Transcript Wernicke Who?: a look at neurological effects of chronic

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
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
The power of denial
PMH



COPD (by history)
HTN
Alcohol Abuse
SurgHx

Fx left clavicle repair
FH
Parents Deceased: Father: MI; Mom CA
Uncle: alcoholic
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

Medications




Albuterol Inhaler
Atenolol
Naproxen
Methocarbomol
Allergies

Quinine
ROS

Unable to obtain; patient poor historian;
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
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
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
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
Poor Judgement
More Poor Judgement
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
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.
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 WernickeKorsakoff 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.
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

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

Causes for brain lesions unclear but possible NMDA
receptor excitotoxicity and increased reactive oxygen
species (free radicals)
enzyme, together with transaldolase, provides a link
between the glycolytic and pentose-phosphate pathways.
(possibly alters affinity for thiamine)
Basic Science Quiz

Major disease a/w lung cancer?
BSQ

Premature death
BSQ

What is artificial insemination?
BSQ

When the farmer does it to the bull instead
of the cow
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
Krebs cycle
Pentose Phosphate Pathway
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
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
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.
Anatomy
Anatomy
Anatomy:Coronal Section
BSQ

How are the main parts of the body
categorized? (e.g., abdomen).
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.
BSQ

Give the meaning of the term
"Caesarean Section"
BSQ

The Caesarean Section is a district in
Rome
Clinical



Encephalopathy, Oculomotor dysfunction,
gait ataxia
Encephalopathy: profound disorientation
Oculomotor: nystagmus (usu horizontal),
lateral rectus palsey, conjugate gaze palsey
(usu. Occur in combination)
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.
Clinical






Confusion is most common presenting
symptom
Malnourishment
Vestibular dysfunction (w/o hearing loss)
Peripheral neuropathy
Korsakoff’s amnestic syndrome (80% of
WE)
Confabulation
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)
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.
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
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.
MRI Imaging
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
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
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.
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.
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
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.
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.
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.
BSQ

What does the word "benign" mean?
BSQ

Benign is what you will be after you be
eight
Future of Psychiatry
References





Up to Date
http://www.emedicine.com/med/topic2405.html
http://stilt.genetics.utah.edu/reference/pdf_templa
te.php?tpl=remember_amnesia
http://spinwarp.ucsd.edu/NeuroWeb/Text/br800epi.htm
http://www.people.virginia.edu/~rjh9u/krebs.html
The End

Any questions/comments??????