Wernicke encephalopathy affects thiamine deficient patients typically with chronic alcoholism who present with the classic triad of confusion, ophthalmoplegia, and ataxia, and demonstrate petechial haemorrhage and necrosis around the mammillary bodies and thalamus, and symmetric enhancement around the third ventricle and aqueduct on MRI.
Description
Wernicke Encephalopathy (WE) is an acute neuropsychiatric syndrome resulting from thiamine (vitamin B1) deficiency, primarily affecting the central nervous system. It is characterized by a classic triad of symptoms: mental confusion, ophthalmoplegia, and ataxia, although all three may not be present in every case. WE is commonly associated with alcohol abuse but can also occur in the context of any condition that leads to severe nutritional deficiency.
Pathogenesis
The pathogenesis of WE involves a deficiency in thiamine, which is critical for carbohydrate metabolism, leading to impaired mitochondrial function and cellular energy production. This deficiency results in cytotoxic oedema and petechial haemorrhages in regions of the brain with high metabolic demands, including the mammillary bodies, thalamus, periaqueductal area, and around the third ventricle.
Epidemiology, Risk Factors & Associations
- Commonly associated with chronic alcoholism.
- Other risk factors include conditions causing thiamine nutritional deficiency, such as hyperemesis gravidarum, malignancy, prolonged fasting, and gastrointestinal diseases affecting nutrient absorption, bariatric surgery, chronic dialysis, starvation/fasting, prolonged total parenteral nutrition without vitamin supplementation, chemotherapy and gastrointestinal malignancy.
- WE can occur at any age but is most prevalent in middle-aged adults.
Clinical Features
Classic triad consists of:
- Confusion and changes in mental status.
- Ophthalmoplegia, particularly affecting lateral rectus muscles, leading to diplopia.
- Ataxia, manifesting as unsteady gait and coordination difficulties.
Complications
- Untreated WE can lead to permanent neurological damage or death.
- Progression to Korsakoff’s psychosis, with profound global amnesia and confabulation.
- Persistent ataxia and oculomotor deficits.
Pathological Features
Histopathology
- Macroscopic: Petechial haemorrhages in the mammillary bodies, periaqueductal gray matter, and thalamus.
- Microscopic: Neuronal loss, gliosis, and punctate haemorrhages within affected regions.
Serology
- Non-specific; may show signs of malnutrition or liver dysfunction.
Biochemistry
- Thiamine levels are low, but direct measurement is rarely performed in clinical practice.
Radiological Features
General Features
- MRI is the preferred imaging modality
- Locations affected:
- Dorsomedial thalamus (85%)
- Periaqueductal area (65%)
- Mamillary bodies (58%)
- Tectal plate (38%)
- Dorsal medulla (8%)
- Cranial nerves
- Cortex
- Atypically, the cerebellum can be affected.
- The brain regions typically affected are near the CSF, where the blood-brain barrier is less tight, requiring higher levels of metabolism to maintain osmotic gradients, making them more susceptible.
MRI
- T2/FLAIR: Symmetric increased signal intensity and contrast enhancement in the mammillary bodies, thalamus, periventricular region of the third ventricle, dorsomedial thalami and around the aqueduct of Sylvius.
Differential Diagnosis
- Other causes of acute confusional states, including encephalitis, meningitis, and toxic-metabolic encephalopathies.
- Central pontine myelinolysis – particularly in rapid correction of hyponatremia.
- Thiamine-responsive encephalopathies other than WE, such as those related to bariatric surgery.
Management
- Immediate administration of high-dose thiamine, preferably intravenously, to prevent progression and potentially reverse symptoms.
- Correction of any underlying nutritional deficiencies and electrolyte imbalances.
- Long-term thiamine supplementation and dietary management, particularly in individuals with chronic alcoholism or at risk of recurrent WE.