STEPTRACKERNERVOUS SYSTEM | PATHOLOGY + IMMUNOLOGY + PHARMACOLOGY | HIGH-YIELD REVIEW

Peripheral Nerve & Neuromuscular Junction

Demyelinating and inherited neuropathies, the junction disorders that weaken by antibody or toxin, and common nerve entrapments.

FOCUS ON
Guillain-Barré: after Campylobacter or a virus, ascending flaccid paralysis, areflexia, ↑ CSF protein with normal cells → IVIG/plasmapheresis, watch breathing. Myasthenia gravis: anti-AChR, fatigable ptosis/diplopia, thymoma → pyridostigmine. Lambert-Eaton: anti-presynaptic Ca²⁺ channel, small cell lung cancer, improves with use. Botulism: descending paralysis, dilated pupils.
DISORDER
MECHANISM
FEATURES
CLUE · TREATMENT
Guillain-Barré syndrome
Molecular mimicry after Campylobacter jejuni, CMV, EBV, Zika → macrophages strip myelin (or axons) of peripheral nerves and roots
Ascending symmetric flaccid paralysis, areflexia, mild sensory loss, autonomic instability, facial diplegia
CSF ↑ protein, normal cells · IVIG or plasmapheresis (not steroids) · monitor FVC
Miller Fisher variant
Anti-GQ1b antibodies
Ophthalmoplegia, ataxia, areflexia
Descending pattern
CIDP
Chronic immune demyelination (> 8 weeks)
Relapsing or progressive symmetric weakness and sensory loss; onion bulbs
Unlike GBS, responds to steroids
Charcot-Marie-Tooth
Hereditary motor and sensory neuropathy; PMP22 duplication (CMT1A, AD) → demyelination, onion bulbs
Distal weakness and wasting ("inverted champagne bottle" legs), pes cavus, hammer toes, foot drop
Family history, slow progression
Myasthenia gravis
Antibodies to postsynaptic nicotinic AChR (type II); anti-MuSK in some; thymic hyperplasia or thymoma
Fatigable weakness: ptosis, diplopia worse by evening, bulbar and proximal weakness; normal reflexes and pupils
Decremental response · pyridostigmine, steroids, thymectomy
Myasthenic crisis
Infection, surgery or drugs (aminoglycosides, fluoroquinolones, β-blockers, magnesium) worsen transmission
Respiratory failure, severe bulbar weakness
IVIG or plasmapheresis, ventilatory support
Lambert-Eaton syndrome
Antibodies to presynaptic voltage-gated Ca²⁺ channels; paraneoplastic (small cell lung cancer)
Proximal leg weakness that improves with repeated effort; ↓ reflexes; dry mouth, constipation, impotence
Incremental response · 3,4-diaminopyridine · find the cancer
Botulism
Toxin cleaves SNARE proteins → no ACh release
Descending flaccid paralysis: diplopia, ptosis, dysarthria, dysphagia, dilated pupils; infants: floppy, constipated (honey)
Antitoxin (adults), botulism immune globulin (infants)
Organophosphate poisoning
Irreversible AChE inhibition → excess ACh at muscarinic and nicotinic sites
Miosis, salivation, lacrimation, bronchorrhea, bradycardia, diarrhea, urination + fasciculations → paralysis
Atropine + pralidoxime
Carpal tunnel syndrome
Median nerve compression under the flexor retinaculum: pregnancy, hypothyroidism, acromegaly, RA, dialysis amyloid, diabetes
Night paresthesias of thumb–ring finger (radial half), thenar atrophy; Tinel and Phalen ⁺
Splint, steroid injection, release
Other mononeuropathies
Compression or fracture
Radial (midshaft humerus, "Saturday night palsy") → wrist drop · common fibular (fibular neck, leg crossing) → foot drop · ulnar (elbow) → claw hand
Mononeuritis multiplex → vasculitis, diabetes

Mechanism — the neuromuscular junction

Nerve action potential
→
Voltage-gated Ca²⁺ channelsLambert-Eaton
→
SNARE vesicle fusionBotulinum
→
ACh on nicotinic receptorsMyasthenia gravis
→
AChE clears AChOrganophosphates

Repeated use helps Lambert-Eaton (Ca²⁺ builds up in the terminal) but worsens myasthenia (receptors run out).

Myasthenia vs Lambert-Eaton vs botulism

FEATURE
MYASTHENIA
LAMBERT-EATON
BOTULISM
Target
Postsynaptic AChR
Presynaptic Ca²⁺ channel
SNARE (release)
First muscles
Eyes, bulbar
Proximal legs
Eyes, bulbar (descending)
With use
Worse
Better
—
Reflexes
Normal
↓ (↑ after exercise)
↓
Autonomic
None
Dry mouth
Dilated pupils, ileus
Association
Thymoma
Small cell lung cancer
Canned food, honey, wounds

How it's tested

COMMON CONFUSIONGuillain-Barré ascends from the legs with areflexia; botulism descends from the eyes with dilated pupils; myasthenia spares pupils and reflexes.
THE TRAPIn Guillain-Barré, oxygen saturation drops late — follow forced vital capacity and negative inspiratory force to decide on intubation.
YOUR APPROACHPattern (ascending, descending, fatigable, distal) → reflexes and pupils → trigger (infection, cancer, food, pesticide) → test (CSF, antibodies, repetitive stimulation) → treatment.

If you see… think…

Ascending weakness 2 weeks after bloody diarrhea, no reflexes → Guillain-Barré (Campylobacter)
CSF protein 200 with 2 cells → albuminocytologic dissociation (GBS)
Ophthalmoplegia + ataxia + areflexia, anti-GQ1b → Miller Fisher
High arches, hammer toes, thin lower legs, family history → Charcot-Marie-Tooth
Double vision and droopy lids worse in the evening → myasthenia gravis
Myasthenia + anterior mediastinal mass → thymoma — thymectomy
Smoker with proximal weakness that improves with effort, dry mouth → Lambert-Eaton (small cell)
Infant fed honey, constipated and floppy → infant botulism
Farmer with pinpoint pupils, drooling, wheezing, fasciculations → organophosphate — atropine + pralidoxime
Pregnant woman with night hand tingling, positive Phalen → carpal tunnel syndrome