The Massachusetts General Hospital Handbook of Neurology
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 > Metabolic, Toxic, and Deficiency Disorders
Metabolic, Toxic, and Deficiency Disorders
A. Metabolic disorders
E.g., electrolyte disorders (see p. 195), glucose disorders (see p. 199), hepatic encephalopathy (see p. 202), thyroid dz (see p. 200), uremic encephalopathy (see p. 214).
B. Drugs
1. Alcohol:
a. Dependence: Consider it especially in pts with depression, unexplained neuropathy, frequent falls, liver abnormalities. Talk to pt and family members separately; assess impact on job, etc.
b. Withdrawal:
Table 14. The CAGE screening questions for alcoholism.
Do you ever think about Cutting down on your drinking? Do you ever feel Angry when people ask about it? Does it make you feel Guilty? Do you ever have an Eye-opener? 1) Hx: Ask time of last drink, h/o withdrawal and nonwithdrawal seizures, detox programs. Focal seizures are rarely alcoholic; does pt have a h/o head injuries?
2) PE: Stage withdrawal severity by tremor, anxiety, level of confusion, pulse, N/V, sweatiness.
3) Tests: Chem 20, CBC, PT, PTT, ammonia, B12.
4) All potentially withdrawing pts should get:
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a) Vitamins: Thiamine 100 mg IM/IV qd, folate, MVI.
b) IV fluids: No glucose until thiamine given. D5 1/2 NS + KCl at 150 cc/h.
c) Replete electrolytes: KCl, Ca/Mg/Phos.
d) GI prophylaxis: Ranitidine or sucralfate. Guaiac stools.
5) Rx of withdrawal seizures:
a) Acute: Diazepam 5-10 mg IV, or lorazepam 1-2 mg if pt. has liver dz or if drug must be given IM.
b) Chronic: ACD prophylaxis does not help unless pt also has seizures from TBI, etc.
6) Rx of acute withdrawal: Sx include ANS instability. Doses based on VS, agitation, sweating, tremor, seizures.
a) Benzo: Diazepam 15 mg q4h 20 mg q15min, OR lorazepam 3 mg q4h 4 mg q15min. Hold for somnolence, RR <12, SBP <100.
b) -blocker or clonidine for altered VS.
c) Consider haloperidol IV/PO: Check EKG for QTc.
d) Taper: When VS and sx are stable for 24 h, then taper over 4-7 d.
7) Withdrawal prophylaxis: For pts with behavioral sx but stable VS. Treat like acute withdrawal but with shorter taper and lower doses. Treat pts with more RFs (e.g., previous DTs, szs, >65 yr) more aggressively.
c. Delirium tremens: Severe withdrawal. 5%-10% mortality. Autonomic instability (tachycardia, HTN, sweating, fever); hallucinations, seizures, tremor.
d. Wernicke's syndrome: see p. 72.
e. Hepatic encephalopathy: see p. 202.
f. Alcoholic cerebellar degeneration: Truncal ataxia evolves over weeks or months. Nystagmus and limb ataxia are rarer. Sagittal CT shows vermis atrophy.
g. Alcoholic neuropathy: Sensory > motor neuropathy, often painful. Vibration sense is lost first.
h. Marchiafava-Bignami dz: Corpus callosum degeneration, associated with red wine consumption. Presents as a frontal lobe dementia.
i. Tobacco-alcohol amblyopia: Bilateral optic neuropathy, may progress to blindness over a few weeks. Treat with B vitamins.
2. Intravenous drugs: Neurological complications of IV use include:
a. Cerebral complications of endocarditis: Abscess, mycotic aneurysm, bacterial meningitis.
b. Neuropathies: Mononeuropathy 2-3 h after injection, various polyneuropathies and Guillain-Barr syndrome.
c. Transverse myelitis: Often with reuse after 1- to 6-mo abstinence; mechanism unclear.
d. Toxic amblyopia: Probably from quinine contamination.
3. Opiates: see p. 156.
4. Stimulants: E.g., cocaine, amphetamines.
a. Direct effects: Agitation, progressing to motor stereotypy, psychosis, seizures, coma, malignant hyperthermia, death.
b. Vascular effects: Cerebral bleeds. Occasionally ischemic stroke in intranasal but not IV users. Small-vessel cerebral vasculitis
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from cocaine; multiorgan necrotizing vasculitis (like polyarteritis nodosa) from amphetamines.c. Exogenous toxins:
1. Carbon monoxide:
a. H&P: Exposure; HA, N/V, confusion cherry red lips, cyanosis, and retinal hemorrhages are rare. Globus pallidus necrosis when severe. Delayed neuropsychiatric sx in 10%-30% that resolve after a year in 50%-75%.
b. Rx: 100% O2. In coma, persistent sx, or pregnancy, consider hyperbaric O2.
2. Heavy metals: Arsenic, lead, mercury, and thallium poisoning produce encephalopathy, neuropathy. Large doses of other metals can cause neuropathy, but usually systemic signs predominate.
a. Tests: 24-h urine analysis; blood lead levels.
b. Rx: For arsenic, lead, or mercury, use penicillamine 250 mg PO qid; for thallium, use diphenylthiocarbazone or sodium dicarbamate.
3. Organophosphates: In pesticides, flame retardants. Inhibit acetylcholinesterase. Depressed levels of RBC indicate recent exposure.
a. Acute effects: Respiratory and neck weakness, up to 2 wk.
b. Delayed effects: May see central-peripheral axonopathy 1-3 wk after exposure, with paresthesias, distal to proximal weakness.
Table 15. Heavy metal toxicity. | |||||||||||||||
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D. Vitamin deficiencies
Table 16. Neurological signs of vitamin deficiency. | ||||||||||||||
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1. Vitamin A: Deficiency causes night blindness and optic atrophy. Excess >50,000 IU qd causes pseudotumor cerebri.
2. Thiamine (B1) deficiency:
a. Wernicke's syndrome:
1) H&P: Most common in alcoholics, poor nutrition, hyperemesis. Onset may be subacute or acute. See ophthalmoplegia (often bilateral 6th palsy, nystagmus), confusion, truncal ataxia, sometimes signs of alcohol withdrawal.
2) Rx: Thiamine 100 mg IM/IV 5 d, then PO. Avoid glucose until the first dose of thiamine is given.
3) Prognosis: Death, if untreated. With rx, ocular abnormalities resolve within hours to days; confusion within days to weeks; ataxia within months. Korsakoff's syndrome: anterograde and retrograde amnesia with prominent confabulation, retained attention and social behavior.
b. Beriberi: Rare in developed countries. See sensorimotor polyneuropathy and cardiomyopathy.
3. Pyridoxine (B6): In adults, both excess (>500 mg qd for several wks) and deficiency cause peripheral neuropathy. Excess causes dorsal root ganglionopathy. Deficiency is usually from isoniazid, hydralazine, or penicillamine. Some infants are genetically pyridoxine dependent and require high doses to prevent seizures.
4. Vitamin B12 deficiency:
a. H&P: Usual presentation is distal paresthesias, then weak, unsteady gait. Sometimes confusion, psychiatric sx, or poor vision is first. Exam shows polyneuropathy, myelopathy, or both. There may be central scotomata, brainstem, or cerebellar signs. H/o GI malabsorption, anemia.
b. Tests: Macrocytic anemia is not always present. B12 levels are usually low, but elevation of metabolites methylmalonic acid and homocysteine are more sensitive. Perform a Schilling test for pernicious anemia if suspicion is high, even if B12 levels are normal.
c. Rx: Oral B12 is as well absorbed as IM, even in pernicious anemia. Oral: 2000 g qd for 1-2 wk, then 1000 g qd for life. IM: 100-1000 g IM qd 2 wk, then 1000 g IM q mo. Do not give folate until B12 has been repleted for 1-2 wk.
5. Vitamin E deficiency: Often from fat malabsorption. See spinocerebellar degeneration, often with peripheral neuropathy, sometimes pigmentary retinopathy, nystagmus, ophthalmoplegia, and proximal weakness.
6. Folate deficiency: In alcoholism, pregnancy, DPH use. Can cause B12-like syndrome but not dementia. In first trimester of pregnancy, causes spina bifida.