Alcohol and Alcohol Use Disorders¶

Chapter 464 | Part 13: Neurologic Disorders · Part 13 – Neurologic Disorders · Chapter 464

Key Clinical Points¶

SBIRT (Screening, Brief Intervention, Referral to Treatment) is the standard approach for identifying and treating alcohol-related disorders.
DSM-5 defines Alcohol Use Disorder (AUD) by 11 criteria; severity is mild (2-3), moderate (4-5), or severe (6+).
Thiamine (50-100 mg daily) must be administered before glucose to prevent Wernicke's encephalopathy in withdrawal.
Benzodiazepines are first-line for alcohol withdrawal; chlordiazepoxide 25-50 mg PO q4-6h is typical dosing.
AUDIT score ≥8 indicates harmful alcohol use; GGT >35 U/L and CDT >20 U/L are sensitive markers for heavy consumption.
Fetal Alcohol Spectrum Disorder (FASD) includes facial changes, microcephaly, and intellectual impairment.
Holiday Heart syndrome presents with atrial or ventricular arrhythmias after heavy drinking in patients with no prior heart disease.
Lifetime risk for AUD is ~20% for men and 10% for women; life span is shortened by ~10 years.
Wernicke-Korsakoff syndrome results from thiamine deficiency and presents with ophthalmoparesis, ataxia, and amnesia.
Mallory-Weiss lesion is a longitudinal tear at the gastroesophageal junction caused by violent vomiting.

DEFINITION & CLASSIFICATION¶

• Alcohol: Beverage ethanol with diverse effects on nearly all neurochemical systems. • Impact: Even low doses can exacerbate medical problems, affect liver metabolism of other drugs, and mimic psychiatric conditions (e.g., depression). • Alcohol Use Disorder (AUD): Also known as alcoholism or alcohol dependence. • DSM-5 Definition: > Definition (Harrison's 22e): repeated alcohol-related difficulties in at least 2 of 11 life areas that cluster together in the same 12-month period. • Severity Classification: ◦ Mild: 2 or 3 items endorsed. ◦ Moderate: 4 or 5 items endorsed. ◦ Severe: 6 or more items endorsed.

EPIDEMIOLOGY¶

• Lifetime Risk: ≥20% for men and 10% for women, regardless of education/income. • Morbidity/Mortality: ◦ Drinking >3 standard drinks/day increases risk for cancer and vascular disease. ◦ AUD shortens life span by ~10 years. • Trends: Significant increase in prevalence (2001-2013) in the U.S., particularly among women, African Americans, and individuals aged ≥45.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Genetics: ◦ ~60% of risk attributed to genes. ◦ Risk is polygenic (hundreds of variations). ◦ Specific mutations in ALDH lead to intense skin flushing (reduces risk for alcohol only, not other substances). ◦ Low response/sensitivity to alcohol (due to GABA, nicotinic, dopamine, serotonin systems) predicts future AUD. • Metabolism: ◦ Primary pathway: Ethanol → Acetaldehyde → Acetyl CoA (via dehydrogenase). ◦ Secondary pathway: MEOS (microsomal ethanol-oxidizing system) handles ≥10% of oxidation at high blood alcohol concentrations. ◦ Clinical Significance: High acetyl-CoA leads to fatty liver; inhibition of acetyl-CoA oxidation by NADH leads to accumulation of ketones/lactate (alcohol ketoacidosis). • Neurochemistry: ◦ GABA: Acute alcohol increases GABA activity → anticonvulsant, sleep-inducing, anti-anxiety effects. Chronic use leads to decreased GABA activity. ◦ NMDA: Acute alcohol inhibits postsynaptic NMDA receptors; chronic use/desistance leads to upregulation of these receptors. ◦ Dopamine: Acute increase in ventral tegmentum → reward, craving, and relapse. ◦ Other systems: Serotonin (acute increase), Opioid (β-endorphin release), Nicotinic acetylcholine, and Cannabinol receptors are all impacted.

CLINICAL FEATURES¶

• Pharmacology & Nutrition: ◦ Standard Drink: 10-12g ethanol (340mL beer, 115mL wine, 43mL 80-proof spirit). ◦ Congeners: Methanol, butanol, acetaldehyde, histamine, tannins, iron, lead. ◦ Absorption: Increased by rapid gastric emptying (carbonation), absence of food/fat, and dilution to ~20% volume. ◦ Thiamine Deficiency: Alcohol interferes with B1, B6, Folate, B3, and Vitamin A absorption. • Metabolic Effects: ◦ Hypoglycemia: Occurs in 6-36h post-fasting due to decreased gluconeogenesis. ◦ Alcohol Ketoacidosis: High anion gap; β-hydroxybutyrate/lactate ratio of 2:1 to 9:1 (normal is 1:1). • Organ System Effects: ◦ Cardiovascular: ◦ Chronic use: Risk for cardiomyopathy, heart failure, and dilated chambers. ◦ Holiday Heart: Atrial or ventricular arrhythmias after heavy drinking in patients without prior heart disease. ◦ Reproductive: ◦ Men: Testicular atrophy, reduced sperm count (even without liver impairment). ◦ Women: Amenorrhea, decreased ovarian size, infertility. ◦ Pregnancy: Fetal Alcohol Spectrum Disorder (FASD). ◦ Fetal Alcohol Syndrome (FAS): Seen in ~5% of children; includes facial changes, microcephaly, and heart defects. ◦ Musculoskeletal: Myopathy (common), reduced bone density, risk for fractures/osteonecrosis. ◦ Immune: Decreased white blood cell production, impaired delayed-hypersensitivity (false-negative Tuberculin test). ◦ Gastrointestinal: Hemorrhagic gastritis; Mallory-Weiss lesion (longitudinal tear at gastroesophageal junction from vomiting). ◦ Pancreatitis: Incidence ~3x higher in AUD patients. • Neurological/Psychiatric: ◦ Blackouts: 35% of drinkers; en bloc (>0.20 g/dL) or fragmentary (>0.12 g/dL). ◦ Sleep: Disrupted REM and deep sleep; increased snoring/apnea (75% of men ≥60 years with AUD). ◦ Peripheral Neuropathy: Bilateral limb numbness, tingling. ◦ Cerebellar Degeneration: 1% of AUD patients; unsteady gait, nystagmus. ◦ Wernicke-Korsakoff: 1 in 500 AUD cases; ophthalmoparesis, ataxia, and amnesia (thiamine deficiency). ◦ Psychiatric Comorbidity: Mood/anxiety disorders often resolve within 4 weeks of abstinence. Only substance-induced psychoses may require short-term antipsychotics.

DIFFERENTIAL DIAGNOSIS¶

• Substance-Induced vs. Primary Disorders: ◦ Symptoms appearing only during intoxication or withdrawal are likely substance-induced and resolve within days to weeks of abstinence. ◦ Persistent symptoms (e.g., schizophrenia, MDD) may overlap with AUD due to shared genetic vulnerabilities or coping mechanisms.

DIAGNOSTIC APPROACH¶

Screening: ◦ Use tools like AUDIT (Table 464-3). ◦ Note: GGT >35 U/L and CDT >20 U/L are sensitive markers for heavy consumption.
Clinical Assessment of Blood Alcohol Levels (Table 464-1): ◦ 0.02 g/dL → Slight feeling of intoxication. ◦ 0.20 g/dL → Slurred speech, motor incoordination, irritability. ◦ 0.40 g/dL → Death.
DSM-5 Diagnosis (Table 464-2): ◦ Identify presence of ≥2 out of 11 criteria in a 12-month period. ◦ Determine severity: Mild (2-3), Moderate (4-5), Severe (6+).

MANAGEMENT & TREATMENT¶

Initial Approach: ◦ Implement SBIRT (Screening, Brief Intervention, Referral to Treatment) and FRAMES.
Withdrawal Management: ◦ First-line: Benzodiazepines. ◦ Example: Chlordiazepoxide 25-50 mg PO q4-6h.
Critical Nutritional Support: ◦ Thiamine (50-100 mg daily) must be administered BEFORE glucose to prevent Wernicke's encephalopathy.
Relapse Prevention: ◦ Provide supportive care, "talk therapy" (cognitive-behavioral), and education on the risks of alcohol.

COMPLICATIONS & PROGNOSIS¶

• Long-term Outcomes: ◦ Liver: Alcohol-induced hepatitis, perivenular sclerosis, and cirrhosis (15% of AUD patients). ◦ Cancer: Increased risk for breast (1.4x), oral/esophageal (~3x), and rectal cancers. ◦ Cognitive: "Alcoholic dementia" refers to irreversible changes in the context of chronic use.

SPECIAL POPULATIONS¶

• Pregnancy: ◦ Risk of FASD due to rapid placental transfer of ethanol and acetaldehyde. ◦ Recommendation: Complete abstinence for pregnant women. • Adolescents: ◦ Vulnerable to alcohol-related brain changes affecting cognition, reward recognition, and cue processing.

KEY PEARLS & HIGH-YIELD POINTS¶

• Thiamine Rule: Always give Thiamine before Glucose in suspected Wernicke's or heavy drinkers to prevent permanent neurological damage. • Metabolic Mimicry: Alcohol ketoacidosis presents with high anion gap and β-hydroxybutyrate/lactate ratio of 2:1 to 9:1; it can be misdiagnosed as DKA. • Holiday Heart: Sudden arrhythmias in a healthy person after drinking is a classic clinical pearl. • Mallory-Weiss: Common cause of GI bleeding in heavy drinkers due to vomiting.

Reference Tables¶

TABLE 464-1 Effects of Blood Alcohol Levels in the Absence of Tolerance¶

Harrison's 22e, p.3676

BLOOD LEVEL, g/dL	USUAL EFFECT
0.02	Decreased inhibitions, a slight feeling of intoxication
0.20	Obvious slurred speech, motor incoordination, irritability, and poor judgment
0.40	Death

TABLE 464-2 Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition, Classification of Alcohol Use…¶

Harrison's 22e, p.3678

Criteria
Two or more of the following items occurring in the same 12-month period must
be endorsed for the diagnosis of an alcohol use disordera:
Drinking resulting in recurrent failure to fulfill role obligations
Recurrent drinking in hazardous situations
Continued drinking despite alcohol-related social or interpersonal problems
Tolerance
Withdrawal, or substance use for relief/avoidance of withdrawal
Drinking in larger amounts or for longer than intended
Persistent desire/unsuccessful attempts to stop or reduce drinking
Great deal of time spent obtaining, using, or recovering from alcohol
Important activities given up/reduced because of drinking
Continued drinking despite knowledge of physical or psychological problems
caused by alcohol
Alcohol craving

TABLE 464-3 The Alcohol Use Disorders Identification Test (AUDIT) a ITEM 1. How often do you have a drink containing 2.…¶

Harrison's 22e, p.3679

ITEM	5-POINT SCALE (LEAST TO MOST)
1. How often do you have a drink containing alcohol?	Never (0) to 4+ per week (4)
3. How often do you have six or more drinks on one occasion?	Never (0) to daily or almost daily (4)
5. How often during the last year have you failed to do what was normally expected from you because of drinking?	Never (0) to daily or almost daily (4)
7. How often during the last year have you had a feeling of guilt or remorse after drinking?	Never (0) to daily or almost daily (4)
9. Have you or someone else been injured as a result of your drinking?	No (0) to yes, during the last year (4)