Wernicke's encephalopathy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Wernicke encephalopathy
Thiamine
ICD-10	E51.2
ICD-9	265.1
eMedicine	emerg/642

Overview

Wernicke encephalopathy is a severe syndrome characterised by ataxia, ophthalmoplegia, confusion and loss of short-term memory. It is linked to damage to the medial thalamic nuclei, mammillary bodies, periaqueductal, and periventricular brainstem nuclei , and superior cerebellar vermis. In the brain, it is the result of inadequate intake or absorption of thiamine (Vitamin B) coupled with continued carbohydrate ingestion. The most common cause of an onset is prolonged alcohol consumption that is sufficient enough to cause a thiamine deficiency. Alcoholics are therefore particularly at risk, but it may also occur due to other causes of malnutrition. Other causes of thiamine deficiency may be found in patients with carcinoma, chronic gastritis, or continuous vomiting.

Differentiating Wernicke's encephalopathy from Other Diseases

Wernicke's encephalopathy must be differentiated from other causes of headache, altered mental status and seizures such as brain tumors and delirium trmemns.

Diseases	Diagnostic tests				Physical Examination					Symptoms			Past medical history	Other Findings
	Na+, K+, Ca2+	CT /MRI	CSF Findings	Gold standard test	Neck stiffness	Motor or Sensory deficit	Papilledema	Bulging fontanelle	Cranial nerves	Headache	Fever	Altered mental status
Brain tumour		?	Cancer cells	MRI		?	?	?	?	?		?		Cachexia, gradual progression of symptoms
Delerium Tremens		?		Clinical diagnosis		?	?		?	?	?	?	Alcohal intake, sudden witdrawl or reduction in consumption	Tachycardia, diaphoresis, hypertension, tremors, mydriasis, positional nystagmus, tachypnea
Subarachnoid hemorrhage		?	Xanthochromia	CT scan without contrast	?	?	?	?	?	?	?	?	Trauma/fall	Confusion, dizziness, nausea, vomiting
Stroke		?	Normal	CT scan without contrast		?	?		?	?		?	TIAs, hypertension, diabetes mellitus	Speech difficulty, gait abnormality
Neurosyphilis		?	? Leukocytes and protein	CSF VDRL-specifc CSF FTA-Ab -sensitive	?	?	?	?		?		?	Unprotected sexual intercourse, STIs	Blindness, confusion, depression, Abnormal gait
Viral encephalitis		?	Increased RBCS or xanthochromia, mononuclear lymphocytosis, high protein content, normal glucose	Clinical assesment	?	?	?		?	?	?	?	Tick bite/mosquito bite/ viral prodome for several days	Extreme lethargy, rash hepatosplenomegaly, lymphadenopathy, behavioural changes
Herpes simplex encephalitis		?		Clinical assesment			?	?	?	?	?		History of hypertension	Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy			Normal				?	?			?		History of alcohal abuse	Ophthalmoplegia, confusion
CNS abscess		?	? leukocytes >100,000/ul, ? glucose and ? protien, ? red blood cells, lactic acid >500mg	Contrast enhanced MRI is more sensitive and specific, Histopathological examination of brain tissue	?	?	?		?	?	?	?	History of drug abuse, endocarditis, ? immune status	High grade fever, fatigue,nausea, vomiting
Drug toxicity											?	?		Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder				Diagnosis of exclusion		?		?		?	?	?		Tremors, blindness, difficulty swallowing
Electrolyte disturbance	? or ?			Depends on the cause						?		?		Confusion, seizures
Febrile seizures			Not performed in first simple febrile seizures	Clinical diagnosis and EEG					?	?	?	?	Family history of febrile seizures, viral illness or gastroenteritis	Age > 1 month,
Subdural empyema		?		Clinical assesment and MRI	?	?	?	?	?			?	History of relapses and remissions	Blurry vision, urinary incontinence, fatigue
Hypoglycemia	? or ?			Serum blood glucose HbA1c		?				?		?	History of diabetes	Palpitations, sweating, dizziness, low serum, glucose

Wernicke's encephalopathy must be differentiated from other causes of headache,seizures and loss of consciousness.

Diseases	Symptoms				Physical Examination					Past medical history	Diagnostic tests			Other Findings
	Headache	↓LOC	Motor weakness	Abnormal sensory	Motor Deficit	Sensory deficit	Speech difficulty	Gait abnormality	Cranial nerves		CT /MRI	CSF Findings	Gold standard test
Meningitis	+	-	-	-	-	+	+	-	-	History of fever and malaise	-	↑ Leukocytes, ↑ Protein ↓ Glucose	CSF analysis	Fever, neck rigidity
Encephalitis	+	+	+/-	+/-	-	-	+	+/-	+	History of fever and malaise	+	↑ Leukocytes, ↓ Glucose	CSF PCR	Fever, seizures, focal neurologic abnormalities
Brain tumor	+	-	-	-	+	+	+	-	+	Weight loss, fatigue	+	Cancer cells	MRI	Cachexia, gradual progression of symptoms
Hemorrhagic stroke	+	+	+	+	+	+	+	+	-	Hypertension	+	-	CT scan without contrast	Neck stiffness
Subdural hemorrhage	+	+	+	+	+	-	-	-	+	Trauma, fall	+	Xanthochromia	CT scan without contrast	Confusion, dizziness, nausea, vomiting
Neurosyphilis	+	-	+	+	+	+	-	+	-	STIs	+	↑ Leukocytes and protein	CSF VDRL-specifc CSF FTA-Ab -sensitive	Blindness, confusion, depression, Abnormal gait
Complex or atypical migraine	+	-	+	+	-	-	+	-	-	Family history of migraine	-	-	Clinical assesment	Presence of aura, nausea, vomiting
Hypertensive encephalopathy	+	+	-	-	-	-	+	+	-	Hypertension	+	-	Clinical assesment	Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy	-	+	-	-	-	+	+	+	+	History of alcohal abuse	-	-	Clinical assesment and lab findings	Ophthalmoplegia, confusion
CNS abscess	+	+	-	-	+	+	+	-	-	History of drug abuse, endocarditis, immunosupression	+	↑ leukocytes, ↓ glucose and ↑ protien	MRI is more sensitive and specific	High grade fever, fatigue,nausea, vomiting
Drug toxicity	-	+	-	+	+	+	-	+	-	-	-	-	Drug screen test	Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder	+	+	+	+	+	+	+	+		History of emotional stress	-	-	Diagnosis of exclusion	Tremors, blindness, difficulty swallowing
Metabolic disturbances (electrolyte imbalance, hypoglycemia)	-	+	+	+	+	+	-	-	+	-	-	Hypoglycemia, hypo and hypernatremia, hypo and hyperkalemia	Depends on the cause	Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Multiple sclerosis exacerbation	-	-	+	+	-	+	+	+	+	History of relapses and remissions	+	↑ CSF IgG levels (monoclonal bands)	Clinical assesment and MRI	Blurry vision, urinary incontinence, fatigue
Seizure	+	+	-	-	+	+	-	-	+	Previous history of seizures	-	Mass lesion	Clinical assesment and EEG	Confusion, apathy, irritability,

=Other differentials

Wernicke's encephalopathy must also be differentiated from other diseases that cause personality changes, altered level of consciousness and hand tremors (asterixis). The differentials include the following:

Diseases	History and Symptoms			Physical Examination				Laboratory Findings
	Personality changes	Altered level of consciousness	Hand tremors (asterixis)	Slurred speech	Writing disturbances	Voice monotonous	Impaired memory	Elevated blood ammonia	Hyponatremia	hypokalemia
Hepatic encephalopathy	++	++	++	++	++	++	++	++	++	++
Alcohol intoxication	+	+	-/+	++	+	-	+	-	-/+	-/+
Alcohol withdrawal	+	+	-	++	+	-	+	-	-/+	-/+
Uremia	++	++	+	-/+	-/+	-/+		-	++	Hyperkalemia
Wernicke encephalopathy	+	+	-/+	+	+	+	++	-	-	-
Toxic encephalopathy from drugs	+	+	-/+	-/+	+	-/+	+	+	-/+	-/+
Altered intracranial pressure	+	-/+	-	-/+	-/+	-	-/+	-	-	-
Intoxication by chemical agents	-/+	-/+	-/+	-/+	-/+	-	-	-	-/+	-/+
Malnutrition	-/+	-	-	-	-/+	-	-/+	-	-/+	-/+
Hypoxic brain injury	-	-/+	-	-/+	-/+	-/+	-/+	-	-	-
Meningitis and encephalitis	-/+	-/+	-	-/+	+	-	-	-	-/+	-
Hypoglycemia	-/+	-/+	-	-/+	-/+	-	-	-	-/+	-/+

Diagnosis

Physical Examination

Wernicke encephalopathy onsets acutely, and usually presents with nystagmus, gaze palsies, ophthalmoplegia (especially of the abducens nerve, CN VI), gait ataxia, confusion, and short-term memory loss.

The classic triad for this disease is encephalopathy, ophthalmoplegia, and ataxia. Untreated, this condition may progress to Korsakoff's psychosis or coma. Despite its name, Wernicke's encephalopathy is not related to damage of the speech and language interpretation area named Wernicke's area (see Wernicke's aphasia). Instead the pathological changes in Wernicke's encephalopathy are concentrated in the mammillary bodies, cranial nerve nuclei III, IV, VI and VIII, as well as the thalamus, hypothalamus, periaquiductal grey, cerebellar vermis and the dorsal nucleus of the vagus nerve. The ataxia and ophthalmoparesis relate to lesions in the oculomotor (ie IIIrd, IVth, and VIth nerves) and vestibular (ie VIIIth nerve) nuclei.

Treatment

Medical Therapy

Treatment includes an intravenous (IV) or intramuscular (IM) injection of thiamine, prior to the assessment of other central nervous system (CNS) diseases or other metabolic disturbances. Patients are usually dehydrated, and so rehydration to restore blood volume should be started. If the condition is treated early, recovery may be rapid and complete.

In individuals with sub-clinical thiamine deficiency, a large dose of glucose (either as sweet food etc or glucose infusion), can precipitate the onset of overt encephalopathy. Glucose loading results in metabolic disturbances in the brain that exacerbate the signs and symptoms of encephalopathy, and may trigger cellular processes leading to brain damage. . If the patient is hypoglycemic (common in alcoholism), a thiamin injection should always precede the glucose infusion.

See also

• Karl Wernicke
• ataxia
• Beriberi
• human brain
• thiamine
• Korsakoff's syndrome
• Wernicke-Korsakoff syndrome

External links

• The Merck Manual, Amnesias - Wernicke's encephalopathy