Parasitic diseases of the central

nervous system

DR. M OHAM ED AM R N ASR, M SC .

 Introduction

 Parasitic diseases of the central nervous system are

associated with high mortality and morbidity,
especially in resource-limited settings.
 The burden of these diseases is amplified as
survivors are often left with neurologic sequelae
affecting mobility, sensory organs, and cognitive
functions, as well as seizures/epilepsy.
 Introduction

 The complexity of parasitic life cycles and geographic

specificities, as well as overlapping clinical
manifestations in the host reflecting the diverse
pathogenesis of parasites, can present diagnostic
challenges.
 Almost all parasitses involving the human brain can
be associated with seizures and epilepsy, either by a
diffuse encephalitis or encephalopathy, or by
intracerebral location of the parasite.
 Introduction

 Neurocysticercosis (NCC) and malaria, are likely

responsible for most of the seizures attributed to
parasitic disease worldwide.
 Some parasitic diseases cause eosinophilic
meningoencephalitis, which is characterized by
specific clinical manifestations and microscopic
identification of eosinophils in cerebrospinal fluid
(CSF).
 Classification

Helminthes
protozoa

Protozoa
 Helminthes

• Cysticercosis
• Hydatidosis
cystodes • Sparganosis

• Schistosomiasis
Trematodes
• Paragonimiasis

• Toxocariasis
• Strongyloidiasis
nematodes
 Classification

protozoa
• Malaria
• Toxoplasmosis
• African trypanosomiasis
• Amebiasis
• Leishmaniasis
 Helminthes

 TREMATODE INFECTIONS
 Schistosomiasis (Life cycle)

 Humans are the definitive hosts of S. mansoni and S.

haematobium.
 Humans are infected when cercariae penetrate the
skin and enter dermal veins, lose their tail to become
developing worms or schistosomulae, and then
migrate to the lung then to the liver, where they
undergo sexual maturation, pair and migrate either
to the portal venous system or the urinary tract.
 The adult parasites could migrate in the vasculature
to other locations where they lay eggs
 CNS Schistosomiasis(C/P)

 Schistosoma mansoni and Schistosoma

haematobium are almost always associated with
spinal cord infection
 Schistosoma japonicum affects the brain.
 CNS complications, usually as a result of the eggs
causing infarction or granuloma formation
 Acute encephalitis, usually in the presence of a
systemic illness with fever and eosinophilia, occurs
in about 2–3% of cases of acute schistosomiasis
(katayama fever)
 Schistosomiasis ( C/P)

 Patients with cerebral schistosomiasis are commonly

asymptomatic and may present with signs of space
occupying lesions, such as headache, seizures,
papilledema, and visual disturbances
 Spinal schistosomiasis is often seen in young male
patients. Its localization in the lower cord and conus
region is explained by the free anastomosis between
the pelvic veins and the vertebral venous plexus.
 The most frequent form is myeloradiculopathy.
 Schistosomiasis( diagnosis)

 The finding of eggs in the stool/urine or positive serology

provides supportive but not direct evidence of
schistosomal involvement in the central nervous system.
 A definitive diagnosis can only be ascertained with
histopathological study at biopsy, showing schistosoma
eggs and granulomas
 Pathology : In the acute phase, live eggs are surrounded
by eosinophils, lymphocytes, plasma cells, and rimmed
by a zone of reactive gliosis.
 After the egg dies, circumscribed granulomas are seen
around the degenerating eggs .
 Schistosomiasis

MRI images after IV administration

of contrast material show multiple
intensely enhancing small nodules, 1–
3 mm in diameter (arrow), clustered
closely together. ( CNS
schistosomiasis)
 Schistosomiasis

 Schistosomicidal drugs, such as praziquantel,

steroids and surgery, are the mainstay of therapy for
this severe form of schistosomiasis.
 Paragonimiasis (EP/LC)

 Paragonimiasis is infection by trematodes of the

genus Paragonimus with P. westermani being the
most prominent of this species (lung fluke).
 These are endemic in Asia, the Americas, and
Central and Western Africa.
 Human infection is acquired by eating raw or
undercooked fresh water crustaceans that are the
second intermediate hosts.
 Carnivorous mammals are definitive hosts
 Paragonimiasis ( c/p)

 Most infections are asymptomatic, but pulmonary

symptoms may occur
 Symptoms include chronic cough, chest pain, dyspnea
and heamoptysis
 The CNS is affected by the migration of larvae through
the bloodstream or through direct invasion of the neural
foramina of the skull base and intervertebral foramina of
the spine along the cranial and spinal vessels and nerves.
 Toxic substances produced by the parasite are
responsible for aseptic inflammation & abscess or
granulomatous reaction to the parasite or its eggs.
 Paragonimiasis ( c/p)

 The neurologic presentation is nonspecific and can

include headache, seizures and focal neurologic
deficits. Some patients can present intracranial
vascular injury
 Spinal cord lesions cause paraplegia, sensory loss,
and bladder and bowel incontinence
 Paragonimiasis

 Diagnosis by identifing egg through microscopic examination

of sputum and stool
 Serologic test to detect Abs may be useful for diagnosis of
extrapulmonary paragonimiasis
 MRI demonstrates characteristic tunnel-like regions of signal
abnormality which represent the migrating track of the adult
worm. Additionally, ring-like shapes or clusters of multiple
ring-like enhancing lesions have been reported

 Praziquantel is the drug of choice, corticosteroids may be

given with the praziquantel to help reduce the inflammatory
response around dying flukes.
 (A and B) MRI shows cerebromalacia and
ventriculomegaly with a round calcified
mass on the left frontal lobe. (C and D)
Several well-defined calcified masses in the
left inferior frontal lobe are seen
 CYSTODE INFECTIONS
 Neurocysticercosis

 Cysticercosis is a parasitic infection caused by the

larval form of the pork tapeworm, Taenia solium
 Globally endemic, this infection is usually seen in
poor regions
 Cysticercosis occurs when man, who is normally the
definitive host, accidentally ingests eggs and
becomes the intermediate host.
 The adult worm resides in the human gut, and
excreted eggs are eaten by pigs.
 Neurocysticercosis(C/P)

 When the larvae penetrate GIT to blood stream then

invade the brain and spinal cord, the condition is
referred to as neurocysticercosis
 The clinical manifestations of NCC are
heterogeneous and depend mainly on the
localization of cysts and immune response by the
host. However, the vast majority of cases are
asymptomatic.
 Seizures, headache, focal deficits and cognitive
abnormalities are the most frequent manifestations
 Neurocysticercosis (C/P)

 Acute hydrocephalus related to intraventricular

cysts, or chronic hydrocephalus may occur.
 Spinal cord cysticercosis is rare and patients may
experience nonspecific clinical manifestations such
as nerve root pain or spinal cord compression
syndromes.
 NCC predominantly affects adults in their third and
fourth decade of life
 Neurocysticercosis(diagnosis)

 Histological confirmation of the parasite is not possible

in most cases; therefore, diagnosis is usually based on
neuroimaging and confirmed by serology.
 Radiological imaging (MRI and CT scans) show the
morphology and localisation of cysts, burden of infection
and the presence of surrounding inflammation.
 The number of cysts varies and range from a solitary
cysticercus to several hundred.
 EIA and ELISA are also used to detect antigens
associated with the pathogen
 Peripheral esinophillia
CT images of the brain in a
patient with neurocysticercosis
show numerous parenchymal
lesions
MRI imaging of human neurocysticercosis .
Viable cysts in structural MRI (A); and enhancing nodule (B); many brain
calcifications visible (C); massive parenchymal neurocysticercosis (D); basal
subarachnoid neurocysticercosis (E); and intraventricular cysticercosis (F).
 Neurocysticercosis

 ttt includes albendazole and praziquantel,

 Ttt may provoke an inflammatory response caused
by the release of Taenia cysticerci antigen,
corticosteroids can be used.
 Surgical intervention may be required to remove
intraventricular cysts causing hydrocephalus.
 Echinococcosis (hydatidosis)

 The parasites Echinococcus

granulosus and Echinococcus multilocularis causing
cystic echinococcosis (hydatid disease) and alveolar
echinococcosis(alveolar disease) respectively.
 The definitive hosts of E. granulosus are canines.
 In humans, the disease is caused by accidental ingestion
of eggs.
 The definitive host of E. multilocularis is the fox, and this
infection, although rare, is more aggressive.
 Hydatid disease is common in sheep raising areas of
mediterranean, Middle east, australia and new Zealand
 Echinococcosis (hydatidosis)

 Brain echinococcosis is rare representing 1% to 2%

all cases with hydatid disease. It is more common in
children and young adults with male predominance.
 The infection may be primary or secondary to the
spontaneous or traumatic rupture of a primary
cerebral cyst or because of embolization of cardiac
cysts.
 Echinococcosis (hydatidosis)

 Cysts may remain asymptomatic until they are large

enough to cause a mass effect.
 Cerebral lesions occur in 1–4% of individuals with
cystic echinococcosis, with nonspecific clinical
findings related to those of space occupying lesions,
increased intracranial pressure and seizure.
 Cysts can reach up to 10 cm in diameter.
 These cysts could be unilocular or contain several
daughter cysts and are surrounded by a fibrous wall
formed by host tissues.
 Echinococcosis (hydatidosis)

 Spilling of cyst fluid due to trauma or surgery may

trigger anaphylaxis as well as disseminated infection.
 CT provides definitive results of diagnosis. It shows
hydatid cyst as a spherical, well defined, thin walled,
homogeneous and non-enhancing cystic lesion
without peripheral oedema.
 Positive CSF serology, and rarely biopsy.
 Echinococcosis (hydatidosis)

 Surgical treatment remains the milestone of

treatment for CNS hydatid disease. Anti-helminthic
medications, such as albendazole, are
complimentarily used in case of systemic disease,
perioperative setting, recurrence, or cyst rupture.
 The primary aim of surgery is the intact cyst removal
without spillage of the contents.
 Dowling technic is the most commonly done
procedure designed to give birth to the intact cyst by
irrigating saline between cyst wall-brain interfaces
a) Plain computed
tomography scan of
brain, axial view:
Showing a large multi-
cystic lesion in left
parieto-occipital region
with mass effect.
b) Plain magnetic
resonance imaging scan
of brain T1, coronal view:
Showing a large multi-
cystic lesion in left
parieto-occipital region
with mass effect.
c) Intraoperative findings
confirm multiple
daughter cysts inside a
large cyst
 Sparganosis

 This is a zoonotic larval infection by Sparganum

species.
 The adult worm is found in cat and dog intestine.
 Humans are infected by drinking water containing
copepods ( cyclops) or by eating undercooked meat
of the intermediate hosts ( fish, reptiles)
 Sparganosis

 The larvae migrate in tissues in humans without

maturing to muscles, sub cutenous tissue forming
slowly growing masses
 CNS affection much less common
 Focal neurological deficits, seizures, and hemorrhage
are seen depending on the location of the parasite
(mass effect)
 Sparganosis

 The lesions are in the form of abscesses or cysts

 Granulomatous inflammation can also occur
surrounding the parasite
 Diagnosis based on history of consuming raw meat,
radiological evidence, positive CSF serology, and
rarely a biopsy.
 Surgical removal is required when the lesion is
acccessible, coadministration of albendazole &
praziquantal to prevent dissemination
Cranial postcontrast MRI obtained at the onset of headache revealed an irregular
enhancement lesion with perifocal edema in the right frontal lobe (a) and tunnel sign
involving the bilateral brain (b). Postcontrast MRI performed after the second two-
day praziquantel treatment, the irregular enhancement lesion was obviously reduced
(c) and tunnel sign was almost invisible (d)
 Nematode infections
 Strongyloidiasis

 Strongyloides stercoralis is an intestinal infection with

man as the definitive host.
 Strongyloidiasis is globally distributed but is more
common in the tropics and subtropics, which have a
warm, wet climate.
 Strongyloidiasis is transmitted through direct
penetration of human skin by infective larvae when in
contact with soil
 The parasite has a unique character among helminth
parasites in that it can multiply within its hosts via
autoinfection.
 Autoinfection in augmented in IC people leading to a
hyperinfection syndrome
 Strongyloidiasis ( C/P)

 Chronic strongyloidiasis is associated with

gastrointestinal symptoms and recurrent respiratory and
allergic features
 CNS manifestations, caused by larval migration, are rare
but serious, and are dominated by picture of meningitis
or menigoencephalitis.
 The patient with CNS disease may present with
headache, altered mental state, seizures, signs of
meningeal irritation, and rarely coma.
 Disseminated strongyloidiasis usually with bacterial
sepsis occurs in immunocomprimized patients. CNS may
be affected by aseptic or septic meningitis in such cases
 Strongyloidiasis ( diagnosis)

 Definitive diagnosis depends on isolation of larvae

from stool, intestinal aspirate, and/or sputum, and
occasionally from CSF.
 Serological tests may be useful especially in non-
endemic people. Furthermore, persistent but
fluctuating eosinophilia, is another clue but
eosinophilia may not be present in
immunosuppressed patients
 Ttt with ivermectin or albendazole
 Toxocariasis

 Toxocariasis is a soil transmitted helminthic zoonosis

due to infection of humans by larvae of Toxocara canis
(T. canis), or less commonly T. cati.
 The definitive host is dog.
 Human Infection by accidental ingestion of eggs from
contaminated food with stool of infected animal causing
either
i. Visceral larva migrans (fever, Headache, rash, HSM,
pneumonitis, ashma)
ii. Covert toxocariasis ( milder version)
iii. Ocular larva migrans (restricted to the eye and the
optic nerve causing uveitis & chorioretinitis).
 Toxocariasis

 CNS infestation is rare, being recently diagnosed

with increasing frequency due to improved
diagnostic tools
 Patients may present with seizures, eosinophilic
meningitis, optic neuritis and transverse myelitis.
 Serology is useful, although cross-reactions with
other nematode species may give false positive
reactions.
 Toxocariasis

 Ttt with albendazole or mebendazole

 Ttt of occular toxocariasis is more difficult aiming to
prevent progressive damage to the eye, steroids
indicated to reduce inflamation, the role of
antihelminths is uncertain.
Protozoa
 Toxoplasmosis

 Toxoplasmosis is caused by the intracellular parasite

Toxoplasma gondii.
 T. gondii is found worldwide and the prevalence
varies widely.
 Nearly 25%-50% of patients with HIV infection have
latent T. gondii infection
 T. gondii exists in three forms: oocysts, tachyzoites,
and bradyzoites.
 Cats are the definitive host.
 Toxoplasmosis

 Humans get infected either by

1. ingesting food or water contaminated with cat
feces or by eating undercooked or raw meat
containing tissue cysts
2. Blood transfusion or organ transplantation
3. Transplacentally from mother to fetus

 Toxoplasma gondii cysts may develop in any tissue,

but most commonly develop in the brain, retina,
skeletal muscle and cardiac muscle.
 Toxoplasmosis

 The clinical syndromes associated with

toxoplasmosis fall into the following three
categories:
 1.Primary toxoplasmosis in immunocompetent
individuals.
Clinical manifestations in this set of individuals are
rare
 2.Toxoplasmosis in immunosuppressed patients.
Most common opportunistic infection in HIV patients
 Toxoplasmosis

 HIV-infected patients with toxoplasmosis develop

encephalitis and ring-enhancing intracranial mass
lesions
 Risk is greatest among those with CD4 counts of <
50/mcL; rare when CD4 counts are > 200/mcL.
 These patients typically have headache, altered
mental status, seizures, coma, fever, and sometimes
focal neurologic deficits, such as motor or sensory
loss, cranial nerve palsies, visual abnormalities, and
focal seizures.
 Toxoplasmosis

 3.Congenital toxoplasmosis.
Primary infection during pregnancy could be clinically
silent, symptoms include fever, headache, and
lymphadenopathy.
The risk of transmission rises with gestational age;
however, the severity of manifestations are less with
advancing pregnancy.
Spontaneous abortion, stillbirth, or birth defects may
occur.
 Toxoplasmosis

 Diagnosis with MRI or CT with contrast typically

show single or multiple rounded, ring-enhancing
lesions. Although these lesions are not
pathognomonic, their presence in patients with AIDS
and CNS symptoms warrants a trial of chemotherapy
for T. gondii.
 Cerebral spinal fluid (CSF) examination may
demonstrate the presence of antibodies and
Toxoplasma DNA.
 (a) Post-contrast axial CT showing
a large deep lesion in the
left hemisphere with significant edema,
mass effect, and contrast ring
enhancement.
A second smaller lesion seems to be
present behind the bigger one.
(b) Post-contrast axial T1-weighted MRI
taken 3 weeks after anti-Toxoplasma
treatment showing a marked
reduction in lesion size, mass effect, and
edema
 Toxoplasmosis

 Treatment requires six weeks of multi-drug therapy

with pyrimethamine, sulfadiazine, and folinic acid.
Long-term maintenance doses are often required to
prevent recurrence.
 Trimethoprim/sulfa Prophylaxis in HIV patients
with CD4 count < 100
 Primary amoebic meningoencephalitis

 Primary amoebic meningoencephalitis (PAM) is

caused by Naegleria fowleri found in soil, river, and
lake water.
 It enters via the nasal mucosa and travels along
olfactory nerves to enter the brain
 The disease has a fulminant course and is usually
fatal.
 Inflammation and destruction of gray matter leads to
severe headaches and fever. Within days, confusion,
convulsions coma, and death may occur
 Primary amoebic meningoencephalitis

 The progression can be very rapid, and the disease is

often not diagnosed until autopsy.

 N. fowleri infections can be confirmed by direct

observation of CSF
 Detection of antigens with indirect immunofluorescence,
or genetic analysis with PCR, can be used to confirm
diagnosis.
 A new experimental drug called miltefosine shows some
promise for treating these infections
 Granulomatous Amoebic Encephalitis

 Acanthamoeba and Balamuthia species are free-

living amoebae.
 Human infections by these amoebae are rare.
However, they can cause amoebic keratitis in contact
lens wearers, disseminated infections in
immunocompromised patients, and granulomatous
amoebic encephalitis (GAE) in severe cases.
 The CNS is affected in immunocompromised
individuals. The infection reaches the CNS via the
bloodstream from a site of skin injury.
 Granulomatous Amoebic Encephalitis

 The clinical course is more prolonged than that

caused by Naegleria and varies from 1 week to
several months between the appearance of cutaneous
lesions and the recognition of central nervous system
(CNS) disease
 The disease manifests as headache, meningism,
seizures, and focal neurological deficits.
 Nausea, vomiting, lethargy, or low-grade
fever, hemiparesis, visual disturbances, facial nerve
palsy and ataxia may occur.
 GAE is nearly always fatal
Granulomatous Amoebic Encephalitis

 Pathology
brain is edematous with multiple areas of meningeal
softening and inflammation overlie necrotic and
hemorrhagic lesions in the cortex. Such lesions extend into
the white matter in the brainstem, cerebral hemispheres,
and cerebellum and have the appearance of hemorrhagic
infarcts.
There are areas of necrosis, hemorrhage, and inflammatory
infiltrates, consisting of neutrophils, mononuclear cells,
and multinucleated giant cells. Trophozoites and cysts
of Acanthamoeba are seen extracellularly or within
macrophages
Granulomatous Amoebic Encephalitis
 Granulomatous Amoebic Encephalitis

 GAE is often not diagnosed until late in the infection.

Lesions caused by the infection can be detected using
CT or MRI.
 The live amoebae can be directly detected in CSF or
tissue biopsies.
 Serological tests are available but generally are not
necessary to make a correct diagnosis, since the
presence of the organism in CSF is definitive
 Granulomatous Amoebic Encephalitis

 Some antifungal drugs, like fluconazole, have been

used to treat acanthamoebal infections. In addition,
a combination of miltefosine and voriconazole has
recently been used to successfully treat GAE,
however, the mortality rate for patients with these
infections is high.
 Cerebral Malaria

 Cerebral malaria (CM) is caused by infection with

Plasmodium falciparum and is still a leading killer of
children in Africa.
 Cerebral malaria typically occurs in tropical regions
where P. falciparum is rampant, such as, Africa,
South-East Asia, and Central and South America.
 Cerebral malaria can occur as early as 1-2 days after
the onset of symptoms.
 Presentation can vary from seizures, confusion to
coma, and even focal neurological deficits.
 Malaria

 brain involvement is related to the degree of

parasitemia.
 pathophysiology likely related to the adhesion and
sequestration of paratized RBCs, inflammatory and
immunological responses, endothelial cell (EC)
activation, resulting vascular and perivascular
damage, apoptosis and loss of BBB integrity.
 Malaria

 Although the encephalopathy is potentially reversible,

mortality rates range from 10% to 50%, even in
adequately treated cases
 Residual complications, including cognitive impairment,
seizures, and neurological deficits may occur in about
10% of cases.
 In adults, cerebral malaria is part of a multi-organ
disease. Patients develop fever, headache, body ache and
progressively, delirium and coma.
 Anemia, hemoglobinuria, jaundice, shock, renal failure,
lactic acidosis, abnormal bleeding, pulmonary edema
and adult respiratory distress syndrome.
 Bacterial co-infection may be observed
 Malaria

 The diagnosis of cerebral malaria is based on the clinical

picture and demonstration of the parasite in blood ( thick
& thin blood film) rather than a biopsy.
 the WHO definition of cerebral malaria includes
(1) Non arousal coma (no local responses to pain) that
persists for more than six hours after experiencing a
generalized convulsion
(2) Presence of asexual forms of P. falciparum on both
thick and thin blood smears.
(3) Exclusion of other causes of encephalopathy (e.g. viral
encephalitis, poisoning and metabolic disease).
 Malaria

 The intravenous administration of Artemisinin-

based combination therapies (ACTs), artesunate and
quinine are the drugs of choice.
 African trypanosomiasis (sleeping sickness)

 It is caused by the insect-borne

hemoflagellate Trypanosoma brucei.
 T.b. rhodesiense is found in in East and South Africa
whereas T.b. gambiense is found in West Africa
 transmitted to humans by the bite of the tsetse fly
(Glossina spp.)
 CNS involvement occur weeks to months after an
infected bite.
 T.b. rhodesiense has a more rapid and acute course
 African trypanosomiasis (sleeping sickness)

 Trypanosomal ulcer (chancre) forms at the site of

infection, the flagellates then spread, moving into the
circulatory system
 Systemic infection result in fever (intermittent),
headaches (severe), joint pains, itching, weakness,
malaise, fatigue, weight loss, lymphadenopathy
(Posterior cervical lymph nodes are most commonly
affected), and hepatosplenomegaly.
African trypanosomiasis (sleeping sickness)

 Neurological phase (meningoencephalic stage)

symptoms include daytime sleepiness, insomnia, and
mental deterioration.
 tremor, general muscle
weakness, hemiparesis, paralysis of a limb, abnormal
muscle tone, gait disturbance, ataxia, speech
disturbances, paraesthesia, hyperaesthesia,
anaesthesia, visual disturbance, abnormal reflexes,
seizures, and coma.
 Death occurs without treatment.
 African trypanosomiasis (sleeping sickness)

 Diagnosis start with clinical presentation

 Winterbottom’s sign refers to the enlargement of
lymph nodes on the back of the neck—often
indicative of cerebral infections
 Trypanosoma can be directly observed in stained
samples including blood, lymph, CSF, and skin
biopsies of chancres.
 Serologic testing is generally not used for diagnosis
 Treatment of African trypanosomiasis is guided by
species and stage of disease.
 Without CNS involvement, fexinidazole or,
alternatively, pentamidine for T. b. gambiense;
suramin for T. b. rhodesiense
 With CNS involvement, fexinidazole for nonsevere T.
b. gambiense; eflornithine (if available) alone or in
combination with nifurtimox.
 patients still need to have follow-up examinations of
their CSF for two years to detect possible relapses of
the disease