Post on 08-Nov-2014
description
NEUROPSYCHIATRIC COMPLICATIONS OF
ALCOHOL DEPENDENCE SYNDROME
PRESENTER- Dr. PAVITHRA
C/P- Dr. SIDDHARTH SHETTY
INTRODUCTION
Alcohol is remarkable both for its long history & ubiquity of use & for diverse range of neuropsychiatric disorders it can produce.
Half of drinkers experience temporary alcohol related problems like impaired memory & blackouts etc..
Common during intoxication & withdrawal.
Clinician has to distinguish between temporary alcohol-related psychopathology which is likely to disappear after abstinence and independent psychiatric syndromes that may require long-term support and medications.
80% of ADS patients develop temporary symptoms out of which around 40% persist enough to meet the criteria for major psychiatric disorders.
Neuropsychiatric complications can be classified as:
1. Direct effects- alcohol intoxication, aggression, blackouts,
2. Disorders due to withdrawal- tremors, seizures, hallucinoses, delirium tremens.
3. Associated nutritional deficiencies- Wernicke’s encephalopathy, Korsakoff’s syndrome, Peripheral neuropathy, Cerebellar degeneration.
4. Alcohol induced conditions- dementia, mood disorder, anxiety disorder, psychotic disorder.
5. Resultant end stage liver disorder or bone marrow suppression ensuing their own neuropsychiatric complications- hepato-cerebral degeneration.
ALCOHOL INTOXICATION
Effects of alcohol are sensitive to dose (blood level alcohol), timing ( rising/ declining), & social context.
CNS depressant- target on GABA A receptor augmentation of GABA neurotransmission.
Associated with early net effects on opioidergic & dopaminergic neurotransmission in ventral striatal reward pathways.
Early effects produce stimulation, subjective exhilaration, excitement & loquacity.
Personality factors, environmental & cultural influences shape outward evidence of intoxication.
At higher doses there is net depressant effects on wide spread cortical networks leading to:
Level
20–30 mg/dL
(.2–.3g/dL)
30–80 mg/dL
80–200 mg/dL
200–300 mg/dL
>300
Likely Impairment mg/dL
Slowed motor performance and decreased thinking ability
Increases in motor and cognitive problems
Increases in incoordination and judgment errors. Mood lability. Deterioration in cognition
Nystagmus, marked slurring of speech, and alcoholic blackouts
Impaired vital signs and possible death
Mellanby effect- symptoms depend on rate of rise of blood concentrations to given level & length of time alcohol is present in body.
Quick rise will produce effects at a lower level of blood alcohol than gradual rise.
For a given rate of rise the effects will be less marked if alcohol has been present at a constant level sometime before
AGRESSION
Mechanism:Psychostimulant effect
Diminished anxiety & pain perception
Impaired inhibition.
Severe form- pathological intoxication,
alcohol idiosyncratic intoxication, acute
alcoholic paranoid state, manie a potu
Presents as an outburst of uncontrollable rage & excitement leading to destructive actions against other persons & property.
Behavior is described as out of character for the individual concerned, duration is short, & there is subsequently amnesia for entire episode.
Coid- found nothing to support the notion.
ALCOHOLIC BLACKOUT’S
characterized by memory impairment (anterograde amnesia) for the period when a person was drinking heavily but remained awake.
Is the result of the ability of high doses of any brain depressant (e.g., alcohol or benzodiazepines) to interfere with the acquisition and solidification of memory.
40 percent of drinkers have at some time had a blackout
The memories might return with passage of time & some times recall was facilitated by further drinking.
Occurrence is directly related to
severity & duration of drinking.
Pathogenesis- uncertain.
State dependent training-learning transfer was proved to be better when the subject was intoxicated in both the first & 2nd tests sessions than when intoxicated in the first but sober in the 2nd.(Goodwin et al)
SLEEP IMPAIRMENT
Alcohol helps a person fall asleep more quickly, but if the intake in an evening is > 1 or 2drinks, the subsequent sleep pattern is likely to be impaired.
Alcohol Suppresses REM sleep,
inhibits stage 4 sleep late in the night,
subsequently associated with frequent alternations between sleep stages (sleep fragmentation) & more intense & disturbing dreams late in the night as blood alcohol level falls.
WITHDRAWAL SYNDROMES
consists of two components.Physical signs such as tremor which are determined by the degree of physical dependence developed during the most recent drinking bout.
Seizures hallucinations & delirium that reflect long term CNS dysfunction accruing over many years of repeated intoxication & withdrawal
Tremors, nausea & transient hallucination in clear consciousness- 3-12 hrs
Seizures- 12- 48 hrs
Delirium tremens- 3- 4 days
Temporary alleviation on
taking alcohol.
TREMORS
Commonest, associated with general weakness, nausea & irritability.
Mild forms- occur after a single night’s abstinence & after a period of drinking for only several days.
Severe forms- 12- 24 hrs after stopping, only after continuous weeks of drinking.
Subsides over several hrs or
days but after severe attacks
may take 1- 2 weeks
HALLUCINOSIS
¼ of tremulous patients have disordered sense perception- transitory misperceptions of familiar objects to illusions & hallucinations
Benign lasting less than 24 hrs- few days.
Hallucinations- visual/ auditory, fleeting in clear consciousness.
Auditory- simple, tinnitus common
Visual- blurring, flashes of light, moving animals usually distorted
Cause- withdrawal of alcohol, ? Thiamine deficiency.
Alcoholic hallucinosis- rare, verbal auditory hallucinations occur alone.
Buzzing, roaring, ringing of bells, threatening voices, derogatory remarks, command hallucinations, third PAH.
Secondary delusional interpretations follow
Similar to schizophrenia- no thought disorder, delusions follow only hallucinatory experience, no incongruity of affect & insight is regained.
90% transient & disappears within a week, few persists for months – years.
Factors which determine prolongations of hallucinations or transit to schiz like illness remain unknown.
Repeated attacks may make patient ultimately more vulnerable to the type of attack leads on to schizophrenic deterioration.
WITHDRAWAL SEIZURE
Consumption of alcohol can precipitate seizures in person with seizure disorder.
Withdrawal seizures or rum fits occurs in person without predisposition of seizure
Occur after heavy consumption, usually within 12- 24 hrs of termination of long continued bout
Occasionally occur while consumption continues due to transient fall in blood alcohol levels
Usually GTCS bouts of 2- 6 at a time, rare- status epilepticus
30 % fits DT. 30% DT & 10% AH seizures
EEG- abnormal during episode but reverts back to normal
DELIRIUM TREMENS
Most serious with mortality of upto 5%
Fully developed consists of vivid hallucinations, delusions, profound confusion, tremor, agitation, sleeplessness & autonomic overactivity..
Uncommon- < 5% of withdrawals.
McNichol (1970) recognised 3 grades in development of complete syndrome.
Mental sluggishness with tremor & evidence of residual intoxication.
Emotional lability, agitation, fearfulness, increased PMA, autonomic disturbance, nightmares,& disorientation.
Onset of definitive DT.
Autonomic hyperactivity- diagnostic importance.
C/F- sudden onsetUsually at night,
Restlessness, fear, insomnia
Startles with least sound
Vivid nightmares
Transient illusions & hallucination
(visual, auditory, tactile)
Insight retained
Fluctuating levels of consciousness
tremulous
Severe cases- ataxia, dehydration
Autonomic disturbance- perspiration, flushing, pallor, dilated pupils, weak rapid pulse & mild pyrexia
Epileptic seizures- 1/4th
Slurred speech with paraphasias, incoherent, fragmented
EEG- fast activity
Outcome- short lived, less than 3 days
COGNITIVE IMPAIRMENT & CEREBRAL ATROPHY
Long continued abuse of alcohol lead to severe cognitive impairment- contributory cause
10% of patients suffer from mild- severe forms.
Deficits in memory, visuospatial competence, abstracting ability, & complex reasoning.
Psychological assessments during first few weeks of abstinence show substantial recovery of intellectual & memory functions for a period of several months.
By 1 yr psychological deficits persists in:Tests of psychomotor speed,
perceptual- motor functioning
visuospatial competence
Abstracting ability & reasoning
memory
New learning capacity impaired
Impaired capacity for complex figure ground analysis.
Deficits in frontal lobe functions- personality change, circumstantiality, plausibility, weakness of volition
Vicious cycle with worsening of cognitive status contributing to potentiation of addiction.
Women more vulnerable. With visuospatial function & verbal & non verbal memory impairment.
Abstainers improve more than alcoholics who initially abstain but return to drinking.
Older age- brain damage+ alcohol+ other pathologies ( ageing, trauma, vascular changes, hepatic dysfunction) serious & irreversible changes.
Neuropathology: Cerebral atrophy- mild- moderate
White matter in cerebrum is reduced & ventricles enlarged by 1/3rd.
Thickness of corpus callosum reduced by 20%.
Micro- arachnoidal thickening & cell degeneration & loss in smaller of superficial & intermediate laminae
Marked alterations in dendritic morphology in hippocampal pyramidal neurons, dentate granular layers & cerebellar vermis cell degeneration & loss.
22% reduction in number of neurons in superior frontal cortex with reduction in size of neurons in motor & cingulate cortices
Disintegration of nerve fibres.
More lesions in base of brain & cerebellum- wernicke
Direct toxic affects + thiamine def disruption of monoaminergic & cholinergic inputs to cortex cognitive deficits.
Quantitative study of extent of dendritic arborisation in layer III pyramidal neurons from frontal & motor cortex- significant reductions in mean dendritic length, number of branches, & mean width of basal dendritic fields.
Abstinence allows regrowth of dendritic branching & return to normal thickness of strata plasticity inherent in adult brain with regard to dendritic growth & sprouting.
Neuroimaging: 50- 70% of severe chronic alcoholics show cortical
shrinkage or ventricular dilations or both.
Changes found in young alcoholics within the first decade of alcohol abuse, more marked in older age groups.
Planimetric measures of lateral ventricular size show 50% enlargement
Atrophy of cerebellar vermis & frontal lobes- high proportion.
Females more vulnerable.
1/3rd subjects show normal scans.
MRI: ventricular enlargement & increase in CSF over cortical surface.
Significant reductions in grey matter in medial temporal, superior frontal & parietal regions
Subcortical grey matter was reduced- caudate nucleus & diencephalon
Changes in cerebellar volume
White matter degradation on diffuse tensor imaging.
Clinical association:Duration & severity of alcohol abuse- little relation severity of cerebral changes
Indirect evidence that episodic drinking may be less harmful.
Duration of abstinence- increasing length of abstinence prior to scanning, changes become less pronounced.
Some degree of persistent ventricular enlargement remains.
Significant decrease in both ventricular size & suarachnoid spaces during early weeks of abstinence- ? Dehydration & rehydration of brain, increased protein synthesis, or incresed dendritic growth.
WERNICKE’S ENCEPHALOPATHY
Neuropsychiatric reaction to severe thiamine deficiency.
Disorder of acute onset characterised by nystagmus, abducens & conjugate gaze palsies, ataxia of gait & global confusional state.
Wernicke first described it in 1881 as polioencephalitis haemorrhagica superior.
Alexander in 1940 demonstrate lesions
in the brains of thiamine deficient
pigeons
Alcohol leads to thiamine deficiency:Replacement of vitamin containing foods by alcohol
Impaired absorption of thiamine from gut.
Impairment of storage by liver
Decreased phosporylation to thiamine pyrophosphate.
Excessive requirements for metabolism of alcohol
In 50% of patients suffering from WE evidence of alcohol is reported.
Place to place prevalence varies- beverage consumed, its thiamine content, patterns of drinking & patterns of dietary neglect.
Thiamine in form of thiamine pyrophosphate is important for:
Transketolase- essential for maintenance & synthesis of myelin.
Pyruvate dehydrogenase & alpha ketoglutarate dehydrogenase- role in brain glucose metabolism & energy production.
Personal susceptibility in form of inborn abnormality by way of reduced affinity between TPP & enzymes.
Transketolase exists in a number of isoenzyme variants.
WERNICKE’S ENCEPHALOPATHY:
Encephalopathy appeared when acute & severe thiamine depletion was superimposed on partial deficiency whereas other forms (cardiac & neuritic) resulted from less severe&& more prolonged lack.
CLINICAL FEATURES:
Onset- abruptly.
Commonest presentations- mental confusion or staggering gait.
Triad- global confusion, ophtalmoplegia, ataxia
Harper et al found classic triad in 16%, 28% with 2 signs, 37% with one & 19% with no signs.
Other features- prodromal anorexia, nausea, vomiting, marked memory disturbance, lethargy, hypotension, hypothermia, stupor coma.
Age- throughout adult life.
Males twice affected.
Pattern- steady drinking extending over months or years coupled with inadequate food intake.
O/E Victor et al found: Ocular abnormalities- 96%
Nystagmus, sixth nerve palsies producing lateral rectus weakness, conjugate gaze paralysis.
Pupils- sluggish. Signs evanescent, resolves easily with treatment.
Ataxia- 87% Inability to stand, differences in heel toe walking. Intention tremor in legs/ arms- rare.
Peripheral neuropathy- 82% confined to legs Subjective complains of weakness, paraesthesia & pain
Serious malnutrition- 84% Redness or papillary atrophy of tongue, cheilosis, angular
stomatitis, telangiectases, dryness & discolaration of skin.
Evidence of liver disorder in 2/3rd. Abstinence syndrome – 13%
Epileptic fits, hallucinoses, delirium tremens
Mental abnormalities- 90% Commonest- global confusion with disorientation, apathy,
derangement of memory. Drowsy, marked indifference & inattention to their
surrounding.
Impairment of consciousness rarely profound or persistent. Spontaneous activity & speech minimal- irrational or
inconsistent. grasp, awareness, responsiveness impaired Misidentifications, physical & mental fatigability,
concentration difficulties Perceptual distortions,, vivid hallucinations, insomnia,
agitation, autonomic overactivity- evanescent & not severe. When confusion reduces- defect in memory with 14% of
typical Korsakoff memory defect. Confabulation common in early stages.
Subclinical forms common
Pathology:Symmetrical lesions found predominantly around wall of third ventricles, periaqueductal region, floor of fourth ventricle, thalamic nuclei ( paraventricular parts of medial dorsal nuclei, anteromedial nuclei & pulvinar). Mamillary bodies, terminal portions of fornices, brain stem, anterior lobe & superior vermis of cerebellum.
Convolutional atrophy- 27%
Micro- affects neural elements (neurons, axis cylinders, blood vessels & glia)
- myelinated fibers affect more
- astrocytic & histiocytic proliferation, proliferation of blood vessels, petechial heamorrhages ( terminal)
Ophthalmoplegia- lesion of 3 & 6 CN nuclei & adjacent tegmentum.
Nystagmus- vestibular nuclei
Ataxia- vestibular nuclei & anterior lobes & vermis of cerebellum.
Lesion in mamillary body, mamillo thalamic tract, anterior nuclei of thalamus critical for persistent & severe anterograde memory deficit ok Korsakoff syndrome.
Investigations:
EEGdiffuse slowing- 50%
prominent generalised asynchronous slow waves
bysynchronous slow waves
Decrease of alpha rhythm
CSF- mild elevation of protein
CT- symmetrical areas of decreased attenuation in region of thalamus.
MRI- atrophy of mamillary bodies, hyperintensities surrounding third ventricle & aqueduct, reductions in both white & grey matter cerebral blood flow.
COURSE & RESPONSE TO TREATMENT:
Sixth nerve palsies recovered – hrs to days
Horizontal nystagmus persist- 2/3rd
Ataxia improve within first week- month
1/4rd ataxia persists,1/2 left with permanent unsteadiness of some degree.
Polyneuropathy disappears slowly
Diminution or absence of tendon reflexes- permanent
Global confusion- recovers 2-3 weeks & disappears by 1-2 months.
84% develop- typical amnesic syndrome.
KORSAKOFF’S SYNDROME
Described by Korsakoff in 1887
Named as psychosis polyneuritica
Cause- ? Thiamine deficiency/ ? Direct effect of alcohol.
Link between WE & KS
Onset- delayed for weeks to months.
Continues for 2 yrs.
Clinical features: anterograde & retrograde (several years) amnesia,
Relative preservation of other cognitive functions
Subtle deficits in visuoperceptive & abstract ability
Confabulation in chronic stage.
Impaired executive functions & frontal lobe tests
Course-Complete recovery in ¼
Partial recovery in ½
Rest no improvement.
Neuroimaging:
CT-Wider third, lateral ventricle, sylvian fissures & interhemispheric fissures.
Atrophy in frontal sulcal & perisylvian areas
MRI-Greater grey matter losses in medial temporal & orbitofrontal cortex
Significant reduction in thalamic volumes
SPECT- impaired flow in frontal regions
PET- 20% reduction in glucose metabolism with hypometabolism in cortical areas, thalamus & BG
- hypometabolism in 3 areas- thalamic, venteromedial frontal, retrosplenial regions
EEG- mild- moderate generalised slowing
PERIPHERAL NEUROPATHY
Cause- thiamine deficiency with pyridoxine & pantothenic acid deficiency, neurotoxic effect of alcohol, toxins in beverages
C/F-Symptomless
Sensory disturbances- numbness, pins & needles, burning sensation in feet
Weakness progress to foot drop with wasting of leg muscles
Cutaneous sensory loss peripherally in hands & feet
Intense hyperasthesia on stoking skin
Tenderness in calf muscles
Odema of different parts
Dysphoric changes in skin & nails.
Loss of ankle reflexes
Isolated, associated with WE, KS, or DT
CEREBELLAR DEGENERATION
Uniform cerebellar degeneration with ataxia of stance & gait.
Arms little affects & nystagmus & dysarthria absent.
Slow progression- weeks – months, static for years
CT/ MRI- cerebellar cortical atrophy
PET- hypometabolism in superior cerebellar vermis
Pathological changes restricted to anterior & superior aspect of vermis & cerebellar hemispheres
Purkinje cell loss
AMBLYOPIA
Retrobulbar neuritis- complete blindness, rare
Progress over 1- 2 weeks
Dimness for central vision, red & green
Associated with peripheral neuropathy
Smoking associated
Deficiency of thiamine & vit B 12
Acute blindness- common in methyl alcohol poisoning due to direct toxic effects
MARCHIAFAVA- BIGNAMI DISEASE
Rare, formerly thought to be restricted to Italian males & vine consumption
C/F- ataxia, dysarthria, epilepsy & severe impairment of consciousness, slowly progressive forms with dementia, spastic paralysis of limbs.
Extensive demyelination affects corpus callosum, adjacent subcortical white matter, optic tracts & cerebellar peduncles
Mortality high, recovery late
CT/ MRI-lesions in corpus callosum
? Nutritional deficiency
CENTRAL PONTINE MYELINOLYSIS
Acute & fatal complication
C/F- obtundation, bulbar palsy, quadriplegia, loss of sensation in limbs & trunk
- vomiting, confusion, disordered eye movements, coma- common
- locked in syndrome- mutism & paralysis but relatively intact sensation & comprehension
Lesion lies in center of basal pontis & adjacent areas
MRI- focus of demyelination
Also seen in conditions causing hyponatraemia- severe burns, hyperemesis over rapid correction affecting pons osmotic demyelination syndrome
ALCOHOL INDUCED PSYCHIATRIC CONDITIONS
Present during intoxication or withdrawal states
Usually remit by 4 weeks & completely disappear by 6 months of abstinence
If persists >6 months consider independent disorderMOOD DISORDER
Depressive/ mania symptoms which meet criteria
80% report h/o intense depression, 30- 40% depressed > 2 weeks & only 10- 15% meet criteria for MDD= general population
Several weeks to 1 month patients presents with mood swings or intermittent symptoms of sadness- cyclothymia/ dysthmia
ANXIETY DISORDER
80% report panic attack, other symptoms like that of social phobia, agoraphobia
PSYCHOTIC DISODER
3% experience auditory hallucinations, or paranoid delusions
UNSPECIFIED
HEPATOCREBRAL DEGENERATION
Hepatic encephalopathy- altered sensorium, frontal release signs, ‘metabolic' flapping tremor, hyper-reflexia, extensor plantar responses, and occasional seizures.
some patients progress from stupor to coma and then death, others recover and suffer recurrent episodes.
brain shows enlargement and proliferation of protoplasmic astrocytes in the basal ganglia, thalamus, red nucleus, pons, and cerebellum, in the absence of neuronal loss or other glial changes.
Patients who do not recover fully after an episode of hepatic encephalopathy go on to develop a progressive syndrome of tremor, choreoathetosis, dysarthria, gait ataxia, and dementia.
Hepatocerebral degeneration may progress in a stepwise fashion,
APPROACH TO PATIENT
Detailed history from patient ( if possible), family members, regarding the symptoms, onset, variation, past history etc.(Rule out organic causes & independent psychiatric disorders.)
Detailed examination (MSE, GPE, Systems)
Investigations.Treatment
a timeline should be established noting:
(1) the approximate age of onset of alcohol problems severe and repetitive enough to justify a diagnosis of alcohol dependence
(2) periods of abstinence of several months or more, and
(3) the ages at which the patient met the criteria for the major psychiatric disorders, taking care to emphasize full-blown psychiatric clinical conditions, not isolated symptoms.
Other specific tests-Frontal lobe tests
Neuropsychological battery
Intelligence tests
INVESTIGATIONS • Hemogram• ABG• ECG• LFT,RFT, TFT• Electrolytes• Blood sugar• Urine drug screen/ blood alcohol concentrations• Blood ammonia levels• ECG, ECHO, CXR• Lumbar puncture & CSF analysis• CT/ MRI/ EEG/ SPECT/ PET
DIFFERENTIAL DIAGNOSIS
Mood disorder
Psychotic disorder
Dementia
Medical causes
Anxiety disorders
ADHD
Other substance disorders
COMORBIDITIES
Personality disorders
Mood/ psychotic disorders/ anxiety disorders/ anxiety disorders/ dementia
Other substance use disorders
TREATMENT
Intoxication- acute episode/ severely intoxicated observation in case of alcoholic coma
Aggression- sedation with antipsychotics/ benzodiazepines
Intravenous high potency vitamin B & C can reduce subjective effects of intoxication & improve performance- rarely needed
Alcoholic coma- managed in hospital, rule out head injury, hypoglycemia, & other complications of alcohol
Maintain airway, breathing & circulation
May require IV fluids, vasopressor drugs & steroids
Thiamine supplementation before glucose transfusion
IV fructose or peritoneal dialysis- rare
Withdrawal – minor- OP, long acting sedatives
Complications- admission, sedatives titrated according to symptoms
Delirium- adequate fluid replacement, & sedation
Other complications to be treated accordingly
Wernicke’s encephalopathy- acute medical emergency
IV/ IM infusion of large doses of thiamine ( 200- 300 mg) slowly over 10 mins twice daily for a period of minimum 5 days
Oral thiamine for several months
Refractory- hypomagnesaemia ruled out
Other complications- infections, dehydration, electrolyte imbalance, cardiac failure
Korsakoff’s syndrome- treatment disappointing. High dose thiamine replacement by parenteral followed by oral for many months
Paripheral neuropathy- vitamin supplementation- slow improvement
Alcohol induced psychotic disorder- no treatment required. Spontaneously remits on abstinence.
Role of psychiatrist is not only to manage the treatment of withdrawal symptoms of ADS & prevention of relapse but also to treat the associated complications, especially neuropsychiatric, as they cause severe impairment & socio- occupational dysfunction.
Goal should be aimed at a better symptom free life for the patient which not only improves the work performance but also may also act to prevent relapse
THANK
YOU