Neurology · Topic 13 of 22

Metabolic & Toxic Encephalopathy

Neurology · metabolic and toxic encephalopathy

Metabolic & Toxic Encephalopathy

Diffuse brain failure from a systemic cause: give thiamine first, look for a focal cause, then treat the driver — dialysis for uremia, blood pressure control for PRES.

Key numbers

Give IV thiamine before any glucoseThiamine 500 mg IV TID

PRES: lower blood pressure about 25%BP ↓ ~25%

01 · GiveGive IV thiamine before any glucose

Treat suspected Wernicke encephalopathy with IV thiamine before any carbohydrate — commonly 500 mg IV three times daily for 2 days, then 250 mg daily for 5 days.

02 · Defined byPRES: headache, vision loss, seizures, hypertension

PRES presents acutely with headache, visual disturbance, seizures and encephalopathy, usually with a blood pressure surge; MRI (FLAIR) shows symmetric parieto-occipital vasogenic edema.

03 · DoUremic encephalopathy: start dialysis

Neurologic uremic symptoms — confusion, asterixis, myoclonus, seizures — that cannot otherwise be controlled are an indication to start dialysis.

What it is

Core idea

Septic encephalopathy affects about half of ICU sepsisSepsis-associated encephalopathy — acute brain dysfunction from sepsis with no other cause — affects about half or more of septic ICU patients, usually as coma or hypoactive delirium, and independently predicts mortality.

Causes & risk factors

Why it happens

Glucose without thiamine can precipitate WernickeWernicke risk: alcohol use disorder, hyperemesis, starvation, bariatric surgery, dialysis, cancer; a carbohydrate load (IV dextrose, refeeding) can trigger it — give parenteral thiamine to every at-risk admission.

PRES triggers: hypertension, eclampsia, tacrolimus, chemotherapyPRES triggers include severe hypertension, preeclampsia/eclampsia, kidney disease, sepsis, autoimmune disease, immunosuppressants such as tacrolimus, and cytotoxic or antiangiogenic drugs (bevacizumab); about 30% have normal or only mildly raised blood pressure.

Diagnosis & monitoring

Work-up

Wernicke: diagnose clinically with 2 of 4 signsWernicke is a clinical diagnosis — in alcohol use disorder, 2 of 4: dietary deficiency, eye signs, cerebellar signs (ataxia), altered mental state or memory impairment; a normal thiamine level does not exclude it.

Do right now

In this order

First moves

Give IV thiamine before any glucoseThiamine 500 mg IV TID

→

Focal signs or seizures: image the brain

→

Septic encephalopathy: exclude seizures, stroke and drugs

Why each step

Give IV thiamine before any glucoseTreat suspected Wernicke encephalopathy with IV thiamine before any carbohydrate — commonly 500 mg IV three times daily for 2 days, then 250 mg daily for 5 days.

Focal signs or seizures: image the brainMetabolic and toxic encephalopathy is diffuse — fluctuating attention and arousal, reactive pupils, symmetric findings, often asterixis or multifocal myoclonus; focal deficits or seizures demand brain imaging for another cause.

Septic encephalopathy: exclude seizures, stroke and drugsSepsis-associated encephalopathy is a diagnosis of exclusion: seizures or focal signs warrant imaging (MRI finds lesions in over half), and persistent encephalopathy warrants EEG for nonconvulsive seizures; treat the infection.

Management

Orders

PRES: lower blood pressure about 25% must knowTreat PRES by lowering blood pressure about 25% from baseline with a titratable IV agent, avoiding fluctuations, and by removing the trigger (e.g., holding or switching tacrolimus).

Replace magnesium with thiamineMagnesium is a cofactor for thiamine-dependent enzymes — correct hypomagnesemia (e.g., magnesium sulfate 1–2 g IV) alongside thiamine in Wernicke encephalopathy.

Hepatic encephalopathy: lactulose plus rifaximinHepatic encephalopathy (asterixis, confusion in liver disease): find the precipitant — GI bleed, infection, electrolytes — and give lactulose titrated to 2–3 soft stools daily plus rifaximin; do not restrict protein.

Red flags & don'ts

Avoid harm

Untreated Wernicke leads to Korsakoff syndrome complicationUntreated Wernicke encephalopathy carries 10–20% mortality, and about 80% of survivors develop Korsakoff syndrome (amnesia with confabulation); eye signs usually improve within 24 hours of thiamine.

PRES seizures: treat, get EEG, keep magnesium high-normal complicationSeizures occur in about two thirds of PRES and progress to status epilepticus in 3–13% — treat with antiseizure drugs, obtain EEG for nonconvulsive seizures, and keep magnesium in the high-normal range.

Cefepime neurotoxicity in kidney dysfunction complicationCefepime causes encephalopathy, myoclonus and nonconvulsive seizures, mainly with kidney dysfunction (median onset about 4 days); get an EEG and reduce or stop the drug — symptoms usually improve within days.

Valproate: check ammonia even with normal LFTs complicationValproate can cause hyperammonemic encephalopathy even with normal liver tests (risk rises with topiramate) — measure ammonia with unexplained lethargy, vomiting or mental status change.

Wernicke or hepatic encephalopathy?

Commonly confused

Cause	Thiamine deficiency
Hallmark signs	Confusion, eye signs (nystagmus, ophthalmoplegia), ataxia
Typical trigger	Glucose or refeeding without thiamine
Treatment	High-dose IV thiamine before glucose, plus magnesium

More detail

Reference

Show 4 reference facts

Lassitude, fatigue and decreased mental acuity are often the earliest uremic manifestations; twitching, hyperreflexia and seizures appear with more severe CKD (eGFR below 15).

PRES likely reflects blood pressure exceeding the upper limit of cerebral autoregulation (hyperperfusion) or endothelial injury from toxins, causing vasogenic edema; most cases reverse clinically and radiologically.

Wernicke lesions surround the third and fourth ventricles and aqueduct (mamillary bodies, dorsomedial thalamus, periaqueductal gray); MRI supports but does not exclude the diagnosis.

Sepsis survivors often have long-term cognitive, psychiatric and functional impairment after sepsis-associated encephalopathy.

Pearl

In any confused patient who drinks or is malnourished, thiamine goes in before the glucose.

Sources · Merck Manual Professional — Wernicke Encephalopathy (Jun 2025) · Merck Manual Professional — Thiamine Deficiency (Wernicke-Korsakoff regimen) · Galvin R et al. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol 2010;17:1408–1418 · Fischer M, Schmutzhard E. Posterior reversible encephalopathy syndrome. J Neurol 2017;264:1608–1616 · Sonneville R et al. The spectrum of sepsis-associated encephalopathy: a clinical perspective. Crit Care 2023;27:386 · Merck Manual Professional — Overview of Coma and Impaired Consciousness (Jul 2026) · Merck Manual Professional — Chronic Kidney Disease · Merck Manual Professional — Overview of Kidney Replacement Therapy (indications for dialysis) · Merck Manual Professional — Portosystemic (Hepatic) Encephalopathy · Merck Manual Professional — Seizure Disorders (table: causes of seizures, incl. cefepime) · Depakote (divalproex sodium) prescribing information — DailyMed (§5.9–5.10 hyperammonemia) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).