This document provides an overview of alcohol-related neurologic disorders. It discusses the definition and epidemiology of alcoholism and defines units of alcohol. It describes various neurologic effects of alcohol including withdrawal syndrome, Wernicke-Korsakoff syndrome, alcoholic neuropathy, and fetal alcohol syndrome. It provides details on the pathogenesis and treatment of Wernicke's encephalopathy and Korsakoff's psychosis. The document also discusses various imaging findings and emphasizes the importance of early thiamine treatment.
3. Alcohol has been consumed by humans for
thousands of years
StoneAge beer jugs from the Neolithic
period have been discovered
Effects on the central and peripheral nervous
system are varied
Role of alcoholism in the development of
cognitive and functional decline has been
known since the time of Hippocrates
Received serious study withinWestern
medicine for more than a century.
4. Alcohol is likely to exacerbate most medical
conditions
Affect almost any medication metabolized in
the liver
Temporarily mimic many medical (e.g DM) and
psychiatric (e.g., depression) conditions
Low doses of alcohol have some healthful
benefits
Alcohol use disorders decrease the life span by
about 10 years.
5. “Alcoholism” was first used by a Swedish physician
in 1849 to describe adverse systemic effects of
alcohol
DSM-IV defines alcoholism as “maladaptive alcohol
use with clinically significant impairment.”
National Council on Alcoholism and Drug
Dependence and the American Society of Addiction
Medicine defines it as “a primary, chronic disease
characterized by impaired control over drinking,
preoccupation with the drug alcohol, use of alcohol
despite adverse consequences, and distortions in
thinking.”
6.
7. Alcohol is measured in unit for convenience
1 unit contains about 8 g of absolute alcohol
This raises the blood alcohol concentration by about 15–20
mg/dL
The amount that is metabolized in 1hr
1 unit of alcohol is found in half a pint of ordinary beer (3.5%
alcohol by volume, ABV)
And 125 mL of 9% wine
However, some beer and most lager is now 5% ABV; 3 units
per pint.
Wine is often 13%ABV and sold in 175 mL glasses; 2–3 units
per glass.
8. Guidelines
Frequency and quantity drunk during typical week
should be established:
Up to 21 units/week for men and 14 units for women:
this carries no long-term health risk
21–35 units/week for men and 14–24 units for
women: there is unlikely to be any long-term health
damage, provided the drinking is spread throughout
the week
>36 units /week for men and 24 for women: damage
to health becomes increasingly likely
>50 units/week for men and 35 for women: this is a
definite health hazard
9.
10. 80% of people inWestern countries have
consumed alcohol by middle age
two-thirds have been drunk in the prior year
the annual socioeconomic cost of alcoholism is
about $100 billion.'
Rate is higher in homeless and psychiatric
inpatients
11. > 20% of hospital admissions involve medical
complications of excessive drinking including
neurologic disorders
Women more susceptible
0.8 to 2.8% at autopsy in general population
(typical brain lesions)
Mortality/Morbidity: 10-20% (of WE)
12. Alcohol effects on the brain and nervous system
depends on:
Frequency of drinking
Quantity alcohol
Age onset of drinking
Duration of drinking
Gender
Genetic factors(MAOb,Alcohol dehyd subtype,
dopamine-2-receptor allele A1)
Family history of alcoholism
Diet and general health
14. Alcoholic neuropathy was documented at least as
early as 1787 by Lettsom
Other neurologic complications of alcoholism were
not recognized until the end of the 19th century
Deficits in memory and intellectual ability were
reported by Lawson in 1878
Korsakoff described a profound memory
impairment that occurred in some patients with a
history of alcohol abuse.
Subsequently, it was realized that Korsakoff
psychosis was one potential outcome from
Wernicke encephalopathy, first described in 1881
The two terms became linked asWernicke-
Korsakoff syndrome
15. 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.
16. Ethanol enters and distributes rapidly throughout the body after
ingestion.
Intoxication occurs because ethanol readily crosses the blood-brain
barrier.
Acts directly on neuronal membrane and interacts with numerous
neurochemical receptors.
Behavioral effects may include euphoria, dysphoria, social disinhibition,
drowsiness, belligerence, or aggression.
In nonalcoholic individuals, these may occur at serum concentrations as
low as 50 to 150 mg per dL.
Lethargy, stupor coma or eventual death from respiratory depression
and hypotension occur at progressively higher concentrations.
The lethal dose varies widely, as tolerance develops with repeated
exposures.
Many alcoholics appear sober at a serum level of 500 mg per dL; whereas
the same level can be fatal in non-alcoholic individuals.
17. Effects of Blood Alcohol Levels in the
Absence ofTolerance
Blood Level, g/dL Usual Effect
0.02 Decreased inhibitions, a slight feeling of
intoxication
0.08 Decrease in complex cognitive functions
and motor performance
0.20 Obvious slurred speech, motor
incoordination, irritability, and poor
judgment
0.30 Light coma and depressed vital signs
0.40 Death
18. AssessVital signs
Rx Resp depression, Arrythmia and BP liability if
present
R/O other intoxicants: opioids, BZD
Manage aggression with reassurance and show
of force
Low dose BZD: Lorazepam PO/IV 1-2mg
Alternative: Antipsychotic Haloperidol or
Olanzenpine
Intervention: Motivational interviewing and brief
interventions
19. Occurs during heavy drinking
characterized by hours of amnesia while awake.
Immediate recall and long-term memory are
normal
But new events are forgotten, as in patients with
transient global amnesia.
Alcoholic blackouts have been related to
reduced plasma tryptophan levels
Ethanol inhibition of N-methyl-D-aspartate
(NMDA) receptor-stimulated calcium flux in the
hippocampus may be more important.
20. Sudden cessation of drinking in a chronic alcoholic
leads to a withdrawal syndrome of central nervous
system hyper-excitability
The earliest symptom is generalized tremulousness
Others:
-Insomnia
-agitation,
-delirium,
-auditory or visual hallucinations,
- other perceptual disturbances may follow
21. Also characterized by
autonomic hyperactivity: tachycardia, profuse
sweating, hypertension, and hyperthermia.
Withdrawal symptoms commonly begin 6 to 8
hours after abstinence
Most pronounced 24 to 72 hours after abstinence
May lead to tonic-clonic (grand mal) seizures
Convulsions occur typically 6 to 48 hours after the
last drink and may occur singly or in a brief cluster.
22. Unless an underlying neuropathology exists, seizures are
rarely focal.
EEG are mildly abnormal and usually revert to normal within
few days
Status epilepticus is rare.
Seizures sometimes occur during heavy drinking or after
more than a week without alcohol
Possibility of pathogenic mechanisms other than withdrawal
Withdrawal seizures do not represent "latent" epilepsy;
therefore, treatment with anticonvulsants is not
recommended
Arrhythmias and sudden cardiac death can occur.
Results from a shift in the balance of the sympathetic-
parasympathetic myocardial excitability
23. Associated electrolyte abnormalities,
hyperthermia,
Dehydration with circulatory collapse can be
fatal
Fluid replacement
Correction of associated electrolyte disorders:
hypokalemia and hypomagnesemia,
Sedation with tapered dose of
BZD(Chlordiazepoxide or Diazepam) over 5 days
24. Best example of acquired nutritional deficiency in
alcoholism
Wernicke encephalopathy and Korsakoff psychosis are
successive stages of thiamine deficiency.
Initial phase is Wernicke encephalopathy, an acute
syndrome characterized by
- mental confusion,
-oculomotor disturbance
-cerebellar ataxia
overt delirium tremens(mental confusion, agitation,
fluctuating consciousness)
25. Encephalopathy may progress to stupor, coma, and death
if unrecognized or untreated.
Patients may have nystagmus, abducens or conjugate
gaze palsies, and gait ataxia (Victor et al 1989; Caine et al 1997).
Encephalopathy occurs due to leakage of capillaries
around the third ventricle,
Whereas the ophthalmoplegia and ataxia are secondary to
hemorrhages around the aqueduct of Sylvius in the
midbrain and the fourth ventricle in the medulla.
Capillary dysfunction is due to thiamine deficiency and not
a direct toxic effect of alcohol.
Clinical presentation may be clouded by signs of alcohol
withdrawal
26. Unique disorder of memory that typically emerges as
the acute features ofWE subside.
Characterized by an inability to recall events for a
period of a few years before the onset of illness
(retrograde amnesia) and an inability to learn new
information (anterograde amnesia).
Patients have limited insight into their memory
dysfunction.
Other cognitive deficits may manifest themselves but
are mild relative to the amnesia.
Confabulation may be caused by the addition of
frontal lobe dysfunction to the amnesia (Benson et al 1996)
27. When frontal lobe function improves, the
confabulation can disappear.
Most patients confabulate and pretend to
remember people/events they have
forgotten.
Attention, language, and spatial navigation
are usually normal.
Usually acute in onset, but can develop
insidiously without evidence for theWE (Victor
1994).
28. Can develop in non-alcoholic individuals who suffer from
poor dietary intake (Wilson et al 2006).
Recognition can lead to its reversal if quickly treated with IV
thiamine.
If the injury is sustained, a memory disturbance remains.
Many patients who recover fromWernicke encephalopathy
are left with a severe amnesia (Korsakoff syndrome),
Whereas in others there is partial or even complete recovery
(Kopelman et al 2009).
29. Thiamine: cofactor of several enzymes,
includingTransketolase, alpha ketogluterate
dehydrogenase, and pyruvate
dehydrogenase
Thiamine plays important role in cerebral
energy utilization
Deficiency initiates neuronal injury by
inhibiting metabolism
30. 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
31. Lesions in area ofThird 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
-petechial hemorrhages
Chronic cases, there is
-demyelination
-gliosis, with
-relative preservation of neurons.
Neuronal loss is most prominent in the relatively
unmyelinated medial thalamus
32. 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.
33. Rx takes priority over diagnosis, and
response to Rx may be diagnostic
No laboratory studies are diagnostic of
WE
Erythrocyte thiamine transketolase
(ETKA)
Serum thiamine or thiamine
pyrophosphate level can also be
measured by chromatography
Imaging studies are not necessary in
all patients with suspected WE and
should not delay treatment.
34. Imaging abnormalities have been reported
in a few 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
Findings are uncommon in other disorders,
and when present are strongly suggestive
However, CT is an insensitive test for WE;
Normal CT scan does not rule out the
diagnosis
35. MRI more sensitive than CT
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.
Distribution of these findings is
consistent with the pathologic lesions.
36.
37. Mamillary body atrophy is a relatively
specific abnormality in 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
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
38. IV thiamine 100 mg (or IM) for 5 days
DT prophylaxis (Benzo taper)
REMEMBER: Never give glucose before
thiamine
Daily oral thiamine (100 mg) following
discharge
Referral for Drug/AlcoholTreatment
39. 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
Gaze palsies recovered completely in
most cases
60 percent may have permanent
horizontal nystagmus
40. 40 percent recover from ataxia;
Remaining deficits ranged from inability
to walk at all to a wide-based slow
shuffling gait.
As the acute encephalopathy and
confusion receeds,
Deficits in learning and memory
become more obvious;
The latter recover completely or
substantively in only about 20 percent;
Remainder has a permanent amnestic
syndrome
41. 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.
Widespread oral administration of thiamine
to outpatients at risk.
Enrichment of flour with thiamine
decreased the autopsy prevalence of WE in
Australia
Fortification of alcoholic beverages has also
been proposed.
42. Disease of cerebral function attributed to deficiency
of nicotinic acid or tryptophan (Serdaru et al 1988; Victor 1994).
Rare now because of widespread practice of niacin
supplementation of cereals and bread
Initial symptoms are mood changes and
neurasthenia
May progress to lethargy and confusion,
Variably accompanied by spastic paresis, paratonia,
or myoclonus.
43. Distinct syndrome of corpus callosum degeneration named after
the 2 pathologists who first described it.
Clinical presentation is varied
Premortem diagnosis was almost impossible before the era of
modern neuroimaging (Victor 1994; Shiota et al 1996).
Patients present with slowly progressive psychomotor slowing,
incontinence, frontal release signs, and wide-based gait.
Dysarthria, hemiparesis, apraxia, or aphasia may be present in
other patients.
Occasional patients may present in stupor or coma.
MRI or CT may reveal lesions in the corpus callosum, anterior
commissure, and, less commonly, in the centrum semiovale (Niclot et al
2002) and lateral-frontal regions of the cortex (Johkura et al 2005).
44. Syndrome characterized by deficits in memory and intellectual
abilities severe enough to interfere with daily functioning.
Although no formal diagnostic criteria have been established,
Oslin and colleagues proposed that:
- clinical diagnosis of dementia that remains at least 60 days after
the last exposure to alcohol and
- history of excessive alcohol consumption for > 5 years (Oslin et al
1998).
Increasing evidence this syndrome has multiple etiologies
Presents with a range of clinical symptoms and abnormalities.
Dementia attributed to alcoholism is actually dementia due to
other etiologies present in an individual who drinks alcohol (Peters et
al 2008).
There is evidence that extreme quantities of alcohol can cause
dementia (Brun 2001),
Moderate levels may prevent dementia (Berger et al 1999; Ruitenberg 2002)
and mortality (Ellison 2002).
45. Alcohol-associated cognitive impairment
may be due to liver diseases such as cirrhosis
Memory, abstract reasoning, mental
processing speed, and attention are
frequently impaired.
Neurologic abnormalities may include
dysarthria, cerebellar ataxia,
choreoathetosis, and signs of corticospinal
disease (Victor 1994).
46. Chronic alcohol abuse in the absence of nutritional deficiencies or
organ failure has also been associated with changes in cognitive
abilities.
A large corpus of literature describes:
- deficits in recent memory,
-visuospatial ability
-abstract reasoning
-speed of information processing, and
-novel problem solving
occuring in detoxified chronic alcoholics (Ryan and Butters 1986; Kramer et al 1989;
Ridley et al 2013).
Commonly, neuropsychological testing shows a decline in
performance IQ but not verbal IQ.
Aphasia, apraxia, and agnosia are uncommon.
Typically, the degree of impairment is mild, with patients able to
carry out daily activities.
47. Prevalent neurologic syndromes in alcoholism is a distal,
predominantly sensory or sensorimotor polyneuropathy
(Behse and Buchthal 1977; Claus et al 1985; Monforte et al 1995).
Tingling or burning pain is often the symptom that brings
the patient to medical attention.
Dysesthesia is most prominent over the soles and toes and
may be severe enough to interfere with walking.
With progression neuropathic pain develops which often
paradoxically lessens in severity.
Neurologic examination reveals abnormally elevated
sensory thresholds to vibration, temperature, and
pinprick.
48. Distal muscle atrophy and mild weakness are
sometimes seen.
Ankle tendon reflexes are absent or diminished
Romberg sign, gait disturbances, areflexia, weakness,
and sensory loss may be seen in advanced cases.
Autonomic disturbances such as impotence, sweating
abnormalities, and orthostatic hypotension are
probably more prevalent than is recognized (Monforte et al
1995).
Neuropathic "Charcot" joint may rarely develop from
deafferentation
Hoarseness from recurrent laryngeal neuropathy.
49. Disorder of slowly progressive cerebellar degeneration is
sometimes seen in severe alcoholism (Victor et al 1959).
The anterior and superior vermis are preferentially
affected
Gives rise to a remarkably stereotypic syndrome of ataxic
stance and gait.
A wide-based gait and an inability to tandem walk are the
most prominent signs.
Limb ataxia, if present, occurs primarily in the legs.
Arms are involved only to a slight extent, if at all.
Gait disturbance usually develops over several weeks.
A mild gait instability may be present for some time and
then deteriorate suddenly after binge drinking or an
intercurrent illness.
50. Alcoholism has also been linked to the development of myopathy
(Urbano-Marquez et al 1989; Fernandez-Sola et al 1994; Klopstock et al 2010)
Commonly manifests as a chronic, painless syndrome of proximal
muscle wasting and weakness.
A wide range of severity exists, and milder cases are seldom
recognized.
May coexist with alcoholic cardiomyopathy, and severity of both
appears to be proportional to alcohol consumption
Less common manifestation is an acute syndrome of severe
muscle pain and tenderness, proximal weakness, elevated serum
CK, rhabdomyolysis, and myoglobinuria.
Symptoms appear after several days of heavy binge drinking.
Severe cases are life-threatening with complications like
hyperkalemia and renal failure due to rhabdomyolysis.
51. Widely recognized disorder of infants born to alcoholic mothers (Streissguth et
al 1980).
Prenatal exposure to ethanol impairs fetal growth and neurodevelopment with
research supporting long-lasting neural circuit dysfunction (Sadrian et al 2013).
Affected infants often have distinctive dysmorphic facial features that are
characterized by
- short palpebral fissures,
- thin upper lip,
-long flat philtrum,
- flat midface.
Short stature and microcephaly are common and may persist into adulthood.
Almost one half of the affected children have mental retardation
Others have a mild degree of intellectual impairment.
Speech delay, other learning disabilities, and hyperactivity are common.
No amount of alcohol is safe in pregnancy, total abstinence is the key
52.
53. Alcoholic patients are prone to traumatic injuries of the brain
and the peripheral nerves.
Well-recognized central nervous system complications
include subdural and epidural hematoma, cerebral
contusion, and posttraumatic epilepsy
Compressive neuropathies may appear after a period of
prolonged unconsciousness.
These may involve the radial nerve at the spiral groove
(Saturday night palsy),
Peroneal nerve at the fibular head, or the sciatic nerve in the
gluteal region.
54. Rapid changes in electrolyte concentration, most commonly of
sodium, are associated with central pontine and extra pontine
myelinolysis (Adams et al 1959).
Though not exclusive to alcoholics, alcoholic liver dysfunction
appears requisite.
Prognosis is poor, with a mortality approaching 75%.
Central pontine myelinolysis is associated with rapid onset of
- quadriparesis,
-pseudobulbar palsy,
-pupillary abnormalities, and
-sometimes coma.
Encephalopathy, tremors, myoclonus, and asterixis may be
encountered in end-stage liver disease from alcoholic cirrhosis
(Neiman et al 1990).
55. Alcohol use offers some health benefits, misuse
presents with adverse health consequences
Neurologic disorders are variable and diverse
involving CNS and PNS
Commonest include acute intoxication and
withdrawal syndrome
WKP is a thiamine responsive encephalopathy with
subsequent amnestic syndromes
Treatable, preventable but potentially fatal
Other neurological sequealle include neuropathy,
dementia, neuropraxia, and cereballar degeneration
Prognosis is guided
Management may be multidisciplinary
56. “Every form of addiction is bad, no matter
whether the narcotic be alcohol or morphine
or idealism.”
Carl Gustav Jung (1875 - 1961)
Swiss psychoanalyst.
(Memories, Dreams, Reflections)
57. After one year from the ratification of this article the
manufacture, sale, or transportation of intoxicating
liquors within, the importation thereof into, or the
exportation thereof from the United States and all
territory subject to the jurisdiction thereof for
beverage purposes is hereby prohibited.
(Constitution of the United States )
U.S. system of fundamental laws.
Section 1 of the eighteenth amendment of the
Constitution of the United States.This ban on alcohol
was repealed in 1933.
Amendments to the Constitution
