Neurologic Manifestations of Alcoholism

Tajudin A. Adetunji OAUTHC Ile-Ife

Outline

Introduction Definition Pharmacology Epidemiology Spectrum of Neurologic disorders Other Manifestations Summary References

Introduction1

Alcohol has been consumed by humans for thousands of years

Stone Age 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 within Western medicine for more than a century.

Introduction2

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.

Definitions

“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.”

 

Pharmacology

Alcohol Estimate

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.

Benefits of Alcohol and TresholdGuidelines 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

Effects of Alcohol

Epidemiology

80% of people in Western 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

Epidemiology2

> 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)

Determinant Factors

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

Disorders sec to Chronic Abuse

Alcohol withdrawal syndrome Wernicke-Korsakoff syndrome

(Wernicke’s encephalopathy and Korsakoff psychosis)

Alcoholic neuropathy Alcoholic cerebellar degeneration Alcoholic myopathy Fetal alcohol syndrome Dementia and other cognitive deficits Others

Historical Leanings

 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 as Wernicke-Korsakoff syndrome

Historical Leanings2

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.

Acute Intoxication

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.

Effects of Blood Alcohol Levels in the Absence of Tolerance

Blood Level, g/dL Usual Effect0.02 Decreased inhibitions, a slight

feeling of intoxication0.08 Decrease in complex cognitive

functions and motor performance0.20 Obvious slurred speech, motor

incoordination, irritability, and poor judgment

0.30 Light coma and depressed vital signs

0.40 Death

Rx

Assess Vital 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

Alcoholic “Blackouts”

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.

Withdrawal Syndrome

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

Withdrawal Syndrome2

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.

WS3

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

Rx

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

The Wernicke-Korsakoff syndrome 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)

WKP

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

KP

Unique disorder of memory that typically emerges as the acute features of WE 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)

KP

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 the WE (Victor 1994).

WKP

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 from Wernicke encephalopathy are left with a severe amnesia (Korsakoff syndrome),

Whereas in others there is partial or even complete recovery (Kopelman et al 2009).

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

Pathophysiology2

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 -petechial hemorrhages Chronic cases, there is -demyelination -gliosis, with -relative preservation of neurons. Neuronal loss is most prominent in the relatively unmyelinated

medial thalamus

Pathology2

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.

Diagnosis

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.

Diagnosis: Imaging

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

Diagnosis: Imaging

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.

MRI

MRI

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

Rx

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/Alcohol Treatment

Clinical Course

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

Clinical Course

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

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.

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.

Alcoholic Pellagra

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.

Marchiafava-Bignami syndrome 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).

Alcohol-induced dementia 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).

Others

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).

Others

  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.

Peripheral neuropathy

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.

Peripheral Neuropathy

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.

Cerebellar Degeneration

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.

Alcoholic Myopathy

  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.

Fetal alcohol syndrome

  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

FAS

others

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.

Others

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). 

Summary

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

Quotable Quote

“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)

April Fool!

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

References

Harrison”s principles of Internal medicine, 18th ed Neurology discovery Eighth Special Report to the US Congress on Alcohol and Health. Rockville, Md, US Dept of Health and Human Services, 1993 2. Chamess ME, Simon RP, Greenberg DA: Ethanol and the nervous system. N EnglJ Med 1989; 321:442-454 3. Goldstein DB: Pharmacology of Alcohol. New York, NY, Oxford University Press, 1983 4. Bosron WF, Li TK: Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism. Hepatology 1986; 6:502-510 5. Koch-Weser J: Drugs to decrease alcohol consumption. N Engl J Med 1981; 305:1255-1262 6. Wright C, Moore RD: Disulfiram treatment of alcoholism. Am J Med 1990; 88:647-655 7. Johnson RA, Noll EC, Rodney WM: Survival after a serum ethanol concentration of 1%% (Letter). Lancet 1982; 2:1394 8. Lindblad B, Olsson R: Unusually high levels of blood alcohol? JAMA 1976; 236:1600-1602 9. Urso T, Gavaler JS, Van Thiel DH: Blood ethanol levels in sober alcohol users seen in an emergency room. Life Sci 1981; 28:1053-1056 10. Watanabe A, Kobayashi M, Hobara N, Nakatsukasa H, Nagashima H, Fujimoto A: A report of unusually high blood ethanol and acetaldehyde levels in two surviving patients. Alcoholism (NY) 1985; 9:14-16 11. Branchey L, Branchey M, Zucker D, Shaw S, Lieber CS: Association between low plasma tryptophan and blackouts in male alcoholic patients. Alcoholism (NY) 1985; 9:393-395 12. Hoffman PL, Rabe CS, Moses F, Tabakoff B: N-methyl-D-aspartate receptors and ethanol: Inhibition of calcium flux and cyclic GMP production. J Neurochem 1989; 52:1937-1940 13. Lovinger DM, White G, Weight FF: Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 1989; 243:1721-1724 Up to Date http://www.emedicine.com/med/topic2405.html http://stilt.genetics.utah.edu/reference/pdf_template.php?tpl=remember_amnesia http://spinwarp.ucsd.edu/NeuroWeb/Text/br-800epi.htm http://www.people.virginia.edu/~rjh9u/krebs.html Microsoft ® Encarta ® 2009. © 1993-2008 Microsoft Corporation