Misuse Of Alcohol And Alcohol-related Disorders

• Alcohol is the 7th leading risk factor for death and disability globally (GBD 2016 data, confirmed in 2019 updates)
• Contributes to > 3 million deaths/year (5.3% of all deaths worldwide) — WHO Global Status Report on Alcohol and Health
• Responsible for > 200 disease and injury conditions
• Heavy episodic drinking (binge drinking) prevalence ~18.2% globally among drinkers

These HK-specific figures are frequently tested.

• 23.7% drank alcohol occasionally, 9.4% at least once/week, 61.6% non-drinkers ^[2]
• 66.5% usually drink beer, 19.6% table wine, 10.6% Chinese rice wine, 6.9% spirits ^[2]
• Among drinkers, M:F ≈ 2:1; 7.2% were binge drinkers ^[2]
• 16.9% reported drinking beyond daily limit. 5.8% exhibited signs of drunkenness ^[2]
• Alcohol-related deaths contributed to 0.14% of deaths (58 in 2009) ^[2]

• Males consistently have higher rates of AUD (2–3× females) — this gap is narrowing in younger cohorts
• Peak onset of AUD: late teens to mid-20s
• Women develop alcohol-related organ damage (liver, brain, cardiomyopathy) at lower cumulative doses and shorter durations than men — the so-called "telescoping effect"

Why are women more susceptible? Two key reasons ^[2]:

1. Lower total body water (proportionally more adipose tissue) → higher blood alcohol concentration (BAC) for the same dose per kg
2. Lower gastric alcohol dehydrogenase (ADH) activity → less first-pass metabolism → more ethanol reaches systemic circulation

Understanding metabolism is critical because it underpins intoxication, withdrawal, organ damage, and drug interactions.

Step 1: Ethanol → Acetaldehyde

• Enzyme: Alcohol dehydrogenase (ADH) — primarily in gastric mucosa and hepatocytes
• Cofactor: NAD⁺ → reduced to NADH
• Also via Microsomal Ethanol Oxidizing System (MEOS/CYP2E1) — inducible with chronic use (explains metabolic tolerance)
• Also via catalase (minor pathway, in peroxisomes)

Step 2: Acetaldehyde → Acetate

• Enzyme: Aldehyde dehydrogenase (ALDH) — primarily mitochondrial ALDH2
• Cofactor: NAD⁺ → NADH
• Acetaldehyde is toxic and carcinogenic — responsible for the "flush reaction," hangover symptoms, and long-term tissue damage

Step 3: Acetate → CO₂ + H₂O

• Acetate enters peripheral tissues, converted to acetyl-CoA → enters TCA cycle

Key metabolic consequence: Chronic ethanol metabolism massively shifts the hepatic NAD⁺/NADH ratio toward NADH. This has widespread metabolic consequences:

• ↓ Gluconeogenesis → alcoholic hypoglycaemia (occurs 6–36h after ingestion of > 30g alcohol) ^[2]
• ↓ Fatty acid oxidation → fatty liver (steatosis)
• ↑ Lactate (pyruvate → lactate is favoured) → lactic acidosis
• ↑ Uric acid (lactate competes with urate for renal excretion) → gout

Alcohol is fundamentally a CNS depressant that acts on multiple neurotransmitter systems:

• In HK, 1 unit of alcohol = 10g pure ethanol ^[2]
• Number of standard drinks = drink volume (L) × alcohol content (%vol) × 0.789 ^[2]
  • The 0.789 factor accounts for the density of ethanol (0.789 g/mL)
• Safe drinking limit = 2 units/day (M) vs 1 unit/day (F) ^[2]

Practical unit estimates ^[2]:

Blood Alcohol Concentration (BAC):

• 0.1 mg/L on breathalyser corresponds to 21 mg/dL in blood ^[2]
• BAC of 5 mg/dL (22 µg/100 mL on breathalyser) is the driving limit in HK ^[2]

1. Episode of harmful use of alcohol — single episode causing damage
2. Harmful pattern of use of alcohol — repeated pattern causing damage
3. Alcohol dependence — chronic relapsing condition with compulsion, tolerance, withdrawal
4. Alcohol intoxication — acute reversible syndrome
5. Alcohol withdrawal — physiological syndrome upon cessation/reduction
6. Alcohol-induced disorders — e.g. alcohol-induced mood disorder, psychotic disorder, neurocognitive disorder

• Alcohol Use Disorder (AUD) — mild (2–3 criteria), moderate (4–5 criteria), severe (6+ criteria out of 11)
• Alcohol intoxication
• Alcohol withdrawal
• Alcohol-induced mental disorders (specify type: depressive, anxiety, psychotic, sleep, sexual dysfunction, neurocognitive)

The ICD-10/ICD-11 dependence syndrome requires 3 or more of the following in the past 12 months. DSM-5 AUD uses a single list of 11 criteria (≥ 2 for diagnosis). The core features and their pathophysiology:

Chronic alcohol causes damage through multiple mechanisms:

1. Direct toxicity (ethanol and acetaldehyde are directly cytotoxic)
2. Nutritional deficiency (B1/thiamine, B3/niacin, B6, B12, folate, zinc, magnesium)
3. Metabolic disruption (NAD⁺/NADH ratio, oxidative stress, lipid metabolism)
4. Immune dysregulation (↓ immune function → infections)

Neurological Complications (High Yield — "6 Causes of Confusion in Alcoholism") [1]

The lecture specifically highlights "6 causes of confusion in alcoholism" ^[1] — this is a critical exam framework:

1. Acute intoxication — GABA potentiation, NMDA blockade
2. Alcohol withdrawal / Delirium Tremens — GABA/NMDA imbalance → excitotoxicity
3. Wernicke encephalopathy — thiamine (B1) deficiency → impaired glucose metabolism in vulnerable brain regions (mamillary bodies, medial thalamus, periaqueductal grey, cerebellar vermis)
4. Hepatic encephalopathy — ↑ ammonia (failed hepatic metabolism in cirrhosis) → astrocyte swelling, altered neurotransmission
5. Hypoglycaemia — ↓ NAD⁺ for gluconeogenesis
6. Subdural haematoma — falls + coagulopathy (↓ clotting factors from hepatic dysfunction + thrombocytopenia) → bridging vein tears

Wernicke-Korsakoff Syndrome — the hallmark nutritional neuropsychiatric complication:

• Wernicke encephalopathy (acute, reversible if treated early):

  • Classic triad: Confusion, Ophthalmoplegia (especially CN VI palsy → lateral rectus paralysis → diplopia), Ataxia (cerebellar vermis degeneration)
  • Why these areas? Thiamine (as thiamine pyrophosphate, TPP) is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase — areas with high metabolic demand and turnover (periventricular structures) are most vulnerable to energy failure
  • Only ~10% present with the classic triad — have a low threshold for diagnosis
  • Treatment: IV thiamine 500 mg TDS for 3 days (high-dose Pabrinex) — must be given before or with glucose

• Korsakoff syndrome (chronic, largely irreversible):

  • Develops in ~80% of untreated Wernicke patients
  • Profound anterograde amnesia (inability to form new memories) + retrograde amnesia (loss of old memories, with temporal gradient)
  • Confabulation — production of fabricated memories to fill gaps (not intentional lying; the brain's attempt to make sense of memory gaps)
  • Why? Damage to mamillary bodies and medial thalamic nuclei — key structures in the Papez circuit of memory
  • Only ~20% recover significantly even with thiamine supplementation

Other key neurological complications:

Psychiatric comorbidity in alcoholism is very common (lifetime diagnosis occurs in 55% of alcoholics) ^[2]

Causation: alcoholism often co-occurs with psychiatric disorders but causation is often unclear ^[2]

The relationship is bidirectional, with confounding factors ^[1]:

• Alcoholism → Psychiatric symptoms (alcohol-induced disorders)
• Psychiatric symptoms → Alcoholism (self-medication)
• Confounding factors complicate the picture ^[1]

Diagnosing comorbid psychiatric disorder in alcoholics is supported by ^[1][2]:

• Evidence of psychiatric disorder before onset of alcohol abuse or dependence ^[1]
• Evidence of persistent psychiatric symptoms during extended alcohol-free periods (over 4 weeks) ^[1]
• First-degree biological relative has documented psychiatric disorder ^[1]

Specific Comorbidities [1][2]

Alcohol-related mood disorders ^[2]:

• Moderate/heavy alcohol use can cause mood disorders
• Major depression: 4× risk in patients with Hx of alcohol dependence ^[2]
• Rarely easy to untangle cause and effect between mood disorder and alcoholism ^[2]
• Response to treatment is much less likely if comorbid alcoholism is NOT dealt with ^[2]
• Mx: abstinence (clears up upon abstinence but may persist for up to 4 weeks afterwards) ^[2]

Alcohol-related anxiety disorders ^[2]:

• Any form of anxiety (GAD, phobic anxiety, OCD…) while on heavy alcohol consumption ^[2]
• Must be distinguished from alcohol withdrawal syndrome ^[2]
• Mx: abstinence (subside gradually, but may persist up to 6 months) ^[2]

Alert to potential alcohol misuse in the following situations ^[2]:

• General: issues with ADL, family/work, finances, law (especially if frequent absences on Monday — because weekend binge → Monday withdrawal/hangover)
• Medical: intoxication, withdrawal, other medical consequences of alcohol
• Psychiatric: anxiety, depression, erratic moods, ↓ concentration/memory lapses, DSH/suicide

A comprehensive drinking history should include ^[2]:

• Initiation: reason for drinking, triggers, when did daily drinking start
• Use: current, regular, maximal use, describe a typical day (especially note time of first drink — an early morning drink strongly suggests dependence/relief drinking)
• Signs/symptoms of dependence: compulsion/craving, difficulty in control behaviour, stereotyped behaviour, tolerance, withdrawal, persistent use despite negative consequences, neglect of other interests and activities
• Impact: physical, mental health, ADL, family, work, social relationships
• Quitting: dates and reasons of abstinence, dates and reasons of relapses, attitude

Laboratory features of chronic alcoholism include ^[2]:

DSM-5 collapsed the older DSM-IV distinction between "alcohol abuse" and "alcohol dependence" into a single dimensional diagnosis: Alcohol Use Disorder (AUD), graded by severity. The logic: abuse and dependence exist on a continuum, not as discrete entities.

A problematic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period: ^[1]

Severity grading:

• Mild: 2–3 criteria
• Moderate: 4–5 criteria
• Severe: 6+ criteria

Specify remission: ^[2]

• In early remission: none of criteria met for ≥ 3 months but < 12 months
• In sustained remission: none met for ≥ 12 months
• In a controlled environment: where access to alcohol is restricted

ICD-10 retains the older two-tier system. This is important because HK clinical practice still uses ICD codes.

ICD-10 Harmful Use (F10.1): ^[2]

• A pattern of substance use that is causing actual damage to physical or mental health
• The damage may be physical (e.g. hepatitis) or mental (e.g. depression)
• NOT diagnosed if: (1) acute intoxication or "hangover" alone; (2) dependence syndrome, psychotic disorder, or another specific alcohol-related disorder is present
• Why this exclusion? Because harmful use is meant to capture the "intermediate" stage — if the patient already meets criteria for dependence, you code that instead (it's more severe and more specific)

ICD-10 Dependence Syndrome (F10.2): ^[2]

• ≥ 3 of 6 criteria present together at some time during the previous year:

These are historically influential — they directly informed the ICD-10 dependence criteria. Think of them as the clinical description that preceded the formal criteria.

Edwards and Gross — Alcohol Dependence Syndrome: ^[2]

Alcohol Intoxication DSM-5: ^[1]

DSM-5 criteria for Alcohol Withdrawal:

• A. Cessation of (or reduction in) alcohol use that has been heavy and prolonged
• B. ≥ 2 of the following developing within hours to days after criterion A: (1) autonomic hyperactivity (sweating, tachycardia > 100 bpm); (2) increased hand tremor; (3) insomnia; (4) nausea or vomiting; (5) transient visual, tactile, or auditory hallucinations/illusions; (6) psychomotor agitation; (7) anxiety; (8) generalised tonic-clonic seizures
• C. Symptoms cause clinically significant distress or impairment
• D. Not attributable to another medical condition or mental disorder
• Specify if: with perceptual disturbances (hallucinations with intact reality testing)

The name is a mnemonic — each letter stands for one question:

• Scoring: ≥ 2 "yes" answers = screen positive
• ↑ Sensitivity but modest specificity only ^[2] — many false positives
• Strength: very quick (4 questions, takes 30 seconds)
• Weakness: does not quantify consumption; does not detect hazardous drinking below the dependence threshold; poor specificity in populations with high baseline drinking rates

↑ Sensitivity + ↑ Specificity, probably most useful. 10-item screening tool by WHO ^[2]

The AUDIT is the gold-standard screening tool. It covers three domains in 10 questions:

• Scoring: 0–40; ≥ 8 = hazardous drinking (screen positive)
• Cut-offs for clinical action: 8–15 (brief intervention), 16–19 (extended intervention), ≥ 20 (further diagnostic evaluation for dependence)
• Why AUDIT is superior to CAGE: it quantifies consumption (not just consequences), it has better specificity, it detects the full spectrum from hazardous use through to dependence

CIWA-Ar assesses 10 domains: nausea/vomiting, tremor, paroxysmal sweats, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache/fullness, and orientation/clouding of sensorium. It is used to guide symptom-triggered benzodiazepine therapy (start at CIWA-Ar ≥ 8) ^[2].

Why symptom-triggered is preferred: it allows titration to the individual patient's actual withdrawal severity, avoids over-sedation in mild withdrawal, and has been shown to reduce total BZD dose and duration of treatment compared to fixed-dose schedules. However, it requires intensive monitoring (e.g. hourly assessments) ^[2].

Best combination for screening: GGT + MCV together have higher sensitivity than either alone. CDT is more specific and useful for relapse monitoring.

• Urine toxicology ^[2]: essential to rule out co-ingestion of other substances (benzodiazepines, opioids, stimulants, cannabis)
• Why? 20% of drug abusers are alcoholic; alcoholics are 6× more prone to become drug abusers ^[1] — polypharmacy is common and can complicate withdrawal and management
• Also important to check: paracetamol level (common co-ingestant in deliberate self-harm)

Minimum workup in any acutely presenting patient:

Diagnostic approach: ^[1]

• Moderate or heavy alcohol use ^[1]
• Major depression or mania ^[1]
• Persists for up to 4 weeks after abstinence ^[1]
• Clears up on stopping alcohol ^[1]

• Symptoms occur while patient is on heavy alcohol consumption ^[1]
• Symptoms subside gradually on abstinence, but may persist up to 6 months ^[1]
• Generalised anxiety disorders / Panic disorder / Phobic anxiety disorders / Social phobia / Obsessive compulsive disorder / PTSD ^[1]
• Must be distinguished from alcohol withdrawal syndrome ^[1]

• Chronic heavy drinkers ^[1]
• Auditory hallucinations ^[1]
• In clear consciousness ^[1]
• Distressing in content ^[1]
• Some develop schizophrenia, some remit after stopping alcohol use ^[1]
• Differentiate from delirium tremens — reduction in alcohol intake, clouded sensorium, visual hallucinations ^[1]

A comorbid primary psychiatric disorder (rather than alcohol-induced) is supported by: ^[1]

• Evidence of psychiatric disorders before onset of alcohol abuse or dependence ^[1]
• Evidence of persistent psychiatric symptoms during extended alcohol-free periods (over 4 weeks) ^[1]
• First-degree biological relative has documented psychiatric disorder ^[1]

The management is primarily supportive ^[2]. Why? Because ethanol is metabolised at a fixed rate (~7–10 g/hour, zero-order kinetics) — there is no antidote that speeds this up. Your job is to keep the patient alive and safe while the alcohol clears.

Delirium tremens is a medical emergency requiring hospitalisation ^[1]:

• Severe form of alcohol withdrawal ^[1]
• Occurs in about 24–96 hours of abstention ^[1]
• Confusion, hallucination, severe agitation, seizure ^[1]
• Mortality 5% ^[1]

Management of DT ^[1]:

• Most alcohol withdrawal seizures are self-limiting (< 5 minutes, generalised tonic-clonic)
• Immediate treatment: IV lorazepam 4 mg (or IV diazepam 10 mg)
• Status epilepticus: BZDs, phenobarbital, propofol ^[2]
• Long-term anticonvulsants are generally NOT indicated for isolated withdrawal seizures — the seizures are provoked by withdrawal, not by an underlying epileptic disorder
• Always CT head to rule out structural cause (subdural, SAH) — especially if focal features, first seizure, or atypical presentation

Wernicke's encephalopathy ^[1]:

• Medical emergency ^[1]
• 20% mortality ^[1]
• Only 20% detected in life ^[1] — highlighting the need for high clinical suspicion and low threshold for treatment
• IM/IV Thiamine ^[1]
• Progression to Korsakoff's Psychosis in 84% ^[1] if untreated

• May be useful in those with comorbid depression ^[2]
• SSRIs are first-line if treating comorbid depression
• NOT effective for alcohol dependence in the absence of comorbid depression
• Important: response to treatment of mood disorder is much less likely if comorbid alcoholism is NOT dealt with ^[2] — always treat the alcohol problem alongside the depression

• Efficacious for non-dependent, at-risk alcohol use ^[2]
• Involves: simple education and advice about safe levels of alcohol consumption ^[2]
• Efficacy: usually modest reduction in alcohol consumption over next few years ^[2]
• Utility: best for those with at-risk drinking (alcohol use above limit but non-dependent) ^[2]
• Typical format: 5–15 minute structured conversation (FRAMES: Feedback, Responsibility, Advice, Menu of options, Empathy, Self-efficacy)

• Basis: transtheoretical model of behaviour change — asserts that there are different levels of readiness to change among individuals ^[2]
  • Stages: precontemplation → contemplation → preparation → action → maintenance → (relapse is part of the cycle)
• MI assesses readiness for change followed by attempts to build internal motivation to change based on patient's stage ^[2]
• Principles: express empathy, develop discrepancy, roll with resistance, support self-efficacy ^[2]
• Techniques ^[2]:
  • Engage patient thoughtfully by reflective listening
  • Focusing on a specific issue to be changed
  • Evoking patient's own thoughts that motivate them towards change
  • Planning, at least in the conceptual aspect, for changes
• Efficacy: effective at short- and long-term across all substances ^[2]
• Utility: allows patient to generate own arguments and motivation for change; facilitates change especially when patient is ambivalent ^[2]

• Structured goal-directed form of psychotherapy ^[2]
• Involves ^[2]:
  • Psychoeducation to let patient understand how their thought processes contribute to their behaviour
  • Behavioural treatment to help patients develop new and adaptive ways of behaving and alter their social environment → in turn leads to change in thoughts and emotions
• Efficacy: modest positive effects on substance use ^[2]
• Specific CBT techniques for alcohol include: identifying high-risk situations, developing coping strategies, cognitive restructuring of pro-drinking beliefs, relapse prevention training

• Alcoholics Anonymous (AA) ^[2]: 12-step programme; peer support; emphasis on powerlessness over alcohol, spiritual growth, and lifelong commitment to abstinence
• Efficacy: strong evidence for AA/12-step facilitation; comparable to CBT in maintaining abstinence
• Not suitable for all (some patients find the spiritual emphasis off-putting; alternatives include SMART Recovery)

• Cue exposure therapy: to ↓ effect of drinking cues and to prevent relapse ^[2] — based on classical conditioning principles; repeated exposure to alcohol-related cues without drinking leads to extinction of the conditioned craving response
• Contingency management: offer incentives to encourage abstinence or discourage substance use ^[2] — operant conditioning; positive reinforcement for drug-free urine samples or attendance at sessions

• Dose-dependent CNS depression (covered in detail in prior sections)
• Alcoholic blackouts: transient amnesia lasting hours, without impairment of conscious level; caused by NMDA receptor inhibition in hippocampus → failure of long-term potentiation (LTP) ^[2]
• Traumatic brain injury: falls during intoxication are extremely common; alcoholics have impaired balance (cerebellar), poor judgement (prefrontal), and impaired protective reflexes → head injuries → subdural haematoma (further compounded by coagulopathy and thrombocytopenia)

• Occurs 6–36h after ingestion of > 30g alcohol ^[2]
• Mechanism: alcohol metabolism consumes NAD⁺ → ↑↑ NADH:NAD⁺ ratio → insufficient NAD⁺ for gluconeogenesis → hypoglycaemia ^[2]
• Mimics intoxication exactly (confusion, aggression, stupor, hypothermia) → always check H'stix ^[2]

• Occurs after a binge followed by fasting/vomiting → depleted glycogen stores + ↑ NADH:NAD⁺ ratio + ↑ free fatty acid mobilisation → ↑ ketone body production (β-hydroxybutyrate predominates over acetoacetate because of the shifted redox state)
• Presents with: anion-gap metabolic acidosis, abdominal pain, nausea, vomiting, tachypnoea (Kussmaul breathing)
• Glucose may be low, normal, or mildly elevated (unlike diabetic ketoacidosis where glucose is markedly elevated)
• Mx: IV fluids (NS with dextrose), thiamine, electrolyte correction

This is the single most important neurological complication to understand.

Wernicke Encephalopathy (WE) ^[1][2]:

• Mostly alcoholic / some non-alcoholic ^[1]
• Thiamine deficiency ^[1]
• Only 20% detected in life (Harper 1983) ^[1] — the classic triad is only present in ~10–16% of cases; most are diagnosed post-mortem
• Medical emergency ^[1]
• 20% mortality ^[1]
• IM/IV Thiamine ^[1]
• Progression to Korsakoff's Psychosis in 84% (Victor 1989) ^[1]
• Clinical triad ^[2]:
  • Encephalopathy: delirium with profound disorientation, apathy, inattention, amnesia ^[2]
  • Oculomotor dysfunction: ophthalmoplegia (combination of bilateral palsies), nystagmus (most commonly horizontal but can be vertical), pupillary abnormalities (sluggish or unequal pupils) ^[2]
  • Truncal ataxia: vermis-type — ataxic, wide-based gait with short steps ^[2]
  • Other features: polyneuropathy (50%), hypothermia (1–4%), vestibular dysfunction, coma (rare) ^[2]
• Diagnosis ^[2]: Caine criteria (≥ 2 out of 4): dietary deficiency, oculomotor abnormalities, cerebellar dysfunction, altered mental state or amnesia ^[2]
• Imaging: T2/FLAIR hyperintensity in mammillary bodies, medial thalami, periaqueductal grey ^[2]
• Course with treatment: ocular signs improve within hours to days; confusion subsides in days to weeks ^[2]
• Prognosis: mortality 17% in acute stage; majority have residual deficits (nystagmus, ataxic gait, memory deficits) ^[2]

Korsakoff Syndrome ^[2]:

• Develops in 84% of untreated WE patients ^[1]
• Profound anterograde amnesia (inability to form new memories) with relative preservation of other cognitive functions
• Confabulation — fabricated memories to fill gaps (the brain's attempt to make narrative sense of missing data; not deliberate lying)
• Retrograde amnesia with temporal gradient (more recent memories lost preferentially)
• Pathology: bilateral mammillary body and medial thalamic nuclei damage — these are key nodes in the Papez circuit (hippocampus → fornix → mammillary bodies → mammillothalamic tract → anterior thalamus → cingulate cortex → hippocampus), which is the circuit for memory consolidation
• Largely irreversible — only ~20% show significant recovery even with thiamine supplementation

• Pathogenesis: nutritional deficiency + direct neurotoxicity → degeneration of Purkinje cells in cerebellar cortex → vermis atrophy ^[2]
• S/S: subacute/chronic onset of ataxic gait followed by other features of truncal ataxia ^[2]. Heel-shin test is usually abnormal with severe gait disturbances, but finger-nose testing may reveal only mild abnormalities ^[2] — why? Because the vermis controls midline/truncal coordination (gait, posture), while the lateral cerebellar hemispheres control limb coordination (finger-nose). Alcohol preferentially damages the vermis.
• A midline section of the cerebellum from a non-alcoholic (left) and an alcoholic (right) patient shows atrophy of the folia and widening of the sulci in the anterior superior aspect of the cerebellar vermis in the alcoholic patient ^[1]
• Course: stabilises with abstinence, but progresses with continued drinking ^[2]
• Dx: clinical + CT/MRI showing cerebellar cortical atrophy especially affecting anterior vermis ^[2]
• Mx: cessation of drinking and nutritional supplementation ^[2]

• Prevalence: ~50–70% of alcohol abusers have some degree of cognitive deficits ^[2]
• Pathophysiology: usually multifactorial — NOT solely attributed to ethanol use ^[2]
  • Aetiological factors: head injury, vascular changes, direct alcohol neuronal toxicity ^[2]
  • Light/moderate use may paradoxically lead to ↓ risk of dementia, especially in wine drinkers ^[2]
• S/S: cognitive impairment simulating frontal lobe dementia (the frontal lobes are more susceptible to alcohol damage) ^[2] — executive dysfunction, personality change, disinhibition, impaired planning
• Alcohol-induced neurological deficit ^[1]:
  • Impairment in visuospatial processing ^[1]
  • Memory impairment ^[1]
  • EEG abnormalities ^[1]
  • Reduction in cerebral blood flow ^[1]
  • Reduction in cerebral glucose metabolism ^[1]
• Dx: diagnosed ≥ 8 weeks after abstinence, based on multiple criteria (Oslin 1998, DSM-5) ^[2]
• Neuroimaging findings ^[2]:
  • Cerebral cortical atrophy with enlarged lateral ventricles
  • Loss of grey matter in cortical and subcortical areas
  • White matter changes with demyelination on DTI

Alcohol and stroke ^[1]:

• Haemorrhagic stroke (15% of all strokes): heavy drinking → ↑ risk ^[1]
• Ischaemic stroke (85%): light/moderate drinking → ↓ risk ^[1]
• Wine is associated with ↓ risk of stroke, but no such relationship for beer/spirits ^[2]

Why does heavy drinking increase haemorrhagic stroke risk? Multiple mechanisms: (1) chronic hypertension (alcohol activates the RAAS and sympathetic nervous system); (2) impaired coagulation (hepatic dysfunction → ↓ clotting factors + thrombocytopenia); (3) direct vascular endothelial damage from acetaldehyde.

Why might light/moderate drinking decrease ischaemic stroke risk? (1) ↑ HDL cholesterol; (2) ↓ platelet aggregation; (3) ↓ fibrinogen. However, this is controversial — current WHO guidance (2023) and recent large studies suggest there is no safe level of alcohol for overall health.

• Symmetric distal sensorimotor polyneuropathy — "stocking-glove" distribution
• Painful paraesthesiae, burning feet, ↓ ankle jerks, distal sensory loss
• Mechanism: direct neurotoxicity of ethanol + B-vitamin deficiency (B1, B6, B12) → axonal degeneration ("dying-back" neuropathy — the longest axons are most vulnerable because they depend most on axonal transport, which requires energy/nutrition)
• Affects up to 50% of chronic alcoholics

• Rare demyelinating disorder of corpus callosum ^[2]
• Pathology: demyelination or necrosis of corpus callosum and adjacent subcortical white matter due to hypo-vitamin B (especially B₁) ^[2]
• S/S: usually in 40–60 y/o, with subacute onset of ^[2]:
  • Frontal syndrome: frontal dementia, personality changes
  • Others: seizures, spasticity, rigidity, paralysis, coma, death
• Neuroimaging: classically hypodense/vacuolation of corpus callosum with white matter lesions ^[2]
• Prognosis: variable — death, demented state, or recovery possible ^[2]

• Cause: rapid correction of hyponatraemia in acute intoxication → demyelination of pons ^[2]
• S/S: spastic paralysis of 4 limbs, pseudobulbar palsy, personality changes, inappropriate affect, delusions; "locked-in" syndrome in severe cases ^[2]
• Prevention: never correct hyponatraemia quicker than ~10 mmol/24h ^[2]
• Why the pons? The basis pontis has a unique vascular supply (end-artery territory) and a high density of oligodendrocytes that are vulnerable to osmotic stress. Rapid Na⁺ correction → rapid water efflux from brain cells → oligodendrocyte shrinkage and apoptosis → demyelination

• Moderate or heavy alcohol use ^[1]
• Major depression or mania ^[1]
• Persist for up to 4 weeks after abstinence ^[1]
• Clears up on stopping alcohol ^[1]
• 4× risk of major depression in patients with history of alcohol dependence ^[2]

• Symptoms occur while patient on heavy alcohol consumption ^[1]
• Symptoms subside gradually on abstinence, but may persist up to 6 months ^[1]
• Generalised anxiety disorders / Panic disorder / Phobic anxiety disorders / Social phobia / Obsessive compulsive disorder / PTSD ^[1]
• Must be distinguished from alcohol withdrawal syndrome ^[1]

• Chronic heavy drinkers ^[1]
• Auditory hallucinations ^[1]
• In clear consciousness ^[1]
• Distressing in content ^[1]
• Some develop schizophrenia, some remit after stopping alcohol use ^[1]
• Treatment with antipsychotics and advice to abstain from alcohol ^[1]
• Differentiate from delirium tremens: reduction in alcohol intake, clouded sensorium, visual hallucinations ^[1]

• Chronic heavy drinking ^[1]
• Clear sensorium ^[1]
• Schizophrenia-like syndrome ^[1]
• Remission on stopping alcohol ^[1]
• Recur with relapse of alcoholism ^[1]

• Delusional disorder with theme of partner's infidelity ^[2]
• Most commonly in men ^[2]
• Risk of violence: 56% of men and 43% of women ^[2]
• Mx: antipsychotics ^[2]

Why does alcohol disrupt sleep? Acutely, alcohol promotes sleep onset (GABA potentiation → sedation → ↓ sleep latency), but it suppresses REM sleep and disrupts sleep architecture in the second half of the night (as BAC falls, a "mini-withdrawal" hyperexcitability occurs → awakenings, vivid dreams). Chronically, tolerance develops to the sedative effect, but the sleep-disrupting effects persist. After abstinence, the upregulated excitatory systems take a very long time to re-equilibrate — hence the 2-year persistence.

Alcohol and suicide ^[1]:

• 7% of alcohol abusers die of suicide ^[1]
• Alcoholism is a factor in 30% of all completed suicides ^[1]
• 50% of suicide attempts have consumed alcohol at the time of the attempt ^[1]
• 96% of alcoholics who die by suicide continue alcohol use up to the end of their lives ^[1]

Why is alcohol so strongly linked to suicide? Multiple convergent mechanisms:

1. Acute disinhibition — alcohol removes inhibitory control over impulsive suicidal acts (prefrontal cortex depression)
2. Chronic depression — alcohol-induced mood disorder; hopelessness
3. Social isolation — progressive loss of relationships, employment, purpose
4. Comorbid psychiatric disorders — depression (40%), anxiety (32%), personality disorders
5. Means availability — intoxicated individuals are more likely to act on suicidal thoughts with available means
6. Cognitive constriction — alcohol narrows attentional focus to immediate distress, reducing ability to see alternative solutions