Organic brain syndrome

by hidayat at drhidayat.com

1. Organic brain syndrome Tai Zu Huang Teoh Wee Loon

2. Introduction Brain dysfunction caused by organic pathology inside or outside of the brain Can be classified by: Global syndromes Delirium Dementia Specific syndromes Amnesic syndrome Organic mood disorder Organic delusional state Organic personality disorder

3. Dementia DEFINITION: An acquired, generalized and usually progressive impairment of cognitive functions ( ie memory, recall, orientation, language, abstraction etc) Content being affected but not level of consciousness

4. Epidemiology Affect predominantly elderly people Prevalence increases with age: 15% >65y/o (different studies have different prevalence) 25% >85y/o F > M A community survey (n=223) amongst Malays age 60 years and above in Selangor:24% were cognitively impaired Another study found the prevalence of dementia in urban communities of Malays (>60y/o) in KL was 6% Study of elderly in Malaysia yielded a prevalence of organic mental disorder (inconclusive of dementia) at 14.4% Down syndrome is also associated with the development of dementia

5. Classification

6. Part of brain affected

7. Aetiology

8. Aetiology

9. VITAMIN D VEST V – Vitamin Deficiency [B12, folate and thiamine( Wernicke-korsakoff )] I – Intracranial masses ( tumour , abscess) T – Trauma (head injury, dementia pugilistica ) A – Anoxia M- Metabolic (diabetes) I – Infection (HIV, syphilis, Creutzfeldt-Jakod ) N- Normal pressure hydrocephalus

10. We must always think of treatable causes of dementia before we start to manage them although it is very rare (10%) D – Degenerative (Alzheimer’s, Hungtington’s , CJD) V – Vascular (multi-infarct dementia) E – Endocrine (hypothyroid) S – Space occupying lesion (subdural hematoma) T – Toxic (alcohol)

11. Diagnosis of dementia Dementia is diagnosed based on: History (based on aetiology ) Mental state examination including MMSE Other lab investigation depend on aetiology Most type of dementia can be diagnosed based on criteria in DSM –IV

12. Clinical features: Personality changes: become more hostile, irritable and explosive Hallucination and delusions 20-30% pts have hallucinations 30-40% have delusions (delusion of paranoid or persecutory) Mood changes: depression and anxiety (40-50% of pts) Cognitive changes Thinking: slow and impoverished Insight: poor Catastrophic changes – when patient are taxed beyond their restricted abilities, there maybe sudden change to anger and tears Sundowner syndrome – confusion, ataxia, drowsiness after “sundown”

13. Investigation: Depend on suspected etiologies CBC (note MCV), glucose, TSH, B12, folate electrolytes, LFTs, renal function CT head MRI as indicated as clinically indicated – VDRL (syphilis), HIV, ANA, anti- dsDNA (SLE), caeruloplasmin , copper ( wilson’s disease), cortisol , toxicology, heavy metals

14. Management of dementia: Treat treatable causes Treat the cause of superimposed delirium Biological: medication Psychosocial: home care, day care, inpatient care, residential care, avoidance of driving

15. Management of dementia: Non- pharmacological Pharmacological Caregivers Intervention Cognition Behaviour Mood Promoting independence: communication, ADL skill training, exercise, rehabilitation, combination Maintainence of cognition: reality therapy, Validation, life review Cholinesterase inhibitors: donepezil Mild, moderate and severe AD Vascular dementia Dementia with Lewy Body (DLB) Atypical antipsycotics : can be used agitation and psychosis Avoid in DLB Antidepressants Evaluate caregiver needs Multicomponent intervention: Psychotherapy Psychoeducation Supportive therapy Respite/day care training

16. Non-pharmacological Pharmacological Caregivers intervention Cognition Behaviour Mood Challenging behaviours Behaviour management Music Reminiscence therapy Reduction of co-morbid emotional problem ( eg depression and anxiety) Memantine (glutamate NMDA antagonist) Severe AD Cognitive enhancers: Cholinesterase inhibitors Memantine (NMDA receptor antagonist) Antidepressant in fronto -temporal dementia

17. Alzheimer disease First described by Alois Alzheimer in 1907 Although cause remains unknown, progress had been made to try to understand molecular basic of amyloid deposits genetic factors a minority (<7%) of AD cases are familial, autosomal dominant 3 major genes for autosomal dominant AD have been identified: amyloid precursor protein (chromosome 21) presenilin 1 (chromosome 14) presenilin 2 (chromosome 1) the E4 polymorphism of apolipoprotein E is a susceptibility genotype (E2 is protective Biochemical factors Neurotransmitter such as Ach and Norepinephrine become hypoactive Neuroactive peptides somatostatin and corticotrophin also decreased in concentration

18. DSM-IV-TR diagnostic criteria for dementia of Alzheimer’s type A. Development of multiple cognitive deficits manifested by both: 1) memory impairment 2) ≥1 of the following cognitive disturbances: Aphasia Apraxia Agnosia Disturbances in executive functioning

19. B. cognitive deficits in criteria A1 and A2 cause significant impairment in social and occupational functioning and represent a significant decline from a previous level of functioning C. gradual onset and continuing cognitive decline D. not due to any other CNS conditions Systemic conditions Subtance -induced conditions E. Deficits do not occur during the course of delirium F. Disturbance is not better accounted by other Axis-I disorder (MDD, Schizophrenia)

20. Risk factors Aging (elderly people > 65 years of age) Female Family history -Defective genes on chromosomes 1,14,21 Hypothethical risk factor : aluminium toxicity Having history of head injury Low education level Smoking Down syndrome (y?)

21. Pathology Macroscopic appearance of brain : diffuse atrophy, esp frontal, parietal and temporal lobes, flattened sulci & enlarged cerebral ventricles Microscopic findings : senile plaques ( amyloid plaques – amount indicates severity), neurofibrillary tangles (composed of cytoplasmic skeleton, mainly phosphorylated tau protein), neuronal loss(in cortex & hippocampus), synaptic loss ( 50 % in cortex) & granulovascular degeneration of neurons

22. Course, prognosis & treatment Slowly progress memory impairment Aphasia, apraxia and agnosia also present May later develop motor & gait disturbances; may become bedridden Mean survival is 7 years from onset Treatment : cholinesterase inhibitor ( eg : galantamine , rivastigmine , donepezil )

23. There is a new case of dementia every 7 seconds in our world Alzheimer is the most common cause of dementia and is not part of aging process There are currently no prevention and cure for it

24. Vascular dementia Caused by blockage of in brain’s blood supply Leading to progressive decline in memory & cognitive functioning ♂>♀ , affects people between the ages of 60 and 75, HTN or CV dss Approximately 10-15% have coexisting vascular dementia and dementia of Alzheimer’s type Pathology : a/w multiple infarcts coz by thromboembolism fr extracranial arteries arteriosclerosis in main vessels

25. Vascular dementia Clinical features: - sx are fluctuating & episodes of confusion are common esp at night - Neurological signs is common -in some cases emotional & personality changes may be apparent b4 impairment of memory & intelect Diagnosis, other signs and symptoms are as according to DSM-IV diagnostic criteria Prognosis -lifespan averages is 4-5 years from time of diagnosis

26. Delirium acute generalized impairment of mental disorder Hallmark symptoms :impairment of consiousness, in association with global impairment of cognitive functions Common psychiatric symptoms : abnormalities of perception, mood, behaviour Common neurological symptoms : tremor, nystagmus, incoordination, urinary incontinence, asterixis.

27. Epidemiology: general population: 1.1% medically ill patient who are hospitalized: 10-30% surgical intensive unit: 30% cardiac intensive care unit: 40-50% AIDS: 30-40%

28. Risk factor Hospitalization Nursing home resident Childhood (example: febrile illness) Old age especially male Severe illnesses like cancer, AIDS Pre-existing cognitive impairment or brain pahtology Recent anesthesia Substance abuse

29. Etiology: Common pathway to any brain insult. Is thought to involve dysfunction of the reticular formation & acetylcholine transmission. Reticular formation →attention & arousal Study shown decrease in acetylcholinergic activity Other neurotransmitter: serotonin & glutamate

30. INTRACRANIAL CAUSES Epilepsy and postictal states Brain trauma (especially concussion) Infections Meningitis Encephalitis Neoplasms Vascular disorders

31. EXTRACRANIAL CAUSES Drugs (ingestion or withdrawal) and poisons ( Anticholinergic , anticonvulsants, antihypertensives , antiparkinsonians , antipsychotics, cardiac glycosides, insulin, opiates, sedatives and hypnotics, steroids, alcohol) Endocrine dysfunction ( hypofunction or hyperfunction ) ( Pituitary, Pancreas, Adrenal, Parathyroid, Thyroid) Diseases of nonendocrine organs (Hepatic encephalopathy, Uremic encephalopathy, Carbon dioxide narcosis, Hypoxia, Cardiac failure, Arrhythmias, Hypotension )

32. Deficiency diseases (Thiamine, nicotinic acid, B12, or folic acid deficiencies) Systemic infections with fever and sepsis Electrolyte imbalance of any cause Postoperative states ( postoperative pain, insomnia, pain medication, electrolyte imbalance, infection, fever, blood loss) Trauma (head or general body)

33. I mpaired delivery (of brain substrate eg . vascular insufficiency due to stroke) M etabolic D rugs E ndocrinopathy L iver disease I nfrastructure (structural disease of cortical neurons) R enal failure I nfection O xygen U rinary tract infection S ensory deprivation

34. CLINICAL FEATURES OF DELIRIUM Impairment of consciousness – disorientation & poor concentration, fluctuating course & often worse in the evening. Behavior – overactive or underactive, sleep is often disturbed. Thinking – slow, muddled, ideas of reference & delusions are transient and poorly elaborated. Mood – anxious, irritable or depressed, often labile. Perception – is distorted, misinterpretations of illusions, hallucination (mainly visual). Tactile and auditory hallucination can occur but less frequent. Memory – impaired. Insight – impaired

35. Diagnosis DSM-IV diagnostic criteria for delirium due to a general medical condition Disturbance of consciousness (i.e. reduced clarity of awareness of the environment) with reduced ability to focus, sustain or shift attention. A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of perceptual disturbance that is not better accounted for by a preexisting, established or evolving dementia. The disturbance develop over a short period of time (usually hours to days) & tends to fluctuate during the course of the day. There is evidence from the history, PE or laboratory findings that the disturbance is caused by the direct physiologic consequences of a general medical condition.

36. Course & prognosis Onset usually sudden. Symptoms persist as long as the causative factors are present, although delirium generally lasts less than a week. After removal of the causative factors, the symptoms of delirium usually recede over a 3- to 7-day period, although some symptoms may take up to 2 weeks to resolve completely. The older a patient and the longer the patient has been delirious, the longer the delirium takes to resolve.

37. Differential diagnosis : Dementia Schizophrenia & mania No rapidly fluctuating course, do not impair the level of consciousness or significantly impair cognition Acute amnesic syndrome Depression

38. Investigation: First line Other useful test Blood test FBC, ESR, Urea and electrolyte (BUSE) Calcium, Magnesium Liver function test Thyroid function test Cardiac enzyme Vitamin B12 Anti-nuclear antibody Tumour marker Anti-thyroid antibody Copper studies CNS investigation Head imaging ( CT, MRI) Lumbar puncture EEG Others ABG ECG Infection screening (blood culture, urine culture) Viral screen

39. Amnesic syndrome Characterized by a prominent disorder of recent memory in the absence of generalized intellectual impairment (dementia) or impaired of consciousness (delirium) Clinical features: Recent memory severely impaired Remote memory spared Disorientation in time Confabulation Other cognitive function preserved Organic Brain syndrome

40. Korsakoff syndrome Amnesic syndrome accompany with acute neurological symptoms caused by neuronal damage that results from thiamine deficiency in association with chronic alcohol abuse. It usually is preceded by an episode of Wernicke encephalitis (eg, ataxia, confusion, oculomotor palsy), typically precipitated by administration of glucose to a malnourished alcoholic without concomitant parenteral thiamine. Confabulation is a hallmark finding of Korsakoff syndrome (also called Korsakoff psychosis). Treatment: IV thiamine Organic Brain syndrome

41. Organic personality disorder Frontal lobe damage Clinical features: - behaviour is disinhibited - overfamiliar - overtalkative - inappropriate jokes - euphoria - concentration and attention will be reduced - insight impaired Organic Brain syndrome

42. Head injury major head injury has both immediate and long-term neuropsychiatric consequences. Acute psycholoqical effects of head injury: Impairment of consciousness Delirium Post-traumatic amnesia: transient amnesia with retrograde (events prior to injury) and anterograde (events following injury) features. Long-term consequences: Personality changes Emotional symptoms Organic Brain syndrome

43. Dementia Delirium Pseudodementia of depression Onset gradual/step-wise decline acute(hours-days) subacute Duration months-years days-weeks variable Natural History Progressive , usually irreversible fluctuating, Reversible, high morbidity/mortality in very old recurrent,usually reversible Level of consciousness normal fluctuating(over 24hours) normal Orientation intact initially impaired(usually time and place) intact Mood and Affect labile but no usually anxious anxious, irritable, fluctuating depressed,stable

44. Thank you!