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John R. Roy Organic : Conditions of Acquired Intellectual Deficit SUMMARY The term 'organic brain ' covers a Clinical aspects of acquired mental deficit multitude of ills, many of which are are also outlined. The approach to organic treatable conditions. Diagnosis must brain syndromes is the classic medical concentrate on defining which syndrome is observation of . (Can involved; this article presents a diagnostic Fam Physician 25:1351-1356, 1979). schema with illustrative case histories.

Dr. Roy is director of geriatric duced personality disorders, neuroses adaptive behavior must have their services and assistant and psychoses. I neurophysiological substrates which professor of psychiatry at It is not clinically useful to think in can be disturbed by many neurologi- McMaster University. Reprint terms of a unitary, basic 'organic brain cal, metabolic and medical condi- requests to: Room 3G56, Dept. of syndrome'. It is important to be alert tions. Psychiatry, McMaster University to the multifarious psychiatric mani- Though the brain evidently has a Medical Centre, 1200 Main St. W., festations of organic conditions and re- limited repertoire of responses to a Hamilton, ON. L8S 4J9. lentless in search of treatable causes. wide variety of noxious agents, it is Unlike mental retardation, which is important on practical grounds to dis- a condition of arrested or incomplete tinguish between so-called "func- ETABOLIC, TOXIC or infective development of the mind characterized tional" , or disturbances of brain cell metab- by subnormality of intelligence, the in- and the sometimes very similar olism, as well as brain damage from a tellectual deficit in the organic brain schizophreniform, depressive and variety of causes, are often associated syndromes is acquired at a time when manic syndromes caused by identifi- with disturbed behavior, intellectual the brain has achieved mature develop- able neurologic or medical disorders. deficits, alterations of consciousness ment. The symptomatology therefore These syndromes showing distur- and abnormalities of emotion, thinking comprises loss of intellectual faculties bance of attention, altered level of or perception. previously in existence, together with consciousness, disturbance The term emotional and other secondary reac- and prominent intellectual impairment given to this constellation of symp- tions to these losses. are more readily recognized as imply- toms is sometimes further subdivided ing a disturbance of brain functioning according to mode of onset and poten- Classification of and thus prompt a search for underly- tial reversibility into organic Organic Brain Syndromes ing, potentially treatable coarse brain brain syndrome-otherwise known as It is important not to be clinically pathology or metabolic . confusional state or -and handicapped by adopting too narrow a The following case history illus- chronic organic brain syndrome or de- view of organic brain syndromes. trates some of these considerations: mentia. These are both conditions of Many psychiatric disorders could be A woman of 33 was admitted to a global or multiple cognitive impair- termed organic brain syndromes in the psychiatric hospital with a two year ment. There are also syndromes of se- sense that they likely have their causa- history of depression, listlessness and lective or limited disturbance of higher tion in a subtle neurophysiological or undue fatigue. She had formerly been mental function, e. g. the amnestic biochemical disturbance of brain func- a very active, competent person. In the syndrome, as well as organically in- tion. Emotion, thinking, memory and four weeks prior to admission she had

CAN. FAM. PHYSICIAN Vol. 25: NOVEMBER 1979 1351 developed an acute with came afraid to go to sleep and eventu- appropriate studies and she made a marked behavior disturbance. She be- ally left home in a very agitated state. complete recovery on replacement lieved that she heard the neighbors The psychiatric picture was one of thyroid therapy. The psychiatric symp- commenting on her actions and wa- acute paranoid schizophrenia but on toms cleared and showed no recur- kened her husband in the night to in- examination she was noted to have rence at outpatient follow up more form him of her beliefs. This symptom coarse features, brittle hair and her than five years later without the use of of "commentary voices" has been re- mental processes were slowed. An psychotropic medication at any point. garded as one of the pathognomonic electroencephalogram showed a gener- features of schizophrenia. alized slowing of brain wave activity Causes of Later she developed many paranoid in keeping with the presence of a me- Organic Brain Syndromes including one that her hus- tabolic condition. Table I lists various possible causes band was trying to kill her. She be- Hypothyroidism was confirmed by of organic brain syndromes. For clinical use a helpful classifica- TABLE I tion is that of Adams and Victor2 who consider the causes of in CAUSES OF ORGANIC BRAIN SYNDROMES three categories: in which de- mentia is associated with laboratory or Metabolic and nutritional disorders 3. : obstructive, clinical evidence of other medical dis- 1. Carbohydrate: functional and communicating ease, e.g. hypothyroidism; diseases in secondary hypoglycemia, diabetic which dementia is associated with pre-coma 1. other neurological disease, e.g. 2. : 2. , subacute encephalitis, Schilder's disease or brain tumor, and -Aneurine hydrochloride limbic encephalitis diseases in which dementia is the only (thiamine): Korsakoff's psychosis, 3. Syphilis: general paralysis of the evidence of neurological or medical Wernicke's . insane, meningovascular syphilis diseases e.g. Alzheimer's disease, se- -Nicotinic acid: pellagra 4. Others, e.g. typhoid, cysticercosis, nile dementia. -Vitamin B12: pernicious anemia toxoplasmosis, systemic infections 3. Porphyrins: porphyria The Vocabulary 4. Hormones: Intoxications of Neuropsychiatty -Thyroid: thyrotoxicosis, 1. Exogenous myxedema -Medication: reactions to Precision in definition and use of -Adrenal: Addison's disease, , stimulants, terms is important,3 since semantics Cushing's syndrome. chemotherapy, hormones, can pervasively influence diagnostic -Pituitary: Simmonds' disease hypotensive drugs, thinking and treatment or placement -Parathyroid: antihistamines, antidepressants, decisions. hyperparathyroidism, bromides. is often wrongly used to hypoparathyroidism -Self-administered: , drugs mean disorientation. It really means 5. Oxygen: of addiction perplexity, lack of ability to think -Anesthesia -Occupational: lead, manganese, clearly or incoherence of thought. -Pulmonary disease methyl chloride, carbon disulfide. Confusion as defined thus is not -Renal dialysis. -Poor carrying power, carbon specific to organic mental distur- monoxide poisoning, anemia it can occur as a 6. Malabsorption syndrome 2. Endogenous bances, though result 7. Electrolyte imbalance, alkalosis, Uremia, portal-systemic of impairment of consciousness or acidosis encephalopathy in cirrhosis of liver, brain damage. 'Delirious states' would 8. Copper: Wilson's disease non-metastatic manifestations of be a better term. neoplasms. Clouding of consciousness means a of the level of full conscious- Cerebrovascular disorders Degenerative disorders lowering 1. Cerebral atherosclerosis: 1. Senile dementia ness, alertness or awareness of envi- 'arteriosclerotic dementia' 2. Presenile : Huntington's ronment. This is the characteristic (multi-infarct dementia) symptom that appears when brain 2. chorea, Alzheimer, Pick and Slow cerebral blood flow: cardiac Jakob-Creuzfeldt diseases and function is disturbed by a process of failure, myocardial infarction, recent or rapid (acute) onset. Mild de- postural hypotension, cardiac arrest non-specific types 3. Rarer vascular diseases: 3. -dementia complex grees of clouding are indicated by dif- polyarteritis nodosa, disseminated 4. Demyelinating disorders: multiple ficulty in maintaining attention, dis- lupus, temporal arteritis, sclerosis, Schilder's disease tractability, slowness of thought, easy thrombo-angiitis obliterans fatigue and subsequent partial or com- 4. Hypertensive encephalopathy Idiopathic and secondary, especially plete . 5. Carotid occlusion temporal lobe epilepsy. Delirium (acute organic brain syn- 6. Cerebral thrombosis or embolism Psychomotor attacks, petit mal status drome). In delirium, in addition to 7. Transient cerebral ischemia Postictal psychotic episodes (twilight quite marked impairment or clouding states) of there is evidence of dementia and consciousness, Mechanical stresses Epileptic personality widespread disturbance of the brain's 1. Space occupying lesions: primary change and secondary tumor, abscess perceptual and integrative functions, Neuropsychological producing illusions, , in- 2. Trauma: acute and chronic brain Depression, psychosis, emotional damage, subdural hematoma, trusion of past mental content into con- disturbance reactive to losses, giving sciousness, delusions and marked post- syndrome, up, . punch-drunk syndrome emotional and behavioral disturbance

1 352 CAN. FAM. PHYSICIAN Vol. 25: NOVEMBER 1979 TABLE 2 as well as global intellectual impair- the possibilities of organic brain syn- Early Symptoms of Disorders of ment. The severity of symptoms drome, as would a negative past his- Higher mental Function characteristically fluctuates, worsen- tory of psychiatric illness or the clini- ing at night. There may be lucid inter- cal findings of disorientation for time vals when the patient appears com- and place, disturbance of recent or Intellect pletely normal in mental function. short term memory or any alteration of Impaired abstract ability, calculation There is a partial or complete amnesia the level of consciousness. Deficits of reasoning, judgment and of the illness after recov- planning for the events Particular caution should be used Impaired concentration ery. with the diagnosis of ''. The Failure to grasp new situations Coma is a degree of impairment or apparent psychodynamic meaningful- lowering of consciousness in which ness of symptoms does not exclude an Personality the patient is incapable of awareness organic basis.5 Exaggeration of premorbid traits of, or adequate response to, external Loss of interest and initiative, reduced stimuli or inner needs and cannot be The Diagnostic Assessment spontaneity aroused even by strong stimuli. of Organic Brain Syndromes Withdrawal Dementia (chronic organic brain The approach is essentially that of a Social misconduct syndrome). This term should be re- classical medical diagnostic workup in Personal neglect served for a clinical syndrome of glo- which emotional, behavioral and intel- Development of irritability, aggression, bal impairment of intellect, memory lectual symptoms and signs as well as self-centred attitudes. and higher mental functioning but medical and neurologic manifestations Memory without impairment or clouding of are carefully elicited and diagnostic in- Forgeffulness consciousness. Memory, attention, ferences drawn from their analysis.6 Inability to learn thinking and comprehension are par- TABLE 3 Disorientation in time and space ticularly prominently affected. Unawareness of recent happenings The concepts of progression and ir- DIAGNOSTIC SCHEMA FOR reversibility should not be included as ORGANIC BRAIN SYNDROMES Speech essential parts of the definition, since Loss of fluency, paucity of content many types of dementia are reversible, 1. History and mode of onset of Nominal dysphasia symptoms. Limitation (to self and situation, in choice potentially treatable, remediable or not 2. Past history of illness and treatment of words) progressive. response. Disorganization and fragmentation Dementia and delirium are both de- 3. Family history. Impaired comprehension fined as global impairments of cogni- 4. Personal life history. tive functioning. The essential distinc- 5. Present social, interpersonal Affective disturbance tion between them rests in the fact that functioning and home situation. Anxiety, depression, irritability, perplexity, in delirium, but not in dementia, there 6. Findings at Examination suspicion is always clouding or impairment of -General behavior, level of Labile emotions, disinhibition, petulance consciousness which can be tested by consciousness and attention. Flatness, blunting, , vacancy, the digit span test.4 The non-clouded -Mood and affect. euphoria -Thinking and ideas (content and Unexplained aggression, child-like individual, even when significantly form of thought) reactions demented, can repeat immediately -Orientation for time, place, Increased emptiness, shallowness, 7±2 digits presented randomly in a de- person dullness of affect liberate, uninflected voice. -Memory: immediate, recent, 'Functional' syndromes of depression or remote, general knowledge, mania How To Recognize ability to learn new material Early Brain Syndrome -Intellectual functioning: calculation, abstract and Behavior Table 2 indicates some early symp- Slowness, obsessional orderliness, constructional abilities, higher mannerisms toms of higher mental function-dis- cognitive functions. Impairment of performance orders which could occur as manifesta- -Language Episodes of muddle or confusion tions of organic brain syndromes. -Emotional reactivity Bizarre, inappropriate behavior One should have a high index of -Personality Hoarding suspicion when confronted with any -Physical state Deteriorated personal habits psychiatric syndrome with atypical -Neurologic status Incontinence clinical phenomena. The older the pa- -Attitude and insight Perseveration (continuation or repetition of tient, the more one should consider or- 7. Special Investigations a behavior or thought pattern despite ganic brain syndrome as a cause. The Medical, neurologic, radiologic withdrawal or cessation of the of visual hallucinations including CAT scan, biochemical, appropriate stimuli) presence sug- hematologic, electrophysiological Paranoid or other delusions gests an organic syndrome, as does (esp. electroencephalography), 'Functional' schizophreniform syndromes acute onset of symptoms. Fluctuating psychological, social and symptoms and onset or worsening at interpersonal skills, abilities and Focal neurological manifestations night also indicate organic causation. safety in daily living, motor abilities, Apraxias for dressing, everyday activities An apparent precipitating event response to treatment (therapeutic Agnosias does not necessarily imply a psycho- trial). Major or focal epilepsy genic etiology. The presence or pre- 8. Diagnostic Formulation Geographical disorientation vious history of significant medical or 9. Treatment and follow-up Plan neurologic disease would strengthen

CAN. FAM. PHYSICIAN Vol. 25: NOVEMBER 1979 1353 Table 3 shows a comprehensive the personal history of even an ap- getful, absentminded with loss of am- diagnostic schema for organic brain parently demented or confused pa- bition and decrease of social interest. syndromes. tient. In special circumstances, e.g. an inter- The most important parts of this are On examination she was found to be view with the doctor, patients can at the history of the duration, mode of slow and dull in mentation. Her level this stage achieve a relatively normal onset, development of symptoms and of consciousness varied from time to intellectual and social functioning for a the mental status examination. time but she did not show the psy- short space of time. Various structured and quantified chological features of dementia and Stage 2. There is increasing diffi- test instruments are available for sys- could in fact give quite a good account culty with memory which shows itself tematically assessing the important of her symptoms. She performed tasks in disorientation, a tendency to get lost cognitive functions. Especially recom- related to higher intellectual abilities outside of home, to be careless with mended are the Memory and Informa- adequately though slowly. fires, stoves and cooking and neglect tion Test and the Dementia Rating Her personal complaints were of the household or forget to buy food. Scale developed by the Newcastle- lack of energy, pains and weakness of Perhaps in reaction to awareness of upon-Tyne group, 8 9 which have been legs, severe 'bursting' headaches, nau- these intellectual defects there is a ten- correlated with histological brain sea, vomiting and failing eyesight. She dency to social withdrawal and hostil- changes of dementia at autopsy. Other had been aware of significant weight ity towards others, antisocial behavior, shorter screening tests have been de- increase over two years. restlessness, sleeplessness, and de- vised for epidemiological and clinical Her right optic disc showed atrophy, pression. studies and could be adapted to family the left disc showed papilledema (the Stage 3 is characterized by more se- practice. Particularly useful are the Foster-Kennedy Syndrome). vere memory impairment with dis- Cognitive Capacity Screening exam- The electroencephalogram showed orientation and poor judgement. The ination developed by Jacobs et aliO to an excess of slow activity on the right gaps in memory might be filled by screen for organic mental syndromes side. confabulation and the patient becomes in the medically ill, Isaac's Set Test of Skull X-ray revealed erosion of the unfit to live alone, or if living with a abstract intellectual functioningi and dorsum sellae due to increased intra- relative requires a great deal of support the Pfeiffer Scalel" developed at Duke cranial pressure and a right cartoid an- night and day. Urinary incontinence is University. giogram demonstrated a large menin- well established by this stage. Something of the challenge and sat- gioma in the region of the right Stage 4. In addition to gross intel- isfaction of diagnostic assessment in sphenoidal wing. lectual and memory deficits with ne- the field of organic brain syndromes is This was successfully removed and glect of personal hygiene, there is very illustrated by the following case his- the patient made a very good recovery often double incontinence and loss of tory: with only some residual visual impair- ability for self care. The conversation A woman of 61 was referred for ment. is rambling and incoherent and spe- longterm placement with a diagnosis A practical screening battery for or- cific neurological signs appears, e.g. of dementia due to degenerative brain ganic brain syndrome is shown in snout and suck reflexes, the forced disease. She had been an adequate, so- Table 4. grasp reflex. The patient declines to a ciable, competent person employed as vegetative existence; death comes a bookkeeper in her husband's busi- Dementia from intercurrent , a fall or ness until one year prior to referral, (Acquired Mental Deficit): non-specific failure of vital functions. when she began to seem 'mixed up' Some Clinical Aspects about everyday activities. She grad- ually became unable to do any cooking Incidence and Course or household tasks. There was increas- Epidemiological studies throughout TABLE 4 the world have been con- ing memory impairment, particularly remarkably Suggested Laboratory Tests for for recent events-even for incidents sistent in estimating prevalence rates Pat ents with Organic Brain occurring only one hour previously. for dementia. In any community it is Syndromes Personality changes included irrita- likely that four or five percent of those bility, difficult behavior, apathy and 65 and older will have severe organic Complete blood count and film depression as well as deterioration in brain disease and a further five percent Erythrocyte sedimentation rate personal habits, messiness in eating or more would have early, mild or bor- Serological test for syphilis and incontinence of urine. Failing of derline organic brain syndromes. Electrolytes, blood urea nitrogen and vision for one had been attributed Dementia becomes progressively blood sugar year Liver function tests to cataracts. more frequent with advancing age. Thyroid function tests The history thus far certainly indi- Among those aged 65, two percent Vitamin B12 and folate levels cates dementia, with a global deficit of were found to have dementia in the Calcium and phosphorus levels higher intellectual functioning. The Newcastle-upon-Tyne surveys, Urinalysis relative shortness of history is, how- whereas 20% of those 80 and over X-ray chest and skull ever, against degenerative brain dis- were affected. 13 Electroencephalogram ease as the cause. The presence of The progress of a dementing illness Electrocardiogram for the same dura- due to degenerative brain disease can in certain cases tion of time as the main symptoms somewhat arbitrarily be divided into Cerebrospinal fluid examination 14, 15 Computerized axial tomography should not be attributed to cataract four stages. Serum barbiturate, bromide, alcohol, without further confirmation. Also, Stage 1. Lessening of abstract intel- ammonia levels one should always listen carefully to lectual functioning, tendency to be for-

1354 CAN. FAM. PHYSICIAN Vol. 25: NOVEMBER 1979 Alzheimer's Disease autosomal gene with partial pene- 'Arteriosclerotic Dementia' Early this century Alois Alzheimer trance. The current view is that the patho- in Germany described a progressive, Most cases of Alzheimer's disease logical lesions in the condition for- degenerative brain condition in a occur sporadically with no known merly referred to as arteriosclerotic de- woman of 51. family history of the disease. Data mentia are actually based upon the It can be estimated from U.S. fig- from large series suggest multi-facto- occurrence of multiple small infarcts ures that this disease may be the fourth rial inheritance in most cases, though due to fibrin emboli or platelets from most common cause of death in Can- there are a number of reports of a fami- atheromatous plaques on the walls of ada and that as many as 60,000 per- lial form of Alzheimer's disease, the carotid or vertebrobasilar arteries, sons may suffer from it. 16, 17 sometimes clinically atypical, that hence the modern term multi-infarct Pathologically there is atrophy of shows dominant inheritance.24 dementia. the cortex and white matter of the It is as yet undecided whether com- Contrary to prevalent belief this is a brain with degeneration and loss of bined genetic and acquired factors relatively rare cause of dementia, oc- neurones. Numerous "senile plaques" could operate in the causation of Alz- curring in 15-20%, at most, of care- containing amyloid and neurofibrillary heimer's disease. fully studied series and being present tangles containing an abnormal protein together with Alzheimer's changes in a material are distributed throughout the Distinguishing further 15-20%, whereas Alzheimer's cortex and the limbic system (espe- dementia from depression pathology alone accounts for about cially the hippocampus and amygda- Kiloh25 drew attention to the fact 50% of dementia of neuropathological loid nuclei). that functional psychiatric states, espe- cause in the elderly.30 The exact significance of these find- cially depression, can mimic dementia Multi-infarct dementia has a dif- ings is at present uncertain, as is the and lead to the serious error of denying ferent natural history and . cause of this condition, but research in treatment for a potentially reversible, Alzheimer's dementia is slowly pro- Canada'8 and around the world may be disabling condition. Depression, even gressive, whereas the multi-infarct approaching the discovery of a meta- in the elderly, can be treatable by anti- type is characterized by a step-wise bolic cause.19 depressant medication or by electro- progression with some degree of re- Patients with mongolism who sur- convulsive therapy. covery between sudden episodes of vive to middle age may develop the More recent follow-up studies have small . The end result is one of pathological features of Alzheimer's found functional, treatable psychiatric dementia with emotional lability, disease. illness, usually depression, in 15-20% pseudobulbar palsy, bilateral pyra- of patients originally considered de- midal signs and epileptic seizures. i Senile Dementia mented. 26-28 This term has undergone nosologi- Pointers to the diagnosis of depres- cal refinement in recent years. Origi- sion rather than dementia would be a nally used loosely to cover all serious relatively recent onset of symptoms References mental symptomatology occurring in starting with loss of interest rather than Roth20 distinguished it as a 1. Lipowski ZJ: Organic brain syndromes: the elderly, memory impairment, the presence of A reformulation. Compr Psychiatry progressive, degenerative brain dis- depressive mood alterations and evi- 19:309-322, 1978. ease from delirious, psychotic or de- dence of distress-though some of 2. Adams RD, Victor M: Principles of pressive states in the elderly and also these symptoms are also common in . New York, McGraw-Hill Book from the effects of cerebrovascular Co., 1977, p. 275. the course of dementing illness. A 3. Lishman WA: Organic Psychiatry. Ox- disease on the brain-all of which careful history of the onset and mode ford, Blackwell Scientific Publications, have different natural histories and of progression of all symptoms is of 1978, p. 3-10. symptomatologies. 4. Marsden CD: The diagnosis of demen- paramount importance.29 in Isaacs AD, Post F (eds): Studies In The average age of onset is in the Patients in this category might not tia, a of Geriatric Psychiatry. Chichester, John 70's and there is preponderance give a subjective account of depression Wiley and Sons Ltd., 1978, p. 95-98. females. but the appearance would be quite un- 5. Lazare A, Anderson WH: Or- There is considerable clinical, men- ganic/functional of like the rather euphoric, uncaring A pathological and histological overlap tal state of most demented patients. psychiatric symptoms, in Lazare (ed): between senile dementia and Alz- Outpatient Psychiatry: Diagnosis And Analysis of the mental status will Treatment. Baltimore, Williams and Wil- heimer's disease; many investigators often indicate that though the patient kins, 1979. are convinced that they represent the with depression has genuine cognitive 6. Wells CE: Diagnostic evaluation and same disease differing only in age of impairment-the result of psychomo- treatment in dementia, in Wells CE (ed): onset. Dementia, ed. 2. Philadelphia, F. A. tor slowing-there is patchiness in re- Davis Coy, 1977, p. 247-273. However, some genetic studies with sponses to tests, surprising areas of 7. Strub RL, Black FW: The Mental Status careful quantitative histological analy- normal functioning especially if not Examination In Neurology. Philadelphia, sis of have provided evidence F. A. Davis Co., 1977. time-stressed, and excess of "don't M: Clinical that they may be distinct processes, so know" answers and self-criticism at 8. Slater E, Roth Psychiatry, for ed. 3. London, Bailliere, Tindall and Cas- that the question must remain open failures. sell, 1969, p. 554-556. the present.21 The possibility of depression should 9. Blessed G, Tomlinson BE, Roth M: The be suspected at all times when one is association between quantitative measures ofDementia of dementia and of senile changes in the Evidence from studies on twins and faced with a patient who appears de- cerebral gray matter of elderly subjects. Br other genetic investigations of many mented and in many cases it is justifi- JPsychiatry 114:797-811, 1968. patieIntS22' 23 have suggested that senile able to give a therapeutic trial of an 10. Jacobs JW, Bernhard MR, Delgado A, dementia is inherited by a dominant antidepressant. Strain JJ: Screening for organic mental 1355 CAN. FAM. PHYSICIAN Vol. 25: NOVEMBER 1979 syndromes in the medically ill. Ann Intern Gastric lavage or inducdon ofemesis with syrup of Med 86:40-46, 1977. ipecac should be carried out immediately, followed by 11. Isaacs B, Kennie AT: The Set Test as administration ofactivated charcoal. Circulatory an aid to the detection of dementia in old collapse and shock may be counteracted by use of people. Br J Psychiatry 123:467-470, dextran, plasma, or concentrated albumin and vasopressor drugs, e.g. norepinephrine. Short-acting 1973. TABLETS barbiturates, e.g. thiopental may be used cautiously to 12. Pfeiffer E: A short portable mental control convulsions. Avoid the use of analeptic drugs. status questionnaire for the assessment of WITH CODEINE NO. 1 Acetaminophen patients. J SYMPTOMS: Patients who have ingested 10 g or more organic brain deficit in elderly ofacetaminophen as a single massive overdose are at risk Am Geriatr Soc 23:433-441, 1975. for hepatotoxicity. The clinical course ofacetaminophen 13. Kay DWK: The epidemiology and overdose occurs in a three-phase sequential pattern. The identification ofbrain deficit in the elderly, patient may be during the early phases. Therefore, in cases of suspected acetaminophen in Eisdorfer C, Friedel RO (eds): Cogni- overdose, begin specific antidotal therapy as soon as tive And Emotional Disturbance In The El- possible, derly. Chicago, Year Book Medical Pub- Phase 1: The first phase begins shortly after ingestion ofa lishers Inc., 1977, p. 14-15. potentially toxic overdose and lasts for 12 to 24 hours. The patient may manifest signs of gastrointestinal 14. Brockelhurst JC, Hanley T: Geriatric irritability, nausea, vomiting, anorexia, diaphoresis and Medicine For Students. Edinburgh, pallor. Churchill Livingstone, 1976, p. 68. Phase 2: Iftoxicity ensues, there is a latent phase of 24 to 48 hours but it may last as long as four days. The earlier 15. Ban TA: Organic problems in the symptoms abate and the patient may feel well. During aged: Brain syndromes and . this interval, hepatic enzymes, serum bilirubin and Psychiatric aspects of the organic brain prothrombin time begin to rise as hepatic necrosis progresses. Right upper quadrant pain may develop as syndrome and pharmacological ap- the liver becomes enlarged and tender.The vast majority proaches to treatment. J Geriatr Psychia- of cases do not progress beyond this phase and their try 11:135-159, 1978. 'TYLENOL* Tablets with Codeine-Acetaminophen subsequent clinical course is characterized by a gradual 16. Terry RD: Dementia-A brief and se- -Codeine-Caffeine return pf liver function tests to normal. ACTIONS Phase 3: For the relatively few patients who develop lective review. Arch Neurol 33:1-4, 1976. Acetaminophen is an analgesic and antipyretic: codeine significant hepatic necrosis, the signs and symptoms of 17. Katzman R: The prevalence and ma- is an analgesic and antitussive. the third phase of the clinical course depend on the lignancy of Alzheimer Disease. Arch INDICATIONS severityofhepatic damage, and usuallyoccur from three TYLENOLTablets with Codeine No. I is indicated for to five days following ingestion. Symptoms may be Neurol 33:217-218, 1976. the reliefofmild to moderate pain. Also as an analgesic- limited to anorexia, nausea, general malaise and 18. De Boni U, Dalton AJ, et al: Senile antipyretic- antitussive in the symptomatic treatment of abdominal pain in less severe cases or may progress to dementia: Recent concepts of pathophysi- colds. confusion, stupor and hepatic necrotic sequelae ology, in Research In Dementia. London, CONTRAINDICATIONS including jaundice, coagulation defects, hypoglycemia Ontario, Proceedings of a Colloquium of Hypersensitivity to codeine or acetaminophen. and encephalopathy as well as renal failure and PRECAUTIONS myocardiopathy. Death, when it occurs, is due to hepatic the Ontario Psychogeriatric Association. Codeine Pbosphate failure. Vol. 3, June 1977. The use of codeine phosphate over a prolonged period TREATMENT Estimate as carefully as possible the 19. Lishman WA: Research into the de- may lead to drug dependence. Warn patients against quantity ofacetaminophen ingested and the time of driving or operating machinery if they show impaired ingestion. The stomach should be emptied promptly by mentias. Psychol Med 8:353-356, 1978. mental and/or physical abilities while taking codeine. gastric lavage or by induction ofemesis with syrup of 20. Roth M: The natural history of mental Caution should be exercised and dosage may need to be ipecac. Activated charcoal will interfere with the disorder in old age. J Ment Sci 101:281- reduced when codeine is administered with other drugs absorption ofthe antidote. Ifactivated charcoal has been 301, 1955. which depress the CNS (including alcohol), other administered, lavage before initiating treatment with the narcotic analgesics, phenothiazines, other tranquilizers, antidote. Regardless of the quantity ofacetaminophen 21. Lishman WA: Organic Psychiatry. -, tricyclic antidepressants, and MAO reported to have been ingested, immediately administer Oxford, Blackwell Scientific Publications, inhibitors. When used postloperatively in sedated or N-acetylcysteine orally if 24 hours or less have elapsed 1978, p. 529, 540, 546. debilitated patients, or in patients with chronic since alleged time of ingestion ofacetaminophen. Draw obstructive pulmonary disease, indiscriminate use may blood for acetaminophen assay, liver function tests, and 22. Kallmann FJ: Twin data on the gene- precipitate respiratory insufficiency resulting in part other clinical laboratory tests. Maintain supportive tics of aging, in Wolstenholme GEW, from increased viscosity of bronchial secretions and the treatment throughout. O'Connor CM (eds): CIBA Foundation retention of secretions due to suppression of the cough The use of N-acetylcysteine as an antidote in on Aging. London, J & A reflex. acetaminophen overdose is experimental. More detailed Colloquia Acetamnopben information on the treatment ofacetaminophen Churchill Ltd., 1957, vol 3, p. 131-143. Patients who have ingested a single massive overdose of overdose, including the availability of N-acetylcysteine, 23. Larsson T, Sjogren T, Jacobson G: acetaminophen are at risk for hepatotoxicity. Clinical the preparation of N-acetylcysteine for administration of Senile dementia: A clinical, sociomedical evidence of hepatotoxicity may be delayed up to one an antidote, recommended dosage regimen and week. Close clinical monitoring and serial hepatic acetaminophen assay methods is available from McNeil and genetic study. Acta Psychiatr Scand, enzyme determinations are, therefore, recommended. Laboratories (Canada) Limited, 600 Main St. West, Supp. 167: 1-259, 1963. Acetaminophen toxicity may be enhanced by recent Stouffville, Ontario or a Poison Control Centre. 24. Sjogren T, Sjogren H, Lindgren AGH: barbiturate ingestion. ADULT DOSAGE Morbus Alzheimer and Morbus Pick: A ADVERSE EFFECTS I or 2 tablets every 4 hours as required. Codeine Pbosphate SUPPLIED genetic, clinical and patho-anatomical The most frequently observed adverse reactions to Each round, white tablet, uncoated with slightly beveled study. Acta Psychiatr et Neurol Scand codeine phosphate include lightheadedness, dizziness, edges and imprinted "McNEIL' on one side and " I " on 82:1-152, 1952. sedation, nausea and vomiting. These effects seem to be the reverse side contains: 300 mg acetaminophen, 15 mg more prominent in ambulatory than in nonambulatory caffeine, and 8 mg codeine phosphate. Available in 25. Kiloh LG: Pseudo-dementia. Acta patients and some of these adverse reactions may be bottles of 30 and 100 tablets. Psychiatr Scand 37:336-351, 1961. alleviated if the patient lies down. Other adverse effects 26. Marsden CD, Harrison MJG: Out- include euphoria, dysphoria, constipation and pruritus. REFERENCES Respiratory depression is seen in higher dosage. 1. Ivey, K.J., Settree, P., and Gemmell, R.: Comparison come ofinvestigation ofpatients with pres- Acetaminnpben ofacetaminophen and aspirin on gastric mucosal barrier entile dementia. Br Med J 1:249-252, The incidence of gastrointestinal upset is less than after in man: Correlation with ultrastructural changes. 1972. salicylate administration. Ifa rare hypersensitivity Abstract ofa paper presented to the 76th Annual 27. Smith JS, Kiloh LG, et al: The investi- reactionoccurs, discontinue the drug. Hypersensitivity is Meeting of the American Gastroenterological Associa- manifested by rash or urticaria. Regular use of aceta- tion, San Antonio, Texas, May 17-22, 1975. In: Gastro- gation ofdementia: The results in 100 con- minophen has shown to produce a slight increase in pro- enterology 68(4 pt.2): A61/918 (Apr.) 1975. secutive admissions. Med J Aust 2:403- thrombin time in patients receiving oral anticoagulants, 2. Rainsford, K.: The effects of Aspirin and other non- 405, 1976. but the clinical significance of this effect is not clear. steroid anti-inflammatory/analgesic drugs on gastro- 28. Seltzer B, Sherwin I: Organic brain OVERDOSE intestinal mucus glycoprotein biosynthesis in vivo: Codeine Phosphate Relationship to ulcerogenic actions; Biochemical Phar- syndromes: An empirical study and critical SYMPTOMS: Codeine phosphate in sufficient macology 27(6): 877-885, March, 1978. review. Am J Psychiatr 135:13-21, 1978. overdosage produces narcosis, sometimes preceded by a 3. Ivey, K.J., et al.: Effect of paracetamol on gastric and followed convulsions. mucosa; British Med. J.; 1, 1586-1588, 1978. 29. Post F: Dementia, depression and feeling of exhilaration by 4. J.R.: Gastritis Induced by Long-Term D Nausea and vomiting are usually prominent symptoms. Hoon, pseudo-dementia, in Benson DF, Blumer The pupils are contracted and the pulse rate is usually Release Aspirin; Journal of the American Medical (eds): Psychiatric Aspects of Neurologic increased. Cardiorespiratory depression accompanied Association, Vol. 229, Aug., 1974. Disease. New York, Grune & Stratton, by cyanosis occurs, followed by afail in body 197S, p. 99-120. temperature, circulatory collapse, coma and death. tMcNEILI 30. Marsden CD: The diagnosis ofdemen- TREATMENT. Maintain a patent airway through the use of an oropharyngeal airway or endotracheal tube. McNEIL LABORATORIES (CANADA) LIMITED tia, in Isaacs AD, Post F (eds): Studies in Oxygen should be administered, and respiration should STOUFFVILLE, ONTARIO LOH IL0 Geriatric Psychiatry. Chichester, John be assisted by artificial respiration. A specific antagonist Wiley & Sons, 1978, p. 103-104, 115. such as naloxone should be administered immediately. *Trademark ©rMcNEIL* 1979 TJA-4 1356 CAN. FAM. PHYSICIAN Vol. 25: NOVEMBER 1979