Wernike-Korsakoff syndrome - or Wernicke's encepatholopathy and Korsakoff's syndrome

 

I am now on the General Neurology service which has been very interesting compared to the stroke service. I had a patient with transverse myelitis and another with Wernike-Korsakoff syndrome today! Pretty interesting for my first day!

 

Introduction - Wernicke-Korsakoff syndrome is the best known neurologic complication of thiamine/vitamin B1 deficiency. The term is a combination of two different syndromes, each representing a different stage of the disease. Wernicke's encephalopathy is the acute syndrome which requires emergent treatment (thiamine and glucose) to prevent death and neurologic morbidity. Korsakoff's syndrome refers to a chronic neurologic condition that usually occurs as a consequence of WE.

 

Etiology - Although Wernike-Korsakoff is most often associated with chronic alcoholism, it can also occur in the setting of poor nutrition caused by malabsorption, poor dietary intake, increased metabolic requirement (cancer or systemic illness/inflammation) or increased loss of the water-soluble vitamin thiamine (eg, in renal dialysis). My patient has both a history of chronic ETOH abuse as well as a gastric bypass 8 years ago. Causes of Wernike-Korsakoff are listed below.

 

-Chronic alcoholism

-Anorexia nervosa or dieting

-Hyperemesis of pregnancy

-Prolonged intravenous feeding without proper supplementation

-Prolonged fasting or starvation, or unbalanced nutrition, especially with refeeding

-Gastrointestinal surgery (including bariatric surgery)

-Systemic malignancy

-Transplantation

-Hemodialysis or peritoneal dialysis

-Acquired immunodeficiency syndrome

 

Pathophysiology - It is unclear how thiamine deficiency causes brain lesions. Thiamine is a cofactor for several key enzymes important in energy metabolism such as transketolase, alpha-ketoglutarate dehydrogenase, and pyruvate dehydrogenase (You need to give thiamine before you give glucose in these patients). Because of its role in cerebral energy utilization, it has been proposed that its deficiency initiates neuronal injury by inhibiting metabolism in brain regions with high metabolic requirements and high thiamine turnover. 

 

Pathology - Acute lesions are characterized by vascular congestion, microglial proliferation, and petechial hemorrhages. In chronic cases, there is demyelination and gliosis. You will see neuronal loss most prominently in the unmeylinated areas of the medial thalamus. Necrosis/Atrophy of the mamillary bodies is a highly specific finding in chronic WE and Korsakoff syndrome and is present in up to 80 percent of cases. The lesions of WE occur in a characteristic, symmetrical distribution in structures surrounding the third ventricle, aqueduct, and fourth ventricle.

 

Clinical Manifestations

 

The classic triad of WE is encepthalopathy, gait ataxia and oculomotor dysfunction.

 

- Encepathopathy - characterized by profound disorientation, indifference, and inattentiveness. If these are less severe and permit higher cognitive testing, impaired memory and learning are also evident. My patient was attentive but didn't know where she was exactly and didn't have any insight as to why she was in the hospital. She seemed to think it was about 20 years ago when she still lived with her mom and dad (who had passed 15 years ago).

 

-Oculomotor dysfunction - Nystagmus, lateral rectus palsy, and conjugate gaze palsies reflect lesions of the oculomotor, abducens, and vestibular nuclei. Nystagmus is the most common finding and is typically evoked by horizontal gaze to both sides. My patient had horizontal nystagmus that was evident when she looked both to the right and to the left.

 

-Gait ataxia - When the WE is severe, walking is impossible. Less affected patients walk with a wide-based gait and slow, short-spaced steps. The portion of the cerebellum often affected is the vermis so you will see more truncal ataxia and less ataxia of the arms and the legs.

 

Treatment

 

Immediate parenteral administration of thiamine is the course of treatment in any patient that has suspected WE. A recommended regimen is 500 mg of thiamine intravenously, infused over 30 minutes, three times daily for two consecutive days and 500 mg intravenously or intramuscularly once daily for an additional five days, in combination with other B vitamins. Daily oral administration of 100 mg of thiamine should be continued after the completion of parenteral treatment and after discharge from the hospital until patients are no longer considered at risk. My patient has finished her IV thiamine and is now on 100mg PO daily. She will continue this regimen as an outpatient.