PBL 5- Wernickes-Korsacoff Flashcards
Where does first pass metabolism occur for alcohol?
- Stomach
- Liver ( 80-85%)
- 3-10% of alcohol is excreted unmetabolised in breath, urine and sweat
Why is the BAC different to the content of alcohol in the drink?
some is metabolised by FPM
When is BAC first detectable and when does it reach its peak?
- Detectable within 5 minutes
* Peak is after 30-90 minutes
What causes the effects of alcohol?
- the metabolites of alcohol
* Dependent on environmental factors
Why does the BAC stop rising after a while?
• The enzymes that are metabolising alcohol are saturated
How much individual variation is there for alcohol metabolism?
What contributes towards this?
• 3 fold variation in absorption, distribution, metabolism and elimination
Attributed to:
• Genetic variation in alcohol metabolizing enzymes
• Gender and age
○ Increased BAC in women (lower ADH, lower liver intake and less water volume)
○ Increased BAC in older people
• Speed of gastric emptying
○ Increased emptying (ie food intake) decreases the BAC
• Drinking pattern
○ Decreased metabolism in chronic alcoholism
• Drugs and smoking
What is the MAIN oxidative pathway of alcohol metabolism?
ADH pathway : Major pathway of metabolism
• Ethanol is converted to acetaldehyde via Alcohol Dehydrogenase (ADH) in the cytosol
○ Converts NAD to NADH as side product
○ Mostly occurs via Class 1 ADH in the liver however some genetic variation can change the affinity of the enzyme for alcohol.
○ In chronic drinking you can start to use Class 3.
○ Gastric mucosa have Class IV ADH
• Acetaldehyde is then converted to acetate via Acetaldehyde dehydrogenase (ALDH) in the mitochondria
○ Converts NAD to NADH
○ ALDH 2 is the predominant isoform
○ Asian populations have a polymorphism in the ALDH2 and have a reduced rate of metabolism- leads to an accumulation of acetaldehyde
• Acetate then enters the circulation
What accumulates in excessive drinking and why?
- Toxic acetaldehyde accumulation
* Saturation of Acetaldehyde
What pathway is induced in large alcohol consumption?
Microsomal ethanol oxidising system (MEOS)
• Induced 4-10 fold by large alcohol consumption ○ In a normal person this pathway has a low affinity so makes up a small amount of oxidation in the liver ○ Can occur in other tissues- brain • Contributes to alcohol tolerance (metabolic adaption) • Mediated by CYP 450 • Converts Ethanol + NADPH + o2 to Acetaldehyde • Occurs in the microsomes in the ER membrane
Risks:
• Used up a lot of O2
○ Can cause oxidative stress due to increased ROS formation
• Same enzymes used to metabolise drugs and other compounds
○ Causes increased hepatotoxicity of drugs like acetominophen
What oxidative pathway increases in the fasted state?
Where is this pathway predominant?
Catalase mediated alcohol metabolism
• Usually a marginal pathway except when in the fasted state • Converts ethanol + hydrogen peroxide to acetaldehyde via CATALASE ○ Hydrogen peroxide is sourced through beta oxidation of fatty acids in the liver • Occurs in peroxisomes
Major pathway in the BRAIN
• Because ADH is not physiologically active in the brain
• Small amounts are done by CYP 450 pathway
What is the main alcohol metabolism pathway in the brain?
- Catalase mediated alcohol oxidation
- Done in Peroxisomoes
- Converts Brain ETOH to brain Acetalaldehyde and then acetate
What is the non oxidative pathway of alcohol metabolism?
- only occurs in high BAC
- Not well understood
- Found in chronic alcohol abuse
- Develop alcoholic pancreatitis
- There is a low ADH level in the pancreas so the non oxidative pathway is used
- It is a marker of acute and chronic ethanol consumption
What is the recommended alcohol consumption?
• MEN ○ No more than 4 drinks per day ○ No more than 14 a week • Women ○ No more than 3 drinks on any day ○ No more than 7 drinks per week
Low risk limits may be lower for individuals due to genetic and environmental differences
What are the beneficial effects of alcohol consumption?
• Rosveratrol is concentrated in skin and seeds of grapes
• Lowers risk of CVD
• Protects against atherosclerosis
• Mechanisms
○ Anti-oxidant
○ Anti-thrombotic activity ( inhibits thromboxane synthesis and platelet aggregation, increases vasodilation)
○ Inhibits oxidation of LDL cholesterol and increases HDL cholesterol
What causes the toxicity of heavy drinking?
Accumulation of acetaldehyde
What occurs in accumulation of acetyl dehyde?
• Alcohol sensitivity in the periphery
○ Facial flushing, throbbing in head an neck
○ Headache, nausea, vomiting
○ Sweating, thirst, chest pain, palpitation
○ Dyspnea, hyperventilation, tachycardia
○ Hypotension, syncope, marked uneasiness
○ Weakness, vertigo, blurred vision, confusion
What are the health effects of heavy alcohol use?
• Thiamin deficiency • Vitamin B6 and folate deficiency • Disease risk increased: ○ Arthritis ○ Cancer ○ Foetal alcohol syndrome ○ Heart disease ○ Hypoglycaemia ○ Infertility ○ Kidney disease ○ Liver disease § Fatty liver § Fibrosis due to excessive accumulation of ECM proteins - collagen type 1 § Progression to cirrhosis after 10-20 years ○ Nervous disorders ○ Malnutrition ○ Obesity
What is the interaction between ethanol toxicity and malnutrition?
Causes primary and secondary malnutriation
• Primary
○ Replaces other nutrients
○ Empty calories (7.1 hcal/g)
• Secondary
○ Direct toxic effects on GI tract and liver
○ Maldigestion and malabsorption
How does liver injury occur in heavy drinking?
• chronic alcohol leads to increased gut permeability and therefore an increase in endotoxins
• Activation of Kupffer cells
○ Largest group of liver macrophages
○ Responsible for the immune response
• Increase in the number of cytokines and ROS
○ Inflammatory response
○ Oxidative stress
○ Activation of hepatic stellate cells
• Start to proliferate, migrate and sythesize more matrix collagen type 1
○ Stellate cells usually store vitamin A
○ Usually maintain the ECM
• Liver scarring and fibrosis
• Deterioration of liver function
What are the detrimental effects of the oxidation of alcohol for each pathway?
What is the effect of this?
• ADH pathway
○ Increase NADH: NAH ratio
○ Indirect formation of ROS due to the excess NADH needing to be oxidised by mitochondria
• CYP 450 pathway
○ Increase ROS formation due to increase in MEOS CYP2EI
• All
○ Acetaldehyde adducts formation
○ Excess acetaldehyde combines with protein, DNA or lipids to form a new compound - adducts
○ Produce Acetaldehyde which needs NAD to be metabolised- effect on NAD/NADH ratio
Effects of Adducts:
○ Are toxic
○ Interferes with protein function and secretion
○ Impaired DNA repari- carcinogenesis
○ Membrane alterations
○ Secretion of inflammatory chemokines- due to unknown substance
○ Liver damage
Effects of Oxidative stress
• Due to increased MEOS pathway forming ROS
• Due to increased NADH excess which is oxidised by mitochondria to NAD
• ETC components reduced creating ROS
• Initially the liver can buffer this through antioxidants like glutathione
• When depleted hepatocytes become damaged
Effects of NADH formation:
• Altered carbohydrate Metabolism
○ Inhibition of the TCA cycle
○ No gluconeogenesis and depletion of glycogen stores
○ Leads to hypoglycaemia
○ Increase in lactate leads to lactic acidosis
• Altered fatty acid metabolism
○ Decreased metabolism and increased FA synthesis
○ Acetyl coa does not go into TCA cycle and accumulates
○ Formation of lipids, cholesterol and ketone bodies induced
○ Aft accumulates in the liver causing Fatty liver and hyperlipidaemia
• Causes a redox state due to mitochondria oxidising excess NADH
• Hypoxia in perivenous hepatocytes
○ Excess NADH oxidised in mitochondria requires increase in O2 uptake
• Liver damage
What are the effects of BAC on brain function?
• Alcohol drinking markedly reduces brain metabolism
• Damage in heavy drinkers is worse in thiamin deficiency
• Brain shrinkage
○ Decreased white and grey matter volume
○ White matter loss can be partially reversed by alcohol abstinence
• Permanent neuronal loss
○ Superior frontal association cortex
○ Cerebellum
○ Mammillary bodies of the hypothalamus
○ Dorsomedial nucleus within the thalamus
○ Amygdala
What are the effects of alcohol on Neurotransmitters?
- Inhibits excitatory glutaminergic neurotransmission
- Agonist of GABA a receptors = increased GABA release
- Increased serotonin transmission
- Activation of opioid or cannabinoid receptors
- Increased dopamine release
- Complex regulatory interactions
Chronic use induces neuroadaptive responses in various NT systems resulting in
• Alcohol tolerance
• Alcohol withdrawal symptoms
• Alcohol dependence- relapse drinking behaviour
What is Vitamin B1 found in?
- fortified breads and creals
- Fish
- Lean meats
- Milk
What is the difference between dry beri beri and wet beri beri?
Lesions in the CNS
Dry = peripheral neuropathy
Wet = similar to congestive heart failure
How frequent is Thiamine deficiency in alcoholics?
• 25-80%
What is the importance of Thiamine in metabolism?
• Thiamine is an essential cofactor for many cellular reactions ○ Nucleic acid synthesis ○ Myelin ○ Protein synthesis • Critical for conversion of carbohydrates to energy ○ Glycolysis • Critical for CNS function ○ Synthesis of ACH ○ Synthesis of GABA
What are the effects of thiamine deficiency?
• major factor causing brain damage in alcoholics
○ After 10 years of heavy drinking 40% of alcoholics develop cerebellar degeneration
• Wernickes encephalopathy (lesions in CNS)
• Korsakoffs psychosis
• Beri Beri (Lesions in PNS)
Due to : • Altered cerebral energy metabolism ○ Decreased activity of KGDH ○ Impaired glucose metabolism ○ Lactic acidosis • Oxidative stress and inflammation ○ BBB disruption ○ Brain oedema in vulnerable cerebral areas • Impaired neurotransmitter function
How common is Korsacoffs psychosis?
• 80-90% of alcoholics with WE develop Korsakoffs psychosis
What are the acute effects of alcohol and what is the mechanism?
• Acutely it acts as a CNS depressant-
○ Disinhibition
○ Anxiolytic
○ Sedative
○ Decreases motor coordination
• Mechanism
○ Enhance inhibition
○ Reduces excitation
○ Enhances GABA function through the GABA a receptor (enhances chloride flux) in some areas of the brain such as the amygdala
○ Inhibition of NMDA glutamate receptor (inhibiting the passage of Na and Ca currents)
○ Activates endogenous opiates- enkephalin and b-endorphin
○ In the VTA causes inhibition of GABA interneurons through mu-opiod receptors. This then disinhibits the dopamine neurons
What drugs cause the greatest impact for society?
• Alcohol and nicotine
What are the neurological consequences of alcoholism?
• can occur with uncomplicated alcoholism (ie no other drugs or secondary consequences)
• Hepatic encephalopathy- large livers
• Wenickes encephalopathy
○ Dietary deficiency
○ Ocular motor abnormality (nystagmus)
○ Cerebellar dysfunction
○ Altered mental state or mild memory impairment
• Korsakoff syndrome
○ Global amnesia- deficits in encoding memory for new material
○ Working memory, problem solving and personality changes
○ Gait and balance problems
• Caused by
○ Up to 12.5 % of alcoholics can have deficiency of thiamine
○ Decreased absorption from GIT
○ Treated with thiamine
○ Decreased in countries with thiamine supplementation
How does alcohol consumption effect the bodies level of thiamine?
- Decreased thiamine in diet due to poor nutrition
- Decreased thiamine phosphorylation in the brain
- Decreased thiamine absorption from the GIT
- Decreased thiamine storage in the liver
- Decreased biosynthesis of amino acids and proteins
- Decreased ATP
What brain changes are seen in alcohol use that may contribute to cognitive decline?
What is the proposed mechanism of this?
Shrinkage of:
• White matter: ○ Cerebellum ○ Corpus callosum • Gray matter: ○ Thalamus ○ Hypothalamus ○ Cerebellum (purkinje cells) ○ Frontal cortex ○ Mammillary bodies (important for memory)
Mechanism:
• Increased oxidative stress from pro-inflammatory enzymes activated during ethanol intoxication and recruitment of NF-kB
• Decreased CREB family transcription that promote neuronal survival
○ Usually protect neurons from apoptosis through recruitment of survival factors
• The brain is capable to produce new neurons through neurogenesis
○ Alcohol binge drinking results in inhibition of neurogenesis
• Abstinence from ethanol can recovery neurogenesis
What is the effect of alcohol on the flow on ions?
- Ca/NA = inhibition via inhibition glutamate receptors
- Cl = enhances via stimulation of GABA a receptors
- K = enhances
- Ca = inhibits
How does alcohol become addictive?
• alcohol ingestion results in the VTA release of dopamine to the Ventral striatum nucleus accumbens
What effect to psychostimulants such as cocaine or amphetamines have on dopamine release?
What is the mechanism?
• acute effects: ○ Intense euphoria ○ Arousal/alertness ○ Suppression of appetite • Withdrawal effects ○ Dysphoria ○ Fatigue ○ Depression ○ Anxiety ○ Increased appetite • Mechanism ○ Cocaine: Inhibition of the reuptake transporter ○ Amphetamine : Cause monoamine release AND blocks the reuptake transporter
How does alcohol increase the dopamine release in the nucleus accumbens?
How does it differ from amphetamines?
- Usually the dopaminergic neurons in the VTA are under GABA inhibition (by a GABA interneuron)
- Alcohol acts on neurons in the brain that express mu-opioid receptors
- When alcohol stimulates then endogenous opioids such as b-endorphins are released
- The endorphins inhibit the GABA interneurons and therefore disinhibit the Dopaminergic neuron
- This causes release of dopamine into the nucleus accumbens
- Amphetamines work on the terminal end of the dopaminergic neurons
- Alcohol works in the VTA
What is the addiction cycle?
• acute reinforcement /recreational drug use
○ Self-medication of comorbid psychiatric disorders
○ Risk taking behavior
○ Early life trauma
○ Low socioeconomic status
• Escalating/compulsive use
○ Not all people who take drugs become addicted
○ Combination of genetic and epigenetic and environmental.
• Dependence
• Withdrawal
• Protracted withdrawal
○ Can lead to relapse
§ Stress, withdrawal effects
§ Stimulus response habits
• Recovery
What part of the brain is related to habit formation?
Dorsal striatum
What is addiction?
- uncontrollable desire to seek drugs in the knowledge that this pursuit may have serious adverse consequences such as death, imprisonment or loss of job or family
- Desire for drug reward is accompanied by a loss of desire for other rewards
- Loss of control over drug use or compulsive seeking behaviour
What is the DSM criteria for dependence?
• three or more of the following:
• tolerance
○ Need for increased amounts to achieve intoxication
○ Diminished effect with the same amount
• Withdrawal
○ Syndrome associated with the substance
○ The substance taken relieves the symptoms
• Taken in larger amounts over a longer time than intended
• Persistent desire or unsuccessful efforts to cut down or control it
• Persistent use despite harm or problems causes by the drug
• Important other things are given up
Large amounts of time taken to obtain the substance
What is acquired tolerance?
• pharmacokinetic:
○ Changes to absorption and distribution, increased metabolism/excretion of the drug
• Pharmacodynamic
○ receptor desensitization- uncouple from G proteins or reduced density
• Learned tolerance- behavioural and conditioned
What is physiological dependence?
- develops as a result of adaptation produced by resetting of homeostatic mechanisms in response to repeated drug use
- In the absence of the drug these mechanisms are once again out of balance
- Hyperarousal of the CNS occurs due to the Re-adaption to the absence of the drug
- Withdrawal occurs
What is psychological dependence?
- Adaptations in the brain cause the user to want to continue taking the drug
- When the drug is withheld neuroadaptions manifest as dysphoria and drug cravings
- Dopamine can have a role in drug craving AND also with visual or physical cues paired with drug craving
What are the symptoms and signs of withdrawal?
• Early stage: from a few hours to 48 ○ Anxiety ○ Anorexia ○ Insomnia ○ Tremor ○ Mild disorientation ○ Convulsions- between 24-48 hours ○ Sympathetic response- elevated blood pressure, increased heart rate § This may warn of impending delerium tremens
• Late stage : 2-4 days . Can last for 2-3 days ○ Delerium tremens
What are the signs of Delerium Tremens?
- Marked tremor, anxiety and insomnia
- Marked paranoia and disorientation
- Severe autonomic overactivity, including sweating, nausea, vomiting, diarrhea and fever
- Agitation, vivid hallucinations
- Reality testing fails, patient must be protected from self harm
- Seizures are RARE
- High fever = poor prognosis
- Death usually occurs due to secondary complication ie infection or injury
- Shock and hyperthermia can be fatal
- Fatality - 1-2%
Does everyone withdrawal?
What is the onset and how long does it last?
- 95% of alcohol dependent individuals can stop without major withdrawal
- Onset is 6-24 hours
- Lasts for 7-10 days
How common is a seizure in alcohol withdrawal?
• 5% of patients who present to ED with have a tonic clonic seizure
How Is alcohol withdrawal treated?
• Diazepam (long acting benzodiazepine)
○ Exhibit cross dependence with GABA a receptors - can act as alcohol and reduces the physical symptoms associated with withdrawal
• Thiamine ( always given with glucose)
Other less important options:
• clonidine
○ A 2 adrenceptor agonist- inhibits transmitter release from presynaptic neurons
• Beta-Blocker
○ B2 adrenoceptor antagonist
○ Blocks the sympathetic ove-ractivity
• Acamprosate
○ Reduces neuronal hyper-excitability caused by withdrawal of alcohol
○ Either decreases glutamate activity by inhibiting NMDA or increases GABA inhibition
○ Helps reduce alcohol craving in some people
What is the relationship between Alcohol, Benzodiazepine and GABA a receptors?
- The initial effects of alcohol result from facilitation of GABA a receptors
- Not all GABA a receptors are ETOH sensitive
- GABA a receptors are targets of Benzos so can be used in withdrawal to mimic alcohol.
What happens in the in stress response of withdrawal?
• There is activation of the extra-hypothalmic CRF system in the amygdala
What score do you need on the DSM 5 to have substance use disorder?
- 2-3 mild
- 4-5 moderate
- > 5 = 5 severe
What drugs have particular risks for withdrawal?
• alcohol and benzos
○ Seizures and delirium tremens
If a seizure occurred during drug withdrawal- when would it happen?
- 6-24 hours after the last drink
* Tonic clonic in type
How should concomitant drug dependence and mental health be managed?
- combined treatment from ONE service
- Integration should be organized by the clinician not the patient
- Provide comprehensive treatment
- Long term commitment needed
- Stage wise motivational treatment
Where is Thiamine sourced, metabolised and stored?
• sources from liver, kidney, meat, wholegrains , legumes, fortified cereals and bread
• Metabolism:
○ Readily absorbed in the GIT
○ Turned into the active form - Thiamine pyrophosphate
• Storage:
○ Very little stores
• Function:
○ Required in carbohydrate and amino acid metabolism
○ Functions as a coenzyme
§ Glycolysis, TCA and pentose phosphate cycel
How does a thiamine deficiency effect the nervous system?
• CNS depends almost entirely on carbohydrate metabolism for energy
• Processes that require thiamine in the CNS:
○ ATP production
○ Myelin production
○ Neurotransmitter synthesis
○ Axonal conduction
○ Acetylcholine and serotonin synaptic transmission
• IN deficiency
○ Decreased utilization of glucose by 50-60%
○ Increased utilization of ketone bodies derived from fat metabolism
○ Neurons undergo apoptosis
○ Focal acidosis in susceptible areas
○ Oxidative stress and endothelial dysfunction
○ Degeneration of myelin sheaths in PNS and CNS
○ Peripheral lesions extremely irritable resulting in polyneuritis
§ Pain radiating along the course of a peripheral nerve
○ Fibre tracts in the cord can degenerate so much that paralysis occasionally results
○ Muscle can atrophy resulting in severe weakness
What are the features and the classic triad of Wenickes encephalopathy?
- Acute
- Medical emergency
- Reversible
○ Death
○ Permanent neuropathy
○ Cognitive impairment• Triad: usually not all present
○ Ophthalmoplegia
§ Nystagmus (horizontal/horizontal and vertical)
§ Bilateral lateral rectus muscle palsies
§ Conjugate gaze palsies
§ Caloric test is usually abnormal and reveals unilateral or bilateral absence of ocular movement
○ Ataxia
§ Truncal ataxia (most common)
§ Wide based unsteady gait
§ Limb ataxia- less common (legs > arms)
§ Affects lower limbs much more common than the upper limbs
○ Confusion § Mental state changes in 80% of patients § Delerium § Inattention § Drowsiness § Decreased spontaneous speech § Marked impairment of recent memory § Inability to retain new information § Confabulation is common § If untreated will progress to lethargy, coma and death
• Commonly associated with heavy alcohol use or malnutrition or both
What are some non-alcoholic causes of Wernickes?
- Anorexia
- Dieting
- Hyperemesis
- Gastrointestinal surgery- ie bariatric surgery
- Haemodialysis or peritoneal dialysis
- Prolonged intravenous feeding
- Refeeding after prolonged fasting or starvation
- Systemic malignancy
- Acquired immunodeficiency syndrome
What is the epidemiology of Wernickes?
- Incidence is 1-2%
- Mean age of death is 55 years
- 95% are males
- Pre-mortem diagnosis is only made in 16% of cases
What is the Caines criteria for diagnosis of Wenickes?
Diagnosis can be made with 2 of the following:
• Dietary Deficiency
• Occulomotor abnormalities
• Cerebellar dysfunction
• Altered mental state or mild memory impairment
What are the radiological features of Wernickes encephalopathy?
CT • Reduced attenuation density ○ Periaqueductal grey matter ○ Medial portion of the thalamus • May be negative in the acute phase of WE
MRI • Signal intensity alterations • Typical lesions ○ Thalami ○ Mammillary bodies ○ Tectal plate ○ Periaqueductal area • Atypical lesions ○ Cerebellum ○ Cranial nerve nuclei ○ Cerebral cortex
What Pathological features are consistent with Wernickes?
Characteristic lesions are found:
* Mammillary bodies * Hypothalamus * Thalamus * Periaqueductal gray matter * Colliculi * Floor of the fourth ventricle
Acute pathology:
* Astrocyte swelling * Vascular dilation * Endothelial swelling * Early demyelination
Chronic Pathology: • Incomplete loss of neurons • Damage of axons • Demyelination • Loosening or vacuolization of the neuropil • Punctate Haemorrhages
What are the features of Korsakoff syndrome?
• Chronic and late neuropsychiatric manifestation
Features:
• Confabulation
• Anterograde and retrograde amnesia
• Intact sensorium
• Long term memory and cognitive skills relatively preserved
• Attention and social behaviour preserved
• Memory impairment will correlate with the lesion in the anterior/medial thalamus
• Irreversible- little chance of recovery
Alcoholic cerebellar degeneration:
How long does this take ?
What is the mechanism and features?
Caused by:
• Alcohol dependence in the long term (More than 10 years)
• Can occur without WE
• There is a role of nutritional deficiency and ethanol neurotoxicity
• Loss of purkinje neurons within the anterior and superior vermis of the cerebellum
• Lesions are confined to the superior vermis
Features:
• Slow insidious onset
• Ataxia- lower limbs
What is alcoholic neuropathy?
What causes it?
Features:
• Most common peripheral neuropathy seen in GP
• Insidious and progressive
• Gait difficulty
• Distal muscle wasting
• Loss of tendon reflexes
• Sensory loss (glove and stocking distribution)
• Burning paresthesia, hyperpathia and dysaesthesia
• Legs always more affected than the arms
• Muscle weakness and cramps
• Sensory ataxia caused by loss of joint position sense may coexist with alcoholic cerebellar ataxia
• Autonomic dysfunction- vagal nerve or sympathetic nerve involvement
Caused by:
• Deficiency of thiamine and other B vitamins
• Inadequate dietary intake, impaired absorption
How is Thiamine deficiency diagnosed?
- clinical features on the background of nutritional deficiency or high metabolic demands
- Serum thiamine assays are not reliable
- Erythrocyte transketolase activity and the percentage increase in activity (in vitro) following the addition of thiamine pyrophosphate (TPP) may be more accurate
- Electrodiagnostic studies shows non-specific findings of an axonal sensorimotor polyneuropathy
What is the Management of thiamine deficiency?
• Replacement of thiamine initially IV for 3-5 days then orally for several weeks
• Other water soluble B vitamins should be given because multiple deficiencies are common
• The need for folate and B12 should be assessed
• Glucose loading can precipitate WKS in patients with thiamine deficiency
• Nutritionally balanced diet
• Treatment of alcohol dependence
○ Disulfiram, Naltrexone, Acamprosate
○ Counselling
What is the prognosis of Wernickes encephalopathy?
If treated:
• Oculomotor signs improved within minutes to hours
• Ataxia and vestibular function takes a week
• Some deficits remain:
○ Nystagmus
○ Ataxia
○ Memory deficits
• Peripheral neuropathy is slow to recover because it requires axonal regeneration
If not treated:
• 20% will die
• 85% will get Korsakoff syndrome
What is the commonest cause of peripheral neuropathy in Australia?
Alcohol related neuropathy
