NEUROMUSCULAR AND PERIPHERAL NERVE DISORDERS

Steven Arkin M.D. St. Lukes Hospital Kansas City, MO

Case 1: 72 year old diabetic woman

2 years progressive numbness and tingling in the feet Occasional sharp foot pain, especially at night Staggers frequently Mild weakness, sometimes trips on rugs Insulin requiring for 10 years slowed nerve conductions with low amplitudes

Peripheral Neuropathy

Weakness or sensory loss or both based on nerve injury Generally distal symptoms, legs before arms, but there are exceptions Mostly symmetrical but can be asymmetric or focal Small fiber - diminished pain/temperature, preserved strength, reflexes Large fiber - loss position, vibration touch/pressure, areflexia

Axonal Neuropathy

Metabolic changes within the axon Failure of axonal transport leads to distal nerve degeneration Degeneration than proceeds proximally at a slow pace - dying back Reversing the inciting event leads to regeneration Insidious onset, slow recovery Stocking glove sensory and motor loss

Demyelinating Neuropathy

Primary destruction of the myelin sheath

Axons remain intact throughout or degenerate later Muscle generally does not denervate Faster onset/recovery than axonal Mild sensory loss with prominent muscle weakness which can start proximally Absent reflexes, slowed conduction, elevated CSF protein

Neuropathy - Etiology

Toxic - Drugs and Environmental Toxins Metabolic - Diabetes, Uremia, Endocrine, Porphyria Deficiencies - Thiamine, B6, B12 Infection - HIV Immunologic - Guillain Barre, Chronic inflammatory Collagen vascular Hereditary - Charcot Marie Tooth Monoclonal Gammopathy Neoplastic - direct infiltration or paraneoplastic disorder

Diabetic Neuropathy

Large fiber - proprioception, vibration and light touch Small fiber - impaired pain/temperature Autonomic - cardiovascular and GI (gastroparesis) Most commonly presents with slow onset numbness and tingling then pain in distal extremities, feet before hands Absent reflexes early, distal weakness later Cranial nerve dysfunction, especially extraocular, pupil sparing Focal entrapments or ischemic neuropathies Amyotrophy - asymmetrical proximal leg weakness and pain

Case 2: 24 year old man

4 weeks progressive weakness both legs Hands and feet ache early in the course No bowel or bladder symptoms Preceded by mild respiratory illness Exam: prominent leg and mild hand weakness, no reflexes Lumbar puncture: elevated protein, 3 white blood cells Respiratory: Forced vital capacity 2 Liters

Guillain Barre Syndrome - 1

Weakness, areflexia, usually preceded by distal paresthesia 67% have previous URI or GI infection Impaired breathing, requiring intubation in 25-50% Autonomic dysfunction may be prominent - blood pressure lability and bradycardia or tachycardia Cranial nerve abnormalities - facial diparesis, ophthalmoparesis in 10%

Guillain Barre Syndrome - 2

Diagnosis - clinical history/exam, CSF and EMG Elevated spinal fluid protein without increased white count Conduction slowing or block on EMG Treat acutely - plasma exchange or IV immunoglobulin 5% mortality, 10% severe residual Poor prognosis - advanced age, early intubation Limit complications - DVT prophylaxis, cardiopulmonary monitoring, early physical therapy Miller - Fisher variant - ophthalmoparesis, ataxia, areflexia

Chronic Inflammatory Demyelinating Polyneuropathy

Sensory and motor deficits, evolving > 8 weeks Rarely involves cranial nerves Follows infection in only 30% Progressive (66%) or stepwise/progressive (34%) Increased spinal fluid protein, slowed conduction velocities Treat - steroids, plasma exchange, IV Immunoglobulin

Toxic Neuropathies

Antimicrobials - Metronidazole, Nitrofurantoin, ddI, ddC Chemotherapy - Cis-Platinum, Vincristine, Taxol Other drugs - Phenytoin, Disulfiram, Dapsone Environmental - Hexane, thallium, lead, arsenic Alcohol - partly due to nutritional deficiency (thiamine)

Neuropathy Treatment - 1

Immune modulation - Steroids - vasculitic, chronic inflammatory - Azathioprine - steroid sparing, allow > 3 months to work - Methotrexate - weekly oral dosing - Plasma exchange - Guillain Barre, 3-5 days - Intravenous Immunoglobulin - for neuropathies associated with IgM or IgG proteins, Guillain Barre, chronic inflammatory; 0.4 gm/kg/d x 5 days

Neuropathy Treatment - 2

Symptomatic for pain - Antidepressants - tricyclics, serotonin reuptake inhibitors - Anticonvulsants - Phenytoin, carbamazepine, gabapentin - Others - mexilitine, capsaicin, some low dose neuroleptics

HIV - Associated Neuropathy

Early onset - Acute inflammatory demyelinating neuropathy - CSF protein elevation WITH increased white cells and seropositivity Late onset - Chronic inflammatory demyelinating neuropathy - CMV polyradiculoneuropathy - multiple mononeuropathies with cranial nerves involved - chronic distal sensory polyneuropathy

Neuropathy Workup

Routine evaluation yields diagnosis in 50% of cases - BUN/Cr, glucose, B12, thyroid, immunofixation, ESR Of the rest: - 42% - Inherited - 21% - Chronic inflammatory demyelinating - 13% - DM, toxic, paraneoplastic, dysproteinemia - 24% - still idiopathic

Case 3: 34 year old man

2 years numbness in both hands Numbness increased while preparing PowerPoint slides Pain/tingling awaken him at night Shaking the hands relieves the symptoms No proximal complaints, legs normal Exam: weak thumb abduction, positive Tinels at wrist, Phalens sign

Carpal Tunnel Syndrome - 1

Entrapment of median nerve at the wrist Numbness, tingling, burning in hands and fingers Pain in anterior wrist - might radiate into anterior forearm Pain/paresthesias prominent at night, relieved by shaking Weakness in thenar muscle group with atrophy late Tinels - tapping wrist elicits symptoms Phalens - forced flexion of wrist reproduces symptoms

Carpal Tunnel Syndrome - 2

Bilateral in 40% Associated with the following - frequent overuse of the wrist or direct injury - diabetes - pregnancy - myxedema - rheumatoid arthritis and other collagen vascular disease Diagnosis - clinical, slow nerve conduction across wrist Treat - underlying cause, splint, injection, surgery

Other Common Entrapment Neuropathies

Ulnar - elbow (cubital tunnel) or wrist Radial - wrist drop (Saturday night palsy) Femoral - hip Lateral femoral cutaneous - meralgia paresthetica Peroneal - foot drop - knee at fibular head Tibial - ankle (tarsal tunnel)

Case 4: 57 year old woman

Awoke with right facial weakness - unable to smile properly or close her right eye Pain behind the right ear Decreased sensation right side of face with sense of swelling Exam: unable to close right eye, loss of nasolabial fold on the right, normal taste, intact corneal reflex

Bells Palsy -1

Lower AND upper facial weakness Weakness severe in 67% Progression to plateau of weakness in days to 2 weeks Rarely bilateral Dysesthesias on the same side of the face as weakness Other symptoms - taste abnormal (25%), abnormal tearing (10%), hyperacusis

Bells Palsy - 2

Preceding viral illness in 60% Possible association with herpes virus Untreated, 80-85% recover completely Treat - prednisone 1mg/kg/d for 5-10 days, then quickly taper - with or without Acyclovir 2000mg/d for 5 days Exclude other causes - Lyme, neoplasm, sarcoid, TB, syphilis

Case 5: 38 year old man

6 months progressive weakness in the right leg Twitching in upper and lower extremities Occasional cramps in the right calf No sensory or bladder symptoms Starting to choke on solid food Exam: Isolated right leg weakness, widespread fasciculations, hyperactive reflexes, extensor plantar responses

Amyotrophic Lateral Sclerosis - 1

Onset generally asymmetric weakness Lower motor neuron - weakness, atrophy, fasciculations Upper motor neuron - hyperreflexia, Babinski Bulbar dysfunction - facial weakness, dysarthria, dyphagia, spastic dysphonia pseudobulbar affect - excess or inappropriate crying/laughing Rarely presents with diaphragmatic weakness Preserved mentation, sensation, bowel/bladder function

Amyotrophic Lateral Sclerosis - 2

Survival 3-5 years Incidence 1-3/100,000 Familial in 5-10% Symptomatic treatment - cramping, dysphagia, respiratory compromise Treat - Riluzole - decreases glutamate release - slows progression

Case 6: 71 year old man

3 months intermittent unilateral ptosis and diplopia 8 weeks intermittent dysphagia for liquids, especially with the evening cocktail Exam reveals proximal leg more than arm weakness Normal sensation and reflexes Decremental response to repetitive nerve stimulation Positive edrophonium test using ptosis as objective finding Acetylcholine receptor antibody positive

Myasthenia Gravis - 1

Autoimmune dysfunction of nicotinic acetylcholine receptor at postsynaptic region of neuromuscular junction Fluctuating weakness of VOLUNTARY muscles Most commonly begins with ocular dysfunction ptosis/diplopia Also neck weakness, then proximal legs/arms Bulbar/respiratory generally later Remains solely ocular in 16% If to proceed to generalized, 87% occur in 1st year

Myasthenia Gravis - 2

Thymic hyperplasia in 65% , thymoma in 15% Diagnostic testing: - Edrophonium (tensilon) test - corrects objective deficit - Repetitive nerve stimulation - decremental response - Acetylcholine receptor antibody - positive in 85-90%, more likely if generalized weakness - CT chest - screen for thymoma - antistriatal muscle antibody - positive with thymoma

Myasthenia Gravis - 3

Treatment - Acetylcholinesterase inhibitor - pyridostigmine - Alternate day prednisone - may initially worsen - Thymectomy - best response for remission in young woman with hyperplasia - Plasma exchange - for crisis and pre-op thymectomy - IV Immunoglobulin - alternative to plasma exchange - Azathioprine - steroid sparing, allow 3 months for effect Avoid aminoglycosides, quinine, quinidine, procainamide

Lambert-Eaton Syndrome

Weakness improves with effort Autonomic dysfunction Defective presynaptic release of acetylcholine at neuromuscular junction Associated with malignancy - especially oat cell lung Dx - EMG shows facilitated (incremental) response to repetitive nerve stimulation Treat - underlying malignancy - immunosuppression - 3,4 - diaminopyridine increases acetylcholine release