It was a matter of controversy whether the coincident influenza epidemics had predisposed the host to react abnormally to some relatively innocuous organism, and some evidence suggested that the herpes virus might itself be responsible. These questions were not decisively settled, but the great majority of contemporary 444 Chapter 7 epidemiological evidence suggested that an independent virus was responsible. In retrospect it appeared that this was not entirely a new disease, and similar widespread epidemics could be traced in history. In England a second peak of encephalitis lethargica occurred in 1924, but thereafter there was a striking fall-off of new cases throughout the 1930s, although sporadic cases continued to be seen and small local epidemics appeared from time to time. Acute clinical picture A prodromal stage lasting several days consisted of malaise, mild pharyngitis, headache, lassitude and low pyrexia, all symptoms being slight and resembling the prodomata of influenza. Somnolence developed after the prodromal phase, with slight signs of meningeal irritation. Initially there was merely a tendency to drowsiness from which the patient could easily be roused, sometimes with evidence of confusion or mild delirium. If recovery did not occur at this stage, the disorder progressed further to more or less permanent sleep for weeks or sometimes months, often deepening to coma. On recovery, disturbances of sleep function might persist for many months during convalescence. Pareses of the cranial nerves set in early, especially of the third and sixth, with ptosis, paralysis of ocular movements and less commonly pupillary abnormalities or nystagmus. In the limbs isolated pareses and reflex abnormalities were seen, with spasticity, hypotonia or ataxia. In other cases the picture was dominated after the prodromal stage by signs of motor unrest. This was the hyperkinetic form, with myoclonic twitches, severe jerking chorea, wild jactitations and anxious excited behaviour. Delirium could be marked, with constant unrest by day and night, sometimes closely resembling delirium tremens with anxiety amounting to terror in response to vivid hallucinations. Typically the acute disturbance lasted only a few days, but insomnia or reversal of sleep rhythm then usually persisted for weeks or months after recovery. Movements were remarkably slowed and sparse, the patient lying still for hours at a time or responding with profound psychomotor retardation. Speech, like motor movements, was greatly delayed, yet the patient could be shown to be mentally intact despite the appearance of dementia. Along with these features somnolence, sleep inversion and oculomotor signs might be in evidence. The psychotic forms were rare, but presented with acute psychiatric disturbance as the initial feature. Here mistakes in diagnosis frequently occurred until neurological signs declared themselves. The usual picture was of an acute organic reaction, but stupor, depression, hypomania and catatonia were also reported. Sometimes impulsive and bizarre behaviour was the sole manifestation for several days, accompanied by bewildered and fearful affect. Alternatively, mental conflicts were brought to the fore, adding a psychogenic colouring to the presenting symptoms. She became extremely fearful, asking whether she was about to die or if something terrible was going to happen to her family. The pupils were later found to be irregular with sluggish reactions, and the tendon reflexes were diminished. In the following week she developed choreiform and athetoid movements and a left facial weakness. She died a few days later after a period of disorientation, high pyrexia and noisy disturbed behaviour. A woman of 32 suddenly became restless and noisy, sang and screamed, and claimed to be the daughter of Christ and impregnated by him. She lay in bed in a strained attitude, and was markedly deluded and uncooperative. The pupils were widely dilated and reacted sluggishly to light, and the tendon reflexes were diminished.
Every attempt must be made to avoid withdrawal after early failures, to keep the patient involved and active, and to stimulate a continuing desire to communicate. Formal speech therapy has rarely been rigorously tested, which is surprising in view of the magnitude of the problem. Nevertheless, although it is uncertain whether the final level achieved exceeds that which would have occurred spontaneously, few doubt the effects of retraining programmes on emotional adjustment and morale. Impairment of memory must be specially catered for with a more gradual programme, frequent rehearsals and the provision of props and supports by way of notes and written instructions. The relative preservation of old memories may initially produce a misleading impression until ability to acquire new knowledge is specifically tested. Strategies for rehabilitation of memory impairments rest largely on the premise that it will not be possible to affect the degree of impairment, but that by using compensatory strategies it may be possible to reduce the consequent disability and handicap that the memory impairment produces. More general techniques concentrate on organising the study of material to be learned, chunking information into subsets and breaking down new skills into a series of steps. A review of memory rehabilitation across patients with different acquired brain injuries, including stroke, found errorless learning to be effective, whereas the case for the method of vanishing cues was not so robust (Kessels & de Haan 2003). However, there have been rather few attempts to demonstrate in stroke patients alone that rehabilitation can improve memory (Majid et al. Other intellectual impairments are a serious barrier to progress when at all extensive. Ill-sustained attention, perseveration, fatiguability and failure to grasp instructions may Cerebrovascular Disorders 491 combine to render attempts at rehabilitation fruitless. To maximise the chances of success, verbal instructions must be presented in simple language with deliberate methodical repetition. Practical demonstrations of what is expected may get the ideas across when other methods have failed. The pace will necessarily be slow, and allowance must be made for variability in performance from day to day. Motivation is among the most crucial determinants of progress and every means must be taken to optimise and maintain it. All through the programme, proper communication must be maintained so that he is aware of the plans and goals at every stage. Motivational interviewing is a specific technique that was originally designed to help patients with addictions, but more recently has been used in a variety of setting where poor motivation may jeopardise improvements in health. A watch must be kept for evidence of depression, which may well respond to appropriate medication or psychological therapy. Tactful handling may be required in the face of discouragement, withdrawal or obstinacy. Clear guidelines must sometimes be drawn up, especially for patients with intellectual impairment who will benefit from a structured environment. In contrast, flexibility must be built into the programme to allow for patients with differing needs and personalities. Rigid conformity to set standards cannot always be expected, and in some persons will be counterproductive. They too will need full discussion of aims and procedures, and help in adjusting to the disabilities that are likely to remain. Careful physical rehabilitation may be doomed to failure if insufficient attention has been given to the family situation and to the impact of the problem on family members. Here the social worker has a vital part to play, and should be brought into the picture at an early stage. Much time may be needed to allay unrealistic expectations or needless anxieties and fears. The stroke and its repercussions may have had a far-reaching effect on many members of the household, disturbing the family equilibrium and requiring a reorganisation of roles. Preparations for discharge must be made well in advance, on a practical as well as an emotional level. Physical adaptations may be needed in the home by way of ramps or simple supports. Where work is being considered, extended evaluation and retraining will often be indicated.
In an examination of the clinical features of suicide attempts, Simpson and Tate (2005) found that overdoses accounted for 62% of 80 suicide attempts committed by 45 people with head injuries, followed by cutting (17%) and miscellaneous other means. Precipitating factors included depression/hopelessness, relationship breakdown or conflict, social isolation and other stressors. Almost half (48%) went on to make one or more further attempts, Head Injury 223 typically within 1 year of the index attempt. Two reviews of people who completed suicide after head injury identified post-injury rates of suicide attempt of 25% and 62. The relative contribution of premorbid, injury and postinjury factors to suicide and suicide attempts is still unclear. One major difficulty is that suicide and head injuries share a number of antecedent risk factors, including the predominance of young adult males, a history of substance abuse or psychiatric illness, and aggressive personality traits. In the case of mild head injuries, Teasdale and Engberg (2001) have suggested that these type of factors, present premorbidly or concomitant to the head injury, may be of more significance than the brain damage per se in the subsequent suicides. In contrast, after severe injuries it is likely that the pattern of neuropathology, residual adaptive abilities, psychological reactions to the injury and the presence of psychiatric disorders play a significant role, both in completed suicide (Teasdale & Engberg 2001) and suicide attempts (Simpson & Tate 2005). In the case of suicides, lesions were commonly found in the frontal and temporal lobes of the brain (Vaukhonen 1959). Risk factors for suicide attempts include a post-injury history of psychiatric/emotional disturbance or substance abuse, as well as clinically significant levels of suicide ideation (Simpson & Tate 2002, 2005). There was a powerful interaction between risk factors such that patients with both a post-injury history of psychiatric disturbance and substance abuse were 21 times more likely to have made a post-injury suicide attempt than patients with neither (Simpson & Tate 2005). Premorbid risk factors cannot be discounted, even in those with more severe injuries. With regard to treatment, practice options suggested by current research include reducing the lethality of the environment, following published guidelines in the prescription and administration of medication, treatment of comorbid substance abuse or depressive disorders, and increased monitoring/support for at least 1 year following a suicide attempt. However, because post-concussion syndrome may also follow moderate and severe injuries, it is discussed separately. Some of these matters have already been considered, but with reference to the full range of head injury severity. Studies of concussion in sport have provided unique opportunities for observation. In terms of the boundary between no significant head injury and mild head injury, most will allow any disturbance of consciousness, not necessarily loss of consciousness, such that the patient meets the criterion of having suffered a concussion (see Impairment of consciousness, under Acute effects of head injury, earlier in chapter). More recently there has been interest in the potential effects of blast injury, and there is uncertainty as to the extent of any brain damage caused by the air pressure wave of an explosion. Even more restrictive are those definitions that do not allow focal intracranial abnormalities on brain imaging. However, for the purposes of the discussion here, these more restrictive definitions are not used. On the one hand there appears to be no stepwise effect of loss of consciousness on outcome (see below). It will also cover somebody who is unconscious for 20 minutes after a fall from 10 metres and is still a little confused 12 hours later in casualty. The second question is much more difficult to answer and therefore contentious: how many suffer diffuse axonal injury, perhaps invisible on neuroimaging, which nevertheless explains some of the postconcussional symptoms The first question is of most interest to the neurosurgeon or emergency physician in relation to triage and follow-up of patients presenting after a mild head injury. It is worth noting that although only a very small proportion suffer complications, because mild head injury is so much more common than moderate and severe head injury, a significant proportion of those who do suffer complications requiring surgery have mild injuries. For example, more than 40% of all patients with depressed fractures have never lost consciousness (Jennett 1989). Three lines of evidence suggest that diffuse axonal injury may occur after mild head injury.
Aphasia is an accompanying defect in the great majority of cases and deficient comprehension of commands may sometimes play a part. Agnosia for an object may hinder the patient from carrying out purposive movements appropriate to its use, while agnosia for spatial relationships will similarly interfere with the copying of a movement by imitation. Over and above such complications, however, there is usually a higher-order cognitive impairment with a specific bearing on motor function. Sometimes simple discrete movements are affected, and sometimes complex coordinated sequences as in the use of a tool. Frequently, performance is much better in the actual presence of the tool than when the patient is asked to demonstrate its use in imagination. To a surprising degree, whole-body movements to command are often found to be perfectly preserved, while limb and facial movements are defective. Hence, simple hierarchies of difficulty do not provide an adequate explanation for these anomalies. Apraxia is probably more often seen in diffuse than in strictly focal brain lesions so that other intellectual processes are often involved. With focal lesions, however, other cognitive processes may prove to be largely intact, even though at first sight the severely apraxic patient is sometimes misdiagnosed as having a dementia. Nevertheless, such patients are severely handicapped in many tasks requiring the demonstration of intelligence. It is likely that the schemata for purposive movement are so interwoven in cognitive processes that their disruption is bound to have a more general adverse effect. The more practised the act, and the more automatic it has become, the more it will be carried out without conscious awareness and conscious volition. Apraxia may be regarded as the result of disorganisation in such schemata and as taking place at various levels of complexity. At the highest level will be found disturbance where schemata are involved in the formulation of the idea of a movement; at the lowest, the schema consists of a motor pattern that regulates the selection of appropriate muscles. In contrast, Geschwind (1965) characteristically put forward a disconnection model, in which he postulated that lesions which disrupted connections between auditory association cortex and motor association cortex of the dominant hemisphere would result in an inability to carry out motor commands with the limbs on either side of the body. Lesions of the left motor cortex would produce a right hemiplegia together with apraxia limited to the left arm when the origin of the transcallosal pathway had been destroyed. Lesions of the corpus callosum would result in apraxia to command without dysphasia, and limited to the left arm and leg, since the motor cortex of the right hemisphere would now be isolated from the speech mechanisms of the left. Many varieties of apraxia have been postulated and these are briefly outlined below. Limb kinetic apraxia: the skill and delicacy of movements is disturbed for both complex and simple actions. The difficulty the patient experiences reflects the degree of muscular complexity, rather than the psychomotor processes involved. It may be confined to particular muscle groups, and even to certain fingers of the hand. This form has characteristics intermediate between a paresis and apraxia, and therefore is often excluded from the apraxias proper. Ideomotor apraxia refers to the inability to carry out a requested movement properly. It may be regarded as a disturbance of voluntary movement at a fairly low level of motor organisation or, alternatively, as a disturbance of the use of space centred on the body. The patient can often formulate to himself the idea of a movement that he wishes to perform but is unable to execute it. Thus the voluntary impulse does not evoke the appropriate organisation of the movement in space and time. For example, the patient cannot raise his hand or wave it to command, even though the instructions are understood. Yet essentially the same movements can be performed automatically, as in signalling goodbye or in the course of other activities to which his attention is not directed.
Cutaneous features include photosensitivity, skin fragility, bullous lesions, facial hypertrichosis and hyperpigmentation. Emotional disturbances with anxiety, restlessness and depression often occur and may be persisting features (Patience et al. Detailed psychiatric assessments have been limited to small series or case reports; psychotic features resembling schizophrenia with persecutory delusions, auditory hallucinations, social withdrawal and catatonia have been described (Tishler et al. Clouding of consciousness and confusion may progress to delirium, with hallucinations, delusions and disturbed behaviour. The occurrence of monthly luteal-phase attacks in women may lead to the false Endocrine Diseases and Metabolic Disorders 671 diagnosis of an acute polymorphic psychotic reaction or a cycloid psychosis. Precipitation of attacks Drugs and the menstrual cycle are the most common precipitants of an acute attack (Kauppinen & Mustajoki 1992), though alcohol excess and inadequate malnutrition are also important precipitants. The current list of agents known to precipitate an acute attack is long and the British National Formulary or the Cardiff Porphyria Research Group should be consulted before a drug that is not known to be safe is prescribed. Notorious precipitants include antibiotics such as the sulphonamides and erythromycin; sedatives such as barbiturates, benzodiazepines and sulpiride; hormone products such as the oral contraceptive pill, anabolic steroids, hormone-replacement therapy and tamoxifen; antiepileptics such as phenytoin and carbamazepine; drugs of abuse including cocaine and amphetamines; as well as many commonly prescribed drugs such as antihistamines, diuretics, baclofen, metoclopramide, many of the tricyclic antidepressants and diclofenac. Importantly, many of the drugs that would be considered for use in the mental state disturbances commonly seen in acute porphyric attacks have been associated with their precipitation, necessitating considerable care in the use of the agents. Of the antipsychotics chlorpromazine appears the safest, and there are few data on the atypicals. There are no data on amisulpride though sulpiride is associated with precipitating attacks so it should probably be avoided. There are a few case reports describing the uncomplicated use of olanzapine and cell culture studies have suggested that it may be safe. Mixed reports have been associated with risperidone use and there are currently no data on the use of quetiapine or zotepine; clozapine is believed to be safe. Of the antidepressants, most of the tricyclics should be avoided, but fluoxetine and paroxetine appear to be safe though there are currently too few data to comment on the use of the newer agents, mirtazapine, reboxetine or venlafaxine. The above resources should be consulted before the use of any of these newer agents is contemplated. Other drugs judged safe include aspirin, narcotic analgesics, penicillin, streptomycin, tetracycline, propranolol, paraldehyde and probably clomethiazole (Moore & Disler 1988; Kappas et al. The importance of nutrition is shown by attacks that occur while on reducing diets, especially when these lead to precipitous loss of weight, and cases have been described of attacks occurring after missing several meals (Kappas et al. Previous claims that stress, surgery and infection are precipitants have not been supported by published data. Investigations Most difficulties in the diagnosis of the acute attack occur in patients without a family history of porphyria, especially if the combination of symptoms is atypical. Porphyrins are very light sensitive and break down quickly under normal conditions so urinary samples should be stored in the dark and transported to the laboratory as soon as possible. A negative result does not exclude an acute attack since some patients fail to hyperexcrete. Caution is also required on account of the falsepositive results that can occur in the urine with certain febrile illnesses, in lead poisoning and in patients receiving phenothiazine drugs (Reio & Wetterberg 1969). Isolated records are therefore of little help in the diagnosis, but serial recordings can occasionally be useful in confirming the organic origin of symptoms in attacks of uncertain nature. Some have hypothesised a vascular aetiology for these changes in view of their mild enhancement with contrast, rapid resolution following treatment of the attack and similarity to the lesion distribution seen in hypertensive encephalopathy. Differential diagnosis Porphyria is notorious for leading to mistakes in diagnosis, and patients are sometimes admitted repeatedly to psychiatric units before the condition is discovered. Diagnoses of personality disorder or an anxiety, somatisation or conversion disorder are commonly made when the patient complains of weakness of the limbs and varied aches and pains unbacked by physical signs. Psychotic developments may likewise obscure other aspects of the disorder and lead to a primary diagnosis of depressive illness or acute schizophrenia. Other patients are admitted to general medical wards with suspected appendicitis on account of abdominal pain and vomiting.
Carotid endarterectomy has an important role in the prevention of later infarction in patients with greater than 70% stenosis of the carotid artery (Barnett et al. Neuroimaging of stroke the acute management of stroke, within the first few hours of onset, goes hand in hand with neuroimaging protocols, 480 Chapter 8 developed over the last few years, designed to help the clinician decide whether intravenous thrombolysis is indicated (Masdeu et al. Having confirmed that the neuroimaging findings are indeed those of a vascular lesion, the first priority is then to separate haemorrhagic stroke, in which case thrombolysis is contraindicated, from ischaemic stroke. Subsequently, assessment of the extent of ischaemic but salvageable brain (the penumbra) around the core of non-viable tissue may improve selection of those most likely to benefit from thrombolysis. Neuroimaging may also help identify the cause of the stroke, for example picking up multiple cortical infarcts suggestive of cardiac emboli. In the acute stage, infarcts of the major cerebral arteries are considered to produce three zones of hypoperfused tissue (Muir et al. The core of the infarct, where the opportunity for anastomotic perfusion is least, is defined as the zone where cells will inevitably die. Within the core there may be a zone where only neurones die, surrounding a zone where the ischaemia is so severe that no cell, including glial elements, has a chance of survival. The penumbra is the ischaemic zone surrounding the core and is defined as the zone where tissue may either die or survive in the long term. The consequent ischaemia impairs neuronal function, giving rise to neurological symptoms over and above those arising from neuronal death in the core. Finally, surrounding the penumbra is a zone of oligaemia, with blood flow greater than 20 mL/ min per 100 g but less than the normal value of about 50 mL/ min per 100 g, where oxygen extraction is increased, neuronal function is maintained and cell death in the long term is unlikely. In the acute stage the size of the core determines the extent to which there will be inevitable permanent damage, whereas the size of the penumbra indicates the potential for recovery and for thrombolysis to salvage brain tissue. Therefore identifying the extent of these zones, using neuroimaging, is clinically useful. Cells dying from ischaemia develop intracellular oedema as sodium ions enter the cell; water is thus removed from the extracellular compartment, resulting in reduced free diffusion of water. There is uncertainty as to whether such microbleeds should be regarded as a contraindication to thrombolysis. Other neuroimaging techniques that may have a role in the investigation of stroke include cerebral angiography and Doppler studies of the cerebral vessels. This is best observed in ipsilateral cortex, particularly frontal, after thalamic infarcts, in contralateral cerebellum after large supratentorial infarcts (crossed cerebellar diaschisis) (Sobesky et al. With improvement in blood flow the penumbra shrinks as neurones that were previously unable to function return to activity. This may be followed by a period of improvement over several weeks due to the spontaneous regression of brain oedema and other acute histopathological processes in and around the stroke. Over this same period the remote effects of the stroke, particularly diaschisis, improve. Any later recovery is probably, at least in part, due to reorganisation of function (Butefisch et al. Finger movements on the unaffected side activated regional blood flow in the contralateral sensorimotor and premotor cortex and the ipsilateral cerebellar hemisphere. The same movements in the recovered hand produced more widespread activations, including significant increases bilaterally in sensorimotor and premotor cortex and both cerebellar hemispheres. Thus bilateral involvement of motor systems was seen when the recovered fingers were employed, indicating significant reorganisation and recruitment of ipsilateral motor pathways. Activations were also observed in cingulate and prefrontal areas that are not normally involved in finger movement but are known to be involved in selective attentional and intentional mechanisms, suggesting that these too may play an important part in the recovery process. This reorganisation was only seen in those who were exposed to a motor training programme, compared with those who were not, an observation that has important implications for stroke rehabilitation. Anticoagulant therapy may be indicated where embolism is suspected, or operative intervention may be needed on a stenosed or atheromatous carotid artery, but these are matters for neurological assessment. Patients with intracerebral haemorrhage are at risk of further bleeding and of developing hydrocephalus.
An increased risk of epilepsy following febrile convulsions has most consistently been associated with a family history of epilepsy, the presence of early-onset Anatomically defined localisation-related epilepsy syndromes Seizures originating in different anatomical locations take characteristic forms but there is considerable overlap. The symptoms at the very beginning of a seizure generally provide the most critical clue to localisation, but a focal epileptic discharge may spread to adjacent brain regions so rapidly (within milliseconds) that the clinical manifestations of seizures arising in functionally quite distinct cortical regions become indistinguishable. Nevertheless, typical modes of presentation that correspond to anatomical location are now recognised and are of considerable importance in clinical practice. Skilled appraisal of clinical semiology will help determine which hemisphere and which cortical region are involved. In the following section the primary aim is therefore to describe the semiological features of each syndrome. Aetiological factors, where distinctive, are mentioned but are dealt with in greater detail elsewhere in the chapter. They are of particular interest to the psychiatrist because they often contain elements that echo symptoms seen in psychiatric disorder. Hippocampal sclerosis is strongly associated with a history of childhood febrile convulsions 320 Chapter 6 Table 6. Estimates of the relative frequency in different lobar epilepsies are derived from King and Ajmone Marsan (1977) and Palmini and Gloor (1992). Temporal lobe seizures may take the form of simple and complex partial seizures, with both occurring in some 70% of patients (Janszky et al. Compared with extratemporal seizures, those arising in the temporal lobes characteristically have a gradual onset, usually feature a conspicuous motionless stare and are relatively prolonged, with automatisms often continuing for 2 minutes, occasionally even longer. A variety of autonomic features and visceral sensations figure prominently in temporal lobe auras. Other autonomic effects include changes in skin colour, blood pressure, heart rate, perspiration, salivation and piloerection. Affective experiences are a feature of approximately onequarter of temporal lobe auras. The most common is anxiety, which is often intense (ictal fear) and wells up suddenly without provocation. Pleasurable affects of joy, elation or ecstasy occur less frequently (Stefan et al. Affective auras are an intrinsic part of the seizure, and not merely a reaction to some other aspect of the aura. The emotional content of the aura may nevertheless colour hallucinatory experiences or occasionally be associated with disturbed behaviour. These authors and others have described an association between ictal fear and non-dominant medial temporal foci (Hermann et al. All but one were fully conscious throughout their seizures and the remaining patient had only questionable and momen- Epilepsy tary impairment. Despite preserved awareness, clear oro-alimentary automatisms (lip-smacking, chewing, swallowing) were seen in all but one patient and dystonic posturing or fleeting localised clonic movement were almost as common. In seven cases the epileptogenic lesion was in the temporal lobe (three on the left, three on the right and one bilateral; six involved the non-dominant hemisphere); the remaining patient had a frontal lobe focus. Seizure onset in medial temporal lobe structures was associated with mild subjective mood changes only. The authors propose that the syndrome of intense ictal fear is associated with functional involvement of a distributed limbic network involving medial temporal lobe, orbito-prefrontal cortex and anterior cingulate. It is usually non-verbal, in which case it may be associated with either dominant or non-dominant foci and has no lateralising value. However, speech automatisms (recurrent, irrelevant or emotionally toned utterances), which can be thought of as evidence of preserved speech during the seizure discharge, are strongly related to a non-dominant temporal lobe focus (Williamson et al. Disturbances of memory (dysmnestic aura) range from sudden difficulty with recall to compulsive reminiscence on topics, scenes or events from the past. In the rare panoramic memory, the patient feels that whole episodes from his past life are lived again in a brief period of time as complex organised experiences.
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