Neuromuscular Disorders

Authors: Flaherty, Alice W.; Rost, Natalia S.

Title: Massachusetts General Hospital Handbook of Neurology, The, 2nd Edition

Copyright 2007 Lippincott Williams & Wilkins

> Table of Contents > Adult Neurology > Neuromuscular Disorders

Neuromuscular Disorders

A. See also

Neuromuscular Disorders; Weakness, p. 129.

B. Presenting clinical features

Table 20. Presenting features of neuromuscular diseases.

	Ant. Horn Cell	Neuropathy	NMJ dz	Myopathy
Weakness	Asymmetric	Symmetric, distal	Eyes, face, proximal	Symmetrical, limb > face
Atrophy	Marked, early	Moderate	None	Slight early, marked late
Sensory loss	None	Yes	None	None
Classic features	Fasciculations, cramps, tremor	Sensory and motor	Diurnal fluctuation	Weakness, sometimes pain
Reflexes	Increased or decreased	Lost early	Normal	Decreased if severe weakness

C. Abnormal muscle activity

• 1. Clonus: Repetitive unidirectional contraction of a muscle group.

• 2. Fasciculations: Random twitching of a muscle fiber group.

• 3. Fibrillations: Random single-fiber twitching.

• 4. Myotonia: Delayed muscle relaxation, often triggered by percussion. Worse in cold, improves with exercise.

• 5. Myokymia: Repetitive, undulating fasciculations.

D. Pulmonary function in neuromuscular dz

Characterized by decreased vital capacity (VC), hypercarbia. A bedside test of VC is to have the pt count aloud while maximally exhaling: normal >40. Consider intubating if <20, or for VC <18 mg/kg. Oxygen saturation monitors are not adequate tests, as desaturation may only occur late. For Pulmonary function test findings, see p. 219.

E. Amyotrophic lateral sclerosis (ALS)

• 1. H&P: Weakness without cognitive, sensory, or ANS dysfunction. Combination of upper and lower motor neuron signs. Often asymmetric onset, hand atrophy, foot drop, leg spasticity, bulbar sx, fasciculations, cramps. Ask about family history.

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• 2. DDx: CIDP, other motor system atrophies (dystrophies, spinal muscular atrophy), cervical spinal cord injury, syringomyelia, MS, myasthenia, paraneoplastic syndrome, multifocal motor neuropathy with conduction block, heavy metal poisoning, HIV, HTLV, Lyme, diabetic amyotrophy, postpolio syndrome .

• 3. Tests:

  • a. Consider peripheral neuropathy workup: see p. 93.

  • b. EMG: Much denervation and reinnervation (fasciculations, fibrillations, polyphasic increase in amplitude of motor units, normal conduction speed).

  • c. Biopsy: Usually not indicated. Shows neurogenic atrophy.

• 4. Rx:

  • a. Riluzole (Rilutek): 50 mg PO bid. Slightly slows progression.

  • b. Supportive: E.g., splints, G-tube, ventilator, antispasmodics, control saliva .

F. Botulism

Preformed toxin blocks acetylcholine (ACh) release from NMJ. Infantile form from infection (honey).

• 1. H&P: Bradycardia, ocular, bulbar, respiratory, and somatic paralysis with intact thought and sensation. For EMG findings, see p. 41.

• 2. Treatment: Supportive, antitoxin. Slowly improves over weeks.

G. Lambert-Eaton myasthenic syndrome

Blockage of presynaptic ACh release by antibodies to a voltage-gated calcium channel. 90% of pts. have detectable Ab, 50% have an underlying cancer (small-cell lung, transitional cell).

• 1. H&P: Unlike myasthenia, often begins with proximal limb rather than cranial nerve weakness, and may transiently improve rather than worsen weakness. Respiratory muscles not usually affected. Significant ANS sx.

• 2. Tests: Similar to myasthenia, *below, plus workup for occult cancer.

• 3. Rx: Treat underlying cancer. 3,4-Diaminopyridine (DAP) 5-25 mg bid or qid, steroids, azathioprine. PEx or IVIg for intractable dz. Pyridostigmine is not as effective as it is in myasthenia. Avoid drugs that affect the neuromuscular junction (see p. 82).

H. Myasthenia gravis

Most caused by antibodies to the acetylcholine receptor (measurable in 85% of pts.). Half of seronegative cases have muscle-specific kinase (MuSK) Ab. 10% of pts have a thymoma. Rarely congenital.

• 1. H&P: Ask if sx worse at end of day or after repeated use, diplopia, dyspnea, recent infection, or med change. Check vital capacity (see pulmonary function in neuromuscular dz, p. 80), sustained eye elevation, neck strength, repeated standing. Ice pack on eyelid may improve myasthenic ptosis. Pt. should have normal pupils, sensory, and reflex exam (but reflexes may be depressed if limbs are very weak).

• 2. DDx: Guillain-Barr syndrome, CIDP, botulism, motor neuron dz, organophosphate poisoning, myopathy, muscular dystrophy, thyroid dz.

• 3. Tests: Edrophonium test (if pt currently symptomatic), ACh receptor Ab, MuSK Ab, EMG with 3-Hz repetitive stimulation and single-fiber studies (see p. 41), chest CT for thymoma, electrolytes, Ca/Phos/Mg, CPK, ANA, RF, TSH, antithyroid Ab.

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  • a. Edrophonium test (Tensilon test): A short-acting cholinesterase inhibitor. 1-2 mg IV. If no change, give additional 8 mg (i.e., total 10 mg). Need double-blind, placebo control. Do not perform if pupils miotic (suggests cholinergic crisis). Perform with a cardiac monitor if the pt is elderly. Have atropine ready for bradycardia.

• 4. Myasthenic crisis and cholinergic crisis: Both present with weakness. Both are emergencies because of the danger of respiratory collapse. May have both at once.

  Table 21. Distinguishing myasthenic and cholinergic crises.

  	Myasthenic Crisis	Cholinergic Crisis
  Heart rate	Tachycardic	Bradycardic
  Muscles	Flaccid	Flaccid, + fasciculations
  Pupil	Normal or large	Small
  Skin	Pale, sometimes cool	Red, warm
  Secretions	No change	Increased
  Edrophonium test	Improves strength	Increases weakness

  • a. Tests: Bedside vital capacity, cardiac monitor.

  • b. Rx of myasthenic crisis:

    • 1) Cholinergics: Prostigmine 0.5 mg IV push, then pyridostigmine 24 mg in 500 mL D5 1/2 NS.

    • 2) Respiratory support: Admit to ICU, monitor vital capacity, intubate if it is <15-18 mL/kg or if aspiration risk. Remember that O₂ saturation is not sensitive; pt will become hypercarbic before becoming hypoxic.

    • 3) Remove precipitants: Drugs, infection, heat.

    • 4) Plasmapheresis: ~6 in 2 wk.

    • 5) Steroids: Consider methylprednisolone 60 mg IV qd. Steroids may acutely worsen weakness; monitor closely.

  • c. Rx of cholinergic crisis: Similar to myasthenic crisis since pyridostigmine overdose is usually a response to worsening myasthenia.

    • 1) Atropine: 2 mg IV for nonmuscle effects.

    • 2) Ipratropium inhaler: For bronchospasm.

• 5. Outpatient rx of myasthenia:

  • a. Pyridostigmine (Mestinon): Start 30-60 mg q4-6h. SEs: diarrhea, urinary frequency, bradycardia, cholinergic crisis.

  • b. Prednisone: Pt may worsen for first few weeks. Start 10 mg qd as outpt, or admit for more aggressive load. Increase slowly.

  • c. Azathioprine: Start 50 mg q AM; increase to 150 mg q AM over 3 wk. Takes months to affect symptoms. Monitor LFTs/CBC weekly 2 months, then monthly.

  • d. Thymectomy: In young pts, or if thymoma. Works better if done early.

  • e. Other: Cyclophosphamide, cyclosporine, tacrolimus, mycophenolate.

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• 6. Drugs to avoid in myasthenia and Eaton-Lambert syndrome:

  • a. Anticholinergics.

  • b. Cardiovascular: Beta-blockers, antiarrhythmics (these can sometimes cause transient drug-induced myasthenia).

  • c. Antibiotic: Gentamicin, tetracycline, clindamycin (penicillin and erythromycin are better).

  • d. Neurological: DPH, lithium, neuroleptics, muscle relaxants .

  • e. Antimalarial: Chloroquine.

I. Myopathy

• 1. H&P: Swallowing, diplopia, symmetry of weakness, proximal vs. distal, difficulty with stairs or reaching overhead, tripping, myalgia, myotonia (cannot release grip), Gower's maneuver, rash (violet lids, subungual telangiectasias), edema. Bowel, bladder should be normal.

• 2. DDx: Muscular dystrophy, myasthenia, MS, metabolic, infection (HIV, syphilis, TB, parasites), drugs (steroids, HAART), lupus, sarcoid, amyloidosis, cord lesion, ischemia, polymyalgia rheumatica, diabetic amyotrophy, Beh et's, rhabdomyolysis, glycogen storage dz .

• 3. Tests: CPK, EMG, ESR, ANA, TSH, MCV, muscle biopsy.

• 4. Types:

  • a. Inflammatory (myositis): Myalgias, CPK moderately high.

    • 1) Dermatomyositis: Associated with carcinoma in 20%, butterfly rash, Jo-1 Ab. Rx:

      • a) Steroids: Prednisone 60-100 mg qd until improvement, then 40 qd several months. If pt is already on steroids, try tapering them because it may be steroid myopathy.

      • b) Immunosuppression: Follow WBC, LFTs q week, then q month.

      • c) Azathioprine: Effects take months. Start 50 qd 1 wk, then 100 qd 1 wk, then 150 qd.

      • d) Methotrexate: 0.4 mg/kg/treatment IV at first treatment, increasing to 0.8 mg/kg in 3 weeks. Dose weekly at first, then every 2-3 wk.

    • 2) Inclusion body myositis: Most common myopathy in age >50. Quads and deep flexors affected early. No response to rx.

    • 3) Overlap syndromes: With collagen vascular diseases (e.g., MCTD, SLE).

  • b. Polymyositis: Less common, less pain.

  • c. Dystrophies: Hereditary disturbance of structural protein, extremely high CK. Dystrophin deficiency (Duchenne's, Becker's), limb-girdle muscular dystrophies (LGMD), congenital dystrophies .

  • d. Myotonic dystrophies: Classic dive-bomber EMG, multisystem abnormalities. Most common dystrophy in adults, three types, all AD inheritance, triplet repeat expansion.

  • e. Channelopathies: Range from myotonia to periodic paralyses. Na, Cl, Ca, and K channel abnormalities. Hyper-and hypokalemic periodic paralysis, paramyotonia congenital .

  • f. Metabolic: Thyroid, carbohydrate, and lipid metabolism deficiencies .

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