alcohol perturbs the balance between excitatory and inhibitory influences in the brain, resulting in Anxiolysis. An increased reaction time, diminished fine motor control, impulsivity, and impaired judgement be come evident when the concentionof alcohol in the blood is 20-30mg/dl. More than 50% of persons are grossly intoxicated by a conc. Of 150mg/dl. The defintion of intoxication varies by country. Alcohol can be measured in saliva, urine,sweat,and blood, level in exheled air remains the primary method of assessing the level of intoxication. Ethanol (CH 3 CH 2 OH) is a water-soluble alcohol that rapidly crosses cell membranes. Absorption of ethanol occurs via the gastrointestinal system, primarily in the stomach (70 percent) and duodenum (25 percent), with a small amount absorbed by the remaining intestine . When the stomach is empty, peak blood ethanol levels are reached between 30 and 90 minutes after ingestion.

1. B Y
A L I Y U U S M A N M U H A M M A D
M B C H B
K A M P A L A I N T E R N A T I O N A L U N I V E R S I T Y , U G A N D A
F A C I L L I T A T O R : D R . I S A A C
A P R I L , 2 0 1 8
ACUTE ACOHOL
INTOXICATION,WERNICKE’S
ENCEPHALOPATHY AND WKS

2. INTRODUCTION
Alcohol perturbs the balance between excitatory and
inhibitory influences in the brain, resulting in Anxiolysis,
Ataxia and sedation.
 An increased reaction time, diminished fine motor
control, impulsivity, and impaired judgement be come
evident when the concentionof alcohol in the blood is 20-
30mg/dl.
 More than 50% of persons are grossly intoxicated by a
conc. Of 150mg/dl.
 The defintion of intoxication varies by country.
 Alcohol can be measured in saliva, urine,sweat,and
blood, level in exheled air remains the primary method of
assessing the level of intoxication.

3. FACTORS AFFECTING INTOXICATION RISK
 Body weight and composition
 Rate of absorption from GIT
 Om average, the ingestion of 3 standard drink (42g
alcohol) on an empty stomach results in amaximum
blood conc. Of 67-92mg/dl in men.
 Concentrations of alcohol in blood will be higher in
women because on average women are smaller than
men, have less body water per unit of weight into
which alcohol can distribute, and less gastric ADH
activity than men.

4. ALCOHOL METABOLISM
 — Ethanol is metabolized via several pathways, each of
which can contribute to toxicity.
 The primary hepatic pathway generates acetaldehyde and
reduced nicotinamide adenine dinucleotide (NAD)
 Ethanol is metabolized first in the liver to acetaldehyde;
this process occurs in the hepatocyte cytosol via a
reaction catalyzed by the enzyme alcohol dehydrogenase
(ADH)
 The acetaldehyde that is generated is subsequently
metabolized to acetate, a process that occurs in the
mitochondria and is catalyzed by a different enzyme,
acetaldehyde dehydrogenase (ALDH).

5. PATHOPHYSIOLOGY
 Ethanol (CH 3 CH 2 OH) is a water-soluble alcohol
that rapidly crosses cell membranes.
 Absorption of ethanol occurs via the gastrointestinal
system, primarily in the stomach (70 percent) and
duodenum (25 percent), with a small amount
absorbed by the remaining intestine .
 When the stomach is empty, peak blood ethanol
levels are reached between 30 and 90 minutes after
ingestion.

8. CLINICAL FEATURES
Signs and symptoms of acute ethanol intoxication vary
with severity and can include;
 slurred speech
 nystagmus,
 disinhibited behavior
 Incoordination
 unsteady gait
 memory impairment
 stupor, or coma.
 Hypotension and tachycardia may occur as a result of
ethanol-induced peripheral vasodilation, or secondary to
volume loss.

9. CLINICAL FEATURES CONT…..
Acute alcohol intoxication can also induce multiple
metabolic derangements including
 Hypoglycemia
 lactic acidosis
 Hypokalemia
 Hypomagnesemia
 hypocalcemia, and
 hypophosphatemia

10. CLINICAL FEATURES CONT…..
Among patients who do not abuse alcohol, clinical signs often associated with
particular ranges of the blood alcohol concentration (BAC) are as follow :
 With a BAC between 0.01 and 0.10 percent (<100 mg/dL or
22 mmol/L), euphoria and mild deficits in coordination, attention, and
cognition may be observed.
 With a BAC between 0.10 and 0.20 percent, an individual experiences
greater deficits in coordination and psychomotor skills, decreased
attention, ataxia, impaired judgment, slurred speech, and mood variability.
 With a BAC between 0.20 to 0.30 percent, severe alcohol intoxication
results in a lack of coordination, incoherent thoughts, confusion, and
nausea and vomiting.
 When the BAC exceeds 0.30 percent, stupor and loss of consciousness can
occur.
 Some patients experience coma and respiratory depression, and death is
possible.

11. DIAGNOSIS
 — Alcohol intoxication as a cause of altered mental
status is a diagnosis of exclusion and should be considered
only after ruling out more serious conditions such as
head trauma,
hypoxia,
hypoglycemia,
hypothermia,
hepatic encephalopathy, and other metabolic and
physiologic derangements.

12. LABORATORY EVALUATION
 Serum alcohol concentration and associated
signs — Measurements from serum provide the
most accurate determination of a patient’s alcohol
level.
 Alternative methods, such as breath analysis,
provide more rapid results, but often give slightly
lower ethanol concentrations than those obtained
from venous blood .
 Additional studies — (serum glucose, basic
electrolytes).

13. TREATMENT
 The treatment for acute ethanol intoxication is primarily
supportive.
 As a general rule, all intoxicated patients should receive a
rapid bedside glucose determination, followed by
dextrose infusion if hypoglycemia is present.
 In addition, all patients presenting with acute ethanol
intoxication should be carefully assessed for occult
traumatic injuries.
 Patients presenting with coma secondary to ethanol
intoxication should receive at least 100 mg of parenteral
thiamine to prevent or treat Wernicke's encephalopathy,
along with dextrose.

14. TREATMENT CONT…
 Some patients with acute ethanol intoxication and
altered sensorium can be agitated, violent, and
uncooperative.
 In such cases, the use of chemical sedation may be
needed to prevent the patient from harming
themselves or others.
 Benzodiazepines and typical antipsychotics are
frequently used in these patients, but caution must
be taken as these drugs can worsen the respiratory
depression caused by alcohol

15. WERNICKE'S
ENCEPHALOPAT
HY

16. WERNICKE'S ENCEPHALOPATHY
 Or now often Wernicke's disease refers to the presence of
neurological symptoms caused by biochemical lesions of
the central nervous system after exhaustion of B-vitamin
reserves, in particular thiamine.
 Classically, Wernicke's encephalopathy is characterised
by the triad
 ophthalmoplegia,
 ataxia, and
 confusion.
However, only 10% of patients exhibit all three features,
and other symptoms may also be present.

17. EPIDEMIOLOGY
 — Typical brain lesions of Wernicke's
encephalopathy (WE) are observed at autopsy in 0.8
to 2.8 percent of the general population in the
Western world, and the vast majority of affected
patients are alcoholic

18. Associated conditions
 WE occurs also in the setting of poor nutrition caused by malabsorption,
poor dietary intake, increased metabolic requirement (eg, during
systemic illnesses), or increased loss of the water-soluble vitamin
thiamine (eg, in renal dialysis). Conditions associated with WE include:
 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

19. PATHOPHYSIOLOGY
 Thiamine deficiency and errors of thiamine metabolism,
are believed to be the primary cause of Wernicke
encephalopathy.
 Thiamine, also called B1, helps to breakdown glucose.
Specifically, it acts as an essential coenzyme to the TCA
cycle and the pentose phosphate shunt.
 Thiamine is first metabolised to its more active form,
thiamine diphosphate (TDP), before it is used.
 The body only has 2–3 weeks of thiamine reserves,
which are readily exhausted without intake, or if
depletion occurs rapidly, such as in chronic
inflammatory states or in diabetes.

20. Thiamine is involved in:
 Metabolism of carbohydrates, creating energy.
 Production of neurotransmitters including glutamic
acid and GABA.
 Lipidmetabolism, necessary for myelin production.
 Amino acid modification.
 Probably linked to the production of taurine, of
great importance cardiac. Neuromodulation.

21. Neuropathy
The primary neurological-related injury caused by thiamine deficiency in
WE is three-fold:
 oxidative damage,
 mitochondrial injury leading to apoptosis, and
 directly stimulating a pro-apoptotic pathway.
Thiamine deficiency affects both neurons and astrocytes, glial cells of the
brain.
Thiamine deficiency alters the glutamate uptake of astrocytes, through
changes in the expression of astrocytic glutamate transporters EAAT1
and EAAT2, leading to excitotoxicity.
Other changes include those to the GABA transporter subtype GAT-3,
GFAP, glutamine synthetase, and the Aquaporin 4 channel.
Focal lactic acidosis also causes secondary oedema, oxidative stress,
inflammation and white matter damage.

22.  Thiamine deficiency in alcohol abusers results from a
combination of inadequate dietary intake
 Reduced gastrointestinal absorption
 Decreased hepatic storage, and
 Impaired utilization

23. PATHOLOGICAL ANATOMY
Despite its name, WE is not related to Wernicke's area, a region of the
brain associated with speech and language interpretation.
 In most, early lesions completely reversed with immediate and adequate
supplementation.
 Lesions are usually symmetrical in the periventricular region,
diencephalon,
 the midbrain,
 hypothalamus, and
 cerebellar vermis.
Brainstem lesions may include
 cranical nerve III, IV, VI and VIII nuclei,
 the medial thalamic nuclei, and
 the dorsal nucleus of the vagus nerve.
Oedema may be found in the regions surrounding the third ventricle, and
fourth ventricle, also appearing petechiae and small hemorrhages.
Chronic cases can present the atrophy of the mammillary bodies.

24. CLINICAL MANIFESTATIONS
 Classic signs — The classic triad of Wernicke's
encephalopathy (WE) includes:
 Encephalopathy
 Oculomotor dysfunction
 Gait ataxia
Clinical recognition of WE is straightforward when an
alcoholic presents with this classic triad.
However, this may be the exception, not the rule.

25. CLINICAL MANIFESTATIONS CONT…
 Encephalopathy — The encephalopathy is characterized by
profound disorientation, indifference, and inattentiveness .
 Oculomotor dysfunction — Nystagmus, lateral rectus palsy, and
conjugate gaze palsies reflect lesions of the oculomotor, abducens,
and vestibular nuclei. Ocular abnormalities usually occur in
combination rather than alone.
 Gait ataxia — Ataxia primarily involves stance and gait and is
likely due to a combination of polyneuropathy, cerebellar
involvement, and vestibular dysfunction .
Cerebellar pathology is generally restricted to the anterior and
superior vermis.
 Vestibular dysfunction may be the major cause of acute gait ataxia
in WE.

26. Other signs
Patients with WE may also present with the following
findings:
 Evidence of protein-calorie malnutrition is observed
frequently in patients with WE
 Vestibular dysfunction without hearing loss is a
common finding
 Peripheral neuropathy is common and typically
involves just the lower extremities . Patients complain
of the gradual onset of weakness, paresthesias, and
pain affecting the distal lower extremities.
 Cardiovascular signs and symptoms are common and
include tachycardia, exertional dyspnea, elevated
cardiac output, and EKG abnormalities. These reverse
with thiamine administration.

27. DIAGNOSIS
 — Wernicke's encephalopathy (WE) is primarily a
clinical diagnosis.
 Laboratory studies and neuroimaging studies can be
helpful, but the biggest barrier to diagnosis is a low
index of suspicion when all clinical symptoms are
not present and in the nonalcoholic patient.
 Institution of treatment takes priority over diagnosis,
and response to treatment may be diagnostic

28. LABORATORY TESTING
 — There are no laboratory studies that are diagnostic of
WE.
 Thiamine deficiency can be most reliably detected by
measurement of erythrocyte thiamine transketolase
(ETKA) before and after the addition of thiamine
pyrophosphate (TPP).
 A low ETKA, along with a more than 25 percent
stimulation, establishes the diagnosis of thiamine
deficiency.
 A serum thiamine or thiamine pyrophosphate level in
serum or whole blood can also be measured by
chromatography.

29. TREATMENT
 — The diagnosis of WE is difficult to confirm and,
untreated, most patients progress to coma and
death.
 Fortunately, intravenous administration of thiamine
is safe, simple, inexpensive, and effective.
 Adverse reactions, including anaphylaxis and
bronchospasm are reported but are extremely rare

30. TREATMENT CONT….
 Patients with suspected Wernicke's encephalopathy
(WE) require immediate parenteral administration of
thiamine.
 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.
 Administration of glucose without thiamine can
precipitate or worsen WE; thus, thiamine should be
administered before glucose.
 Because gastrointestinal absorption of thiamine is
erratic in alcoholic and malnourished patients, oral
administration of thiamine is an unreliable initial
treatment for WE.

31. TREATMENT CONT….
dietary requirements for thiamine are only 1 to 2 mg daily,
absorption and utilization of thiamine are incomplete, and
some patients have genetically determined requirements
for much larger doses.
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.
Magnesium and other vitamins are replaced as well, along
with other nutritional deficits if present.

32. PREVENTION
 The prevention of WE and Korsakoff's amnestic
syndrome (KS) might be possible through the
widespread oral administration of thiamine to
outpatients at risk.
 Enrichment of flour with thiamine.
 Fortification of alcoholic beverages has also been
proposed.

33. WERNICKE–
KORSAKOFF
SYNDROME (WKS)

34. INTRODUCTION
 Wernicke–Korsakoff syndrome (WKS)—also called wet
brain, Korsakoff's psychosis, and alcoholic
encephalopathy)—
 The syndrome is a combined manifestation of two
namesake disorders, Wernicke's encephalopathy and
Korsakoff's psychosis, named after Carl Wernicke and
Sergei Korsakoff respectively.
 It is a manifestation of thiamine (vitamin B1) deficiency,
a spectrum of disorders which also encompasses beriberi,
Wernicke's encephalopathy, and Korsakoff's psychosis.
 These disorders may manifest concurrently or separately.
 WKS is usually secondary to alcohol abuse. It mainly
causes vision changes, ataxia and impaired memory.

35. Diagnosis
 Diagnosis of Wernicke–Korsakoff syndrome is by
clinical impression and can sometimes be confirmed
with formal neuropsychological assessment.
 Wernicke's encephalopathy typically presents with
ataxia and nystagmus, and Korsakoff's psychosis
with anterograde and retrograde amnesia and
confabulation upon relevant lines of questioning

36. PATHOPHYSIOLOGY
 Brain atrophy associated with WKS occurs in the
following regions of the brain;
 the mamillary bodies, the thalamus, the periaqueductal
grey, the walls of the 3rd ventricle, the floor of the 4th
ventrical, the cerebellum, and the frontal lobe.
 In addition to the damage seen in these areas there have
been reports of damage to cortex, although it was noted
that this may be due to the direct toxic effects of alcohol
as opposed to thiamine deficiency that has been
attributed as the underlying cause of Wernicke-Korsakoff
Syndrome

37.  The amnesia that is associated with this syndrome is
a result of the atrophy in the structures of the
diencephalon (the thalamus, hypothalamus and
mamillary bodies), and is similar to amnesia that is
presented as a result of other cases of damage to the
medial temporal lobe.
 It has been argued that the memory impairments
can occur as a results of damage along any part of the
mamillo-thalamic tract, which explains how WKS
can develop in patients with damage exclusively to
either the thalamus or the mamillary bodies.

38. CLINICAL MANIFESTATIONS
It involves an acute Wernicke-encephalopathy phase,
followed by the development of a chronic Korsakoff's
syndrome phase.

39. KORSAKOFF'S SYNDROME
 KS is described as an acute onset of severe memory impairment without any
dysfunction in intellectual abilities.
 The DSM IV lists the following criteria for the diagnosis of Korsakoff's Syndrome:
 Anterograde amnesia Variable presentation of retrograde amnesia
 One of:
 Aphasia
 Apraxia
 Agnosia A deficit in executive functions
 In addition, the DSM IV indicates that normal activities and function will be impaired
by the memory deficits and that the experience of amnesia must occur outside of times
where the individual is in a state of delirium, intoxification, or withdrawal.
 Cognitive effects

40. Memory deficits
 As mentioned previously, the amnesic symptoms of
WKS include both retrograde and anterograde
amnesia.
 The retrograde deficit has been demonstrated
through an inability of WKS patients to recall or
recognize information for recent public events. The
anterograde memory loss is demonstrated through
deficits in tasks that involve encoding and then
recalling lists of words and faces, as well as semantic
learning tasks.

41. Confabulation
 Patient's suffering from WKS often show
confabulation, spontaneous confabulation being seen
more frequently than provoked confabulation.
 Spontaneous confabulations refer to incorrect
memories that the patient holds to be true, and may
act on, arising spontaneously without any
provocation.
 Provoked confabulations can occur when a patient is
cued to give a response, this may occur in test
settings.

42.  MANAGEMENT
 PREVENTION
 AS FOR WERNICKE’S ENCEPHALOPATHY