Neurotoxicology & Nutritional Deficiencies

What You'll Learn

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

HighYield Pearls

Thiamine before glucose: in any suspected Wernicke (alcoholic, bariatric, hyperemesis, refeeding), give IV thiamine FIRST — glucose without thiamine precipitates/worsens Wernicke encephalopathy
Wernicke triad: ophthalmoplegia (CN VI, conjugate gaze palsy, nystagmus) + ataxia + confusion; MRI shows mammillary body, medial thalamus & periaqueductal gray hyperintensity; Korsakoff = irreversible amnestic syndrome with confabulation
B12 deficiency = SCD: posterior columns (vibration/proprioception loss) + lateral corticospinal tracts (spasticity, Babinski) ± sensorimotor neuropathy + megaloblastic anemia; ↑ methylmalonic acid AND homocysteine; treat with IM cobalamin
Nitrous oxide (whip-its, dental): oxidizes cobalt → functional B12 deficiency → SCD-like myelopathy + ataxia; check B12, MMA, homocysteine in young patient with myelopathy
B6 (pyridoxine) paradox: deficiency (INH, cycloserine) → seizures + neuropathy; TOXICITY (>200 mg/day from supplements) → pure sensory neuronopathy/ganglionopathy (DRG attack) — one of few vitamins where excess is the danger
Copper deficiency mimics B12 SCD: after gastric bypass or zinc overload (denture cream, supplements); myelopathy + neuropathy + cytopenias with NORMAL B12 — check ceruloplasmin/copper, replace copper, stop zinc
Lead in adults: wrist drop (radial motor neuropathy) + abdominal colic + basophilic stippling + microcytic anemia + Burton gum line; children get encephalopathy + cognitive decline; treat succimer (DMSA) or Ca-EDTA + dimercaprol (BAL) for severe
Manganese parkinsonism: welders, miners, chronic liver disease; T1 hyperintensity in globus pallidus (NOT T2); poor levodopa response, early psychiatric & dystonia — distinguishes from idiopathic PD
Methanol vs ethylene glycol: both cause anion-gap metabolic acidosis; METHANOL → bilateral putaminal necrosis + visual loss (blindness); ETHYLENE GLYCOL → calcium oxalate crystals + AKI; treat both with fomepizole ± dialysis
Organophosphate poisoning: SLUDGE-M cholinergic crisis + miosis + fasciculations; treat ATROPINE + PRALIDOXIME (2-PAM); watch for intermediate syndrome (24–96 hr respiratory/proximal weakness) and OPIDN (delayed neuropathy 1–3 wk)
Carbon monoxide: bilateral globus pallidus necrosis on MRI; delayed neuropsychiatric syndrome (parkinsonism, leukoencephalopathy) days to weeks after recovery; treat ALL suspected CO with 100% normobaric oxygen; reserve hyperbaric oxygen for selected severe/high-risk cases (LOC, neurologic deficits, cardiac ischemia, severe acidosis, very high COHb, or pregnancy per local protocol)

🔍 Quick ReferenceClinical / exposure · Diagnostic / imaging · Treatment / antidote

Clinical / exposure

Ophthalmoplegia + ataxia + confusion in alcoholic / bariatric / hyperemesis → Wernicke encephalopathy (thiamine B1 deficiency)
Amnesia + confabulation, irreversible → Korsakoff syndrome
Posterior column + corticospinal myelopathy + megaloblastic anemia → B12 deficiency / subacute combined degeneration
Whip-it / nitrous oxide / dental assistant with myelopathy → N₂O-induced functional B12 deficiency
Dermatitis + diarrhea + dementia (Casal necklace) → Pellagra (niacin B3 deficiency) — also carcinoid, Hartnup, isoniazid
Sensory ataxia + areflexia + retinitis pigmentosa in fat malabsorption → Vitamin E deficiency / AVED
Wrist drop + abdominal colic + gum lead line in adult → Lead poisoning
Contaminated fish, Minamata Bay, visual field constriction + ataxia → Methylmercury (organic mercury) poisoning
“Mad Hatter” tremor + erethism + gingivitis → Inorganic mercury poisoning
Welder / miner with parkinsonism + “cock-walk” gait → Manganese toxicity
Painful sensorimotor neuropathy + alopecia + Mees lines → Thallium poisoning
Glue / paint sniffing → cerebellar ataxia + cognitive decline → Toluene leukoencephalopathy
Bootleg liquor / windshield fluid → blindness + acidosis → Methanol poisoning
Antifreeze ingestion + anion-gap acidosis + AKI → Ethylene glycol poisoning
Farmer / pesticide exposure with SLUDGE-M + miosis + fasciculations → Organophosphate poisoning
“Chasing the dragon” heroin inhalation → Spongiform leukoencephalopathy
Rave / MDMA + hyperthermia + clonus → Serotonin syndrome / MDMA toxicity
Red wine drinker with corpus callosum demyelination → Marchiafava-Bignami disease
Cassava (konzo) / grass pea (lathyrism) → Tropical spastic paraparesis

Diagnostic / imaging

Mammillary body + medial thalamus + periaqueductal gray T2/FLAIR hyperintensity → Wernicke encephalopathy
↑ Methylmalonic acid AND ↑ homocysteine → B12 deficiency (folate gives high homocysteine with NORMAL MMA)
Posterior + lateral column T2 hyperintensity (“inverted V” sign) → Subacute combined degeneration (B12 or copper)
Bilateral putaminal necrosis + visual loss → Methanol toxicity
Bilateral globus pallidus necrosis → Carbon monoxide poisoning
T1 hyperintensity in globus pallidus (no T2 change) → Manganese deposition (also chronic liver failure)
Basophilic stippling on peripheral smear + microcytic anemia + elevated ZPP → Lead poisoning
Mees lines (transverse white lines on nails) → Arsenic or thallium poisoning
Calcium oxalate crystals in urine + anion-gap acidosis → Ethylene glycol
Red ↑ RBC transketolase activity after thiamine → Thiamine deficiency
Splenium / corpus callosum demyelination in alcoholic → Marchiafava-Bignami
Symmetric central pontine T2 hyperintensity after rapid Na correction → Central pontine myelinolysis (osmotic demyelination)
Giant axonal swellings on nerve biopsy in glue sniffer → n-Hexane neuropathy

Treatment / antidote

IV thiamine 500 mg TID BEFORE any glucose → Wernicke encephalopathy
IM cyanocobalamin 1000 µg weekly ×4 then monthly → B12 deficiency / SCD / N₂O myelopathy
Pyridoxine (B6) supplementation → INH-induced neuropathy / seizures, hydrazine, cycloserine
Stop the supplement (B6 >200 mg/day) → Pyridoxine sensory neuronopathy
Stop zinc + replace copper → Copper deficiency myeloneuropathy
Nicotinamide → Pellagra
Succimer (DMSA, oral) → Mild–moderate lead, arsenic, mercury
Ca-EDTA ± dimercaprol (BAL) → Severe lead encephalopathy
Dimercaprol (BAL) → Acute arsenic, inorganic mercury, severe lead
Penicillamine → Inorganic mercury (also Wilson disease — not in this topic)
Atropine + pralidoxime (2-PAM) → Organophosphate poisoning
Fomepizole (or ethanol) + hemodialysis + folate → Methanol poisoning
Fomepizole + hemodialysis + thiamine/pyridoxine → Ethylene glycol poisoning
100% normobaric oxygen for ALL suspected CO; hyperbaric oxygen (HBO) for SELECTED severe/high-risk cases (LOC, neuro deficits, cardiac ischemia, severe acidosis, very high COHb, pregnancy per protocol) → Carbon monoxide poisoning
Folinic acid (leucovorin) rescue → Methotrexate neurotoxicity
High-dose vitamin E replacement → AVED / abetalipoproteinemia

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