Neuromuscular Junction and Muscle Disorders

Myasthenia Gravis (MG)

•    Clinical features:

o    Fluctuating, fatigable weakness (worse with use, improves with rest).

o    Ocular symptoms common: ptosis (often asymmetric), diplopia.

o    Bulbar weakness: dysarthria, dysphagia.

o    Limb weakness: often proximal.

o    Respiratory involvement → myasthenic crisis.

•    Investigations:

o    Antibodies: Anti-AChR (85% generalised MG), anti-MuSK (~10%).

o    Edrophonium (Tensilon) test: transient improvement (rarely used now).

o    Repetitive nerve stimulation: decremental response.

o    CT/MRI mediastinum: thymoma (seen in ~15% of cases).

•    Treatment:

o    Symptomatic: pyridostigmine.

o    Immunosuppression: steroids, azathioprine.

o    Thymectomy: indicated in thymoma or generalised MG (younger patients).

•    Crisis management:

o    IV immunoglobulin or plasma exchange.

o    Monitor vital capacity.

Lambert–Eaton Myasthenic Syndrome (LEMS)

•    Clinical features:

o    Proximal muscle weakness (especially legs), improves with repeated use (facilitation).

o    Autonomic dysfunction: dry mouth, impotence.

o    Reflexes reduced but may increase after exercise.

•    Associated with:

o    Small cell lung carcinoma (paraneoplastic).

o    Other autoimmune diseases.

•    Investigations:

o    Anti-VGCC antibodies (voltage-gated calcium channel).

o    EMG: incremental response with high-frequency stimulation.

•    Treatment:

o    Treat underlying malignancy.

o    3,4-diaminopyridine; immunosuppression.

Myopathies

•    Inflammatory Myopathies:

o    Polymyositis:

    Symmetrical proximal weakness.

    No skin involvement.

    ↑ CK, EMG changes, muscle biopsy: endomysial inflammation.

o    Dermatomyositis:

    Similar weakness + skin changes:

    Heliotrope rash (eyelids), Gottron’s papules (knuckles), V-sign/shawl sign.

    Malignancy association (ovary, lung, colon, pancreas).

•    Genetic Myopathies:

o    Duchenne Muscular Dystrophy (DMD):

    X-linked, onset ~3–5 years, Gowers’ sign, pseudohypertrophy of calves.

    CK very high; dystrophin absent.

o    Becker Muscular Dystrophy:

    Less severe, later onset; some dystrophin present.

o    Myotonic dystrophy (type 1):

    Autosomal dominant, CTG expansion.

    Features: myotonia (delayed relaxation), frontal balding, cataracts, diabetes, cardiac conduction defects.

•    Toxic and metabolic myopathies:

o    Statin-induced: myalgia, CK ↑.

o    Steroid-induced: proximal weakness, often painless.

Mitochondrial Myopathy

•    Features:

o    Maternal inheritance (mitochondrial DNA).

o    Ophthalmoplegia, ptosis.

o    Proximal weakness, exercise intolerance, lactic acidosis.

•    Examples:

o    MELAS: mitochondrial encephalopathy, lactic acidosis, stroke-like episodes.

o    Kearns–Sayre: external ophthalmoplegia, retinopathy, heart block.

Extra Revision Pearls

•    MG: "Ice pack test" can temporarily improve ptosis (cooling improves neuromuscular transmission).

•    LEMS: Reflexes may increase transiently after repeated contractions ("post-exercise facilitation").

•    Dermatomyositis: Always screen for occult malignancy (CT chest, abdomen, pelvis; tumour markers).

•    Statins: CK monitoring before and during treatment if symptomatic.

•    Myotonic dystrophy: Systemic involvement → multisystem disease, important for preoperative risk.