Guillain-Barre Syndrome

Fisher Syndrome
Landry- Guillain-Barre-Strohl Syndrome
Acute Inflammatory Polyneuropathy
Idiopathic Polyneuritis
Acute Inflammatory Demyelinating Polyradiculopathy (AIDP)
Acute Autoimmune Neuropathy
Is an acquired acute inflammatory demyelinating or axonal polyneuropathy with four
subtypes. These subtypes occur throughout the world, affect children and adults of both
genders and all age groups equally, and occur in all seasons of the year. The annual incidence
rate is 1 to 2 per 100,000 with a 4% to 6% mortality, and a 5% to 10% morbidity rate. This
acute condition, generally referred to as GBS, is the most common cause of acute or subacute
generalized paralysis (It was at one time rivaled by polio in frequency.)
Antecedent infection events or associated illnesses include Campylobacter jejuni, viral
exanthems and other viral illnesses [cytomegalovirus (CMV), Epstein-Barr virus (EBV), HIV],
bacterial infections other than Campylobacter (Mycoplasma pneumoniae, Lyme disease),
exposure to thrombolytic agents, and lymphoma (particularly Hodgkin disease).
Symptomatology The typical case of GBS is readily identified.
Paresthesias and slight numbness in the toes and fingers are the earliest symptoms.
The major clinical manifestation is weakness that evolves more or less symmetrically
over a period of several days to a week or two usually the lower extremities before the
upper (Landrys ascending paralysis) the trunk, intercostal, neck, and cranial muscles
may be affected later.
In severe cases the ocular motor nerves are paralyzed and even the pupils may be
unreactive.
More than half of the patients complain of pain and an aching discomfort in the muscles,
mainly those of the hips, thighs, and back
A few describe burning in the fingers and toes
Deep sensibility (touch-pressure-vibration) tends to be more affected than superficial
(pain-temperature).
Reduced and then absent tendon reflexes are consistent findings.
Facial diplegia occurs in more than half of cases
Disturbances of autonomic function (sinus tachycardia and less often bradycardia, facial
flushing, fluctuating hypertension and hypotension, loss of sweating, or episodic profuse
diaphoresis) are common in minor form.
Urinary retention occurs in about 15 percent of patients soon after the onset of weakness
At the onset of illness, the temperature is normal, and lymphadenopathy and
splenomegaly, are related to a preceding viral infection.
Typical first manifestations are numbness, pain, paresthesias, or weakness in the limbs.
Motor signs manifest as an acute or subacute progressive paralysis. Proximal muscles
may be involved earlier and more significantly than distal muscles. The paresis/paralysis
may be present in an ascending pattern involving limbs, respiratory muscles, and bulbar
muscles. Only bulbar muscles may be involved, resulting in dysphagia and dysarthria.
Weakness usually plateaus or improves by the fourth week in 90% of cases. After
weakness plateaus, strength improves over a period of days to months, with the majority
of individuals reaching activity levels similar to their predisease state. If sensory
symptoms are present in the subtype they may include paresthesias/dysthesias (tingling,
burning, shocklike sensations, particularly in the limbs), pain (throbbing and aching,
particularly in the lower back, buttocks, and legs), and numbness. Position and vibratory
sensations are more affected than superficial sensation. Respiratory muscle weakness
leads to the need for ventilatory support in 10% to 30% of individuals. Cranial nerve
weakness manifests as facial weakness and bulbar weakness involving chewing,
swallowing, and coughing. Autonomic dysfunction may manifest as tachycardia or, less
frequently, bradycardia; hypotension or hypertension; and loss of or significant increase
in sweating in those more severely affected. Persons may undergo a respiratory arrest or
cardiovascular collapse, a cause of death. Hyponatremia caused by the syndrome of

inappropriate antidiuretic hormone (SIADH) is common, especially in individuals whose

lungs have been ventilated.
The Major Diagnostic Tests are the examination of the CSF, nerve conduction studies, and
EMG. The CSF findings include an unusually high protein level (500 mg/ dl) without cellular
abnormality. Nerve conduction studies help identify the subtype. Ventilatory support and
management of the autonomic nervous system dysfunction are two dominant aspects of the
therapeutic management. Intravenous immunoglobulin, plasmapheresis, or plasma exchanges
or combination therapy within the first 2 weeks of onset of clinical manifestations may be
indicated. After the disorder begins to remit, aggressive rehabilitation should be instituted.
Laboratory Findings The most important laboratory aids are the electrodiagnostic studies
and the CSF examination.
The CSF is under normal pressure and is acellular or contains only a few lymphocytes
The CSF protein protein content is normal during the first few days of symptoms, but
then it begins to rise, reaching a peak in 4 to 6 weeks and persisting at a variably
elevated level for many weeks.
A reduction in the amplitude of muscle action potentials, slowed conduction velocity, and
conduction block in motor nerves singly or in combination.
Prolonged distal latencies (reflecting distal conduction block) and prolonged or absent Fresponses (indicating involvement of proximal parts of nerves and roots) reflecting focal
demyelination.
The H-reflex is almost always very delayed, or more often absent, but this does little
more than confirm the loss of ankle reflexes.
Acute GBS have shown gadolinium enhancement of the cauda equina roots on magnetic
resonance imaging (MRI)
T-wave and other electrocardiographic changes of minor degree are reported frequently
but are evanescent.
The sedimentation rate is normal unless there is an additional process of infectious,
neoplastic, or autoimmune nature, any of which can occasionally coexist with GBS.
Hyponatremia occurs in a proportion of cases after the first week
Pathologic Findings These have had a relatively consistent pattern and form.
show perivascular (mainly perivenous) lymphocytic infiltrates.
Later, the characteristic inflammatory cell infiltrates and perivenous demyelination are
combined with segmental demyelination and a variable degree of wallerian
degeneration. The cellular infiltrates are scattered throughout the cranial nerves, ventral
and dorsal roots, and dorsal root ganglia and along the entire length of the peripheral
nerves.
Sparse focal infiltrates of inflammatory cells (lymphocytes and other mononuclear cells)
may also be found in lymph nodes, liver, spleen, heart, and other organs.
Swelling of nerve roots at the site of their dural exit has been emphasized to cause root
damage.
Variations of this pattern of peripheral nerve damage have been observed, each perhaps
representing a different immunopathology.
Rarely, in a clinically typical case, there may be widespread demyelinative changes and
only a paucity of perivascular lymphocytes.
In patients whose electrophysiologic tests display severe axonal damage early in the
illness as discussed later, the pathologic findings corroborate the predominantly axonal
nature of the disease with secondary myelin damage and little inflammatory response.
Pathogenesis and Etiology
Most of the evidence supports a cell-mediated immunologic reaction directed at
peripheral nerve.
Subsequent Investigations indicated that the neuritogenic factor might be a specific
peptide in the P2 protein. However, there is no dominant antigen-antibody reaction in GBS
and that any number of myelin and axonal elements may be involved in inciting the immune
reaction.

Have found high levels of soluble interleukin (IL)-2 receptors, that is shed from activated
T cells, and IL-2 itself in the serum of patients with acute GBS, reflecting activation of these
cells. complement also seems to be a necessary factor in the initial attack on myelin.
Although the transmission of EAN by T cells sensitized to myelin is strong evidence of their
role in GBS, antimyelin antibodies are probably involved in the initial part in the disease. The
serum from patients with GBS causes damage to myelin in tissue cultures and induces a
characteristic (vesicular) form of myelin destruction.
Subepineural injection of serum from GBS patients into the sciatic nerve of rats leads to
local demyelination and electrical conduction block. The studies by Koski and associates of
complement-dependent myelin damage by IgM antimyelin antibodies in GBS provided
evidence that antimyelin antibodies are able to initiate myelin destruction even though T cells
and that macrophages are the ultimate effectors of the damage. Indeed, the very earliest
change that could be detected was the deposition of complement on the inner layer of myelin.
A number of autoantibodies directed at components of nerve ganglioside are detected
inconsistently in patients with GBS, the most important being anti-GQ1b, which is found in
almost all patients with ophthalmoplegia.
Approximately one-third of patients have anti-GM1 antibodies early in their course,
corresponding in most instances to a predominantly motor presentation and to axonal
damage, the highest titers usually being associated with cases that follow Campylobacter
infections. Antibodies directed against GD1a or GT1b have been associated in some cases
with the pharyngeal- brachial-cervical variant. It
would therefore seem that casting GBS
exclusively as a humoral or as a cellular immune
process is an oversimplification.
An unanswered question is how the immune
reaction is initiated in humans. All attempts to
isolate a virus or microbial agent from nerves or
to demonstrate one by electron microscopy have
failed, and it is more likely that a variety of
agentsviral, bacterial (particularly C. jejuni),
certain vaccines, and perhaps neural injury itself
are all capable, in susceptible individuals, of
precipitating an immune response against
components of autologous peripheral myelin. The
occurrence of GBS in patients with acquired
immune deficiency syndrome (AIDS) or with EBV
or CMV infections simply indicates that these
agents, too, induce such an autoimmune
response without implicating a direct viral
infection of nerve. Then observation that only
one of many individuals who are infected with a
particular pathogen go on to develop GBS
suggests that host
factors are significant (there is, however, little
consistency among HLA types in GBS patients).
Whether the aforementioned antibodies against
various gangliosides of peripheral nerve are
pathogenically active is also uncertain.
GBS is considered to be an autoimmune disease triggered by a preceding bacterial or
viral infection. Molecular mimicry (cross-activation of self-epitopes and pathogen-derived
peptides by autoreactive T and B cells) is associated with the immune injury. It has been
recognized that glycolipids, particularly gangliosides, are immune targets in the subtypes of
GBS. Different gangliosides predominate in different locations in peripheral nerves and in
different nerve fiber types. The muscle innervated by the damaged peripheral nerves
undergoes denervation and atrophy. If the cell body survives, regeneration of the peripheral
nerve takes place and recovery of function is likely. If the cell body dies from intense root
involvement in the inflammatorydegenerative process, no regeneration is possible. Collateral
reinnervation from surviving axons and regenerating axons may take place. In this case,
motor recovery is less complete and residual deficits persist.

Differential Diagnosis
The differential diagnosis then includes myasthenia gravis, diphtheria, and botulism and
a lesion affecting the central portion of the cervical spinal cord and lower brainstem.
A syndrome comprising virtual or complete ophthalmoplegia with ataxia and areflexia
that probably represents a variant of GBS was described by Fisher (and is called Fisher
syndrome).
The immediate problem is to differentiate GBS from acute spinal cord disease marked by
sensorimotor paralysis below a defined level and a marked sphincteric disturbance. There
may be particular difficulty in the case of an acute lesion of the cord in which tendon reflexes
are initially lost (spinal shock), or with necrotizing myelopathy, where a permanent loss of
tendon reflexes follows extensive destruction of spinal gray matter.
Also confusing is early and transient urinary retention in a proportion of patients with
GBS. Several rules of thumb are useful in distinguishing the disease from a cervical
myelopathy: in GBS, the facial and respiratory muscles are usually involved if there is
generalized paralysis; the fingertips should be paresthetic once sensory symptoms have
ascended to the level of the midcalves; marked sensory loss proximal to the hands or feet or
only of the trunk is unusual early in the illness; and tendon reflexes are almost invariably lost
in limbs that are too weak to resist gravity.
A predominantly motor paralysis is the major characteristic of GBS, for which reason the
differential diagnosis also includes poliomyelitis, now also caused by the West Nile virus and
by enteroviruses other than the polio agent.
In all these infectious cases the illness is marked by fever, meningoencephalitic
symptoms, early pleocytosis in the spinal fluid, and purely motor and usually asymmetrical
areflexic paralysis. We have been several times misled by cases of carcinomatous meningitis
that caused a subacute and fairly symmetric but mainly distal weakness and appeared similar
to GBS.
An irregular distribution of weakness between proximal and distal parts, the absence of
facial weakness and the appearance of symptoms in one limb after another are always
suggestive of this type of neoplastic infiltration of nerve roots. Sciatica may occur with either
process but radicular pain in the arms is unusual in GBS.
Another distinctive problem arises in distinguishing generalized GBS with
ophthalmoparesis or the Fisher variant from basilar artery thrombosis. The presence of
reactive pupils, areflexia, and F-wave abnormalities in GBS, and of lively reflexes and Babinski
signs in the case of brainstem infarction, dependably separates the disorders. Ptosis and
oculomotor \ weakness, features of GBS in some severe generalized cases and in Fisher
syndrome, may cause confusion with acute myasthenia gravis, but in the latter disease there
are no sensory symptoms and the tendon reflexes are unimpaired.
Treatment
Hypotension from dysautonomia, which occurs in about 10 percent of severely affected
patients, is treated by intravenous volume infusion and by the use of vasopressor agents for
brief periods.
Extremes of hypertension are managed by short-acting and titratable antihypertensive
medications, such as intravenous labetalol.
The distinction between the two conditions that cause hyponatremia determines the
course of treatment: fluid restriction in the case of SIADH or salt replacement in the case of
sodium loss.
Physical therapy (passive movement and positioning of limbsnto prevent pressure
palsies and, later, mild resistance exercises) should begin once they can be comfortably
undertaken.
Specific treatment of the presumed immune disorder that underlies GBS includes plasma
exchange (PE) and intravenous immunoglobulin (IVIG).
As effective as plasma exchange is, IVIG (0.4 g/kg per day for 5 consecutive days) is both
easier to administer and probably safer because there is no need for large intravenous access.
Prognosis
As already indicated, approximately 3 to 5 percent of patients do not survive the illness,
even in the best-equipped hospitals.
In the early stages, death is most often due to cardiac arrest, perhaps related to
dysautonomia, adult respiratory distress syndrome, pneumo- or hemothorax, or some type of

accidental machine failure. Later in the illness, pulmonary embolism and other medical
complications (usually bacterial) of prolonged immobilization and respiratory failure are the
main causes.