DELIRIUM and DEMENTIA are the two main types of organic brain syndrome, with focal lesions also to be considered.

The term organic brain syndrome means a general disturbance of brain function due to a physical disorder. The characteristic feature is a reduction in intellectual functioning (as tested in mental state examination of orientation, concentration and memory).

If the disturbance comes on suddenly, for example, in the context of a very high fever, then there will be acute organic brain syndrome, most often referred to as delirium or acute confusional state, with reduced conscious level- drowsiness- as the cardinal feature.

If however the disturbance comes on gradually, for example, in dementia due to Alzheimerís disease, then the reduction in intellectual functioning will occur in clear consciousness, that is, there is no drowsiness (at least, until the terminal stages). (Dementia could, by extension, be referred to as chronic organic brain syndrome, but the phrase is seldom used.)

FOCAL LESIONS Localized lesions give rise to focal impairments, for example stroke. This tends to be more the province of neurology. But some types can be considered as psychiatric focal lesions. Examples include Korsakovís psychosis, where the main abnormality is memory defect; this is due to isolated damage to mesial temporal lobe structures, such as the mammillary bodies. Frontal lobe syndrome (disinhibition, etc.) due to, for example, frontal lobe tumour is another.

Organic brain syndromes are conditions in which psychiatric symptoms result primarily from a biological disorder affecting brain function. This underlying biological disorder may involve structural cerebral pathology and/or metabolic disturbance. The patientís psychological reaction to the illness is also important in organic cases.

DSM-IV does not include the term ìorganic brain syndromesî because it is thought to encourage a misleading separation between ìorganicî and ìfunctionalî states. DSM-IV uses the concept of ìsecondaryî disorders instead, but it means essentially the same thing as organic for practical purposes.

CAUSES OF ORGANIC BRAIN SYNDROMES

• Cerebral conditions
  
• degenerative, for example senile and presenile dementias, Parkinsonís disease
• space-occupying lesions, for example primary brain tumour, cerebral metastases, subdural haematoma
• infections, for example bacterial or viral meningitis or encephalitis, including HIV, syphilis and TB
• head injury
• epilepsy
• vascular, for example arteriosclerosis, stroke, hypertensive encephalopathy, collagen diseases
• miscellaneous, for example multiple sclerosis, normal pressure hydrocephalus.

• Systemic conditions
• infections, for example septicaemia, pneumonia
• metabolic disturbances, for example renal or hepatic failure, diabetes, electrolyte imbalance, remote effects of carcinoma, porphyria
• endocrine disorders, for example thyrotoxicosis, hypothyroidism, Cushingís syndrome
• poisons, for example alcohol or drug intoxication or withdrawal, carbon monoxide, heavy metals
• cardiac or respiratory conditions causing cerebral anoxia
• vitamin B deficiency.

CLINICAL FEATURES

Organic cerebral disorders in which the whole brain is affected usually present with cognitive impairment and/or clouding of consciousness, which may be accompanied by neurological symptoms or signs. The classical picture in acute cases is called delirium and in chronic cases dementia. Localized lesions give rise to focal impairments. Delirium, dementia and focal syndromes are described below.

Less typical presentations include mood change, lability of mood, paranoid ideation, and changes in behaviour or personality. Organic cases may present with neurotic or psychotic symptoms resembling those found in ìfunctionalî disorders, but often showing atypical features such as fluctuating symptomatology, visual hallucinations, vague or transient paranoid delusions, or first onset of neurotic symptoms in middle or old age. Cognitive testing may reveal unsuspected defects.

The symptom pattern depends more on the time course of the illness, and the part of the brain involved, than on the type of underlying pathology. So that, for example, a confusional state due to fever generally resembles, in its psychiatric aspects, confusion due to say renal failure.

Clinical features may also be modified by the patientís premorbid personality, premorbid vulnerability to psychiatric disorder, past life experience, current medication and social circumstances.

DELIRIUM

Definition Delirium (acute brain syndrome, acute confusional state) is clouding of consciousness ñ that is, reduced awareness of the environment ñ accompanied by abnormalities of cognition, perception, thought and mood, from an organic cause.

The alcohol withdrawal syndrome (delirium tremens) is a common example, but delirium may be due to any acute condition affecting the brain.

Clinical Features The cardinal feature is a reduced level of consciousness, though mild degrees of this can be easy to miss in clinical practice. The patient is confused and disoriented, often restless, overactive and fearful but sometimes underactive and withdrawn. Inattention, including reduced ability to focus, sustain or shift attention, is common. Illusions, hallucinations of visual, auditory or tactile type, and changeable paranoid delusions may be present.

Severity fluctuates, usually being worse at night, because when there is less light, the environment is more likely to be misinterpreted- curtains appearing as threatening monsters, for example.

Management A first priority is diagnosis and treatment of the medical cause, for example diagnosing an occult infection, recognizing an acute intoxication (e.g. opiates) or withdrawal of alcohol or benzodiazepines, or identifying an adverse reaction to medication- polypharmacy being a common cause in the elderly...

These patients will often present in the general hospital, and are frequent on a medical ìtakeî. Probably the commonest type would be ìacute-on-chronicî- that is, a person with a - perhaps unrecognized- background of mild cognitive impairment who becomes acutely confused in association with an intercurrent medical problem such as chest infection- or even something as mild as constipation.

Nursing care, best carried out by one or two familiar people, is important. It includes attention to fluid intake and bladder and bowel function, provision of quiet warm well-lit surroundings without too many strange people around, protection against such hazards as unsupervised smoking in bed, and clear explanations before doing any practical procedures.

Drug treatment, preferably with an antipsychotic started in low dose and increased as necessary, may be required to reduce disturbance or distress. Haloperidol is used, doses of as little as 0.5mg can be effective in the elderly; younger fitter patients may require higher doses. Most cases are treated in general medical wards without involving psychiatrists.

Prognosis Outcome depends on the cause. Young fit patients with a clear cause- say an infection- will usually make a complete recovery if the cause resolves. In older patients, the outlook varies between complete recovery, partial recovery with residual cognitive problems, and death. For general hospital inpatients, development of full-blown delirium is a predictor of increased mortality or, for those who survive, a prolonged hospital stay and/or possible need for long term care or placement in a nursing or residential home.

Many cases of dementia, as indicated above, first present as a confusional state. There will be improvement with the resolution of the medical problem, which precipitated the confusion, but then the underlying cognitive problems become apparent.

DEMENTIA

Definition Dementia is an acquired global impairment of intellect and memory, often accompanied by changes in personality, mood and behaviour, from an organic cause. Dementia is usually progressive and irreversible, though some cases are due to treatable causes, which are important to recognise.

Causes In clinical practice, the three most common types of dementia are:

• Alzheimerís disease (AD),
• vascular (multi-infarct, arteriosclerotic) dementia (VaD) and
• dementia with Lewy bodies (LBD).

AD accounts for 60-70% of dementia cases; the three common types probably together account for over 90% of cases in clinical practice.

The vast majority of clinical cases are of these common types. Most clinical cases would probably have contributions from more than one of the pathologies indicated, if the cellular pathology were examined under the microscope (though brain biopsy in vivo is rarely done in dementia because it will not in most cases change management).

Dementia can also be classified according to neuropathological and other research information. Such classifications vary but would include dementia of Alzheimer type, Lewy body dementia, Pickís disease, Huntingtonís disease and the prion diseases.

A general account of dementia is given below, followed by a description of some individual conditions.

Clinical Features Onset is usually gradual, unless the dementia is the sequel of a delirious illness. Memory loss is usually the first symptom. This involves recent rather than remote memories, and results in disorientation. Other intellectual functions also deteriorate.

In the early stages, the patient may be aware of the memory problems, but if so will tend to make light of them or otherwise confabulate so as to minimize the problem in most cases. Most established cases do not complain very much about their memory.

Self-care (appearance) may decline. Affective changes are common, and may consist either of lability of mood, or a sustained depression or, more rarely, euphoria. Exaggeration of previous personality traits, and a coarsening of personality accompanied by socially unacceptable behaviour, may occur.

Insight may be present in the early stages. Strong emotion, including aggression (sometimes referred to as ìcatastrophic reactionî), can understandably occur when the patient realises their memory is in severe decline; thus, cognitive testing must always be done sensitively, lest the patient be unduly distressed by realization of his intellectual decline.

Insight is usually absent in the later stages. Except in terminal cases, consciousness is unimpaired.

If the patient is in their own familiar environment, with friends or family around, they may go undiagnosed, as they may continue to cope. But when support disappears- for example due to illness of a neighbour who regularly checked on them, or when an acute medical problem presents- then the patient may decompensate and the dementia become apparent.

ìSundowningî is often seen, that is, a worsening in confusion in the afternoon and evening; its cause is not clearly known, but may relate to tiredness, or to vasospasm. It may be helped by simple nursing measure such as change in rest, exercise or toileting routines.

ìCorticalî and ìsubcorticalî types of dementia may be distinguished. Cortical dementia includes disturbance of ìhigher functionsî, for example dysphasia, agnosia and apraxia. In subcortical dementia these functions are preserved, but the patient is forgetful, slow and apathetic and may show marked emotional lability with sudden outbursts of laughter or rage.

Diagnosis is made on clinical grounds from the history and mental state examination including simple cognitive testing.

In taking the history, if there is a suspicion of dementia, it will be appropriate to do cognitive testing early in the interview. This will give guidance as to whether the patient can give a proper history or not (so as to avoid wasting time trying to take an incoherent history).

Disorientation may be unsuspected by the examiner unless tested; short-term memory (as assessed by name and address test or three object recall) will usually be abnormal.

Formal psychometric tests can be used to confirm the diagnosis and specify the type of defects present, and repeated at intervals to monitor progress. The Mini-Mental State Examination (MMSE) is widely used in UK clinical practice.

Investigation All cases require a full medical history and physical examination. Treatable causes (such as brain tumour, subdural haematoma, normal pressure hydrocephalus, infections, hypothyroidism or vitamin B12 deficiency) may be revealed by investigations such as blood count and ESR, urea and electrolytes, liver function tests, thyroid function tests, B12 and folate, calcium and phosphate, serological tests for syphilis, HIV antibody testing (with informed consent), chest X-Ray, EEG and brain scan.

Potentially treatable factors can be identified in many dementia patients, but good results from treatment are obtained in few. Expensive or invasive investigations are only indicated if their results would alter management, and are seldom justified in patients whose dementia is very severe or whose general physical state is very poor.

Differential Diagnosis Depression is the main condition liable to be confused with dementia, especially in the elderly. Depressive pseudodementia, as the name implies, refers to states of depressive illness in the elderly where the presentation mimics dementia. It can usually be distinguished from dementia by the history of comparatively recent and quick onset, in a patient almost always with a history of previous episodes of depressive illness. Mental state examination may show pronounced features of low mood, and psychological testing may produce better results than in true dementia.

In doubtful cases a therapeutic trial of antidepressant drugs or ECT should be undertaken.

In some patients the two disorders co-exist, indeed depression is thought to be a risk factor for the development of dementia.

Management The cause of the dementia should be corrected if possible.

Acetylcholinesterase inhibitors are licensed for use in AD, see details below.

For the majority of cases, specific treatment produces limited benefit. The aim of management is therefore to keep patients functioning at their optimum level by maintenance of good physical health and provision of a suitable environment. It is usually best for patients to remain in their own homes with help from community services, indeed the vast majority of patients with dementia do reside in the community.

Much of the care necessary is provided by relatives and friends. The burden on them can be lessened by arranging respite care every so often, and by offering prompt emergency help in the event of an intercurrent illness or a social crisis.

Admission to hospital or nursing home may worsen confusion and distress, though it can be inevitable in the later stages. Long-term inpatient hospital care for dementia is now almost extinct in the NHS. It is now in England mainly provided through private nursing and residential homes, for which the patient has to pay until almost all his money is gone. This includes his home, which otherwise he might have wished to pass on to his children. In other parts of the UK, this care is provided free by the state.

Prognosis In the minority of patients with a treatable cause, progression of the dementia can be arrested and there may even be partial recovery, but most cases gradually deteriorate. The effect of acetylcholinesterase inhibitors, if any, is to delay decline, for example, putting back the time when the patient will not longer be able to be cared for at home. Acute confusional episodes due to other pathology, such as chest or urinary infections, strokes, faecal impaction, or inappropriate medication may be superimposed.

Drug treatment of behavioural and psychotic symptoms of dementia (BPSD) may be necessary, but carries risks; atypical antipsychotics such as olanxepine and risperidone are contraindicated because of a risk of stroke.

Specific types of dementia will now be described.

Senile Dementia of Alzheimer Type (SDAT)

Epidemiology: SDAT accounts for over half of all cases of dementia in old age. It is present in 5% of people over age 65 and 20% of people over 80. Women are affected nearly twice as often as men, this probably mainly reflecting womenís longer lifespan.

Alzheimerís is also the commonest of the primary presenile dementias. Onset is between the ages of 40 and 60, and women are affected at least twice as often as men.

Cause: genetic predisposition exists and a link with allele e4 of apolipoprotein E is established. About 20-30% of the population has at least one copy of e4; about 50% of AD cases have at least one copy of e4. However, most cases are probably polygenic and multifactorial.

Regarding early-onset AD, most cases arise sporadically but others are inherited, usually in polygenic fashion, though in a few families by a dominant gene.

Mutations in the amyloid precursor protein (APP) gene on chromosome 21 have been found in a few affected families. APP is implicated in the formation of senile plaques, one of the key neuropathological findings in AD. The role of APP ties in with the well known increased rate of AD in trisomy 21 (Downís syndrome) patients.

Genetic testing is seldom done in clinical practice unless the AD is strongly familial.

Neuropathology: shrinkage of the brain causes enlargement of the ventricles and sulci, which can be seen on CT or MRI brain scanning Microscopically, there are three characteristic changes: neuronal loss, senile plaques and neurofibrillary tangles. Neurones are decreased both in number and size, and astrocytes proliferate. Senile plaques, which have argyrophilic cores containing an amyloid-like substance, develop in the grey matter. Nerve fibres form tangles called Alzheimerís neurofibrillary degeneration. Lewy bodies (see below) may also be present.

Neurochemistry and neurophysiology: postmortem brain studies show a deficiency of the enzyme choline acetyltransferase, which is concerned in the synthesis of acetylcholine, and defective cholinergic transmission is considered the likely basis of the symptoms.

Cerebral blood flow and oxygen consumption are reduced. The EEG usually shows theta or delta waves, with alpha rhythm slow or absent. Brain scan shows cerebral atrophy, selectively affecting the medial temporal lobe in early cases.

Symptoms: onset is gradual, over a year or more. Loss of recent memory is usually the first symptom, and is followed by deterioration in other mental functions, emotional lability or sustained depression, and personality change.

Delusions and hallucinations, fits and neurological signs may occur in advanced cases. Insight is usually absent, and the patient comes to medical attention because relatives or neighbours notice failing memory, confusion, poor hygiene and self-neglect.

Diagnosis is made on clinical grounds, as there is no laboratory test for Alzheimerís disease, though tests may be required to exclude other causes of dementia.

In early onset dementia, rapid progression was said to be usual, but there is doubt as to whether deterioration is really quicker on average than in later onset cases. Marked neurological abnormalities are common.

Treatment: Acetylcholinesterase inhibitors donepezil, galantamine and rivastigmine are now licensed for use in AD. Their use was sanctioned by NICE in 2001, but with conditions:

• MMSE >12
• Prescription to be initiated in specialist clinics: most services now run a ìMemory Clinicî for this purpose
• Treatment normally to continue only if MMSE > 12 and judged to be of overall clinical benefit

It is unusual for such conditions to be attached to drug licenses; this reflects the high cost of the drugs, and the continuing doubts about their effectiveness.

Trial data indicate improvements, or at least slower declines, in measures of cognitive function, which is claimed to delay the requirement for the patient to enter institutional care. However, clinical experience is that dramatic responses are unusual. The overall impact of the drugs in clinical practice has been modest.

Memantine is an NMDA-receptor antagonist that affects glutamate transmission; it is licensed for treating moderate to severe Alzheimer's disease, however its cost effectiveness has been doubted (ref. 3).

NICE recently reviewed the effectiveness of all these drugs in relation to their cost; the manufacturers, not surprisingly considering the potential size of the market, have entered appeals, as have other groups; this debate can be followed at the NICE website.

Prognosis: Dementia shortens life. Pneumonia is a frequent terminal event. Five years after the onset of their dementia would be a typical course, but much depends on overall health and the quality of care.

Vascular Dementia Vascular dementia is common; it frequently co-exists with AD.

Epidemiology: VaD usually starts between the ages of 60 and 70 but sometimes earlier. Men are affected slightly more often than women.

Pathology: focal infarction of the brain due to haemorrhage, thrombosis or embolism, usually associated with cerebral arteriosclerosis. There may be a single CVA, or multiple small infarcts, or small vessel disease causing white matter damage. Most patients have hypertension, focal neurological signs, and evidence of arteriosclerosis in other organs.

Symptoms: loss of memory, intellectual deterioration and mood changes occur. Insight and personality are retained longer than for Alzheimerís disease, and the continued insight may contribute to the depression which is often present. Deterioration is stepwise rather than gradual, as repeated small strokes or episodes of hypertensive encephalopathy occur and leave residual damage.

Prevention and treatment: some cases might be prevented by control of hypertension in its early stages, and by attention to potential sources of emboli to the brain. Some improvement in the established condition may be achieved by treatment of very high blood pressure levels, cessation of smoking, and regular low-dose aspirin.

Prognosis: average survival time is about five years, and usual causes of death are ischaemic heart disease and stroke.

Lewy body dementia

Definition and neuropathology Comparatively recently, LBD has been recognised as a distinct condition. This is a type of dementia in which Parkinsonian features are prominent. Conscious level and cognitive function tend to fluctuate; and visual illusions or hallucinations may occur, as may frank psychotic symptoms.

It has been recognised that Parksinsonís disease can sometimes proceed to dementia. Patients with LBD are as it were on a continuum between pure Parkinsonism on the one hand and dementia on the other.

Lewy bodies are oval structures which are in fact eosinophilic inclsuioon bodies within degenerating dopamine-bearing cells in the substantia nigra and related areas; they are the neuropathological basis of Parksinsonís disease. The presence of such Lewy bodies (which are morphologically similar but distinct) in other areas of the brain appears at least partly to underlie the clinical syndrome of LBD.

Epidemiology It is not yet clear what proportion of dementia cases overall should be classified as LBD. Clearly, this would depend no how a case should be defined. It has however, been suggested that it is the second commonest cause of dementia after AD.

Clinical Features LBD is marked by fluctuating cognitive performance and conscious level, Parkinsonism (in the majority of cases), and psychiatric symptoms including visual hallucinations.

Treatment is inherently difficult. Drugs used to help Parkinsonian features tend to exacerbate any psychotic symptoms present. Parkinson treatment should be reviewed and reduced if possible, beginning probably with any anticholinergics.

Conversely, anti-psychotic drugs, if employed for psychotic symptoms- whether inherent or due to side effects of ant-Parkinson drugs- will make Parkinsonian symptoms worse. Patients are often very sensitive to neuroleptics, both typical and atypical, and they should be avoided if at all possible. A difficult balance has to be struck.

Pickís Disease

Pickís disease is regarded as one of the fronto-temporal lobe dementias; although it is a rare cause of dementia overall, it may account for up to 5-10% of early onset cases. Some cases are familial, probably caused by a dominant gene. Onset is between the ages of 50 and 60, and women are affected twice as often as men.

Cerebral atrophy occurs, with loss of neurones and gliosis, most marked in the frontal and temporal lobes. Characteristic Pick bodies (cortical inclusions) are seen.

Symptoms of frontal lobe damage occur first (character change, disinhibition, poor judgement, etc), and language problems if the temporal lobes are affected. Day to day memory may be relatively spared in the early stages, but impairment of memory and intellect gradually develops later. Dysphasia, apraxia, agnosia and extrapyramidal symptoms are sometimes present. Death follows two to ten years after the onset.

Huntingtonís Disease (Huntingtonís Chorea)

Huntingtonís disease is a rare form of inherited presenile dementia. Its molecular genetics, and their clinical implications, have been extensively studied.

Epidemiology: 5 per 100 000 of the population are affected, with marked regional variation. Men and women are equally at risk.

Cause: an abnormality in the IT-15 gene, located on the short arm of chromosome 4, which encodes the protein Huntingtin. This results in an autosomal dominant inheritance pattern with about 90% penetrance. The number of repeat sequences of the abnormal DNA triplicate (CAG)- leading to excessive glutamine in the protein- has some relationship to the age of onset, and severity, of the clinical disorder. However, the role of the protein in brain function is at present unclear in spite of enormous research effort.

Half the children of an affected parent will develop the condition, and because the age of onset is usually in mid-life, many patients have already had children themselves by the time symptoms begin. ìAnticipationî is also seen, that is, age of onset gets less in succeeding generations. Occasionally patients have no family history, and such cases may be explained by spontaneous mutations or concealed illegitimacy.

Neuropathology and neurophysiology: generalised atrophy of the brain is most severe in the frontal lobes, caudate nuclei, and putamen. Low energy metabolism in the caudate nucleus, identified by PET scan, is characteristic and could be used as a presymptomatic test. Deficiency of GABA, and excess of dopamine, have been demonstrated at postmortem.

Clinical features: onset may be at any age, but most often in mid-life (mean age 49). The juvenile form, starting in adolescence, accounts for 10% of cases. Choreiform movements and dementia are the most characteristic symptoms but there may be any type of psychiatric abnormality, for example neurotic, depressive or schizophrenic symptoms or psychopathic personality features, and great variation in the clinical course.

Treatment: choreiform movements can be modified with phenothiazines or tetrabenazine. Any psychiatric symptoms present should be treated with appropriate drugs.

Diagnosis: presymptomatic testing using genetic probes is now available through departments of medical genetics. The test may be carried out on an adult individual or an unborn child. Testing raises ethical issues, since there is no means of preventing or treating the disorder in those carrying the gene, and tests should only be carried out in the context of thorough family counselling. In practice, only a minority of at-risk individuals choose to be tested.

Prognosis: average survival time is about 15 years.

Transmissible Spongiform Encephalopathies (Prion Dementias)

These are rare forms of dementia, caused by accumulation of abnormal prion proteins in the brain. Prion stands for proteinaceous infectious particle. They are a unique form of infective agent, as they contain no genetic material.

Prions are now accepted as the cause of a group of transmissible spongiform encephalopathies including scrapie (in sheep), chronic wasting disease, (in deer),  and bovine spongiform encephalopathy (BSE or mad cow disease).

Human examples of these disorders include CreutzfeldñJacob Disease (CJD), and kuru (formerly found in the cannibals of Papua New Guinea; this epidemic peaked in the 1960s and is now more or less extinct, due to the decline of utilization of this type of food).

Sporadic CJD has always rarely occurred. Iatrogenic CJD cases involved transmission of the condition by use of pituitary tissue (especially to get growth hormone) from CJD-infected brains post mortem. New variant (nvCJD) cases are those linked to BSE. Although at the height of the health scare regarding BSE, huge numbers of cases were predicted. However, as at August 2006, only 156 had been identified.

BSE was described in British cattle in the 1980s and was probably due to use of scrapie-infected sheep products in cattle-feed (the temperature at which such products should be treated to render them safe had been reduced by Government, for reasons of economy). Other countries had similar epidemics, which were not as well publicized.

Gerstmann-Str‰ussler-Scheinker syndrome and fatal familial insomnia are other rare human examples.

Causes: in some families, these dementias appear to be due to an inherited prion gene mutation, which follows an autosomal dominant pattern. Other cases are infective, due to an abnormal prion protein acquired in various ways. The disorders can be transmitted to experimental animals, and human cases have developed following neurosurgery, corneal grafting, or administration of cadaveric growth hormone.

Neuropathological features: prion protein, a modified cell membrane protein, accumulates within the CNS. There is neuronal loss, astrocytic hyperplasia and spongiform vacuolation in grey matter, with amyloid plaques.

Clinical features: dementia, accompanied by myoclonus or ataxia, usually starts in middle life. EEG changes are characteristic, and diagnosis can be confirmed by finding a prion gene mutation in a blood sample. These diseases are always fatal, within a few months typically.

NvCJD is said to differ clinically from ìclassicalî CJD, in that the symptoms are often initially psychiatric, and progression is slower.

HIV Dementia

Cognitive impairment is associated with HIV infection and AIDS. However, it is difficult to generalize about the prevalence of dementia as the outlook for the condition varies greatly between countries where there is good health care and those where access to AIDS drugs is limited and the outlook much poorer. Regarding the UK, the predictions at the start of the epidemic of very large numbers of HIV-dementia cases have fortunately proved wide of the mark.

Nevertheless, substantial numbers of patients in the late stages of this illness do develop a frank dementing syndrome due to invasion of the brain with the HIV virus. Typical features include forgetfulness, slowness and apathy, accompanied by motor weakness, with multiple neurological abnormalities in the later stages. Cerebral atrophy is shown on brain scan. Treatment with antiviral agents may bring about worthwhile clinical improvement.

Differential diagnosis in the HIV-positive patient includes other cerebral infections such as toxoplasmosis, cryptococcus, cytomegalus or herpes simplex; cerebral lymphoma; also depressive illness. Specific treatments are available for several of these conditions, therefore it is desirable to reach an accurate diagnosis.

Prevention of dementia

It has been suggested that ìThe prevalence of dementia would be reduced by 50% if risk reduction strategies were successful in delaying its onset by 5 yearsî, and three strategies have been suggested:

• Treatment of vascular risk factors
• Neuroprotection, through vitamins, anti-oxidants and anti-inflammatory agents
• Building up neuronal reserves, through increased activity.

FOCAL BRAIN DAMAGE

Amnesic syndrome The most common type of amnesic syndrome is Wernicke-Korsakov syndrome, which is fundamentally due to thiamine depletion, almost always in the context of alcohol misuse.

Wenrickeís refers to the acute encephalopathic presentation (confusion and neurological signs, usually in a known alcoholic- parenteral thiamine treatment is mandatory), Korsakovís to the chronic memory defect state.

The brain structures involved, necessary for the laying down of new memories, have been described as the circuit of Papez: hippocampus and nearby areas in the mesial temporal lobe, fornix, mammillary bodies and thalamus.

Causes:

• Thiamine deficiency, usually secondary to alcoholism, occasionally secondary to other causes of nutritional deficiency.
• Carbon monoxide poisoning.
• Vascular lesions.
• The aftermath of hypoxia (such as may follow anaesthetic accidents, or attempted suicide by hanging) or hypoglycaemia.
• Encephalitis.

Clinical features: memory for recent events is grossly impaired, but immediate recall and long-term memory are both preserved, as are other intellectual functions. Many patients confabulate, that is they conceal their memory defect by elaborate falsifications.

Treatment: thiamine may be helpful if thiamine deficiency is present. Memory aids may enable some patients to function adequately but many need constant supervision. Alcohol should be avoided, but therapy for this is inherently difficult due to the memory problems.

Frontal Lobe Lesions

The frontal lobes are the seat of higher mental functions, particularly the carrying out of complex mental operations, so called ìexecutive functionsî. Personality change is often the first sign of a frontal lobe lesion. Behaviour becomes disinhibited, tactless or ill-judged; mood is inappropriately euphoric; drive and concentration are diminished, although there is no formal intellectual impairment; insight is lacking.

Neurological signs include a grasp reflex, anosmia, optic atrophy and incontinence. If the lesion involves the motor cortex there may be epileptic fits or contralateral spastic paresis.

Brocaís area, in the inferior frontal lobe, is involved in language production; lesions here will result in expressive dysphasia but relatively unimpaired comprehnsion.

Temporal Lobe Lesions

Personality change may take the form of increased aggression and emotional lability, or resemble that seen with frontal lobe lesions.

Temporal lobe epilepsy may develop. This condition, even more than other types of epilepsy, has important psychiatric aspects. It has an association with neurotic disorders, mood disorders, and schizophrenia, and a high suicide rate.

Intellectual deficits can be verbal or non-verbal depending which side is involved. Memory defects occur with bilateral lesions.

Neurological impairments include contralateral homonymous upper quadrant visual field defect, contralateral limb weakness or sensory loss, and language difficulties in the case of dominant hemisphere lesions.

Wernickeís area, is required for comprehension; damage here produces reduced understanding, but speech output is fluent albeit inaccurate.

Psychiatric symptoms of schizophrenic or affective type may occur.