Wernicke-Korsakoff syndrome

Definition:

 It is caused by severe thiamine (vitamin B1) deficiency.

 Wernicke encephalopathy: Acute, reversible stage. Will progress to Korsakoff syndrome if
left untreated.
 Korsakoff syndrome: Chronic, irreversible stage.

Pathophysiology:

1. Thiamine metabolism: thiamine absorbed in duodenum  stored in liver

2. Thiamine converted into thiamine pyrophosphate (TPP) by thiamine pyrophosphate
synthetase.
3. TPP is important coenzyme that helps in:
a. Cerebral glucose metabolism
b. Maintain normal amino acid and neurotransmitter level
c. Helps with propagation of neural impulse
4. Thiamine deficiency → decreased cerebral glucose → depleted ATP → injury of neuronal
elements (e.g., myelin sheaths, blood-brain-barrier, decreased neurotransmitters, etc.) →
impaired axonal conduction → symptoms of Wernicke encephalopathy and Korsakoff
syndrome
5. In patients with Korsakoff syndrome: long term thiamine deficiency → permanent damage
to components of the limbic system (e.g., mammillary bodies, anterior thalamic nuclei) →
atrophy of these components → memory loss, apathy, and disrupted emotional processing

Aetiology of thiamine deficiency:

1. Chronic alcoholic (most common cause)

a. Alcohol inhibit conversion of thiamine into its active form (thiamine pyrophosphate)
b. Alcohol decrease gene expression of thiamine transporter-1 at duodenum  lack of
thiamine absorption
c. Chronic alcohol abuse  cirrhosis  interferes with thiamine storage in liver
2. Inadequate intake: anorexia, starvation/fasting, thiamine-deficient diets
3. Malabsorption: Inflammatory bowel disease (Crohn disease), stomach cancer, gastrectomy
4. Increased loss: diarrhea, hyperemesis gravidarum
Clinical features:

Wernicke encephalopathy (acute, reversible):

1. Classic triad: (present in ∼ 30% of patients with Wernicke encephalopathy)

a. Confusion (most common)
b. Oculomotor dysfunction: Due to involvement of the III, IV, VI cranial nerve nuclei
i. Gaze-induced horizontal/vertical nystagmus (most common)
ii. Diplopia (bilateral lateral rectus palsy)
iii. Conjugate gaze palsy (impaired ability of the eyes to move in a single
direction (e.g., horizontal or vertical))
c. Gait ataxia: Due to a combination of peripheral neuropathy, vestibular dysfunction,
and cerebellar dysfunction
2. Autonomic dysfunction: hypotension, syncope
3. Peripheral neuropathy: decreased deep tendon reflexes, paresthesia, foot drop
4. Diencephalic involvement: coma, stupor (in severe case)

Korsakoff syndrome (chronic, irreversible):

 late development in patients with persistent vitamin B1 deficiency

 targets limbic system leading to memory impairment
 CARB mnemonic

1. Confabulation: Patients produce fabricated memories to fill in lapses of memory.

2. Anterograde amnesia: Inability to create new memories
3. Retrograde amnesia: Inability to recall previous memories
4. Behavioural changes (frontal lobe involvement): apathy, indifference, decrease in executive
function

Differential diagnosis:

1. Wernicke encephalopathy (conditions manifest delirium/ataxia)

a. Cerebellar stroke
b. Hypoxia/hypercapnia
c. CNS infection (meningitis)
d. Postictal state
2. Korsakoff syndrome (conditions present with amnesia, dementia)
a. Alzheimer disease
b. Lewy body dementia
c. Normal pressure hydrocephalus
d. Frontotemporal dementia

Diagnostics:

1. Usually a clinical diagnosis.

2. Lab studies: to detect various morbidities in the diagnosis of Wernicke-Korsakoff syndrome
a. FBC: TRO infection, thrombocytosis predisposing to thrombosis and infarction
 b. Serum thiamine levels: decreased
c. Serum lactate and pyruvate: increased
d. LFT: signs of chronic alcoholic (↑ Transaminases, ↑ bilirubin, and ↑ prothrombin
time)
3. Brain MRI findings:
a. periventricular hemorrhage
b. atrophy of mammillary bodies

Management:

1. Wernicke encephalopathy
a. Treatment should be initiated immediately in any patient with a history of chronic
severe alcohol use who presents with new-onset ataxia/confusion/oculomotor
dysfunction.
b. Immediate IV administration of high-dose thiamine (vitamin B1) upon suspicion of
Wernicke encephalopathy until symptoms recede, followed by a lower dose
c. In patients with loss of consciousness, IV glucose must be administered in addition
to IV thiamine and IV naloxone.
 Thiamine must be administered before IV glucose
 If IV glucose administered first before thiamine  glucose will not be
metabolised due to thiamine deficiency  accumulation of glucose 
converted into lactic acid  lactic acidosis  worsening of encephalopathy
d. Cessation of alcohol

2. Korsakoff syndrome
a. Oral thiamine supplementation to prevent further progression to irreversible
complications
b. Psychiatric and psychological therapy
c. Memory strengthening exercises and aids
d. Cessation of alcohol