Guillain-Barré Syndrome (GBS) - A Detailed Overview

1. Definition

• Acute onset (maximum deficit by 4 weeks)
• Elevated CSF protein with low cell counts (cytoalbuminologic / albuminocytological dissociation)
• A monophasic course

• Goldman-Cecil Medicine, p. 4065
• Bradley and Daroff's Neurology in Clinical Practice, p. 2663

2. Epidemiology

• Campylobacter jejuni gastroenteritis is the most common preceding infection, especially in axonal variants
• Zika virus is associated with a significantly increased risk of all GBS forms
• Hepatitis E is a trigger in Belgium and Netherlands (5-10% of cases)
• SARS-CoV-2 infection or most vaccines are NOT substantially associated with GBS (except a slight increase with ChADOx1nCoV-19 vaccine: 0.6 cases/100,000 doses)
• GBS incidence actually declined during the COVID-19 pandemic due to reduced spread of usual infectious triggers
• Goldman-Cecil Medicine, p. 4065-4066

3. Classification / Subtypes

Common Subtypes

Rare Variants

• Miller-Fisher Syndrome (MFS): Classic triad of ophthalmoplegia, ataxia, and areflexia. Facial weakness, ptosis, and pupillary abnormalities may occur. NCS velocities are normal. Anti-GQ1b antibodies in >85% of cases. Accounts for 6% of GBS in Western countries, 18% in Taiwan.
• Pharyngeal-cervical-brachial variant
• Facial diplegia with paresthesias
• Multiple cranial neuropathy variant
• Paraparetic variant
• Acute pandysautonomia
• Bradley and Daroff's Neurology in Clinical Practice, p. 2663-2664

4. Pathobiology / Pathogenesis

• The HS/0:19 serotype of C. jejuni shares GM1-like epitopes with axonal membranes
• This triggers production of anti-GM1 antibodies
• Activated complement components (C3d, C5b-9) and immunoglobulin deposit at nodes of Ranvier
• Macrophages are recruited to targeted nodes and invade the periaxonal space
• This leads to Wallerian degeneration
• Lack of blood-nerve barrier at motor nerve terminals makes distal axons especially vulnerable to circulating GM1 antibodies

• Robbins & Kumar Basic Pathology, p. 809
• Goldman-Cecil Medicine, p. 4066

5. Clinical Features

Classic Presentation

• Weakness is the most common initial symptom - can range from mild difficulty walking to total quadriplegia with respiratory failure
• Classic ascending paralysis: leg weakness spreading to arms over hours to days
• Symmetrical weakness; proximal weakness is very common
• Areflexia/Hyporeflexia: invariable (may be absent early in disease)
• Symptoms progress over days to a maximum of 4 weeks (plateau then recovery)

Sensory Features

• Sensory loss is not prominent - often limited to distal vibration sense impairment
• Pain is underappreciated: moderate-to-severe pain in extremities, interscapular area, or back in ~70% during acute phase; may persist for a year in one-third

Cranial Nerve Involvement (45-75% of cases)

• Bilateral facial paresis in at least 50% of patients
• Extraocular muscle and lower cranial nerve involvement (less common)
• Occasional facial myokymia
• 5% present with isolated cranial nerve involvement that then descends

Autonomic Dysfunction (65% of cases)

• Cardiac arrhythmias (tachycardia, bradycardia)
• Blood pressure lability (hypertension and hypotension)
• Urinary retention
• Ileus
• Pupillary dysfunction
• Autonomic dysfunction is a major cause of mortality in ICU patients

Respiratory Involvement

• Respiratory failure requiring mechanical ventilation in 9-30% of cases (increases with age)
• Predictors of respiratory failure:
  • Rapid disease progression (onset to admission <7 days)
  • Severity of limb weakness
  • Facial weakness
  • Bulbar weakness
• Goldman-Cecil Medicine, p. 4066
• Bradley and Daroff's Neurology in Clinical Practice, p. 2663-2665

6. Diagnostic Criteria

Features Required for Diagnosis (Asbury & Cornblath criteria)

1. Progressive weakness of both legs and arms
2. Areflexia or hyporeflexia

Clinical Features Supportive of Diagnosis

• Progression over days to 4 weeks
• Relative symmetry
• Mild sensory symptoms or signs
• Bifacial palsies
• Autonomic dysfunction
• Absence of fever at onset
• Recovery beginning 2-4 weeks after progression ceases

Laboratory Features Supportive of Diagnosis

• Elevated CSF protein with <10 cells/µL (albuminocytologic dissociation)
  • CSF protein may be normal in the first 7-10 days and remains normal in up to 10% of cases
  • CSF WBC >50/mL suggests HIV or infection (Lyme disease)
• Electrodiagnostic features of nerve conduction slowing or block
  • AIDP: reduced conduction velocities, conduction blocks
  • AMAN/AMSAN: reduced compound muscle action potential (CMAP) amplitudes with relatively preserved conduction velocities

Antibodies

• Anti-GQ1b: present in >85% of Miller-Fisher syndrome cases
• Anti-GM1: present in AMAN, associated with C. jejuni infection
• Bradley and Daroff's Neurology in Clinical Practice, Box 106.10, p. 2663
• Goldman-Cecil Medicine, p. 4066-4067

7. Differential Diagnosis

• Asymmetric weakness
• Persistent bladder/bowel dysfunction
• CSF cell count >50/mL
• Fever at onset
• Sensory level (suggests spinal cord)
• Sharp sensorimotor level on examination
• Goldman-Cecil Medicine, p. 4067
• Bradley and Daroff's Neurology in Clinical Practice, p. 2666

8. Treatment

Supportive Care (Mainstay)

• Any predictors of respiratory failure
• Evidence of dysautonomia
• Signs of respiratory insufficiency

• Vital capacity < 20 mL/kg (or 30% decline from baseline)
• Maximal inspiratory pressure < 30 cm H₂O
• Maximal expiratory pressure < 40 cm H₂O

• FVC falls below 12-15 mL/kg (or <18 mL/kg with severe oropharyngeal weakness)
• Arterial PO₂ falls below 70 mmHg on room air
• Tracheostomy is required when ventilatory support is needed for >2 weeks

Immunotherapy - Two Equivalent First-Line Treatments

• IVIG and plasmapheresis are equally effective - neither is clearly superior
• Corticosteroids are NOT effective in GBS and are not recommended
• Combining IVIG + plasmapheresis offers no additional benefit
• Treatment is most effective when started within 4 weeks of symptom onset

Supportive Measures

• DVT prophylaxis (enoxaparin + compression stockings)
• Pain management (gabapentin, carbamazepine for neuropathic pain; opioids for severe acute pain)
• Urinary catheterization if needed
• Bowel management for ileus
• Cardiac monitoring for arrhythmia
• Nutritional support (NG or PEG feeding in prolonged cases)
• Rehabilitation (physiotherapy, occupational therapy)
• Bradley and Daroff's Neurology in Clinical Practice, p. 2668-2670
• Goldman-Cecil Medicine, p. 4067
• Robbins & Kumar Basic Pathology, p. 809

9. Prognosis

• Older age
• Preceding diarrheal illness (especially C. jejuni)
• Axonal variants (AMAN, AMSAN)
• Severe weakness at nadir
• Reduced CMAP amplitudes in upper extremities (indicating axonal loss)
• Need for mechanical ventilation

• Goldman-Cecil Medicine, p. 4067
• Bradley and Daroff's Neurology in Clinical Practice, p. 2670

10. GBS vs. CIDP - Key Distinction

Summary

How to Examine the Central Nervous System (CNS)

Overview - Components of the CNS Examination

The experienced clinician uses a focused examination guided by the history, plus a screening examination of everything else. More complex functions are tested first - a patient who tandem walks normally does not have a significant cerebellar or proprioceptive problem.

• Bradley and Daroff's Neurology in Clinical Practice, p. 28

1. Mental Status Examination

Consciousness & Alertness

• Note whether the patient is alert, confused, lethargic, or comatose
• Use the Glasgow Coma Scale (GCS) if impaired: Eye (1-4) + Verbal (1-5) + Motor (1-6)

Orientation

• Ask: person (name), place, date, year

Attention

• Ask to recite months backward, or serial 7s (subtract 7 from 100 repeatedly)
• Digit span forward (normal ≥6) and backward (normal ≥4)

Language (4 components)

• Fluency: Is speech fluent or non-fluent?
• Comprehension: Follow a 2-3 step command ("Pick up the paper with your right hand, fold it, and put it on the table")
• Repetition: Repeat a phrase ("No ifs, ands, or buts")
• Naming: Name common objects (watch, pen, knuckle)
• Note: Non-fluent aphasia + impaired comprehension = Broca's area lesion (left frontal); Fluent aphasia + impaired comprehension = Wernicke's area (left temporal)

Memory

• Immediate recall: Repeat 3 words
• Short-term: Recall 3 words after 5 minutes
• Long-term: Ask about past events

Visuospatial Function

• Ask to copy intersecting pentagons or draw a clock face
• Impaired in right parietal lobe lesions (constructional apraxia)

Higher Functions

• Praxis: Can patient mime brushing teeth or combing hair?
• Calculation: Serial 7s, simple arithmetic
• Abstraction: Interpret a proverb
• Judgment & insight

Quick Bedside Cognitive Tools

• Mini-Mental State Examination (MMSE): 30 points; <24 suggests cognitive impairment
• Montreal Cognitive Assessment (MoCA): More sensitive for mild cognitive impairment

Observational clues: hypomimia suggests parkinsonism; a worried/astonished expression may suggest progressive supranuclear palsy; ptosis may indicate myasthenia gravis or a brainstem lesion; the pattern of speech may reveal dysarthria or aphasia from the outset.

• Bradley and Daroff's Neurology, p. 28

2. Cranial Nerve Examination

CN I - Olfactory Nerve

• Test when: spontaneous loss of smell, suspected Parkinson's disease, or head injury
• Method: With eyes closed, ask the patient to sniff a mild familiar odour (coffee, toothpaste) and identify it
• Anosmia: inferior frontal lobe lesion (e.g., meningioma), Parkinson's disease, head trauma

CN II - Optic Nerve

• Visual acuity: Test each eye separately using a Snellen chart (with glasses on)
• Visual fields by confrontation: Face the patient at ~60 cm; compare their fields to yours; move a finger in each quadrant (inferior then superior); test both eyes simultaneously first, then separately
  • Bitemporal hemianopia: optic chiasm lesion (e.g., pituitary adenoma)
  • Homonymous hemianopia: optic tract/radiation or occipital cortex lesion
• Pupillary light reflex / RAPD (Swinging flashlight test): Shine light alternately into each eye; relative afferent pupillary defect (RAPD) = optic nerve lesion on affected side
• Fundoscopy: Examine the optic disc (color, margins, cup-disc ratio), vessels, and retina
  • Papilloedema: raised intracranial pressure
  • Optic atrophy: previous optic neuritis or compression

CN III, IV, VI - Oculomotor, Trochlear, Abducens

• Pupil size and symmetry: Note anisocoria (unequal pupils)
  • Large unreactive pupil: CN III palsy (compression, herniation)
  • Small pupil + ptosis + anhidrosis: Horner syndrome (sympathetic pathway lesion)
  • Pinpoint pupils: pontine lesion
• Accommodation reflex: Ask patient to follow finger moving to nose - pupil should constrict
• Extraocular movements (EOM): Ask patient to follow finger in an "H" pattern; look for:
  • Paresis (limited movement)
  • Diplopia in any direction (ask the patient directly)
  • Nystagmus: fast and slow phases; note direction and type
  • Horizontal nystagmus assessed at 45°, not at extreme gaze
• CN III palsy: Ptosis, "down and out" eye, dilated unreactive pupil
• CN IV palsy: Vertical diplopia; head tilt; hypertropia
• CN VI palsy: Esotropia; failure of abduction; horizontal diplopia

CN V - Trigeminal Nerve

• Sensory: Test light touch and pinprick in all three divisions (V1: forehead/scalp; V2: cheek/upper lip; V3: lower jaw/chin) on each side
• Corneal reflex: Lightly touch the cornea with a wisp of cotton (not conjunctiva); normal = blink bilaterally (afferent = CN V; efferent = CN VII)
• Motor (V3): Ask to clench teeth - palpate masseters; test jaw deviation against resistance (pterygoids)
  • Jaw deviates toward side of lesion (weak pterygoid)

CN VII - Facial Nerve

• Inspect face at rest for asymmetry
• Test:
  • Raise eyebrows (frontalis)
  • Forcefully close eyes (orbicularis oculi) - try to open them
  • Show teeth / smile (orbicularis oris)
  • Puff out cheeks
• Key distinction:
  • UMN (central) facial palsy: Lower two-thirds weakness only (forehead spared) - contralateral hemisphere/cortex lesion
  • LMN (peripheral) facial palsy: Entire ipsilateral face weak including forehead - e.g., Bell's palsy, CN VII compression

CN VIII - Vestibulocochlear Nerve

• Hearing: Rub fingers near each ear; ask patient to detect whisper at ~60 cm
• Rinne test: Vibrating tuning fork (512 Hz) on mastoid until no longer heard, then at ear - normally air > bone (Rinne positive); if bone > air = conductive loss
• Weber test: Vibrating fork on forehead midline - normal lateralizes to neither side; lateralizes to bad ear in conductive loss, to good ear in sensorineural loss
• Vestibular function: Head impulse test, Dix-Hallpike maneuver for BPPV, nystagmus assessment

CN IX & X - Glossopharyngeal & Vagus

• Ask patient to say "Ahh" - palate should rise symmetrically in midline
• Unilateral palsy: uvula deviates away from lesion side
• Gag reflex: Touch posterior pharynx with tongue depressor (afferent CN IX; efferent CN X)
• Listen for hoarseness (recurrent laryngeal nerve, CN X)
• Assess swallowing

CN XI - Spinal Accessory Nerve

• Trapezius: Ask patient to shrug shoulders against resistance
• Sternocleidomastoid: Ask patient to turn head to the opposite side against resistance

CN XII - Hypoglossal Nerve

• Ask patient to protrude tongue
• Tongue deviates toward the side of an LMN lesion (weak side)
• Look for fasciculations or wasting (LMN lesion)
• Tongue deviates away from an UMN (contralateral cortical) lesion
• Harrison's Principles of Internal Medicine 22E, p. 3423-3425
• Goldman-Cecil Medicine, p. 464-480

3. Motor Examination

Step 1: Appearance (Inspection & Palpation)

• Look for muscle wasting/atrophy (LMN lesion, disuse)
• Look for fasciculations at rest (LMN - anterior horn cell disease, e.g., ALS)
• Look for involuntary movements:
  • Resting tremor (Parkinson's disease - "pill-rolling")
  • Postural tremor (essential tremor)
  • Intention tremor (cerebellar disease)
  • Chorea, athetosis, dystonia, myoclonus, tics

Step 2: Tone

• Upper limbs: rapid pronation/supination, wrist flexion/extension
• Lower limbs (supine): hands under knees, raise rapidly - normal heel drags; increased tone = heel lifts immediately

Step 3: Power (MRC Scale)

• Pronator drift: Both arms extended with eyes closed for 10 seconds - weak arm drifts downward and pronates (UMN lesion)
• Upper limb: wrist/finger extensors (radial nerve, C7), grip, finger abduction
• Lower limb: hip flexors, knee extensors, ankle dorsiflexion (L4/5), toe extension
• Harrison's Principles of Internal Medicine 22E, p. 3424

4. Coordination & Cerebellar Examination

Limb Coordination

• Finger-to-nose test: Ask patient to touch their nose, then your finger, repeatedly; look for intention tremor and dysmetria (past-pointing)
• Heel-to-shin test: Ask patient to run one heel down the opposite shin repeatedly
• Rapid alternating movements (dysdiadochokinesis): Alternating pronation/supination of the hand rapidly; slowed, irregular = cerebellar dysfunction

Signs of Cerebellar Disease (DANISH mnemonic)

• Dysdiadochokinesis
• Ataxia (limb and gait)
• Nystagmus (horizontal, towards lesion)
• Intention tremor
• Scanning (slurred, staccato) speech
• Hypotonia

Note:

5. Sensory Examination

Primary Modalities

• Stocking-glove distribution: Peripheral neuropathy (GBS, diabetes)
• Sensory level (below a dermatome): Spinal cord lesion
• Dissociated sensory loss (pain/temperature lost but vibration/proprioception intact): Anterior cord syndrome or syringomyelia
• Hemisensory loss: Contralateral hemisphere or thalamic lesion
• Crossed (face one side, body opposite): Brainstem lesion

Higher Cortical Sensory Functions (parietal lobe)

• Graphesthesia: Trace a number on the palm with eyes closed - patient identifies it
• Stereognosis: Patient identifies object placed in hand (coin, key) with eyes closed
• Two-point discrimination: Minimum distance to distinguish two simultaneous points
• Sensory extinction: Two areas touched simultaneously - parietal lesion causes extinction of one stimulus (usually contralateral)

6. Reflexes

Deep Tendon Reflexes (DTRs)

• 0 = Absent
• 1+ = Diminished
• 2+ = Normal
• 3+ = Brisk (may be normal)
• 4+ = Clonus present (pathological; UMN lesion)

Plantar Response (Babinski Sign)

• Stroke the lateral sole with a blunt object from heel toward little toe, then curve medially
• Normal: Plantar flexion of toes (downgoing)
• Abnormal (Babinski positive / extensor): Big toe dorsiflexion ± fanning of other toes = UMN lesion above S1
• Present normally in infants up to 2 years (myelination not complete)

Superficial Reflexes

• Abdominal reflexes: Stroke each quadrant toward umbilicus; umbilicus moves toward stimulus; absent = UMN lesion ipsilaterally (T8-T12)
• Cremasteric reflex: Stroke inner thigh - testicle rises (L1, L2); absent = UMN or LMN lesion
• Anal reflex (S3, S4): Touch perianal skin; sphincter contracts

Primitive Reflexes (release signs = frontal lobe disease)

• Grasp reflex: Stroke patient's palm - fingers grasp examiner's fingers
• Palmomental reflex: Stroke thenar eminence - chin muscle twitches ipsilaterally
• Snout/pout reflex: Tap philtrum - pursing of lips

Special Reflexes

• Hoffman's sign: Flick terminal phalanx of middle finger; thumb and index flex = hyperreflexia (UMN lesion in cervical cord or above)
• Clonus: Rapidly dorsiflex the foot; rhythmic oscillations = UMN lesion

7. Gait and Balance

Romberg Test

• Patient stands with feet together, arms at sides:
  • Eyes open: stable
  • Eyes closed: if the patient falls = Romberg positive
• Positive Romberg = loss of proprioception (dorsal column or peripheral sensory neuropathy) - the patient compensates visually; removing vision unmasks the deficit
• In cerebellar ataxia, the patient is unsteady with both eyes open and closed (Romberg is negative)

Tandem Gait (Heel-to-Toe Walking)

• Walk heel-to-toe along a straight line
• Fails with cerebellar midline disease or significant sensory loss

Postural Stability (Pull Test)

• Stand behind patient; pull back on shoulders briskly
• Normal: 1-2 corrective steps
• Abnormal (retropulsion): Parkinson's disease, PSP

8. Localisation Summary

• Harrison's Principles of Internal Medicine 22E, Table 433-1
• Bradley and Daroff's Neurology in Clinical Practice, p. 28-30

Quick Reference - Screening Neurological Examination (Bradley & Daroff)

Clinical Examination of a GBS Patient

Step 1: General Inspection (Before Touching the Patient)

Ask the patient about: preceding illness (fever, diarrhoea, URTI 1-4 weeks ago), time of symptom onset, rate of progression, and any breathing difficulty or swallowing problems.

Step 2: Vital Signs - CRITICAL in GBS

The "20-30-40 Rule" for intubation risk:

• Vital capacity < 20 mL/kg
• Maximum inspiratory pressure < 30 cmH₂O
• Maximum expiratory pressure < 40 cmH₂O

If all 3 are met → immediate ICU transfer and elective intubation.

Step 3: Motor Examination - The Core of GBS

3a. Inspect

• Look for muscle wasting (usually absent early; may appear after prolonged disease)
• Look for fasciculations (rare in GBS; their presence suggests anterior horn cell disease - reconsider diagnosis)
• Note posture of limbs: flaccid, lying flat

3b. Tone

• Hypotonia / Flaccidity in all affected limbs - the hallmark of a lower motor neuron/peripheral nerve lesion
• In GBS: tone is reduced or absent (not spastic)
• Test by passive wrist flexion/extension, knee lift with heel drag

3c. Power - Test Systematically Using MRC Scale (0-5)

• Typically symmetrical
• Proximal and distal weakness (unlike polyneuropathy which is usually distal-predominant)
• Classically ascending: legs > arms > respiratory/bulbar muscles
• In severe disease: near-total quadriplegia

Step 4: Reflexes - The Most Consistent Finding

Areflexia or hyporeflexia is the invariable feature of GBS - though it may be absent very early in the disease course. If reflexes are brisk or hyperreflexia is present, seriously question the diagnosis.

• In GBS: typically flexor (normal/downgoing) - as expected with an LMN/peripheral nerve lesion
• An extensor plantar (Babinski positive) in a suspected GBS patient suggests a concurrent UMN (spinal cord/central) lesion - investigate urgently

Step 5: Sensory Examination

What to Test:

• Distal > proximal (glove-and-stocking)
• Mild to moderate - motor deficits dominate
• Vibration sense is the most commonly affected modality
• Pain/paresthesias (burning, tingling) present in ~70% of patients - often severe

Pain Assessment:

• Ask specifically about back pain (interscapular/lumbar - a common early complaint in GBS, sometimes misdiagnosed as musculoskeletal)
• Dysesthetic pain: burning, tingling of limbs
• Deep aching limb pain (muscle/joint pain)

Important: if there is a sensory level on the trunk (sensation normal above a dermatome, absent below), this suggests a spinal cord lesion, NOT GBS - arrange urgent MRI spine.

Step 6: Cranial Nerve Examination

1. Ophthalmoplegia - eyes don't move fully
2. Ataxia - unsteady gait/limbs
3. Areflexia - absent reflexes (often without limb weakness)

Step 7: Coordination

• Finger-nose and heel-shin tests
• In classic GBS: incoordination is mainly due to weakness, not true cerebellar dysfunction
• In Miller-Fisher variant: true cerebellar-type ataxia is present
• Differentiate sensory ataxia (proprioception loss) from cerebellar ataxia using Romberg test

Step 8: Gait Assessment

Step 9: Autonomic Assessment

"Vagal spells": sudden bradycardia, heart block, or asystole triggered by tracheal suction or straining - watch for these in ICU patients. ECG changes (T-wave, ST, QT prolongation) can occur.

Step 10: Look for Complications

Summary of Key Examination Findings in GBS

Red Flags That Suggest Another Diagnosis (NOT GBS)

• Bradley and Daroff's Neurology in Clinical Practice, p. 2663-2670
• Neuroanatomy through Clinical Cases 3rd Edition, p. 407
• Goldman-Cecil Medicine, p. 4066-4067

Additional GBS - Deeper Details

1. Electrodiagnostic Studies (NCS / EMG) - The Cornerstone of Subtype Classification

AIDP (Demyelinating) - NCS Findings

Conduction block = CMAP amplitude drops >50% from distal to proximal stimulation - indicates focal demyelination. This is what causes clinical weakness disproportionate to axonal damage.

AMAN (Axonal Motor) - NCS Findings

AMSAN (Axonal Motor + Sensory) - NCS Findings

• Same as AMAN but SNAPs also reduced or absent
• Needle EMG: abundant fibrillations; persistently inexcitable motor nerves
• Worst prognosis of all subtypes

Miller-Fisher Syndrome (MFS) - NCS Findings

• SNAPs reduced or absent (sural sparing pattern in 1/3)
• Motor NCS usually normal
• F-waves and needle EMG usually normal
• CSF: elevated protein in ~70% at 1 week

Important pitfall: NCS may be normal in the first 7-10 days of GBS. If the clinical picture is strongly suggestive but NCS is normal, repeat in 1 week (see management flowchart below).

• Bradley and Daroff's Neurology, p. 2666-2670

2. Serological / Antibody Testing

Ganglioside antibody testing is only clinically useful for MFS (anti-GQ1b) and axonal variants (anti-GM1). Testing is not recommended routinely in classic AIDP.

3. CSF Analysis - The "Albuminocytologic Dissociation"

• WBC > 50/µL → consider HIV seroconversion, Lyme disease, CMV radiculitis, lymphomatous meningitis
• WBC > 10 but < 50 may occasionally occur in GBS with concurrent HIV or CMV

4. MRI Findings

• Brain MRI: usually normal in classic GBS
• MRI spine with gadolinium: may show nerve root enhancement of the cauda equina - particularly in children. This reflects inflammation at the roots.
• MRI is primarily used to exclude alternative diagnoses (myelopathy, cord compression, brainstem lesion)
• In MFS: MRI brain occasionally shows brainstem lesions or gadolinium enhancement of ocular motor nerves

5. Subtype Deep-Dive

AMAN - Acute Motor Axonal Neuropathy

• First reported in epidemic proportions in children/young adults in northern China (summer months)
• Now the most common GBS subtype in Asia
• Pure motor: no sensory involvement clinically or electrophysiologically
• Normal SNAPs; reduced CMAP; no conduction slowing
• Pathology: macrophage intrusion between axon and myelin at nodes of Ranvier, leading to membrane-attack complex formation → conduction failure
• Anti-GM1 and anti-GD1a IgG antibodies (molecular mimicry with C. jejuni lipopolysaccharide)
• Paradox: most patients improve as rapidly as AIDP despite axonal pattern - because conduction failure is often reversible without true axonal degeneration

AMSAN - Acute Motor-Sensory Axonal Neuropathy

• Fulminant, rare, and severe
• Maximum deficit within <7 days from onset
• Profound quadriparesis, severe muscle wasting, prolonged ventilation
• Absent CMAPs + absent SNAPs; no conduction slowing
• Abundant fibrillations on needle EMG
• Extensive wallerian degeneration in ventral AND dorsal roots
• Poor prognosis - recovery is delayed and often incomplete

Miller-Fisher Syndrome (MFS)

• Classic triad: Ophthalmoplegia + Ataxia + Areflexia
• Diplopia is often the first symptom
• Ocular signs: from complete ophthalmoplegia (dilated unreactive pupils) to partial external ophthalmoparesis ± ptosis
• Ataxia: due to peripheral mismatch between proprioceptive input from muscle spindles and kinesthetic information from joint receptors
• Motor strength: characteristically preserved - but ~5% overlap with classic GBS and develop quadriparesis
• Anti-GQ1b IgG: 95-98% positive (most sensitive and specific test in neurology)
• Precipitants: C. jejuni (20%), H. influenzae (8%)
• Prognosis: excellent - most recover fully within weeks to months
• Related condition: Bickerstaff Brainstem Encephalitis (BBE) - also anti-GQ1b positive, presents with ophthalmoplegia + ataxia + altered consciousness (CNS involvement)

6. Management Flowchart

1. Patient fulfills clinical criteria → proceed to NCS + CSF
2. If NCS/CSF normal → repeat in 1 week; consider other diagnoses
3. If abnormal → confirmed diagnosis
4. Monitor bulbar function, BP, FVC every 4-6 hours; assess severity
5. Walks unassisted, no progression → Conservative management (observe)
6. Walks with support OR bedridden AND symptoms <30 days → IVIG or plasma exchange
7. FVC <12-15 mL/kg → Mechanical ventilation

7. IVIG vs Plasmapheresis - Comparative Details

Timing matters: Treatment within 2 weeks of onset is most effective; treatment up to 4 weeks is still beneficial. After 4 weeks, immunotherapy is unlikely to help.

8. Pain Management in GBS (Often Undertreated)

9. Rehabilitation in GBS (Post-Acute Phase)

• Physiotherapy: progressive resistance and aerobic exercise; reduces fatigue and improves functional capacity
• Occupational therapy: activities of daily living retraining
• Speech therapy: bulbar and swallowing rehabilitation
• Respiratory physiotherapy: breathing exercises, weaning protocols
• Psychological support: depression and anxiety are common; quality of life is significantly affected
• Orthoses: ankle-foot orthoses for foot drop; wrist splints

10. GBS vs Acute-Onset CIDP - A Critical Distinction

1. Disease progresses or deteriorates beyond 8 weeks
2. >2 treatment-related fluctuations (improvement then worsening after IVIG/PE), especially beyond 1 month
3. Prominent sensory symptoms dominate
4. Multifocal enlargement of peripheral nerves on ultrasound
5. >3 treatment-related fluctuations is almost diagnostic of CIDP

11. Prognostic Scoring - EGOS / mEGOS

12. Long-Term Outcomes

• Respiratory failure / ventilator complications
• Autonomic instability (cardiac arrhythmias, sudden cardiac death)
• Pulmonary embolism
• Sepsis / pneumonia (aspiration)
• Acute hypoxic-ischaemic encephalopathy

13. GBS in Special Populations

GBS in Children

• More common form: AMAN (particularly in Asia after C. jejuni)
• MRI spine may show gadolinium enhancement of cauda equina
• Generally better prognosis than adults
• Pain and back pain are prominent early features

GBS in Pregnancy

• Rare but serious
• Physiological changes increase risk of respiratory failure and aspiration
• IVIG is preferred over plasma exchange (haemodynamic safer)
• Does not cross placenta; fetus generally unaffected
• Succinylcholine is contraindicated (risk of hyperkalaemia and cardiac arrest due to upregulated ACh receptors)

GBS in the Elderly

• Higher incidence (3.2 per 100,000 in >60 years)
• More severe disease; greater respiratory failure risk
• Poor prognosis; higher mortality
• Autonomic complications more dangerous

Summary Table: GBS Subtypes at a Glance

• Bradley and Daroff's Neurology in Clinical Practice, p. 2663-2675
• Goldman-Cecil Medicine, p. 4065-4068