Neuromuscular & Peripheral Nerve Disease
Localize weakness from the neuromuscular junction to the nerve, and match the antibody to the syndrome
Localizing neuromuscular weakness
Three bedside questions. Is sensation involved (nerve or root) or spared (neuromuscular junction, motor neuron)? Does weakness worsen with use (myasthenia) or improve with it (Lambert-Eaton)? And what are the reflexes doing: preserved in myasthenia, lost in Guillain-Barré, brisk in ALS despite wasting? The answers usually name the disease before any test is sent.
| Disorder | Lesion | Signature | Key test | Treatment |
|---|---|---|---|---|
| Myasthenia gravis | Postsynaptic NMJ; anti-AChR antibodies | Fatigable ptosis, diplopia, bulbar weakness; normal reflexes | Anti-AChR; decremental repetitive stimulation | Pyridostigmine, immunosuppression, thymectomy |
| Lambert-Eaton | Presynaptic NMJ; voltage-gated Ca²⁺ channel antibodies | Proximal weakness that improves with use; dry mouth; reduced reflexes | Incremental repetitive stimulation; search for small cell lung cancer | Treat the tumor; amifampridine |
| Guillain-Barré | Peripheral nerves and roots; demyelination | Ascending symmetric weakness with areflexia after an infection | CSF albuminocytologic dissociation; slowed conduction | IVIG or plasmapheresis (not steroids) |
| ALS | Upper and lower motor neurons | Mixed UMN and LMN signs; no sensory loss | Clinical; EMG shows widespread denervation | Riluzole, edaravone, supportive care |
Myasthenia gravis and Lambert-Eaton
Presentation. Myasthenia gravis (MG) causes fluctuating, fatigable weakness that worsens with use and at day's end. Ocular symptoms (ptosis, diplopia) are the most common presenting features; bulbar weakness (dysphagia, dysarthria) and proximal limb weakness follow.
Mechanism. Antibodies against the postsynaptic acetylcholine receptor (AChR) reduce the number of working receptors, so transmission fails with repeated firing. The thymus is usually abnormal: thymoma or thymic hyperplasia.
- Anti-AChR antibodies: positive in about 85%; anti-MuSK antibodies explain some seronegative cases.
- Repetitive nerve stimulation: decremental response.
- Single-fiber EMG: the most sensitive test.
- Ice-pack test: cooling the lid improves ptosis at the bedside.
- Chest CT: look for thymoma in every new diagnosis.
Treatment. Pyridostigmine, an acetylcholinesterase inhibitor, is the symptomatic mainstay. Add immunosuppression (corticosteroids, azathioprine) for persistent disease and consider thymectomy; any thymoma is resected. Excess pyridostigmine can itself cause weakness with salivation, miosis, diarrhea, and bradycardia (cholinergic crisis).
Myasthenic crisis. Respiratory muscle weakness produces ventilatory failure. Triggers include infection, surgery, and drugs such as aminoglycosides and β-blockers (fluoroquinolones and magnesium also worsen MG). Follow forced vital capacity (FVC) and negative inspiratory force (NIF) serially, intubate before hypoxia or hypercapnia develop, and treat with IVIG or plasma exchange plus airway support.
Do not wait for a falling oxygen saturation; a declining FVC or NIF signals respiratory failure first.
Lambert-Eaton myasthenic syndrome is the mirror image. Antibodies against presynaptic voltage-gated calcium channels reduce acetylcholine release, classically as a paraneoplastic syndrome of small cell lung cancer. Weakness IMPROVES with repeated use, autonomic symptoms such as dry mouth occur, and repetitive stimulation gives an incremental response. Depressed reflexes that briefly return after exercise are a bedside clue. Treat the cancer; amifampridine (3,4-diaminopyridine) enhances acetylcholine release.
Guillain-Barré syndrome
Presentation. Acute, symmetric, ascending weakness with areflexia, typically 1–3 weeks after an infection: Campylobacter jejuni gastroenteritis (the most commonly identified trigger), CMV, or a viral illness. Distal paresthesias and back pain are common, but objective sensory loss is modest.
Mechanism. The common form, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), is immune-mediated demyelination driven by molecular mimicry between microbial and nerve antigens.
Diagnosis. CSF shows albuminocytologic dissociation: elevated protein with a normal white cell count (protein may still be normal in the first week). Nerve conduction studies show demyelinating slowing.
Monitoring and treatment. Respiratory failure and autonomic instability (arrhythmias, labile blood pressure) are the main dangers, so admit with cardiac monitoring and serial FVC and NIF. Give IVIG or plasmapheresis, which are equally effective. Corticosteroids are NOT effective, unlike in many other neuroinflammatory diseases.
- Miller Fisher variant: ophthalmoplegia, ataxia, and areflexia, with anti-GQ1b antibodies.
- CIDP: the chronic counterpart, progressing beyond 8 weeks; unlike GBS, it responds to corticosteroids.
Amyotrophic lateral sclerosis
Pure motor, both levels. ALS degenerates upper motor neurons (corticospinal tract) and lower motor neurons (anterior horn cells), often in the same limb, with bulbar involvement (dysarthria, dysphagia, tongue fasciculations). There is NO sensory loss, and eye movements are preserved. Cognition is classically spared, although a minority develop frontotemporal dementia.
| Feature | Upper motor neuron | Lower motor neuron |
|---|---|---|
| Site | Corticospinal tract | Anterior horn cell, motor nerve |
| Tone | Spasticity | Flaccid |
| Reflexes | Hyperreflexia | Reduced or absent |
| Plantar response | Babinski sign | Flexor |
| Bulk | Mild disuse atrophy | Marked atrophy with fasciculations |
Management. Riluzole (reduces glutamate release) and edaravone (a free-radical scavenger) modestly slow progression. Care is otherwise supportive: noninvasive ventilation, a feeding tube for dysphagia, and early advance care planning. Death is usually from respiratory failure. Most cases are sporadic; some familial cases carry SOD1 mutations.
Neuropathies and focal palsies
Diabetic neuropathy is the most common cause of peripheral neuropathy: a distal, symmetric, stocking-glove sensory polyneuropathy that removes protective sensation and sets up foot ulcers. Optimize glycemic control, screen the feet regularly (inspection and monofilament testing), and treat neuropathic pain with gabapentin, pregabalin, duloxetine, or a TCA.
Vitamin B12 deficiency causes subacute combined degeneration: dorsal column loss (impaired vibration and proprioception, positive Romberg), corticospinal signs, and peripheral neuropathy, often with a macrocytic anemia. Check B12 with methylmalonic acid and homocysteine (both rise; only homocysteine rises in folate deficiency). Causes include pernicious anemia, a vegan diet, metformin, and nitrous oxide. Replace B12; folate alone can correct the anemia while the neurologic damage progresses.
Bell palsy is an acute, idiopathic lower motor neuron facial (CN VII) palsy that paralyzes the ENTIRE hemiface, including the forehead. A central (upper motor neuron) lesion spares the forehead, which receives bilateral cortical input. Features include hyperacusis, altered taste, and a dry eye; associations include HSV reactivation, pregnancy, and Lyme disease. Treat with corticosteroids (ideally within 72 hours), adding antivirals in severe cases, and protect the eye; most patients recover.
Vesicles in the ear canal suggest Ramsay Hunt syndrome (VZV); bilateral facial palsy suggests Lyme disease, Guillain-Barré, or sarcoidosis.
Carpal tunnel syndrome is median nerve entrapment at the wrist: numbness and tingling of the thumb, index, and middle fingers, worse at night, with thenar atrophy in advanced cases. Phalen and Tinel signs are positive. Associations include pregnancy, hypothyroidism, diabetes, rheumatoid arthritis, and acromegaly. Treat with wrist splinting, steroid injection, or surgical decompression; nerve conduction studies confirm the diagnosis before surgery.
Skin over the thenar eminence is spared because the palmar cutaneous branch leaves the median nerve before the carpal tunnel.