Wernicke encephalopathy

DEFINATION

Wernicke's syndrome, also known as Wernicke encephalopathy, is a neurological disease

characterized by the clinical triad of confusion, the inability to coordinate voluntary movement
(ataxia), and eye (ocular) abnormalities

Etiology
Thiamine plays a vital role in the metabolism of carbohydrates. Thiamine is a cofactor for
several essential enzymes in the Krebs cycle and the pentose phosphate pathway, including
alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and transketolase.[6] In the
setting of thiamine deficiency, thiamine-dependent cellular systems begin to fail, resulting
eventually in cell death. Because thiamine-dependent enzymes play an essential role in
cerebral energy utilization, thiamine deficiency may propagate brain tissue injury by inhibiting
metabolism in brain regions with higher metabolic demands and high thiamine turnover
Pyruvate dehydrogenase and alpha-ketoglutarate are essential enzymes in the Krebs cycle, and
the lack of these enzymes alters cerebral energy utilization. If cells with high metabolic
requirements have inadequate stores of thiamine to draw from, energy production drops, and
neuronal damage ensues. Increased cell death then feeds the localized vasogenic response.
[7] 
Additionally, the reduced production of succinate, which plays a role in gamma-aminobutyric
acid (GABA) metabolism and the electrical stimulation of neurons, leads to further central
nervous system injury.
Increased lactic acid production ensues in the absence of pyruvate dehydrogenase function, as
the reduced conversion of pyruvate to acetyl coenzyme A results in less efficient oxidative
phosphorylation.]
Thiamine pyrophosphate is also essential for nucleotide synthesis, production of nicotinamide
adenine dinucleotide phosphate (NADPH), and maintenance of reduced glutathione within
erythrocytes.

Epidemiology 
 Alcohol-related brain damage may contribute to between 10% and 24% of all cases of
dementia.
 The incidence of the Korsakoff's syndrome has been reported to be rising in recent years.
 Prevalence rates are likely to be higher in areas of socio-economic deprivation and in those
aged 50-60 years.
Symptoms
The classic triad of symptoms found in Wernicke's encephalopathy is:[6]

 ophthalmoplegia (later expanded to other eye movement abnormalities, most commonly

affecting the lateral rectus[6] or any eye sign).
 ataxia (later expanded to imbalance or any cerebellar signs)
 confusion (later expanded to other mental changes. Has 82% incidence in diagnosis cases)

OTHER SYMPTOMS LIKE:

 Vision changes:
 Double vision
 Eye movement abnormalities
 Eyelid drooping
 Loss of muscle co-ordination:
 Unsteady, unco-ordinated walking
 Loss of memory, which can be profound.
 Inability to form new memories.

Signs
The patient is usually mentally alert with vocabulary, comprehension, motor skills, social habits and
naming ability maintained.

 Examination of the nervous system may show polyneuropathy.

 Reflexes may be decreased (or of abnormal intensity), or abnormal reflexes may be present.
 Gait and co-ordination are abnormal on testing.
 Muscles may be weak and may show atrophy.
 Eyes show abnormalities of movement - nystagmus, bilateral lateral rectus palsy and
conjugate gaze palsy.
 Blood pressure and body temperature may be low.
 Pulse may be rapid.
  The person may appear cachectic.

Location of the lesion

Depending of the location of the brain lesion different symptoms are more frequent:

 Brainstem tegmentum. - Ocular: pupillary changes. Extraocular muscle palsy; gaze palsy:
nystagmus.
 Hypothalamus. Medulla: dorsal nuc. of vagus. - Autonomic dysfunct.: temperature;
cardiocirculatory; respiratory.
 Medulla: vestibular region. Cerebellum. - Ataxia.
 Dorsomedial nuc. of thalamus. Mammillary bodies. - Amnestic syndrome for recent memory.

Mamillary lesion are characteristic-small petechial hemorrhages are found.

 Diffuse cerebral dysfunction.- Altered cognition: global confusional state.

 Brainstem: periaqueductal gray.- Reduction of consciousness [36]
 Hypothalamic lesions may also affect the immune system, which is known in alcohol
abusers, causing dysplasias and infections.

Investigations
Diagnosis is based mainly on the history and physical examination, and if the condition is suspected,
treatment should not be delayed whilst waiting for test results.

 FBC, particularly looking at the MCV.

 U&Es (to exclude hypernatraemia, hypercalcaemia, and uraemia).
 LFTs.
 Glucose.
 Blood arterial gases (to rule out hypercarbia and hypoxia).
 Cholesterol.
 Serum thiamine levels (vitamin B1) levels may be low.
 Pyruvate is elevated.
 Red cell transketolase activity is decreased in thiamine deficiency, but not usually necessary
to diagnose the condition.
 Lumbar puncture may be needed to exclude nonfocal CNS infections.
If the history is significant for chronic (long-term) alcohol abuse, serum or urine alcohol levels may
be elevated.

Imaging
CT head scan may be useful in the acute phase, but is less sensitive than MRI. Diffusion-weighted
imaging (an enhanced view based on local water diffusion properties) can improve MRI sensitivity. [8]

Other procedures
Electroencephalography (EEG) may be required to rule out convulsive or non-convulsive status
epilepticus.

Associated diseases
 Peripheral neuropathy.
 Paraesthesia.
 Malnutrition.
 Liver disease.
 Delirium tremens (around 10%).
 Beriberi (about 5%).

Management
 A multidisciplinary service tailored to the needs of individual patients, including the
management of alcohol abuse.
 Assessment and re-assessment of memory and intellectual impairment in the intermediate
term.
 Flexible services ranging from specialised residential home care to domiciliary support
should be available.
 Occupational therapy assessments of daily living and neuropsychological assessments of
current cognitive function can help to determine whether the patient can go home and, if so, the
nature and degree of help and supervision needed.
 The Mental Capacity Act and, on occasions, the Mental Health Act may have to be
considered in the early stages of the syndrome.
General principles
Address the problem of alcohol abuse and diet. Treat as a medical emergency if symptoms are
acute. Patients presenting with altered mental state or pre-coma may need oxygen and intravenous
rehydration. Comatose patients may require intubation to maintain airway patency.

Pharmacological

 Thiamine orally (IM or IV may be used in secondary care) plus vitamin B complex or
multivitamins, which should be given indefinitely. Treatment with thiamine is often started under
specialist care, although when deficiency is suspected, it should be started in primary care.
 Offer oral thiamine to harmful or dependent drinkers if either of the following applies: 
 They are malnourished (or have a poor diet); prescribe oral thiamine 50 mg per day
(as a single dose) for as long as malnutrition may be present.
 They have decompensated liver disease.
 A Cochrane review found there was insufficient evidence from randomised controlled clinical
trials to guide clinicians in the dose, frequency, route or duration of thiamine treatment of WKS
due to alcohol abuse.[10] However, more recent work states that the route of administration and
dose depend on the severity of dependence and overall physical health of the patient. [11]
 Although potentially serious allergic adverse reactions may (rarely) occur during, or shortly
after, parenteral administration, the Commission on Human Medicines has recommended that:
[12]
 
 This should not preclude the use of parenteral thiamine in patients where this route
of administration is required, particularly in patients at risk of WKS where treatment with
thiamine is essential.
 IV administration should be by infusion over 30 minutes.
 Facilities for treating anaphylaxis (including resuscitation facilities) should be
available when parenteral thiamine is administered.

Prevention
 Alcohol avoidance.
 Patients with significant alcohol dependency should be given thiamine supplementation.
 Identifying which patients are at risk is not always easy, but retrospective studies suggest
that homeless patients with inadequate social support are at greatest risk.
  Institution of adequate discharge and follow-up arrangements for such individuals may be as
important as thiamine replacement.

REF: http://patient.info/doctor/wernicke-korsakoff-syndrome

http://www.healthline.com/health/wernicke-korsakoff-syndrome#RiskFactors2

https://en.wikipedia.org/wiki/Wernicke%27s_encephalopathy

http://emedicine.medscape.com/article/794583-treatment