Wernicke-Korsakoff Syndrome: Neurological Effects of Chronic Alcohol Dependence - PowerPoint PPT Presentation

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Wernicke-Korsakoff Syndrome: Neurological Effects of Chronic Alcohol Dependence
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Wernicke-Korsakoff Syndrome: Neurological Effects of Chronic Alcohol Dependence

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  1. 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

  2. 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 DT’s or Seizures

  3. The power of denial

  4. PMH • COPD (by history) • HTN • Alcohol Abuse

  5. SurgHx • Fx left clavicle repair

  6. FH Parents Deceased: Father: MI; Mom CA Uncle: alcoholic

  7. 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

  8. Medications • Albuterol Inhaler • Atenolol • Naproxen • Methocarbomol

  9. Allergies • Quinine

  10. ROS • Unable to obtain; patient poor historian;

  11. 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 pupil>L 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

  12. 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

  13. Labs • Potassium: 3.4; glucose 128; NH3 18; MCV 98.7; ABG pH 7.49; WBC 11.6;Mg 2.3; BAL –tive; UDS –tive;RPR –tive; EKG unremarkable • CT head –tive; CXR emphysematous changes

  14. 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: Sack’s 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

  15. Poor Judgement

  16. More Poor Judgement

  17. 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

  18. 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.

  19. 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.

  20. 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 twins> fraternal twins suggests a genetic predisposition

  21. 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 transketolase:This 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)

  22. Basic Science Quiz • Major disease a/w lung cancer?

  23. BSQ • Premature death

  24. BSQ • What is artificial insemination?

  25. BSQ • When the farmer does it to the bull instead of the cow

  26. 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

  27. Krebs cycle

  28. Pentose Phosphate Pathway

  29. 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

  30. 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

  31. 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.

  32. Anatomy

  33. Anatomy

  34. Anatomy:Coronal Section

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

  36. 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.

  37. BSQ • Give the meaning of the term "Caesarean Section"

  38. BSQ • The Caesarean Section is a district in Rome

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

  40. 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.

  41. Clinical • Confusion is most common presenting symptom • Malnourishment • Vestibular dysfunction (w/o hearing loss) • Peripheral neuropathy • Korsakoff’s amnestic syndrome (80% of WE) • Confabulation

  42. 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)

  43. 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.

  44. 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

  45. 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.

  46. MRI Imaging

  47. 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

  48. 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

  49. 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.