GBS

Mona M. Alkhawajah

Demyelinating diseases of the

peripheral nervous system include:
Guillain-Barr syndrome and its chronic
counterpart, chronic inflammatory demyelinating
polyneuropathy
Anti-MAG peripheral neuropathy
Charcot-Marie-Tooth Disease
Copper deficiency
Progressive inflammatory neuropathy
Other demyelinating peripheral neuropathies

Clinical Vignette
Ahmed is an 18 year old student, otherwise
healthy
Presented with numbness in the toes, gradually
spreading to the feet, legs, all the way up to the
thighs.
Few days into onset, started to trip and fall, and
was experiencing difficulties going downstairs.
The patient recalls lower back pain preceding
onset
One week prior to illness, he had frequent loose
motions which he attributed to eating from
McDonalds.

Epidemiology
1 to 2 per 100,000 per year
All age groups BUT incidence increases by 20%
with every 10-year increase in age beyond the
first decade of life.
Incidence is greater in males.

Pathogenesis
Molecular Mimicry

 Antecedent infection evokes an immune response

cross-reacts with peripheral nerve
components because of the sharing of crossreactive epitopes.
This immune response can be directed towards
the myelin or the axon of peripheral nerve
Invasion by activated T-cells
macrophage-mediated demyelination
(complement and immunoglobulin deposition on
myelin and Schwann cells)

Campylobacter J.
Haemophilus influenzae, Mycoplasma pneumoniae,
cytomegalovirusvaricella-zoster virus, herpes simplex virus,
hepatitis A, B, C, and E viruses, influenza virus, and the
bacteria Haemophilus influenzae and Escherichia coli

If the epitopes on Schwan cells or

myelin were attacked the patient
Multifocal inflammatory demyelination starting at
the level of the
..
The earliest changes are frequently seen at
.

If the epitopes contained in the axonal

membrane were attacked
Acute axonal forms of GBS: acute motor axonal
neuropathy (AMAN) and acute motor and sensory
axonal neuropathy (AMSAN)

C. jejuni infection
60 to 70% of AMAN and AMSAN and up to 30 % of
AIDP cases are preceded by C. jejuni infection
Campylobacter-associated GBS appears to have a
worse prognosis(slower recovery and greater
residual neurologic disability)

With HIV!
GBS also occurs in association with human
immunodeficiency virus (HIV) infection,
predominantly in those who are not profoundly
immunocompromised.
Similar clinical course and prognosis as patients
without HIV infection.
GBS can occur in any stage of HIV infection.

Other antecedent events (??)

Immunization
Surgery
Trauma,
Bone-marrow transplantation
? linked to systemic processes: including Hodgkin
lymphoma, SLE, and sarcoidosis

Acute Monophasic Paralyzing Illness

provoked by a preceding infection
Progressive symmetric muscle weakness
accompanied by absent or depressed deep
tendon reflexes.
Patients usually present a few days to a week
after onset of symptoms.
The weakness can vary from mild difficulty with
walking to nearly complete paralysis of all
extremity, facial, respiratory, and bulbar muscles.

(mostly AIDP)
Where does weakness start?
Legs (arms or facial muscles 10%).
How many develop severe respiratory muscle
weakness necessitating ventilatory support ?
10 to 30 %
Facial weakness >50
Oropharyngeal weakness eventually occurs in 50%.
Oculomotor weakness :15 %
Do patients have sensory abnormalities on exam?
Paresthesia in the hands and feet accompany the
weakness in more than 80 percent of patients, but
sensory abnormalities on examination are
frequently mild.

(mostly AIDP)
Pain:
Typically located in the back and extremities, can be
a presenting feature and is reported during the acute
phase by 66 percent of patients
Dysautonomia:
occurs in 70 percent of patients and manifests as
symptoms that include tachycardia (the most
common), urinary retention, hypertension alternating
with hypotension, orthostatic hypotension,
bradycardia, other arrhythmias, ileus, and loss of
sweating.
Severe autonomic dysfunction is important to
recognize since this is occasionally associated with
sudden death

Which of the above can happen in

GBS?

Papilledema,
Facial Myokymia
Hearing Loss
Meningeal Signs
Vocal Cord Paralysis
Mental Status Changes
SIADH

ll of the above are UNUSUAL Feature in GBS

Progression
GBS usually progresses over two weeks.
90 percent reach the nadir of the disease by 4
weeks
What if disease progresses for more than 4 week?
Disease progression for more than eight weeks is
consistent with the diagnosis CIDP

GBS Variants
Acute inflammatory demyelinating
polyneuropathy
Acute motor axonal neuropathy
Acute motor and sensory axonal neuropathy
Miller Fisher syndrome
Bickerstaff encephalitis
Pharyngeal-cervical-brachial weakness
Other variants

Acute Inflammatory Demyelinating Polyneuropathy

(AIDP)
Most common form
Progressive, fairly symmetric muscle weakness
accompanied by absent or depressed deep tendon
reflexes
Immune attack on peripheral myelin, inflammatory
demyelination starts at the level of the nerve roots
multifocal, patchy, widespread peripheral
nerve demyelination
remyelination and recovery over weeksmonths
axonal degeneration with markedly
delayed
and incomplete recovery

NCS
Early NCS might show normal conduction velocity
Significant slowing of nerve conduction velocities
is usually not seen until the third or fourth week
Sensory NCS reveal absent responses or slowed
conduction velocities.
Sural sparing
average distal motor response amplitude
reduction to less than 20 % of normal(within 30
days after onset of symptoms) predicts poorer
recovery

Acute Motor Axonal Neuropathy

(AMAN)
Most cases are preceded by Campylobacter jejuni
infection
Occurs frequently in Japan and China, particularly
in young people
More frequent in the summer

Similar to AIDP Except..

Deep tendon reflexes are occasionally preserved.
Sensory nerves are not affected.

Acute motor and sensory axonal

neuropathy (AMSAN)

AMSAN is a more severe form of AMAN

Both sensory and motor fibers are affected
Marked axonal degeneration
Delayed and incomplete recovery

AMAN and AMSAN

Strongly associated with antibodies to the
gangliosides GM1, GD1a, GalNac-GD1a, and
GD1b that are present in peripheral nerve axons.
These anti-ganglioside antibodies can be
induced by Campylobacter jejuni infection.

Miller Fisher syndrome (MFS)

Ophthalmoplegia
Ataxia
Areflexia
25% develop some extremity weakness
Incomplete forms include:
acute ophthalmoplegia without ataxia
acute ataxic neuropathy without ophthalmoplegia

MFS
85 to 90%: Antibodies against GQ1b
GQ1b antibody is strongly associated with
involvement of oculomotor nerves

Bickerstaff Encephalitis
Brainstem Encephalitis
Encephalopathy and hyper-reflexia with features
of MFS such as ophthalmoplegia and ataxia.
It is associated with anti-GQ1b antibodies
May respond to IVIG and plasma exchange
(MFS, Bickerstaff encephalitis, and pharyngeal-cervicalbrachial weakness with anti-GQ1b antibodies = ??
overlapping expressions of the anti-GQ1b antibody
syndrome)

Pharyngeal-cervical-brachial
Weakness
Acute weakness of the oropharyngeal, neck, and
shoulder muscles with swallowing dysfunction
+/- Facial weakness.
Leg strength and leg reflexes are usually
preserved.
{localized form of axonal GBS}
May have IgG autoantibodies to GT1a, GQ1b, or
less often to GD1a

Anti-GQ1b antibodies
MFS, Bickerstaff encephalitis, and pharyngealcervical-brachial weakness with anti-GQ1b
antibodies = ?? overlapping expressions of the
anti-GQ1b antibody syndrome

Hx, Ex, then what ?

NCS
CSF
Antibodies

Albuminocytologic Dissociation

50 to 66 % of patients with GBS in the first week

75 % of patients in the third week
Elevated CSF protein: 45 to 200 mg/dL
A minority will have mildly elevated CSF cell
counts: Cell count is >10?

NCS and Needle EMG

Dx
Prognosis
Serial clinical neurophysiology studies are
frequently helpful.

Diagnostic Criteria 1/2

Required features include:
1. Progressive weakness of more than one limb, ranging
from minimal weakness of the legs to total paralysis
of all four limbs, the trunk, bulbar and facial muscles,
and external ophthalmoplegia
2. Areflexia (universal areflexia is typical, but distal
areflexia with hyporeflexia at the knees and biceps
will suffice if other features are consistent)

Diagnostic Criteria 2/2

Supportive features include:
1. Progression of symptoms over days to four weeks
2. Relative symmetry
3. Mild sensory symptoms or signs
4. Cranial nerve involvement, especially bilateral
facial nerve weakness
5. Recovery starting two to four weeks after
progression halts
6. Autonomic dysfunction
7. No fever at the onset
8. Elevated protein in CSF with a cell count <10/mm 3
9. Electrodiagnostic abnormalities consistent with GBS

DDx
CIDP (onset, progression or relapses more than 8
weeks, preceding illness, milder disease with
retained ability to walk and lack of cranial
neuropathies)

DDx
Other polyneuropathies
1. Acute severe vitamin B1 deficiency
2. Acute arsenic poisoning
3. N-hexane (in glue sniffing neuropathy)
4. Vasculitis
5. Lyme disease
6. Tick paralysis (mostly in children)
7. Porphyria
8. Sarcoidosis
9. Leptomeningeal disease
10.Paraneoplastic disease
11.Critical illness

DDx
Spinal Cord Disorders : early bowel and bladder
dysfunction, sensory level , focal lesions on MRI
spine

DDx

Neuromuscular junction disorders:

Botulism
Myasthenia gravis
Lambert-Eaton

DDx
Muscle disorders
1. Acute polymyositis
2. Critical illness myopathy
3. Critical illness neuropathy

Treatment
Supportive care
PE and IVIG

Supportive Care
Close monitoring of respiratory, cardiac, and
hemodynamic function
Prophylaxis for deep vein thrombosis
Bladder and bowel care
Adequate pain control is necessary
Physical and occupational therapy
Psychological support

Respiratory Failure
Can occur rapidly
15 to 30 percent of patients need ventilatory
support
frequent measurement of vital capacity and
negative inspiratory force (NIF) should be
instituted initially in all patients
Bulbar dysfunction with swallowing problems and
inability to clear secretions may add to the need
for ventilatory support.

Indications for Intubation

Impending respiratory arrest
Forced vital capacity <20 mL/kg
Maximum inspiratory pressure <30 cmH2O
Maximum expiratory pressure <40 cmH2O

20, 30, 40 Rule!

Predictors of Respiratory Failure

Time of onset to admission less than seven days
Inability to cough
Inability to stand
Inability to lift the elbows
Inability to lift the head
Liver enzyme increases

Autonomic Dysfunction
Significant source of mortality
70 percent of patients
Tachycardia (the most common), urinary
retention, hypertension alternating with
hypotension, orthostatic hypotension,
bradycardia, other arrhythmias, ileus, and loss of
sweating.
Severe in about 20% of patients, mostly (but not
always) in patients who develop severe weakness
and respiratory failure.
Close monitoring of blood pressure, fluid
status, and cardiac rhythm

Cardiovascular management
Quadriplegic patients should not be left unattended
in the sitting position without assessment of
orthostatic hypotension
Intravascular volume should be maintained,
particularly during positive-pressure ventilation
Drugs with hypotensive side effects should be
avoided if possible
Arrhythmias frequently occur during suctioning
Plasma exchange can cause hypotension and
electrolyte disturbances

Cardiovascular management
Intra-arterial monitoring should be instituted in
the presence of significant blood pressure
fluctuation
Hypotension can usually be treated with fluids +/low-dose phenylephrine
Episodes of severe hypertension (MAP>125) can
be treated with labetalol, esmolol, or nitroprusside
Rule out pulmonary thromboembolism,
hypoxemia, sepsis, GI bleeding, and fluid and
electrolyte disturbances

Arryhtmias
Sustained sinus tachycardia occurs in 37 percent
of patients and requires no treatment
Severe cardiac arrhythmias :4%
Atrial fibrillation, atrial flutter, paroxysmal
tachycardia, ventricular tachycardia, elevated or
depressed ST segments, flat or inverted T waves,
Q-T interval prolongation, axis deviation, and
various conduction block

Bowel and bladder care

Daily abdominal auscultation and monitoring of
opioid administration
For treating ileus, erythromycin or neostigmine
may be effective

Pain control
Neuropathic pain occurs in about 40 to 50 percent
Gabapentin or CMZ during the acute phase of GBS
Simple analgesics or NSAIDS (usually not
sufficient)
Epidural morphine
For the long-term management of neuropathic
pain: tricyclic antidepressants, tramadol,
gabapentin, CMZ, pregabalin.

DISEASE MODIFYING TREATMENT

PE
IVIG

What is the Difference?! Which one should we use?

PE
Most effective when started within seven days of
symptom onset
Up to 30 days
4 sessions superior to 2.. 6 was not superior to
4

PE: SE

Allergic reactions to plasma

Hypotension
Sepsis
Problems with intravenous access
Decrease in clotting factors that may predispose
to bleeding

IVIG
As effective as PE for the treatment of GBS
Patients who were assigned to IVIG were less
likely to discontinue treatment than patients
assigned to plasma exchange
6 days treatment (0.4 gram/kg per day) might be
preferred over 3 days for severe cases

IVIG: SE
Aseptic meningitis
Rash
Acute renal failure (mostly related to sucrose
containing products)
Hyperviscosity leading to stroke (rare)
IgA deficiency can lead to anaphylaxis

Glucocorticoids
No benefit
Might be harmful

Factors Predicting Poor Recovery

Older age
Rapid onset (less than seven days) prior to
presentation
Severe muscle weakness on admission
Need for ventilatory support
An average distal motor response amplitude
reduction to <20 percent of normal
Preceding diarrheal illness

Long-Term
80% walk independently at six months
84% walk independently at 12 months
5 to 10 % of patients with GBS have a prolonged
course with (several months of ventilator
dependency and very delayed and incomplete
recovery)

Relapses
Up to 10 % of GBS patients
About 2 percent of GBS patients will develop CIDP

Death
Within one year of diagnosis 4 to 5 % of patients
with GBS die despite intensive care
Of patients who become ventilator dependent,
about 20 percent will die.
Causes of death include acute respiratory distress
syndrome, sepsis, pulmonary emboli, and
unexplained cardiac arrest .

Good Luck!