Neurotoxicology & Nutritional Deficiencies
Neurotoxicology & Nutritional Deficiencies
What Do You Need to Know?
- Thiamine (B1) deficiency → Wernicke encephalopathy (confusion, ophthalmoplegia, ataxia) — always give thiamine before glucose; mamillary body necrosis is pathognomonic
- B12 deficiency → subacute combined degeneration (posterior columns + lateral corticospinal tracts); elevated methylmalonic acid + homocysteine; nitrous oxide inactivates B12
- B6 excess causes pure sensory neuropathy/ganglionopathy — one of the few vitamins where toxicity (not deficiency) causes neurologic disease
- Copper deficiency mimics B12 deficiency (myelopathy + neuropathy + cytopenias) — check copper in any "B12-like" presentation with normal B12; zinc excess is a common cause
- Lead toxicity: encephalopathy in children, wrist/foot drop in adults, basophilic stippling on blood smear, treat with EDTA/succimer/dimercaprol
- Arsenic: painful sensorimotor neuropathy + Mees lines (transverse white nail lines) + GI symptoms; mercury (organic): Minamata disease with visual field constriction and ataxia
- Manganese toxicity: parkinsonism affecting globus pallidus (not caudate) with T1 hyperintensity on MRI — seen in welders and miners
- Carbon monoxide: bilateral globus pallidus necrosis; delayed neuropsychiatric syndrome days to weeks after exposure
Heavy Metal Toxicity
Overview of Neurotoxic Heavy Metals
| Metal | Source / Exposure | Neurologic Features | Other Key Findings | Treatment |
|---|---|---|---|---|
| Lead | Old paint, contaminated water, batteries, occupational | Children: encephalopathy (irritability, seizures, cerebral edema). Adults: wrist drop (radial nerve), foot drop (peroneal nerve), peripheral neuropathy | Basophilic stippling on blood smear; lead lines on gums (Burton lines); abdominal colic; microcytic anemia; impaired heme synthesis | Succimer (oral, mild); EDTA (moderate-severe); dimercaprol + EDTA (encephalopathy) |
| Arsenic | Pesticides, contaminated groundwater, homicide attempts | Painful sensorimotor neuropathy (axonal, length-dependent); encephalopathy in acute poisoning | Mees lines (transverse white lines on nails); "rain drop" skin pigmentation; GI symptoms (watery diarrhea, garlic breath); QT prolongation | Dimercaprol (acute); succimer (chronic) |
| Mercury (organic) | Contaminated fish (methylmercury), Minamata Bay | Minamata disease: visual field constriction (calcarine cortex), cerebellar ataxia, sensory neuropathy, paresthesias, hearing loss | Constriction of visual fields is characteristic; affects calcarine cortex and granule cell layer of cerebellum; teratogenic | Succimer; selenium supplementation |
| Mercury (inorganic) | Industrial exposure, thermometers, dental amalgam (minimal) | Intention tremor; erethism (psychiatric — irritability, shyness, insomnia); peripheral neuropathy | "Mad Hatter" syndrome (hat-making industry); gingivitis, salivation | Succimer; penicillamine |
| Manganese | Miners, welders, smelters; chronic liver disease (impaired hepatic clearance) | Parkinsonism — affects globus pallidus preferentially (spares caudate/putamen); "cock-walk" gait (strutting on toes); psychiatric symptoms early | T1 hyperintensity in basal ganglia (especially globus pallidus) on MRI; poor response to levodopa (unlike idiopathic PD) | Remove exposure; chelation with EDTA (limited evidence) |
| Thallium | Rodenticides, homicidal poisoning | Painful sensorimotor neuropathy (ascending); encephalopathy | Alopecia (hallmark; 2–3 weeks after exposure); Mees lines (like arsenic); GI symptoms | Prussian blue (potassium ferric hexacyanoferrate); activated charcoal |
| Aluminum | Dialysis patients (contaminated dialysate), antacids | Dialysis dementia: progressive speech difficulty (stuttering/dysarthria), myoclonus, seizures, cognitive decline | Osteomalacia; microcytic anemia; EEG shows generalized slowing with bursts | Deferoxamine; remove aluminum source |
| Bismuth | Pepto-Bismol (bismuth subsalicylate), other bismuth compounds | Myoclonus (prominent); encephalopathy; ataxia; seizures | Reversible with discontinuation; dark discoloration of tongue/stool | Discontinue bismuth-containing products |
Board Pearl
Manganese parkinsonism vs. idiopathic Parkinson disease: Manganese affects the globus pallidus (T1-bright on MRI), not the substantia nigra. It causes a distinctive "cock-walk" gait and does not respond to levodopa. Idiopathic PD affects the substantia nigra pars compacta, causes resting tremor (not action tremor), and responds to levodopa. Look for exposure history (welder, miner) and T1 basal ganglia hyperintensity.
Board Pearl
Mees lines (transverse white bands on nails) are seen in both arsenic and thallium poisoning. To differentiate: thallium causes prominent alopecia (often the most striking finding), while arsenic causes characteristic "rain drop" skin pigmentation. Both cause painful neuropathy. Lead causes Burton lines (blue-black line on gums), not Mees lines.
Organic Solvents & Environmental Toxins
Key Organic and Environmental Neurotoxins
| Toxin | Source / Exposure | Neurologic Features | Key Findings | Treatment |
|---|---|---|---|---|
| Carbon monoxide | Fires, car exhaust, gas heaters, charcoal burning | Acute: headache, confusion, coma, seizures. Delayed neuropsychiatric syndrome (days–weeks later): cognitive decline, parkinsonism, personality changes | Cherry-red skin (classic but unreliable); bilateral globus pallidus necrosis on MRI; carboxyhemoglobin level elevated | 100% O2; hyperbaric oxygen for severe cases (coma, pregnancy, cardiac ischemia) |
| Organophosphates | Pesticides, nerve agents (sarin, VX) | Cholinergic crisis (DUMBELS: Diarrhea, Urination, Miosis, Bradycardia, Emesis, Lacrimation, Salivation). Intermediate syndrome: proximal weakness, respiratory failure (days 1–4). OPIDN: delayed distal neuropathy (weeks later) | Acetylcholinesterase inhibition (irreversible); depressed RBC cholinesterase; fasciculations, muscle cramps | Atropine (muscarinic blockade) + pralidoxime (reactivates AChE if given within 24–48 hours, before "aging") |
| n-Hexane | Glue sniffing, solvents, shoe manufacturing | Sensorimotor peripheral neuropathy (distal → proximal) | Giant axonal swellings on nerve biopsy (accumulation of neurofilaments); metabolite 2,5-hexanedione is the toxic agent | Remove exposure; slow recovery |
| Toluene | Paint thinners, spray paint huffing | Cerebellar ataxia, cognitive decline, dementia, anosmia, hearing loss | White matter changes on MRI; renal tubular acidosis; hypokalemia | Remove exposure; supportive care |
| Methanol | Moonshine, windshield wiper fluid, industrial solvent | Visual loss (optic nerve and retinal toxicity); blindness may be permanent; headache, confusion | Putaminal necrosis (bilateral) on MRI; high-anion-gap metabolic acidosis; formate is the toxic metabolite | Fomepizole (preferred) or ethanol (competitive alcohol dehydrogenase inhibition); dialysis for severe cases |
| Ethylene glycol | Antifreeze | Altered mental status, seizures, cranial neuropathies (especially CN VII) | Calcium oxalate crystals in urine; renal failure; high-anion-gap metabolic acidosis; osmolar gap | Fomepizole or ethanol; dialysis |
Board Pearl
Organophosphate toxicity has three phases: (1) Acute cholinergic crisis (DUMBELS) — treat with atropine + pralidoxime; (2) Intermediate syndrome (1–4 days later) — proximal and respiratory muscle weakness, may need ventilation; (3) OPIDN (organophosphate-induced delayed neuropathy, 2–4 weeks later) — distal axonal neuropathy affecting legs > arms. Pralidoxime must be given early before the AChE-organophosphate complex "ages" (becomes irreversible).
Clinical Pearl
Carbon monoxide poisoning classically causes bilateral globus pallidus necrosis on MRI. The delayed neuropsychiatric syndrome occurs days to weeks after apparent recovery and includes cognitive decline, personality changes, parkinsonism, and incontinence. This delayed syndrome occurs in up to 40% of severely poisoned patients. Hyperbaric oxygen may reduce the risk but evidence is debated.
Drug-Induced Neurotoxicity
Chemotherapy Agents
| Drug | Neurotoxicity | Key Details |
|---|---|---|
| Vincristine | Peripheral neuropathy (dose-limiting toxicity) | Sensorimotor neuropathy (distal → proximal); loss of ankle reflexes earliest sign; autonomic neuropathy (constipation, ileus); avoid in Charcot-Marie-Tooth patients |
| Cisplatin | Sensory neuropathy; ototoxicity | Large-fiber sensory ganglionopathy; high-frequency hearing loss; neuropathy may worsen after stopping treatment ("coasting") |
| Methotrexate | Leukoencephalopathy | Acute (aseptic meningitis with intrathecal use); subacute (stroke-like episodes); chronic (progressive leukoencephalopathy, white matter changes on MRI); risk increased with radiation |
| 5-Fluorouracil (5-FU) | Cerebellar toxicity | Acute cerebellar syndrome (ataxia, dysarthria, nystagmus); usually reversible; risk higher with DPD deficiency |
| Ifosfamide | Encephalopathy | Acute confusion, somnolence, seizures, cerebellar dysfunction; treated with methylene blue |
Antibiotics & Other Medications
| Drug | Neurotoxicity | Key Details |
|---|---|---|
| Aminoglycosides | Ototoxicity; NMJ blockade | Vestibulotoxic (streptomycin, gentamicin) or cochleotoxic (neomycin, amikacin); can unmask or worsen myasthenia gravis; avoid in NMJ disorders |
| Isoniazid (INH) | Peripheral neuropathy (B6-deficiency mediated) | Inhibits pyridoxine (B6) metabolism → neuropathy; prevent with B6 supplementation; overdose causes refractory seizures treated with IV pyridoxine |
| Metronidazole | Neuropathy; cerebellar toxicity | With prolonged use (>4 weeks cumulative); T2/FLAIR hyperintensity in dentate nuclei on MRI; usually reversible with discontinuation |
| Amiodarone | Peripheral neuropathy; optic neuropathy | Sensorimotor neuropathy (demyelinating features); optic disc edema; also causes thyroid dysfunction and pulmonary fibrosis |
| Statins | Myopathy | Myalgia → myopathy → rhabdomyolysis (rare); elevated CK; risk increased with concomitant fibrates or CYP3A4 inhibitors; immune-mediated necrotizing myopathy (anti-HMGCR antibodies) can persist after discontinuation |
| Cyclosporine / Tacrolimus | PRES (posterior reversible encephalopathy syndrome) | Headache, seizures, visual changes, confusion; bilateral parieto-occipital white matter edema on MRI; treat by dose reduction or discontinuation |
| Lithium | Tremor; cerebellar toxicity | Fine postural tremor at therapeutic levels; cerebellar ataxia, nystagmus, and irreversible cerebellar damage with toxicity; narrow therapeutic window; diabetes insipidus |
Antiseizure Medications
| Drug | Neurotoxicity | Key Details |
|---|---|---|
| Phenytoin | Cerebellar atrophy; nystagmus | Chronic use → irreversible cerebellar atrophy (Purkinje cell loss); acute toxicity: nystagmus (first sign), ataxia, confusion; gingival hyperplasia, hirsutism |
| Carbamazepine | Hyponatremia (SIADH); diplopia; ataxia | Dose-dependent diplopia and dizziness; SIADH most common cause of hyponatremia with AEDs; SJS/TEN risk (screen HLA-B*1502 in Southeast Asian patients) |
| Valproate | Tremor; hepatotoxicity; teratogenicity | Postural tremor (most common neurologic side effect); hepatic failure (especially children <2 on polytherapy); neural tube defects (highest teratogenic risk of all AEDs); contraindicated in mitochondrial disease (hepatotoxicity risk); hyperammonemia; weight gain; alopecia |
Board Pearl
Metronidazole cerebellar toxicity is characterized by T2/FLAIR hyperintensity in the dentate nuclei on MRI. This is a classic imaging finding on boards. The toxicity typically occurs with prolonged cumulative use and is usually reversible with drug discontinuation. Other drugs causing cerebellar toxicity include phenytoin (irreversible Purkinje cell loss), lithium, and 5-FU.
Vitamin B1 (Thiamine) Deficiency
Wernicke Encephalopathy
- Classic triad: confusion (encephalopathy), ophthalmoplegia (CN VI palsy most common), and gait ataxia
- The full triad is present in only ~30% of patients — most present with only 1–2 features; a high index of suspicion is essential
- Pathology: hemorrhagic necrosis of mamillary bodies (pathognomonic), periaqueductal gray matter, medial thalami, tectal plate, floor of 4th ventricle
- MRI: T2/FLAIR hyperintensity and diffusion restriction in mamillary bodies, periaqueductal gray, medial thalami
- Causes: alcoholism (most common), malnutrition, hyperemesis gravidarum, bariatric surgery, prolonged TPN without supplementation, refeeding syndrome
Critical Treatment Principle
- ALWAYS give thiamine BEFORE glucose — glucose metabolism requires thiamine (pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, transketolase are all thiamine-dependent)
- Administering glucose without thiamine can precipitate or worsen Wernicke encephalopathy by depleting remaining thiamine stores
- Give IV thiamine 500 mg TID for 3–5 days, then 250 mg daily
Korsakoff Syndrome
- Chronic sequela of untreated/undertreated Wernicke encephalopathy
- Anterograde amnesia (inability to form new memories) > retrograde amnesia
- Confabulation (fabrication of memories without intent to deceive) is characteristic
- Due to damage to mamillary bodies and dorsomedial nucleus of thalamus (part of the Papez circuit)
- Usually irreversible once established; only ~20% recover significantly with treatment
Beriberi
- Dry beriberi: symmetric peripheral neuropathy (distal sensorimotor, length-dependent)
- Wet beriberi: high-output cardiac failure + peripheral edema (due to impaired cardiac energy metabolism)
- Infantile beriberi: seen in breastfed infants of thiamine-deficient mothers; acute cardiac failure and lactic acidosis
Board Pearl
Thiamine before glucose is a cardinal rule in emergency medicine and a board favorite. Glucose metabolism depletes thiamine, and giving dextrose to a malnourished patient without first giving thiamine can precipitate fulminant Wernicke encephalopathy. The classic triad (confusion, ophthalmoplegia, ataxia) is present in only ~30% of cases — any one feature in a malnourished or alcoholic patient should prompt empiric thiamine treatment.
Vitamin B12 (Cobalamin) Deficiency
Subacute Combined Degeneration
- Posterior columns (vibration and proprioception loss, sensory ataxia, positive Romberg) + lateral corticospinal tracts (spasticity, hyperreflexia, Babinski sign) = combined upper and lower motor neuron findings
- The "subacute" onset over weeks to months distinguishes it from acute myelopathies
- MRI: T2 hyperintensity in dorsal columns of spinal cord — "inverted V" sign (or "inverted rabbit ears") on axial imaging
- Also causes: peripheral neuropathy, cognitive decline ("megaloblastic madness"), depression, psychosis
- Megaloblastic anemia (macrocytic) and hypersegmented neutrophils — but neurologic disease can occur without anemia
Causes
- Pernicious anemia (autoimmune destruction of gastric parietal cells → loss of intrinsic factor) — most common cause
- Strict vegan diet (no animal products); malabsorption (celiac disease, Crohn disease, ileal resection)
- Nitrous oxide (N2O) — irreversibly oxidizes cobalt in B12, inactivating it; recreational use ("whippets") or chronic occupational exposure
- Medications: metformin, proton pump inhibitors (long-term)
Laboratory Findings
- Low serum B12 (<200 pg/mL)
- Elevated methylmalonic acid (MMA) — most specific test for B12 deficiency
- Elevated homocysteine — also elevated in folate deficiency (less specific)
- Both MMA and homocysteine elevated = B12 deficiency; homocysteine alone elevated = could be folate deficiency
Clinical Pearl
Nitrous oxide is an increasingly recognized cause of B12 deficiency, especially in young patients presenting with myelopathy. N2O irreversibly oxidizes cobalt in B12, rendering it inactive. Recreational use of "whippets" (N2O canisters) can cause acute subacute combined degeneration even in patients with previously normal B12 stores. Consider this diagnosis in a young patient with progressive myeloneuropathy and check B12, MMA, and homocysteine.
Vitamin B6 (Pyridoxine)
B6 Deficiency
- Neonates/infants: pyridoxine-dependent epilepsy — refractory neonatal seizures that respond to IV pyridoxine; due to ALDH7A1 (antiquitin) gene mutations
- B6 is a cofactor for glutamic acid decarboxylase (GAD), which converts glutamate → GABA; deficiency reduces GABA synthesis → lowered seizure threshold
- Peripheral neuropathy (sensorimotor, length-dependent) with chronic deficiency
- Isoniazid (INH) is the most common drug cause — inhibits pyridoxine metabolism; supplement B6 with INH to prevent neuropathy
- INH overdose → refractory seizures + metabolic acidosis; treated with gram-for-gram IV pyridoxine
B6 Excess (Toxicity)
- Megadose supplementation (>200 mg/day, often in "health food" enthusiasts)
- Causes pure sensory neuropathy/sensory ganglionopathy (dorsal root ganglion involvement)
- Large-fiber modalities affected → sensory ataxia, loss of vibration and proprioception, areflexia
- One of very few vitamins where excess causes neurologic disease
- Usually improves after discontinuation, but recovery may be incomplete
Other Vitamin Deficiencies
Comparison Table
| Vitamin | Deficiency Syndrome | Key Neurologic Features | Board-Yield Points |
|---|---|---|---|
| Vitamin E (alpha-tocopherol) | Spinocerebellar ataxia | Ataxia, loss of proprioception/vibration, areflexia, retinitis pigmentosa — mimics Friedreich ataxia | Fat-soluble vitamin; seen in abetalipoproteinemia (Bassen-Kornzweig), fat malabsorption, cholestatic liver disease; acanthocytes on blood smear |
| Niacin (B3) | Pellagra | 3 Ds: Dermatitis (sun-exposed areas), Diarrhea, Dementia; 4th D = Death if untreated | Seen in alcoholism, carcinoid syndrome (tryptophan diverted to serotonin), Hartnup disease (tryptophan malabsorption), INH use |
| Folate (B9) | Neural tube defects; megaloblastic anemia | Does NOT cause subacute combined degeneration (unlike B12); elevated homocysteine but normal MMA (vs. B12 where both are elevated) | Neural tube defects in pregnancy; supplementation 0.4 mg/day (4 mg/day if prior NTD); megaloblastic anemia identical to B12 |
| Vitamin A (excess) | Pseudotumor cerebri | Idiopathic intracranial hypertension (IIH) — headache, papilledema, visual obscurations, CN VI palsy | Also caused by isotretinoin (Accutane), tetracyclines, excess vitamin A intake; teratogenic (avoid in pregnancy) |
| Vitamin D | Hypocalcemia | Tetany (Chvostek sign, Trousseau sign), paresthesias, seizures, laryngospasm | Seen in renal failure, malabsorption, lack of sun exposure; treat underlying cause + calcium + vitamin D replacement |
Board Pearl
Vitamin E deficiency mimics Friedreich ataxia clinically (spinocerebellar ataxia, posterior column dysfunction, areflexia). The key difference: vitamin E deficiency is treatable and reversible with supplementation, while Friedreich ataxia is a progressive genetic disorder (GAA repeat expansion in FXN gene). Always check vitamin E levels in a patient with a Friedreich-like presentation, especially with fat malabsorption history or acanthocytes on blood smear (abetalipoproteinemia).
Copper Deficiency
Clinical Presentation & Diagnosis
- Mimics B12 deficiency: myelopathy (posterior column + corticospinal tract involvement) + peripheral neuropathy + cytopenias (anemia, neutropenia)
- Can produce an identical picture to subacute combined degeneration with normal B12 levels
- Also causes optic neuropathy (rare)
Causes
- Zinc excess — most important cause; zinc induces metallothionein in enterocytes, which binds copper and prevents absorption
- Denture cream containing zinc — classic board-style vignette (excessive use of zinc-containing denture adhesive)
- Gastric bypass surgery, gastrectomy
- Malabsorption syndromes
- Excessive zinc supplementation
Diagnosis & Management
- Low serum copper and low ceruloplasmin; elevated zinc level (if zinc-induced)
- MRI may show dorsal column T2 hyperintensity (identical to B12 deficiency)
- Check copper levels in any patient with a "B12-like" myeloneuropathy and normal B12
- Treatment: oral copper supplementation (copper gluconate 2–8 mg/day); remove zinc source
Clinical Pearl
Copper deficiency from denture cream is a classic board vignette: an elderly patient with progressive myeloneuropathy, cytopenias, and normal B12 who uses excessive zinc-containing denture adhesive. Zinc induces metallothionein, which sequesters copper in enterocytes and prevents absorption. Always ask about denture cream use and check serum copper/zinc levels in patients with unexplained myeloneuropathy.
Alcohol-Related Neurologic Disease
Spectrum of Alcohol Neurotoxicity
| Condition | Mechanism | Key Features |
|---|---|---|
| Wernicke-Korsakoff | Thiamine (B1) deficiency | See B1 section above; mamillary body necrosis; confusion → ophthalmoplegia → ataxia → amnesia + confabulation |
| Alcoholic cerebellar degeneration | Direct toxicity + nutritional deficiency | Anterior vermis atrophy; predominantly gait ataxia (legs > arms); limb coordination relatively preserved; develops over weeks to months |
| Alcoholic peripheral neuropathy | Direct toxicity + B1/B12 deficiency | Length-dependent, painful, sensorimotor neuropathy; burning feet; distal sensory loss; reduced ankle reflexes |
| Marchiafava-Bignami disease | Corpus callosum demyelination/necrosis | Rare; acute confusion, seizures, interhemispheric disconnection; MRI shows corpus callosum demyelination/necrosis (especially body > genu/splenium) |
| Central pontine myelinolysis (osmotic demyelination) | Rapid correction of hyponatremia | "Locked-in"-like syndrome (quadriplegia, anarthria, preserved consciousness); can also occur extrapontine (basal ganglia, thalami); limit Na correction to ≤8–10 mEq/L per 24 hours |
| Hepatic encephalopathy | Hyperammonemia, portosystemic shunting | Asterixis (negative myoclonus); confusion → coma; T1 hyperintensity in globus pallidus on MRI (manganese deposition from impaired hepatic clearance) |
| Fetal alcohol syndrome | Prenatal alcohol exposure | Smooth philtrum, thin vermilion border, short palpebral fissures; microcephaly; intellectual disability; cardiac defects; most common preventable cause of intellectual disability |
Board Pearl
Osmotic demyelination syndrome (central pontine myelinolysis) results from overly rapid correction of hyponatremia — limit sodium correction to ≤8–10 mEq/L per 24 hours. The classic presentation is a "locked-in"-like state (quadriplegia, anarthria, preserved vertical eye movements and consciousness). It is most common in alcoholics and malnourished patients but can occur in anyone. MRI shows pontine demyelination with sparing of ventrolateral pons and tegmental neurons. If overcorrection occurs, consider re-lowering sodium with DDAVP + D5W.
Quick Reference Table
Neurotoxicology & Nutritional Deficiencies — At a Glance
| Condition | Key Finding / Buzzword | Board-Yield Feature |
|---|---|---|
| Lead toxicity | Basophilic stippling; Burton lines | Wrist drop (adults); encephalopathy (children) |
| Arsenic toxicity | Mees lines; rain-drop pigmentation | Painful neuropathy + GI symptoms |
| Mercury (organic) | Minamata disease; calcarine cortex | Visual field constriction + ataxia |
| Manganese toxicity | T1 hyperintensity in globus pallidus | Parkinsonism (levodopa-unresponsive); cock-walk gait |
| Thallium toxicity | Alopecia; Mees lines | Painful neuropathy; Prussian blue treatment |
| Carbon monoxide | Bilateral GP necrosis on MRI | Delayed neuropsychiatric syndrome |
| Organophosphates | DUMBELS mnemonic | 3 phases: cholinergic → intermediate → OPIDN |
| Methanol | Putaminal necrosis; visual loss | Treat with fomepizole (blocks alcohol dehydrogenase) |
| B1 (thiamine) deficiency | Mamillary body necrosis | Thiamine before glucose; triad present in only 30% |
| B12 deficiency | Inverted V sign on MRI | Elevated MMA + homocysteine; nitrous oxide inactivates B12 |
| B6 excess | Sensory ganglionopathy | Toxicity (not deficiency) causes neuropathy |
| Vitamin E deficiency | Friedreich ataxia mimic | Abetalipoproteinemia; treatable with supplementation |
| Niacin (B3) deficiency | Pellagra (3 Ds + Death) | Dermatitis, Diarrhea, Dementia |
| Copper deficiency | B12 mimic with normal B12 | Zinc excess (denture cream); check copper levels |
| Osmotic demyelination | Pontine myelinolysis | Rapid Na correction; limit ≤8–10 mEq/L per 24 hr |
| Marchiafava-Bignami | Corpus callosum necrosis | Alcoholism; interhemispheric disconnection |
References
- Ropper AH, Samuels MA, Klein JP, Prasad S. Adams and Victor’s Principles of Neurology. 12th ed. McGraw-Hill; 2023.
- Aminoff MJ, Greenberg DA, Simon RP. Clinical Neurology. 11th ed. McGraw-Hill; 2021.
- Dobbs MR. Clinical Neurotoxicology: Syndromes, Substances, Environments. Saunders Elsevier; 2009.
- Kumar N. Nutritional neuropathies. Neurol Clin. 2007;25(1):209–255.
- Kumar N. Copper deficiency myelopathy (human swayback). Mayo Clin Proc. 2006;81(10):1371–1384.
- Sechi G, Serra A. Wernicke’s encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol. 2007;6(5):442–455.
- Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149–160.
- Langan RC, Goodbred AJ. Vitamin B12 deficiency: recognition and management. Am Fam Physician. 2017;96(6):384–389.