Guillain-Barré syndrome

KSMU 2020
 Case 1
• A 39-year-old white male with
hypertension, chronic obstructive
pulmonary disease (COPD), and a history
of multiple back and neck injuries was
brought to the hospital by family members
because of low urinary output during the
previous 12 hours.
 History of current disease
• The patient had a several-month history of
weakness of the lower extremities (right > left) to
the point of being confined to bed for 2 months,
shortness of breath, paresthesias, and
constipation (for about 1 month). He reported
numbness and tingling in all extremities for
about 5 months. During the previous 4 months,
he had noted weakness in all extremities leading
to frequent falls. In addition, he reported that
although he had a long history of shortness of
breath with exertion, this had now progressed to
shortness of breath at rest.
Neurologic Exam
• Mental Status. Mental status was difficult
to assess in the setting of the patient's
discomfort and anxiety. He was alert and
oriented to person, time, place, and
reason for hospitalization, but had difficulty
with tasks that required concentration
(reciting the days of the week backwards,
for example). His speech was fluent and
he was able to read and write. Cranial
Nerves. CN II-XII intact and symmetric.
• Motor.
• Atrophy of the thenar and hypothenar muscles bilaterally
• Mild atrophy of arm and leg muscles
• No tremors or fasciculations
• 5/5 neck flexion and extension
• Upper extremity strength: symmetric approximately 4/5,
except finger extensors 3/5 and interossei 2/5
• Lower extremity strength: symmetric 1-2/5 at
hips, 2/5 at knees, 0/5 at ankles and feet
• Deep tendon reflexes: areflexic, toes mute
• Coordination/gait: not tested
• Sensory.
• Decreased pinprick in lower extremities to knees
and upper extremities to mid-forearm
• Decreased vibration in lower extremities to
knees (right > left)
• Decreased proprioception in all extremities
(lower > upper)
• Normal perianal sensation
 What diagnosis can we put?
• Polyneuropathy
 How to confirm diagnosis?
• Electrophysiological Diagnostic
Procedures
• Laboratory Examinations
• Nerve Biopsy
• MRI
Initial Laboratory Data
• Electrolytes and creatinine were within normal
ranges. Patient had slight uremia, and
urinalysis was consistent with a prerenal state.
WBC and hematocrit (elevated even after
hydration) were elevated. Likely hypercalcemia
(reduced albumin with normal calcium.
Magnetic Resonance Imaging Studies
• MRI of the brain showed grossly normal
nonenhanced cerebral and cerebellar
structures. MRI of C-spine showed a small
disc protrusion (probably nonsignificant) on
right paramedian aspect of C3-C4 interspace.
There was no evidence of spinal stenosis or
abnormal cord signal.
 Electrodiagnostic Testing
Motor Nerve Conduction
• the left peroneal and tibial nerve motor
responses were absent, including the left
peroneal nerve recorded at the tibialis anterior
muscle. In the left arm the median nerve motor
response was absent. The ulnar and radial
nerve responses exhibited significantly reduced
conduction velocities and amplitudes. The F-
wave latency of the ulnar nerve was greatly
prolonged.
Sensory Nerve Conduction and EMG
No sensory nerve responses were found.
Electromyography (EMG) showed elevated
insertional and spontaneous activity throughout,
with widespread positive sharp waves and
fibrillation potentials. The motor unit potential in
upper extremities was normal, with normal
amplitude and duration. These could not be
elicited in lower extremities
What are the differential diagnosis?
Segmental demyelination with motor and sensory
polyneuropathy (motor > sensory) suggests the
following possible diagnoses:
• Acute inflammatory demyelinating
polyneuropathy (AIDP)
• Chronic inflammatory demyelinating
polyneuropathy (CIDP)
• Neuropathies associated with paraproteinemias
• Hypothyroidism
• Infections (HIV, Lyme disease)
• Toxins -- arsenic
• Drugs - amiodarone, perhexilene,
ara-C
• Systemic lupus erythematosis
• Neuropathy associated with glue
sniffing
Axon loss motor and sensory polyneuropathy
(motor > sensory) is associated with:
• An axonal subtype of Guillain-Barre syndrome
• Porphyria
• Lead poisoning
• Dapsone or vincristine side effects
• Hypoglycemia
• Hyperinsulinemia
• Paraneoplastic associated with lymphoma or
carcinoma
Axon loss of mixed polyneuropathy
is associated with many disorders
including:
• Amyloidosis
• Chronic liver disease
• Vitamin B12, folate or thiamine deficiency
• Hypothyroidism
• Sarcoidosis
• Connective tissue disease
• Toxins -- acrylamide, CO, glue, etc
•Drugs -- phenytoin, amitryptiline, lithium,
nitrous oxide, etc
•Heavy metals - arsenic, mercury, thallium,
gold
•Paraneoplastic neuropathy
•Multiple myeloma
•Infection -- HIV, Lyme disease
•Polycythemia vera
•Gout
•Hypophosphatemia
 Is additional test needed?
• Yes
• Lumbar puncture and sural nerve biopsy
were planned but could not be completed
before the patient died. Serum protein
electrophoresis (SPEP) and urine protein
electrophoresis (UPEP) immunofixation
showed a monoclonal spike (M-spike) of
the IgG-lambda (light chain) subtype
 Final diagnosis?
• This patient had myeloma, based on the
radiographic and bone marrow findings. A
bone survey demonstrated no other
lesions. Initially, before the bone marrow
biopsy was performed, we thought that
this patient might have a solitary
plasmacytoma. However, the presence of
the large number of plasma cells in the
bone marrow demonstrated the systemic
nature of this process.
What is the etiology for this diseases?

• Acute polyneuropathy has many causes. It

may be caused by an infection involving a
toxin produced by bacteria (as in diphtheria)
or by an autoimmune reaction (as in Guillain-
Barré syndrome). Toxic substances,
including heavy metals such as lead and
mercury, carbon monoxide, and some drugs
can also cause acute polyneuropathy.
• The drugs include :-

• anticonvulsant -phenytoin
-Dilantin
•some antibiotics -chloramphenicol
-Chloromycetin
-Nitrofurantoin
-Furadantin
-Macrodentin
-Sulfonamides
•some chemotherapy drugs -vinblastine
-Velban
-vincristine
-Oncovin
•sedatives -barbital
-hexobarbital
-Sombule
• Cancer,such as multiple myeloma, may cause
acute polyneuropathy by directly invading or
compressing the nerves or by producing toxic
substances.
• The cause of chronic polyneuropathy is often
unknown. The most common form of chronic
polyneuropathy is most often due to diabetes but
may be due to excessive use of alcohol.
Nutritional deficiencies (such as vitamin B
deficiency) are an uncommon cause of chronic
polyneuropathy in the United States, except
among alcoholics who are malnourished. Anemia
due to vitamin B12 deficiency (pernicious anemia)
may also cause chronic polyneuropathy. Other
causes include an underactive thyroid gland
(hypothyroidism), liver failure, and kidney failure.
Rare causes include certain cancers, such as lung
cancer, and taking excessive amounts of vitamin
B6 (pyridoxine).
•Poor control of blood sugar levels in diabetes (see
Diabetes Mellitus (DM)) causes several forms of
polyneuropathy, collectively referred to as diabetic
neuropathy. (Diabetes can also cause
mononeuropathy or mononeuritis multiplex that
leads to weakness, typically of the eye or thigh
muscles.)
In some people, the cause is hereditary.
 What is the pathogenesis?
• Cellular Immune Response
• Humoral Immune Response
• Axonal Loss
 What is the treatment?
• The goals of treatment include finding the cause,
maximizing self-care ability and independence,
and controlling symptoms.
The cause should be identified and treated
whenever possible. This may include such
things as controlling blood sugar levels for
diabetics, abstaining from alcohol, and taking
daily nutritional supplements. If medications
(such as some treatments for HIV) are causing
the problem, these should be identified and
changed, if possible.
MAXIMIZE SELF-CARE AND INDEPENDENCE

• Physical therapy, vocational therapy,

occupational therapy, and orthopedic
interventions may be recommended to promote
self-care ability and independence.
• For example, exercises and retraining may
increase muscle strength and control.
Appliances such as wheelchairs, braces, or
splints may provide mobility or help support an
extremity so that it can be used.
• CONTROL OF SYMPTOMS

Safety is an important consideration for people with

neuropathy. Lack of muscle control may increase the
risk of falls or other injuries. Also, decreased sensation
may increase the risk of falls and injuries because the
person is unable to perceive a potential source of
harm.

Safety measures for people with difficulty in movement

may include the use of railings, removal of obstacles
(such as loose rugs that may slip on the floor), and
other measures as appropriate.
• Safety measures for people experiencing difficulty with
sensation include awareness of the lack of sensation
and compensation through other measures. Specific
measures may include the use of adequate lighting
(including lights left on at night), testing of water
temperature before bathing, use of protective shoes
(such as those with closed toes and low heels), and
similar measures.
• People with decreased sensation should check their
feet (or other affected area) frequently for bruises,
open skin areas, or other injury, which may go
unnoticed and become severely infected.
• Shoes should be checked inside frequently for
grit or rough spots that may injure the feet.
Patients with sensorimotor neuropathy should
be evaluated by a podiatrist to reduce the risk
of injury to the feet.

People with neuropathy are prone to new nerve

injury at pressure points (such as knees and
elbows). They should avoid prolonged pressure
on these areas from leaning on the elbows,
crossing the knees, or being in similar positions.
•Over-the-counter analgesics or prescription analgesics
may be needed to control pain (neuralgia). Various other
medications may be used to reduce the stabbing pains
that some people experience, including anticonvulsants
(phenytoin, carbamazepine, neurontin) or tricyclic
antidepressants. Whenever possible, medication use
should be avoided or minimized to reduce the risk of
side effects.

Positioning, keeping bedclothes off a tender body part,

or other measures may be helpful to control pain.
 What is the complication?
• Partial or complete loss of movement
• Partial or complete loss of control of
movement
• Partial or complete loss of sensation
• Difficulty swallowing
• Recurrent or unnoticed injury to any part of
the body
• Deformity
 Case N2
• Audrey is a 45-yearold woman who was brought to her local
hospital’s emergency room by her husband because of several days
of progressive weakness and numbness in her arms and legs. Her
symptoms had begun with tingling in her toes, which she assumed
to be her feet “falling asleep.”
• However, this feeling did not disappear, and she began to feel
numb, first in her toes on both feet, then ascending to her calves
and knees. Two days later, Audrey began to feel numb in her
fingertips, and had difficulty lifting her legs. When she finally was
unable to climb the stairs of her house because of her leg
weakness, difficulty gripping the banister, and shortness of breath,
her husband urged her to go to the emergency room.
 Could it be Guillian-Barre
syndrome?
• Yes
• But….. We can’t confirm till history takings
and further investigations.
• The neurologist who examined Audrey in the emergency
room noticed that she was short of breath while sitting in
bed.
• He asked the respiratory therapist to measure her vital
capacity (the greatest volume of air that can be exhaled
from the lungs after a maximal inspiration), and the value
for this was far lower than was expected for her age and
weight.
• Her neurologic examination showed that her arms and
legs were very weak, so that she had difficulty lifting
them against gravity. She was unable to feel a pin or a
vibrating tuning fork at all on her legs and below her
elbows, but was able to feel the pin on her upper chest.
• The neurologist could not elicit any reflexes from her
ankles or knees.
• Where in the nervous system is the damage?
Peripheral nerves and nerve roots

• The absent reflexes are a sign of a lesion of which

portion of the nervous system?
The dorsal horn of the spinal cord or any point distal to
this structure

• Damage to which nervous system structure caused the

difficulty breathing?
Phrenic nerve innervating the diaphragm
 What else can we suspect except
Guillian-Barre syndrome?
• Discitis
• Guillain-Barré syndrome
• Toxic synovitis
• Systemic malignancies (leukemia,
neuroblastoma, bone tumor)
• Occult trauma
• Osteomyelitis
• Rheumatic disease, such as juvenile rheumatoid
arthritis
How to confirm our diagnosis?
• Laboratory exam
• CSF
• Peripheral smear
• Titre of virus
• Electrophysiology
 Laboratory data.
• ESR: 87
• WBC: 8500 (84 lymphocytes)
• Hgb: 10.9
• Hct: 31
• Platelets: 140,000
• LDH: 288 (140-260)
• Uric acid: 4.8
• Calcium: 9.0
• Alkaline phosphatase: 113
 CSF examination.
• 0 WBC;
• 1 RBC;
• glucose 35 (serum not available);
• protein 11.
• Peripheral smear shows no
blastocytes but an atypical
lymphocyte, mild
leukopenia, and
thrombocytopenia.

• Bone marrow biopsy shows

B-cell precursor acute
lymphocytic leukemia
blasts (common ALL) with
CD19+, CD10+, and partial
CD34+ and CD20+ cells.
 Differential diagnosis
• acute myelopathies with chronic back pain and sphincter
dysfunction
• botulism with early loss of pupillary reactivity
• diphtheria with early oropharyngeal dysfunction
• Lyme disease polyradiculitis and other tick-borne paralyses
• porphyria with abdominal pain, seizures, psychosis
• vasculitis neuropathy
• poliomyelitis with fever and meningeal signs
• CMV polyradiculitis in immunocompromised patients
• critical illness neuropathy
• myasthenia gravis
• poisonings with organophosphate, poison hemlock, thallium, or
arsenic
 Final diagnosis?
• Demyelinating polyneuropathy.
Guillian-Barre syndrome.
 What are the etiology to this?
• About 75% of patients with GBS have a history of acute
infection within the past one to four weeks, usually
respiratory or gastrointestinal.
• 20-30% of these cases are due to Campylobacter jejuni
and a similar proportion due to cytomegalovirus or
Epstein-Barr virus.
• Less common infectious agents include Mycoplasma
pneumoniae, HIV, and herpes simplex virus.
• Other associated conditions associated with GBS
include Hodgkin's disease and systemic lupus
erythematosus (SLE).
 Pathophysiology
• All forms of Guillain-Barre syndrome are due to an
autoimmune response to foreign antigens (such as
infectious agents, vaccines) that are mistargeted to host
nerve tissues instead.
• The targets of such immune attack are thought to be
gangliosides, which are complex glycosphingolipids that
are present in large quantities on human nerve tissues,
especially in the nodes of Ranvier.
• An example is the GM1 ganglioside, which can be
affected in as many as 20-50% of cases, especially in
those preceded by Campylobacter jejuni infections.
• Another example is the GQ1b ganglioside, which is the
target in the Miller-Fisher syndrome variant.
• The end result of such autoimmune attack on the
peripheral nerves is loss of myelin and subsequent
conduction block.
• However, axonal function remains intact and recovery
can be rapid as remyelination occurs.
• If axonal degeneration occurs in severe GBS, recovery
becomes much slower and will leave a greater degree of
residual damage.
• If primary axonal damage occurs, such as in the AMAN
or AMSAN variants (see below), nerve connections
become disrupted and recovery depends on axonal
regeneration.
 Treatment
• Supportive care with monitoring of all vital
functions is the cornerstone of successful
management in the acute patient. Of greatest
concern is respiratory failure due to paralysis of
the diaphragm.
• Early intubation should be considered in any
patient with a vital capacity (VC) <20 ml/kg, a
Negative Inspiratory Force (NIF) <-25 cmH2O,
more than 30% decrease in either VC or NIF
within 24 hours, rapid progression of disease, or
autonomic instability.
• Once the patient is stabilized, treatment of the underlying
condition should be initated as soon as possible. Either
high-dose intravenous immunoglobulins (IVIg) or
plasmapheresis can be administered, as they are equally
effective and a combination of the two is not significantly
better than either alone. Therapy is no longer effective
after 2 weeks after the first motor symptoms appear, so
treatment should be instituted as soon as possible. IVIg
is usually used first because of its ease of administration
and safety profile, with a total of five daily infusions for a
total dose of 2 g/kg body weight. The use of intravenous
immunoglobulins is not without risk, occasionally causing
hepatitis, or in rare cases, renal failure if used for longer
than five days. Glucocorticoids have not been found to
be effective in GBS. If plasmapheresis is chosen, a dose
of 40-50 mL/kg plasma exchange (PE) is administered
four times over a week.
 Complications
• With modern methods of respiratory management, most
complications result from long-term paralysis. Possible
complications include the following:
– Persistent paralysis
– Respiratory failure, mechanical ventilation
– Hypotension or hypertension
– Thromboembolism, pneumonia, skin breakdown
– Cardiac arrhythmia
– Ileus
– Aspiration
– Urinary retention
– Psychiatric problems such as depression and anxiety