Assistant Prof.Dr.Imtiaz Ahmad.

FCPS (Medicine)
 Clinical Scenario
A 33 year old woman awoke with a “pins-and-needles” sensations and
accompanying numbness in her hands. Upon arising she became aware
of weakness of her lower extremities. The weakness progressed to
involve upper extremities. She has history hospitalization 2 weeks
earlier for a flu like syndrome. On examination there was diffuse
weakness of all 4 extremities. There was mild facial weakness. Muscle
tone was decreased and distal vibratory loss. Muscle stretch reflexes
were absent.
What is your diagnosis of case
 Electro diagnostic studies revealed abnormal temporal dispersion and
partial conduction block. Subsequent CSF fluid examination revealed
increased protein and normal cell count.
 Guillain-Barré Syndrome
 Guillain-Barré syndrome (GBS) is an
acute, frequently severe, and fulminant
polyradiculoneuropathy that is
autoimmune in nature.
 Clinical Manifestations
 GBS manifests as a rapidly evolving areflexic motor paralysis with or without
sensory disturbance
 The usual pattern is an ascending paralysis that may be first noticed as rubbery
legs.
 Weakness typically evolves over hours to a few days and is frequently
accompanied by tingling dysesthesias in the extremities
 The legs are usually more affected than the arms, and facial diparesis is present
in 50% of affected individuals.
 Deep tendon reflexes attenuate or disappear within the first few days of onset
 sensory deficits (e.g., loss of pain and temperature sensation) are usually
relatively mild
 Clinical Manifestations
 The lower cranial nerves are also frequently involved, causing bulbar weakness
with difficulty handling secretions and maintaining an airwaythe diagnosis in
these patients may initially be mistaken for brainstem ischemia
 Bladder dysfunction may occur in severe cases but is usually transient. If bladder
dysfunction is a prominent feature and comes early in the course, diagnostic
possibilities other than GBS should be considered, particularly spinal cord
disease
 Most patients require hospitalization, and in different series up to 30% require
ventilatory assistance at some time during the illness.
 The need for mechanical ventilation is associated with more severe weakness on
admission, a rapid tempo of progression, and the presence of facial and/or
bulbar weakness during the first week of symptoms
 Clinical Manifestations
 Autonomic involvement is common. The usual manifestations are
loss of vasomotor control with wide fluctuation in blood pressure,
postural hypotension, and cardiac dysrhythmias
 Pain is another common feature of GBS; Pain in the neck, shoulder,
back, or diffusely over the spine is also common in the early stages of
GBS, occurring in 50% of patients .A deep aching pain may be present
in weakened muscles that patients liken to having overexercised the
previous day. Other pains in GBS include dysesthetic pain in the
extremities as a manifestation of sensory nerve fiber involvement.
These pains are self-limited and often respond to standard analgesics
 Subtypes of GBS
Determined primarily by electrodiagnostic (Edx) and
pathologic distinctions
 Acute inflammatory demyelinating polyneuropathy (AIDP)
 Acute motor axonal neuropathy (AMAN)
 Acute motor sensory axonal neuropathy (AMSAN)
 M. Fisher syndrome (MFS)
 Regional variants of GBS
 Other regional variants of GBS include
1) Pure sensory forms;
2) Ophthalmoplegia with anti-GQ1b antibodies as part of severe
motor-sensory GBS
3) GBS with severe bulbar and facial paralysis, sometimes
associated with antecedent cytomegalovirus (CMV) infection
and anti-GM2 antibodies
4) Acute pandysautonomia
 Acute inflammatory demyelinating polyneuropathy
(AIDP)
 Adults affected more than children
 90% of cases in western world. Recovery is rapid.
 anti-GM1 antibodies (<50%)
 Electrodiagnosis; Demyelinating
 Pathology ; First attack on Schwann cell surface; widespread myelin
damage, macrophage activation, and lymphocytic infiltration; variable
secondary axonal damage
 Acute motor axonal neuropathy (AMAN)
 Children and young adults;
 prevalent in China and Mexico; may be seasonal; recovery rapid;
 anti-GD1a antibodies
 Electrodiagnosis ; Axonal
 Pathology ; First attack at motor nodes of Ranvier; macrophage
activation, few lymphocytes, frequent periaxonal macrophages; extent
of axonal damage highly variable
Acute motor sensory axonal neuropathy (AMSAN)
 Mostly adults; uncommon; recovery slow, often incomplete; closely
related to AMAN
 Electrodiagnosis ; Axonal
 Pathology ; Same as AMAN, but also affects sensory nerves and roots;
axonal damage usually severe
 M. Fisher syndrome (MFS)
 Adults and children; uncommon; which presents as rapidly
evolving ataxia and areflexia of limbs without weakness,
and ophthalmoplegia, often with pupillary paralysis. The MFS
variant accounts for 5% of all cases
 Strongly associated with antibodies to the ganglioside GQ1b
 Electrodiagnosis ; Demyelinating
 Pathology ; resembles AIDP
 Pathophysiology
 In the demyelinating forms of GBS, the basis for flaccid paralysis and sensory
disturbance is conduction block. This finding, demonstrable electrophysiologically,
implies that the axonal connections remain intact. Hence, recovery can take place
rapidly as remyelination occurs
 In severe cases of demyelinating GBS, secondary axonal degeneration usually occurs.It
correlates with a slower rate of recovery and a greater degree of residual disability.
 In severe primary axonal pattern axons have degenerated and become disconnected
from their targets, specifically the neuromuscular junctions, and must therefore
regenerate for recovery to take place
 In motor axonal cases in which recovery is rapid, the lesion is thought to be localized to
preterminal motor branches, allowing regeneration and reinnervation to take place
quickly.
 Immunopathogenesis
 All GBS results from immune responses to nonself antigens (infectious agents,
vaccines) that misdirect to host nerve tissue through a resemblance-of-epitope
(molecular mimicry) mechanism.
 The neural targets are likely to be glycoconjugates, specifically gangliosides
 Antiganglioside antibodies, most frequently to GM1, are common in GBS (20–
50% of cases), particularly in those preceded by C. jejuni infection
 Sialic acid residues from pathogenic C. jejuni strains can also trigger activation
of dendritic cells via signaling through a toll-like receptor (TLR4), promoting B-
cell differentiation and further amplifying humoral autoimmunity
 In AIDP, an early step in the induction of tissue damage appears to be
complement deposition along the outer surface of the Schwann cell.
Activation of complement initiates a characteristic vesicular
disintegration of the myelin sheath, and also leads to recruitment of
activated macrophages, which participate in damage to myelin and
axons.
 In AMAN, the pattern is different in that complement is deposited
along with IgG at the nodes of Ranvier along large motor axons
 Antecedent Events
 Approximately 70% of cases of GBS occur 1–3 weeks after an acute infectious
process, usually respiratory or gastrointestinal.
 Culture and seroepidemiologic techniques show that 20–30 % are preceded by
infection or reinfection with Campylobacter jejuni.
 A similar proportion is preceded by a human herpes virus infection, CMV or
Epstein-Barr virus. Other viruses and also Mycoplasma pneumoniae have been
identified as agents involved in antecedent infections, as have recent
immunizations swine influenza vaccine
 Patients with lymphoma (including Hodgkin's disease), in HIV-seropositive
individuals, and in patients with systemic lupus erythematosus (SLE)
 Laboratory Features
 The CSF is often normal when symptoms have been present for less than
48 hours
 By the end of the first week , CSF findings are distinctive, consisting of an
elevated CSF protein level [1–10 g/L (100–1000 mg/dL)] without
accompanying pleocytosis.
 A transient increase in the CSF white cell count (10–100/l )ccurs on
occasion in otherwise typical GBS however, a sustained CSF pleocytosis
suggests an alternative diagnosis (viral myelitis) or a concurrent diagnosis
such as unrecognized HIV infection, leukemia or lymphoma with infiltration
of nerves, or neurosarcoidosis
 Electrodiagnosis
In AIDP, the earliest features are
a. prolonged F-wave latencies,
b. prolonged distal latencies and reduced amplitudes of compound muscle action
potentials (CMAPs),
c. Later, slowing of conduction velocity, conduction block, and temporal dispersion
may be appreciated. .
In cases with primary axonal pathology,
a. The principal finding is reduced amplitude of CMAPs (and also SNAPS with
AMSAN) without conduction slowing or prolongation of distal latencies
Findings Reducing Possibility of Diagnosis
1. Asymmetric weakness
2. Failure of bowel/bladder symptoms to resolve
3. Severe bowel/bladder dysfunction at initiation of disease
4. Greater than 50 mononuclear cells/mm3 in CSF
5. Well-demarcated sensory level

Exclusionary Criteria
1.Diagnosis of other causes of acute neuromuscular weakness (e.g., myasthenia
gravis, botulism, poliomyelitis, toxic neuropathy
2. Abnormal CSF cytology suggesting carcinomatous invasion of the nerve roots
 Differential diagnosis
 Acute myelopathies (especially with prolonged back pain and sphincter disturbances)
 Diphtheria (early oropharyngeal disturbances)
 Lyme polyradiculitis and other tick-borne paralyses
 Porphyria (abdominal pain, seizures, psychosis)
 Vasculitic neuropathy (check erythrocyte sedimentation rate)
 Critical illness neuropathy or myopathy
 Poisonings with organophosphates, thallium, or arsenic; paralytic shellfish poisoning;
 Severe hypophosphatemia
 Poliomyelitis (fever and meningismus common)
 Neuromuscular junction disorders such as myasthenia gravis
 Botulism (pupillary reactivity lost early);
 ;

Treatment
 Treatment should be initiated as soon after diagnosis as possible
 Each day counts: ~ 2 weeks after the first motor symptoms, it is not
known whether immunotherapy is still effective.
 If the patient has already reached the plateau stage, then treatment
probably is no longer indicated unless the patient has severe motor
weakness and one cannot exclude the possibility that an immunologic
attack is still ongoing
 Treatment
 Either high-dose intravenous immune globulin (IVIg) or plasmapheresis
can be initiated, as they are equally effective for typical GBS
 A combination of the two therapies is not significantly better than
either alone
 IVIg is often the initial therapy chosen because of its ease of
administration and good safety record.
 IVIg is administered as five daily infusions for a total dose of 2 g/kg
body weight
 A course of plasmapheresis usually consists of 40–50 mL/kg plasma
exchange (PE) four to five times over a week
 Treatment in worsening phase of GBS,
 Require monitoring in a critical care setting with particular attention to
vital capacity, heart rhythm, blood pressure, nutrition, deep vein
thrombosis prophylaxis, cardiovascular status, early consideration (after 2
weeks of intubation) of tracheotomy, and chest physiotherapy
 30% of patients with GBS require ventilatory assistance
 Frequent turning and assiduous skin care are important, as are daily range-
of-motion exercises to avoid joint contractures and daily reassurance as to
the generally good outlook for recovery
 Prognosis and Recovery
 Approximately 85% of patients with GBS achieve a full functional recovery
within several months to a year, although minor findings on examination (such
as areflexia) may persist and patients often complain of continued symptoms,
including fatigue.
 The mortality rate is less than 5% in optimal settings
 Death usually results from secondary pulmonary complications
 The outlook is worst in patients with severe proximal motor and sensory axonal
damage. Such axonal damage may be either primary or secondary in nature but
in either case successful regeneration cannot occur.
 Between 5 and 10% of patients with typical GBS have one or more late
relapses; such cases are then classified as chronic inflammatory demyelinating
polyneuropathy (CIDP).