Wernicke-Korsakoff Syndrome: Neurological Effects of Chronic Alcohol Dependence

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Wernicke-Korsakoff Syndrome Neurological Effects
of Chronic Alcohol Dependence

• Patrick J. Macmillan, M.D.
• Assistant Professor
• James H. Quillen College of Medicine
• East Tennessee State University

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HPI

• 62 year old WM, divorced veteran brought to ER by
  his brother after falling Reported to have been
  drinking alcohol History of Etoh abuse per
  chart. brother found him conscious on the floor.
  Has been urinating on self. Patient denies
  drinking since 1984 and reports being brought
  here by taxi. Poor historian unknown if patient
  has history of DTs or Seizures

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The power of denial
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PMH

• COPD (by history)
• HTN
• Alcohol Abuse

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SurgHx

• Fx left clavicle repair

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FH

• Parents Deceased Father MI Mom CA
• Uncle alcoholic

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Psychosocial Hx

• Lived with both parents finished 8th grade
• Receives SSI check
• Hx of Alcohol Abuse 40 years(several detox
  admissions)
• Tobacco 75 pack years
• h/o suicidal acts OD/cut wrists 25 yrs ago
• Worked in Cleveland, OH Ford Motor Company
• Hx of Incarceration 2nd degree murder

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Medications

• Albuterol Inhaler
• Atenolol
• Naproxen
• Methocarbomol

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Allergies

• Quinine

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ROS

• Unable to obtain patient poor historian

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PE

• VS T 99.3, BP 167/90, HR 93, RR 18, O2 92
• GEN A/A/OX1 looks older than stated age
• HEENT NC/AT, Nystagmus, ophthalmoplegia R
  pupilgtL pupil (aniscoria) MMM
• CVS RRR NO M/R/G S1,S2
• ABD RUQ/LUQ pain No organomegaly rectal heme
  negative
• Ext Clubbing No edema or cyanosis

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PE

• Mental Status Patient thinks he is Akron, OH
  says he is 38 y/o knows the President.,
  confabulates
• Neurologic CN III, IV and VI deficit
  hyperreflexic (3 DTR) gait unsteady Romberg

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Labs

• Potassium 3.4 glucose 128 NH3 18 MCV 98.7
  ABG pH 7.49 WBC 11.6Mg 2.3 BAL tive UDS
  tiveRPR tive EKG unremarkable
• CT head tive CXR emphysematous changes

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Diagnosis

• Wernicke Korsikoff Syndrome
• Acute neurologic disorder caused by thiamine
  (Vitamin B1) deficiency
• Oliver Sacks book, The Man Who Mistook His Wife
  for a Hat Sacks pt. in 1975. This patient
  thought he was a young man. This man was stunned
  when he looked in a mirror - and saw a
  middle-aged man looking back!
• Patient thought it was 1945. He had been a sailor
  as a young man in World War II. He had lost his
  ability to build and store new memories, and he
  had lost all the intervening years of experience.
  Sig. H/o of Etoh abuse

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Poor Judgement
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More Poor Judgement
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Historical

• Background In 1881, Carl Wernicke first
  described an illness that consisted of paralysis
  of eye movements, ataxia, and mental confusion in
  3 patients. Wernicke detected punctate
  hemorrhages affecting the gray matter around the
  third and fourth ventricles and aqueduct of
  Sylvius. He felt these to be inflammatory and
  therefore named the disease polioencephalitis
  hemorrhagica superioris

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Historical

• S.S. Korsakoff, a Russian psychiatrist, described
  the disturbance of memory in the course of
  long-term alcoholism in a series of articles from
  1887-1891. He termed this syndrome psychosis
  polyneuritica, believing that these typical
  memory deficits, in conjunction with
  polyneuropathy, represented different facets of
  the same disease. In 1897, Murawieff first
  postulated that a single etiology was responsible
  for both syndromes.

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Introduction

• The term Wernicke encephalopathy is used to
  describe the symptom complex of ophthalmoplegia,
  ataxia, and an acute confusional state. If
  persistent learning and memory deficits are
  present, the symptom complex is termed
  Wernicke-Korsakoff syndrome.
• Wernicke's encephalopathy (WE) is an acute
  syndrome requiring emergent treatment to prevent
  death and neurological morbidity. Korsakoff's
  amnestic syndrome (KS) refers to a chronic
  neurological condition that usually occurs as a
  consequence of WE.

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Epidemiology WE

• 0.8 to 2.8 at autopsy in general population
  (typical brain lesions)
• Majority are alcoholics
• Women more susceptible
• Rate is higher in homeless and psychiatric
  inpatients
• Mortality/Morbidity 10-20 (prognosis depends on
  stage of disease and promptness of Tx)
• Deficiency in alcohol abusers results from a
  combination of inadequate dietary intake, reduced
  gastrointestinal absorption, decreased hepatic
  storage, and impaired utilization.
• Only a subset of thiamine-deficient alcohol
  abusers develop WE. identical twinsgt fraternal
  twins suggests a genetic predisposition

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Pathophysiology

• Thiamine deficiency in alcohol abusers
• Evidence thiamine antagonist pyrithiamine causes
  experimental thiamine deficiency in rats,
  resulting in a sequence of ataxia, loss of the
  righting reflex, and convulsions. low levels of
  magnesium may also play role.
• Inherited or acquired abnormality of
  transketolaseThis enzyme, together with
  transaldolase, provides a link between the
  glycolytic and pentose-phosphate pathways.
  (possibly alters affinity for thiamine)
• Causes for brain lesions unclear but possible
  NMDA receptor excitotoxicity and increased
  reactive oxygen species (free radicals)

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Basic Science Quiz

• Major disease a/w lung cancer?

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BSQ

• Premature death

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BSQ

• What is artificial insemination?

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BSQ

• When the farmer does it to the bull instead of
  the cow

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Pathophysiology

• Thiamine cofactor of several enzymes, including
  Transketolase, alpha ketogluterate dehydrogenase,
  and pyruvate dehydrogenase
• Thiamine plays important role in cerebral energy
  utilization
• Deficiency initiates neuronal injury by
  inhibiting metabolism

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Krebs cycle
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Pentose Phosphate Pathway
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Pathophysiology

• Excitotoxicity may be final pathway
• Extracellular glutamate increases following
  seizure in thiamine deficient rats
• NMDA receptor antagonists reduce neurologic signs
  and severity of extent of lesions

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Pathology

• Lesions in area of Third ventricle, aqueduct and
  fourth ventricle
• Mamillary bodies a/w memory access functions,
  particularly accessing stored knowledge to
  interpret sensory input. When damaged, memory
  loss or amnesia of specific areas of knowledge
  can result.
• Acute WE lesions characterized by vascular
  congestion, microglial proliferation, and
  petechial hemorrhages. In chronic cases, there is
  demyelination, gliosis, with relative
  preservation of neurons.
• Neuronal loss is most prominent in the relatively
  unmyelinated medial thalamus

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Pathology

• Cerebellar pathology is generally restricted to
  the anterior and superior vermis thus, ataxia of
  the legs or arms and dysarthria or scanning
  speech are uncommon.
• Vestibular dysfunction may be the major cause of
  acute gait ataxia in WE.

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Anatomy
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Anatomy
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AnatomyCoronal Section
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BSQ

• How are the main parts of the body categorized?
  (e.g., abdomen).             

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BSQ

• The body is consisted into three parts - the
  brainium, the borax and the abdominal cavity. The
  brainium contains the brain, the borax contains
  the heart and lungs, and the abdominal cavity
  contains the five bowels, A,E,I,O and U.

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BSQ

• Give the meaning of the term "Caesarean
  Section"      

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BSQ

• The Caesarean Section is a district in Rome

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Clinical

• Encephalopathy, Oculomotor dysfunction, gait
  ataxia
• Encephalopathy profound disorientation
• Oculomotor nystagmus (usu horizontal), lateral
  rectus palsey, conjugate gaze palsey (usu. Occur
  in combination)

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Clinical

• Gait Ataxia due to polyneuropathy, cerebellar
  involvement and vestibular peresis
• Stance and gait impairment
• May only be appreciated on tandem gait
• Features of triad only present in 1/3rd of pts in
  one study.

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Clinical

• Confusion is most common presenting symptom
• Malnourishment
• Vestibular dysfunction (w/o hearing loss)
• Peripheral neuropathy
• Korsakoffs amnestic syndrome (80 of WE)
• Confabulation

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Diagnosis

• treatment takes priority over diagnosis, and
  response to treatment may be diagnostic
• There are no laboratory studies that are
  diagnostic of WE
• erythrocyte thiamine transketolase (ETKA)

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Diagnosis

• A serum thiamine or thiamine pyrophosphate level
  in serum or whole blood can also be measured by
  chromatography
• Imaging studies are not necessary in all patients
  with suspected WE and should not delay treatment.

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Diagnosis Imaging

• Abnormalities in CT and MRI have been reported in
  a small numbers of patients with acute WE
• CT may show symmetric, low density abnormalities
  in the diencephalon, midbrain, and
  periventricular regions that enhance after the
  injection of contrast. Gross hemorrhages are
  uncommon in acute WE, but they have also been
  detected by CT. These findings are uncommon in
  other disorders, and when present, should
  strongly suggest the diagnosis. However, CT is an
  insensitive test for WE a normal CT scan does
  not rule out the diagnosis

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Diagnosis Imaging

• MRI more sensitive than CT in detecting acute
  diencephalic and periventricular lesions .
  Typical findings include areas of increased T2
  and decreased T1 signal surrounding the aqueduct
  and third ventricle and within the medial
  thalamus and mamillary bodies. Diffusion-weighted
  imaging (DWI) is abnormal in these areas as well.
  The distribution of these findings is consistent
  with the pathologic lesions.

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MRI Imaging
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Diagnosis Imaging

• Mamillary body (diencephalon)atrophy is a
  relatively specific abnormality in patients with
  chronic lesions of WE.
• Large decrease in the volume of the mamillary
  bodies can be identified by MRI in approximately
  80 percent of alcohol abusers with a history of
  classic WE, and it is not found in controls,
  patients with Alzheimer's disease (AD), or
  alcohol abusers without a history of WE.
• Mamillary body atrophy can be detected within one
  week of the onset of WE

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Treatment

• IV thiamine 100 mg (or IM) for 5 days Banana
  Bag. Telemetry
• DT prophylaxis (Benzo taper)
• REMEMBER never give glucose before thiamine
• Daily oral thiamine (100 mg) following discharge
• Referral for Drug/Alcohol Treatment

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Clinical Course/Prognosis

• Prompt administration of thiamine leads to
  improvement in ocular signs within hours to days
• Confusion subsides over days and weeks. Signal
  abnormality on MRI resolves with clinical
  improvement
• While gaze palsies recovered completely in most
  cases, 60 percent had permanent horizontal
  nystagmus.

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Clinical Course/Prognosis

• 40 percent recovered from ataxia remaining
  deficits ranged from inability to walk at all to
  a wide-based slow shuffling gait.
• As the acute encephalopathy and confusion
  receded, deficits in learning and memory become
  more obvious the latter recovered completely or
  substantively in only about 20 percent the
  remainder had a permanent amnestic syndrome.

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Prevention

• WE may be iatrogenically precipitated by glucose
  loading in patients with unsuspected thiamine
  deficiency.
• standard practice in emergency departments to
  administer thiamine prior to or along with
  glucose infusion.
• The prevention of WE and KS might be possible
  through the widespread oral administration of
  thiamine to outpatients at risk.
• Enrichment of flour with thiamine decreased the
  autopsy prevalence of WE in Australia

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Prevention

• The low cost and safety of oral thiamine argues
  for widespread supplementation in alcohol abusers
  and others at risk for developing thiamine
  deficiency.
• Fortification of alcoholic beverages has also
  been proposed.

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Summary

• WE and Korsakoff's amnesic syndrome (KS) are,
  respectively, acute and chronic brain disorders
  that result from thiamine deficiency.
• WE is most often associated with alcoholism but
  can also occur in other situations including
  malnutrition from any cause (e.g dialysis).
• WE produces hemorrhagic necrosis in midline brain
  structures and corresponding deficits in
  mentation, oculomotor function, and gait ataxia.
  Only one-third of patients present with triad.
  Any one of these, but most often encephalopathy,
  may be seen in isolation. WE should be considered
  when one or more occur.

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Summary

• laboratory measurements and neuroimaging are
  often abnormal in WE, but the first imperative is
  to administer thiamine rather than confirm the
  diagnosis, whenever WE is considered.
• Untreated, WE leads to coma and death. Prognosis
  is improved by prompt administration of thiamine.
  
• WE may be precipitated by administration of
  intravenous glucose solutions to individuals with
  thiamine deficiency.
• Thiamine supplementation, along with other
  multivitamin supplementation, is recommended for
  patients at risk for thiamine deficiency.

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BSQ

• What does the word "benign" mean?      

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BSQ

• Benign is what you will be after you be eight

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Future of Psychiatry
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References

• Up to Date
• http//www.emedicine.com/med/topic2405.html
• http//stilt.genetics.utah.edu/reference/pdf_templ
  ate.php?tplremember_amnesia
• http//spinwarp.ucsd.edu/NeuroWeb/Text/br-800epi.h
  tm
• http//www.people.virginia.edu/rjh9u/krebs.html

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The End

• Any questions/comments??????