiene states that, in a patient research study, the spatula test had a
high specificity (zero false-positive test results) and a high sensitivity (94% of infected patients
produced a positive test).[28]

Prevention[edit]
Unlike many infectious diseases, recovery from naturally acquired tetanus does not usually result
in immunity to tetanus. This is due to the extreme potency of the tetanospasmin toxin.
Tetanospasmin will likely be lethal before it will provoke an immune response.
Tetanus can be prevented by vaccination with tetanus toxoid.[29] The CDC recommends that
adults receive a booster vaccine every ten years,[30] and standard care practice in many places is
to give the booster to any patient with a puncture wound who is uncertain of when he or she was
last vaccinated, or if he or she has had fewer than three lifetime doses of the vaccine. The
booster may not prevent a potentially fatal case of tetanus from the current wound, however, as it
can take up to two weeks for tetanus antibodies to form.[31]
In children under the age of seven, the tetanus vaccine is often administered as a combined
vaccine, DPT/DTaP vaccine, which also includes vaccines against diphtheria and pertussis. For
adults and children over seven, the Td vaccine (tetanus and diphtheria) or Tdap (tetanus,
diphtheria, and acellular pertussis) is commonly used.[29]
The World Health Organization certifies countries as having eliminated maternal or neonatal
tetanus. Certification requires at least two years of rates of less than 1 case per 1000 live births.
In 1998 in Uganda, 3,433 tetanus cases were recorded in newborn babies; of these, 2,403 died.
After a major public health effort, Uganda in 2011 was certified as having eliminated tetanus.[32]
Post-exposure prophylaxis[edit]
Tetanus toxoid can be given in case of a suspected exposure to tetanus. In such cases, it can be
given with or without tetanus immunoglobulin (also called tetanus antibodies or tetanus
antitoxin[33]). It can be given as intravenous therapy or by intramuscular injection.
The guidelines for such events in the United States for non-pregnant people 11 years and older
are as follows:[34]

Vaccination status Clean, minor wounds All other wounds

Tdap and recommend catch-up

Unknown or less than 3 doses of tetanus Tdap and recommend
vaccination
toxoid containing vaccine catch-up vaccination
Tetanus immunoglobulin

3 or more doses of tetanus toxoid

containing vaccine AND less than 5 years No indication No indication
since last dose

3 or more doses of tetanus toxoid

Tdap preferred (if not yet
containing vaccine AND 5–10 years since No indication
received) or Td
last dose

3 or more doses of tetanus toxoid

Tdap preferred (if not Tdap preferred (if not yet
containing vaccine AND more than 10 years
yet received) or Td received) or Td
since last dose

Treatment[edit]

Tetanus deaths per million persons in 2012

 0-0

1-1

2-3

4-8

9-13

14-28

29-151

Mild tetanus[edit]
Mild cases of tetanus can be treated with:[35]

 tetanus immunoglobulin (TIG),[1] also called tetanus antibodies or tetanus antitoxin.[33] It can
be given as intravenous therapy or by intramuscular injection.
 metronidazole IV for 10 days
 diazepam oral or IV
Severe tetanus[edit]
Severe cases will require admission to intensive care. In addition to the measures listed above
for mild tetanus:[35]

 Human tetanus immunoglobulin injected intrathecally (increases clinical improvement from

4% to 35%)
 Tracheotomy and mechanical ventilation for 3 to 4 weeks. Tracheotomy is recommended for
securing the airway because the presence of an endotracheal tube is a stimulus for spasm
 Magnesium, as an intravenous (IV) infusion, to prevent muscle spasm
 Diazepam as a continuous IV infusion
 The autonomic effects of tetanus can be difficult to manage (alternating hyper-
and hypotension hyperpyrexia/hypothermia) and may require IV labetalol,
magnesium, clonidine, or nifedipine
Drugs such as diazepam or other muscle relaxants can be given to control the muscle spasms.
In extreme cases it may be necessary to paralyze the patient with curare-like drugs and use a
mechanical ventilator.
In order to survive a tetanus infection, the maintenance of an airway and proper nutrition are
required. An intake of 3,500 to 4,000 calories and at least 150 g of protein per day is often given
in liquid form through a tube directly into the stomach (percutaneous endoscopic gastrostomy), or
through a drip into a vein (parenteral nutrition). This high-caloric diet maintenance is required
because of the increased metabolic strain brought on by the increased muscle activity. Full
recovery takes 4 to 6 weeks because the body must regenerate destroyed nerve axon terminals.

Epidemiology[edit]
Disability-adjusted life year for tetanus per 100,000 inhabitants in 2004.

no data

≤10

10-25

25-50

50-75

75-100

100-125

125-150

150-200

200-250

250-500

500-750

≥750

Tetanus cases reported worldwide (1990-2004). Ranging from some (in dark red) to very few (in light
yellow) (grey, no data).

In 2013 it caused about 59,000 deaths – down from 356,000 in 1990.[7] Tetanus – in particular,
the neonatal form – remains a significant public health problem in non-industrialized countries
with 59,000 newborns worldwide dying in 2008 as a result of neonatal tetanus.[36][37] In the United
States, from 2000 through 2007 an average of 31 cases were reported per year.[8] Nearly all of
the cases in the United States occur in unimmunized individuals or individuals who have allowed
their inoculations to lapse.[8]
History[edit]
Tetanus was well known to ancient people who recognized the relationship between wounds and
fatal muscle spasms.[38] In 1884, Arthur Nicolaier isolated the strychnine-like toxin of tetanus from
free-living, anaerobic soil bacteria. The etiology of the disease was further elucidated in 1884
by Antonio Carle and Giorgio Rattone, two pathologists of the University of Turin, who
demonstrated the transmissibility of tetanus for the first time. They produced tetanus in rabbits by
injecting pus from a patient with fatal tetanus into their sciatic nerves.[8]
In 1891, C. tetani was isolated from a human victim by KitasatoShibasaburō, who later showed
that the organism could produce disease when injected into animals, and that the toxin could be
neutralized by specific antibodies. In 1897, Edmond Nocard showed that tetanus antitoxin
induced passive immunity in humans, and could be used for prophylaxis and treatment. Tetanus
toxoid vaccine was developed by P. Descombey in 1924, and was widely used to prevent
tetanus induced by battle wounds during World War II.[8]
Etymology[edit]
The word tetanus comes from the Ancient Greek: τέτανος tetanos "taut", which is further from
the Ancient Greek: τείνειν teinein "to stretch".[39]

See also[edit]
 Tetanized state
 Tetanospasmin
 Convulsion
From Wikipedia, the free encyclopedia

"Convulse" redirects here. For Finnish death metal band, see Convulse (band).

Convulsion

Classification and external resources

Specialty Neurology

ICD-10 R56

ICD-9-CM 125.7

MeSH D012640

[edit on Wikidata]

A convulsion is a medical condition where body muscles contract and relax rapidly and
repeatedly, resulting in an uncontrolled shaking of the body.[1] Because a convulsion is often a
symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym
for seizure. However, not all epileptic seizures lead to convulsions, and not all convulsions are
caused by epileptic seizures. Convulsions are also consistent with an electric shock and
improper Enriched Air Scuba Diving. For non-epileptic convulsions, see non-epileptic seizures.
The word "fit" is sometimes used to mean a convulsion or epileptic seizure.[2]

Contents
[hide]

 1Symptoms
 2Causes
 3Generalized seizures
 4References

Symptoms[edit]
Nude woman sitting with artificially induced convulsions, photographed by Eadweard Muybridge

When a person is having a convulsion, they may experience several different symptoms. These
may include: a brief blackout, confusion, drooling, loss of bowel/bladder control, sudden shaking
of entire body, uncontrollable muscle spasms, temporary cessation of breathing, and many more.
Symptoms usually last from a few seconds to around 15 minutes. If someone has a fit like this, it
is advised to make sure they don't fall and injure themselves, cushion their head and loosen any
restricting clothing/jewelry, and also call for medical help. Do not try to pin/hold them in place, as
this could possibly cause harm or injury to the individual.[1]

Causes[edit]
Convulsions are often caused by some sort of electrical activity mishap in the brain. Oftentimes,
the cause is not able to be pinpointed. Convulsions can be caused by chemicals in the blood, as
well as infections like meningitis or encephalitis. A very common cause of convulsions is fevers.
Other possibilities include head trauma, stroke or lack of oxygen to the brain. Sometimes the
convulsion can be caused by genetic defects or brain tumors.[1] Convulsions can also be caused
by any type-1 diabetic, whose blood sugar is too low. Hypoglycemia can cause very bad
convulsions until the person's blood sugar is raised to normal level. Convulsions can also be
caused by deficiency of vitamin B6 (pyridoxine).

Generalized seizures[edit]
Main article: Tonic-clonic seizures
The most common type of seizure is called a generalized seizure, also known as a generalized
convulsion. This is characterized by a loss of consciousness which may lead to the person
collapsing. The body stiffens for about a minute and then jerks uncontrollably for the next minute.
During this, the patient may fall and injure themselves or bite their tongue and lose control of
their bladder. A familial history of this puts a person at a greater risk for developing them.[3][4]
Conjunctivitis
From Wikipedia, the free encyclopedia

"Pinkeye" redirects here. For other uses, see Pinkeye (disambiguation).

Conjunctivitis

Synonyms Pink eye

An eye with viral conjunctivitis

Specialty Ophthalmology

Symptoms Reddish eye, scratchiness[1]

Causes Viral, bacterial, allergies[2]

Diagnostic method Based on symptoms, microbial culture[1]

Prevention Handwashing[1]

Treatment Based on underlying cause[2]

 Frequency 3–6 million per year (USA)[1][2]

[edit on Wikidata]

Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part
of the eye and the inner surface of the eyelid.[3] It makes the eye appear pink or reddish. There
may also be pain, burning, scratchiness, or itchiness. The affected eye may have increased tears
or be "stuck shut" in the morning. Swelling of the white part of the eye may also occur.[1] Itching of
the eye is more common in cases due to allergies.[2] Conjunctivitis can affect one or both eyes.[1]
The most common infectious causes are viral followed by bacterial.[2] The viral infection may
occur along with other symptoms of a common cold. Viral and bacterial cases are easily spread
between people.[1] Allergies to pollen or animal hair is also a common cause.[2] Diagnosis is often
based on signs and symptoms. Occasionally a sample of the discharge is sent for culture.[1]
Prevention is partly by handwashing. Treatment depends on the underlying cause.[1] In the
majority of viral cases, there is no specific treatment.[2] Most cases due to a bacterial infection will
also resolve without treatment; however, antibiotics can shorten the illness.[1][2] Those who
wear contact lens and those with either gonorrhea or chlamydia as the cause should be treated.
Allergic cases can be treated with antihistamine or mast cell inhibitor drops.[2]
About 3 to 6 million people get conjunctivitis each year in the United States.[1][2] In adults viral
causes are more common, while in children bacterial causes are more common.[2] Typically
people get better in one or two weeks.[1][2] If there is visual loss, significant pain, sensitivity to light,
signs of herpes, or a person is not improving after a week, further diagnosis and treatment may
be required.[2] Conjunctivitis in a newborn, known as neonatal conjunctivitis, may also require
specific treatment.[1]

Contents
[hide]

 1Signs and symptoms

o 1.1Viral
o 1.2Allergic
o 1.3Bacterial
o 1.4Chemical
o 1.5Other
 2Causes
o 2.1Viral
o 2.2Bacterial
o 2.3Allergic
o 2.4Other
 3Diagnosis
o 3.1Classification
o 3.2Differential diagnosis
 4Prevention
 5Management
o 5.1Viral
o 5.2Allergic
o 5.3Bacterial
o 5.4Chemical
 6Epidemiology
 7History
 8See also
 9References
 10External links

Signs and symptoms[edit]

Red eye, swelling of conjunctiva and watering of the eyes are symptoms common to all forms of
conjunctivitis. However, the pupils should be normally reactive, and the visual acuity normal.
Viral[edit]

Conjunctivitis due to a viral infection resulting in some bleeding

Viral conjunctivitis is often associated with an infection of the upper respiratory tract, a common
cold, or a sore throat. Its symptoms include excessive watering and itching. The infection usually
begins with one eye, but may spread easily to the other.
Viral conjunctivitis shows a fine, diffuse pinkness of the conjunctiva, which is easily mistaken for
the ciliary infection of iris (iritis), but there are usually corroborative signs on microscopy,
particularly numerous lymphoid follicles on the tarsal conjunctiva, and sometimes a punctate
keratitis.
Allergic[edit]

An eye with allergic conjunctivitis showing conjunctival edema

Allergic conjunctivitis is inflammation of the conjunctiva (the membrane covering the white part of
the eye) due to allergy.[4] Allergens differ among patients.
Symptoms consist of redness (mainly due to vasodilation of the peripheral small blood
vessels), swelling of the conjunctiva, itching, and increased lacrimation (production of tears). If
this is combined with rhinitis, the condition is termed "allergic rhinoconjunctivitis". The symptoms
are due to release of histamine and other active substances by mast cells, which stimulate
dilation of blood vessels, irritate nerve endings, and increase secretion of tears.
Bacterial[edit]
An eye with bacterial conjunctivitis

Bacterial conjunctivitis causes the rapid onset of conjunctival redness, swelling of the eyelid,
and mucopurulent discharge. Typically, symptoms develop first in one eye, but may spread to the
other eye within 2–5 days. Bacterial conjunctivitis due to common pyogenic (pus-
producing) bacteria causes marked grittiness/irritation and a stringy, opaque, greyish or
yellowish mucopurulent discharge that may cause the lids to stick together, especially after
sleep. Severe crusting of the infected eye and the surrounding skin may also occur. The gritty
and/or scratchy feeling is sometimes localized enough for patients to insist they must have a
foreign body in the eye. The more acute pyogenic infections can be painful.[citation needed] Common
bacteria responsible for non-acute bacterial conjunctivitis
are Staphylococci, Streptococci,[5] Haemophilus sp. Less commonly Chlamydia trachomatis is
involved.[6]
Bacteria such as Chlamydia trachomatis or Moraxella can cause a non-exudative but persistent
conjunctivitis without much redness. Bacterial conjunctivitis may cause the production
of membranes or pseudomembranes that cover the conjunctiva. Pseudomembranes consist of a
combination of inflammatory cells and exudates, and are loosely adherent to the conjunctiva,
while true membranes are more tightly adherent and cannot be easily peeled away. Cases of
bacterial conjunctivitis that involve the production of membranes or pseudomembranes are
associated with Neisseria gonorrhoeae, β-hemolytic streptococci, and C.
diphtheriae. Corynebacterium diphtheriae causes membrane formation in conjunctiva of non-
immunized children.[citation needed]
Chemical[edit]
Chemical eye injury is due to either an acidic or alkali substance getting in the eye.[7] Alkalis are
typically worse than acidic burns.[8] Mild burns will produce conjunctivitis, while more severe
burns may cause the cornea to turn white.[8] Litmus paper is an easy way to rule out the
diagnosis by verifying that the pH is within the normal range of 7.0—7.2.[7]Large volumes
of irrigation is the treatment of choice and should continue until the pH is 6—8.[8] Local
anaesthetic eye drops can be used to decrease the pain.[8]
Irritant or toxic conjunctivitis show primarily marked redness. If due to splash injury, it is often
present in only the lower conjunctival sac. With some chemicals, above all
with caustic alkalis such as sodium hydroxide, there may be necrosis of the conjunctiva with a
deceptively white eye due to vascular closure, followed by sloughing of the dead epithelium. This
is likely to be associated with slit-lamp evidence of anterior uveitis.
Other[edit]
An eye with chlamydial conjunctivitis

Inclusion conjunctivitis of the newborn (ICN) is a conjunctivitis that may be caused by the
bacteria Chlamydia trachomatis, and may lead to acute, purulent conjunctivitis.[9] However, it is
usually self-healing.[9]
Conjunctivitis is identified by irritation and redness of the conjunctiva. Except in
obvious pyogenic or toxic/chemical conjunctivitis, a slit lamp (biomicroscope) is needed to have
any confidence in the diagnosis. Examination of the tarsal conjunctiva is usually more diagnostic
than the bulbar conjunctiva.

Causes[edit]
Conjunctivitis, when caused by an infection, is most commonly caused by a viral
infection.[10] Bacterial infections, allergies, other irritants, and dryness are also common causes.
Both bacterial and viral infections are contagious and passed from person to person, but can also
spread through contaminated objects or water.
Viral[edit]
Adenoviruses is the most common cause of viral conjunctivitis (adenoviral
keratoconjunctivitis).[11] Herpetic keratoconjunctivitis (caused by herpes simplex viruses) can be
serious and requires treatment with acyclovir. Acute hemorrhagic conjunctivitis is a highly
contagious disease caused by one of two enteroviruses, Enterovirus 70 and Coxsackievirus A24.
These were first identified in an outbreak in Ghana in 1969, and have spread worldwide since
then, causing several epidemics.[12]
Bacterial[edit]
The most common causes of acute bacterial conjunctivitis are Staphylococcus
aureus, Streptococcus pneumoniae, and Haemophilusinfluenzae.[11] Though very rare,
hyperacute cases are usually caused by Neisseria gonorrhoeae or N. meningitidis. Chronic
cases of bacterial conjunctivitis are those lasting longer than 3 weeks, and are typically caused
by Staphylococcus aureus, Moraxella lacunata, or gram-negative enteric flora.
Allergic[edit]
Conjunctivitis may also be caused by allergens such
as pollen, perfumes, cosmetics, smoke,[13] dust mites, Balsam of Peru,[14] and eye drops.[15]
Other[edit]
Conjunctivitis is part of the triad of reactive arthritis, which is thought to be caused
by autoimmune cross-reactivity following certain bacterial infections. Reactive arthritis is highly
associated with HLA-B27. Conjunctivitis is associated with the autoimmune disease relapsing
polychondritis.[16][17]

Diagnosis[edit]
Cultures are not often taken or needed as most cases resolve either with time or typical
antibiotics. Swabs for bacterial culture are necessary if the history and signs suggest bacterial
conjunctivitis but there is no response to topical antibiotics. Viral culture may be appropriate
in epidemic case clusters.
A patch test is used to identify the causative allergen in the case where conjunctivitis is caused
by allergy.[18]
Conjunctival scrapes for cytology can be useful in
detecting chlamydial and fungal infections, allergy, and dysplasia, but are rarely done because of
the cost and the general lack of laboratory staff experienced in handling ocular specimens.
Conjunctival incisional biopsy is occasionally done when granulomatous diseases
(e.g., sarcoidosis) or dysplasia are suspected.
Classification[edit]
Classification can be either by cause or by extent of the inflamed area.
Causes[edit]

 Allergic conjunctivitis, caused by allergens such

as pollen, perfumes, cosmetics, smoke,[13] dust mites, Balsam of Peru (used in food and drink
for flavoring, in perfumes and toiletries for fragrance, and in medicine and pharmaceutical
items for healing properties),[14] and eye drops.[15] A patch test is used to diagnose it and
identify the causative allergen.[18]
 Bacterial conjunctivitis
 Viral conjunctivitis
 Chemical conjunctivitis
 Neonatal conjunctivitis is often defined separately due to different organisms
 Autoimmune
By extent of involvement[edit]
Blepharoconjunctivitis is the dual combination of conjunctivitis with blepharitis (inflammation of
the eyelids).
Keratoconjunctivitis is the combination of conjunctivitis and keratitis (corneal inflammation).
Blepharokeratoconjunctivitis is the combination of conjunctivitis with blepharitis and keratitis. It is
clinically defined by changes of the lid margin, meibomian gland dysfunction, redness of the eye,
conjunctival chemosis and inflammation of the cornea.[19]
Differential diagnosis[edit]
There are more serious conditions that can present with a red eye such as infectious keratitis,
angle-closure glaucoma, or iritis. These conditions require the urgent attention of an
ophthalmologist. Signs of such conditions include decreased vision, significantly increased
sensitivity to light, inability to keep eye open, a pupil that does not respond to light, or a severe
headache with nausea.[20] Fluctuating blurring is common, due to tearing and mucoid discharge.
Mild photophobia is common. However, if any of these symptoms are prominent, it is important to
consider other diseases such as glaucoma, uveitis, keratitis and even meningitis or carotico-
cavernous fistula.
A more comprehensive differential diagnosis for the red or painful eye includes:[20]

 corneal abrasion
 subconjunctival hemorrhage
 pinguecula
 blepharitis
 dacryocystitis
 keratoconjunctivitis sicca (dry eye)
 keratitis
 herpes simplex
 herpes zoster
 episcleritis - an inflammatory condition that produces a similar appearance to conjunctivitis,
but without discharge or tearing.
 uveitis
 acute angle-closure glaucoma
 endophthalmitis

Prevention[edit]
The best effective prevention is hygiene and not rubbing the eyes by infected hands. Vaccination
against adenovirus, haemophilusinfluenzae, pneumococcus, and neisseriameningitidis is also
effective.[citation needed]
Povidone-iodine eye solution has been found to prevent conjunctivitis following birth.[21] As it is
less expensive it is being more commonly used for this purpose globally.[21]

Management[edit]
Conjunctivitis resolves in 65% of cases without treatment, within two to five days. The
prescription of antibiotics is not necessary in most cases.[22]
Viral[edit]
Viral conjunctivitis usually resolves on its own and does not require any specific
treatment.[10] Antihistamines (e.g., diphenhydramine) or mast cell stabilizers (e.g., cromolyn) may
be used to help with the symptoms.[10] Povidone iodine has been suggested as a treatment, but
as of 2008 evidence to support it was poor.[23]
Allergic[edit]
For the allergic type, cool water poured over the face with the head inclined downward constricts
capillaries, and artificial tears sometimes relieve discomfort in mild cases. In more severe
cases, nonsteroidal anti-inflammatory medications and antihistamines may be prescribed.
Persistent allergic conjunctivitis may also require topical steroid drops.
Bacterial[edit]
Bacterial conjunctivitis usually resolves without treatment.[10] Topical antibiotics may be needed
only if no improvement is observed after three days.[24] In people who received no antibiotics,
recovery was in 4.8 days, with immediate antibiotics it was 3.3 days, and with delayed antibiotics
3.9 days. No serious effects were noted either with or without treatment.[25] As they do speed
healing in bacterial conjunctivitis, their use is also reasonable.[26]
In those who wear contact lenses, are immunocompromised, have disease which is thought to
be due to chlamydia or gonorrhea, have a fair bit of pain, or who have lots of discharge,
antibiotics are recommended.[10] Gonorrhea or chlamydia infections require both oral and topical
antibiotics.[10]
When appropriate, the choice of antibiotic varies, differing based on the cause (if known) or the
likely cause of the conjunctivitis. Fluoroquinolones, sodium sulfacetamide,
or trimethoprim/polymyxin may be used, typically for 7–10 days.[11] Cases of meningococcal
conjunctivitis can also be treated with systemic penicillin, as long as the strain is sensitive
to penicillin.
When investigated as a treatment, Povidone-iodine ophthalmic solution has also been observed
to have some effectiveness against bacterial and chlamydial conjunctivitis, with a possible role
suggested in locations where topical antibiotics are unavailable or costly.[27]
Chemical[edit]
Conjunctivitis due to chemicals is treated via irrigation with Ringer's lactate or saline solution.
Chemical injuries (particularly alkali burns) are medical emergencies, as they can lead to severe
scarring and intraocular damage. People with chemically induced conjunctivitis should not touch
their eyes, regardless of whether or not their hands are clean, as they run the risk of spreading
the condition to another eye.

Epidemiology[edit]
Conjunctivitis is the most common eye disease.[28]

History[edit]
An adenovirus was first isolated by Rowe et al. in 1953. Two years later Jawetz et al. published
on epidemic keratoconjunctivitis.[29]:437 "Madras eye" is a colloquial term that has been used in
India for the disease, with one explanation relating to a connection with a former superintendent
of the Regional Institute of Ophthalmology in the city of Madras (the present-
day Chennai).[30][dubious – discuss]

See also[edit]
 Conjunctival suffusion
 Episcleritis
 Urethritis
From Wikipedia, the free encyclopedia

This article needs additional citations for verification. Please help improve
this article by adding citations to reliable sources. Unsourced material may
be challenged and removed. (November 2012) (Learn how and when to remove
this template message)

Urethritis

Classification and external resources

Specialty urology

ICD-10 N34

ICD-9-CM 597 099.4

DiseasesDB 27902

MedlinePlus 000439

eMedicine med/2342

MeSH D014526

[edit on Wikidata]

Urethritis is inflammation of the urethra. The most common symptom is painful or difficult
urination.[1][2] It is usually caused by infection with bacteria. The infection is often a sexually
transmitted infection (STI), but some are just non-STI urinary tract infections. Urethritis can
be idiopathic, but it usually is not.

Contents
[hide]

 1Causes
 2Diagnosis
 3Prevention
 4Treatment
 5References
Causes[edit]
The disease is classified as either gonococcal urethritis, caused by Neisseria gonorrhoeae,
or non-gonococcal urethritis (NGU), most commonly caused by Chlamydia trachomatis. NGU,
sometimes called nonspecific urethritis (NSU), has both infectious and noninfectious causes.
Other causes include:[1][2]

 Adenoviridae
 Uropathogenic Escherichia coli (UPEC)
 Herpes simplex
 Cytomegalovirus
 Mycoplasma genitalium
 Reactive arthritis
 Trichomonas vaginalis[3]
 Ureaplasmaurealyticum
 Methicillin-resistant Staphylococcus aureus[4]
 Group B streptococcus[5]

Diagnosis[edit]
In female patients, urethritis can be caused by pelvic inflammatory disease.[6] With male patients,
the physician examines the penis and testicles for soreness or any swelling. The urethra is
visually examined by spreading the urinary meatus apart with two gloved fingers, and examining
the opening for redness, discharge and other abnormalities. Next, a cotton swab is inserted 1-
4 cm into the urethra and rotated once. To prevent contamination, no lubricant is applied to the
swab, which can result in pain or discomfort. The swab is then smeared onto a glass slide and
examined under a microscope. A commonly used cut-off for the diagnosis of urethritis is 5 or
more granulocytes per High Power Field, but this definition has recently been called into
doubt.[7] The physician sometimes performs a digital rectal examination to inspect the prostate
gland for swelling or infection.
A urinary tract infection may cause similar symptoms.

Prevention[edit]
Risk of some causes of urethritis can be lessened by avoiding unprotected sexual activity,
chemicals that could irritate the urethra; this could include detergents or lotions as well
as spermicides or contraceptives, and irritation caused by manual manipulation of the
urethra.[medical citation needed]

Treatment[edit]
A variety of drugs may be prescribed based on the cause of the patient's urethritis. Some
examples of medications based on causes
include:[2] azithromycin, doxycycline, erythromycin, levofloxacin, metronidazole, ofloxacin,
or tinidazole.
Proper perineal hygiene should be stressed. This includes avoiding use of vaginal deodorant
sprays and proper wiping after urination and bowel movements. Intercourse should be avoided
until symptoms subside.