Develop. Med. Child Neural. 1980.22.97-104

Annotations

INTRACTABLE EPILEPSY IN CHILDHOOD

IT is naturally a matter of great concern if a child starts to suffer from epileptic seizures. How much more worrying it is if the fits continue in spite of anti-epileptic treatment. In a paediatric neurology centre seeing a selected group of children with epilepsy, the percentage of them showing a poor response to treatment may not be very meaningful, but it is a problem which occurs sufficiently frequently to lead to dissatisfaction with the present methods of treatment. For example myoclonic fits are notoriously difficult to treat and, excluding infantile spasms (West’s syndrome) and petit ma1 variant (Lennox-Gastaut syndrome), may constitute about 5 per cent of children attending a special clinic’. An overriding reason for including children in the syndromes of West and Lennox-Gastaut is the severity of the cerebral insult at a particular age, whatever the type of fit or the cause, so it is not surprising that the response to treatment and prognosis is so poor for nearly all such children.

If medical treatment proves to be unsatisfactory and the history, clinical examination and initial investigations have shown no reason for this, it will be necessary to review the appropriateness of the drugs used and whether they have been given in a dose sufficient to result in a serum level which has been shown to be effective. Even among children, treatment prescribed may not be given, as many mothers are reluctant to give their children ‘drugs’, and the older children to take them. There can be defects of absorption, and some patients metabolise these drugs at an unusually rapid rate. As an alternative, ketogenic diets of different types can be tried, although the principles are the same with a relationship between the seizure control and the level of ketones in the blood.

The ability to estimate the serum levels of most of the common therapies for epilepsy has been a major advance, although ifcontrol is adequate and there is no question of toxicity there is no necessity to check the levels as a routine. Sometimes the fits stop when the levels are low, and so much the better. If the levels are high and toxic states are induced there is no doubt that the fits may become worse rather than better. This is particularly true with phenytoin poisoning2. Although many of the tales of diminished fit frequency on reducing treatment are anecdotal (but not to be ignored on that account) there is some better evidence than this. HANSON and MENKES3 found in a trial of a new anticonvulsant that in 8 per cent of cases reducing or stopping the patient’s present treatment brought seizures under satisfactory or complete control before the new drug was started. It has also been suggested that in so-called pyridoxine responsive seizures the improvement may be due to the action of pyridoxine on phenytoin metabolism, resulting in a reduced level of phenytoin in the body and the correction of a toxic state4. Even in the desperate situation of a child in status epilepticus, whose fits continue in spite of heroic measures,

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it has been occasionally noted that curarising the patient on a life-support machine and stopping all drugs will coincide with the cessation of the convulsions.

Efforts to explain some of these phenomena, especially when there is no definite toxic state, must remain theoretical until more is known about the pathophysiology of epilepsy. There is no doubt that it is a particular characteristic of brain cells that they like to discharge in unison, and if this gets out of hand a seizure occurs. Therefore there must surely be built-in mechanisms to prevent this happening, though it is not clear whether these are biochemical, perhaps related to the metabolism of gamma-aminobutyric acid or other neurotransmitters, or electrophysiological, comparable to the action of the Renshaw cell in the spinal cord. May it sometimes happen that the treatment given has a greater effect on these protective mechanisms than on the epileptic activity itself’? There is no evidence that this happens very often, and plenty of support from well-designed drug trials that anti-epileptic treatment is successful. All that can be suggested at the moment is that the possibility be kept in mind in the management of these children, and if care is taken it can easily be put to the test. Parents often ask if treatment can be stopped when it does not seem to be controlling the seizures, a question that sometimes must be taken seriously.

If there is no evidence of inadequate or excessive treatment as a cause of persistent seizures, the possibility of emotional disturbances must be considered. There is no doubt that stress and unhappiness at home and at school can increase the liability to fits. It is relatively common for a child to be admitted to the hospital ward with frequent fits, and before the drugs are changed their frequency is markedly reduced or they stop. The same can happen if a child with epilepsy is unhappy or under excessive strain at school, in which case a change of school can have a profound effect. This not only emphasises the influence of emotional disturbances on the incidence of seizures but also the fact that there is much more to the treatment of epilepsy than the dispensing of pills. The effects of the environment must be assessed and if there are obvious adverse factors these must be modified, if possible. It is easy and understandable for excessive anxieties to develop at home, and counselling of parents and child can help to prevent this.

Advice on activities must be governed by common sense; a life without risk is likely to be a life not worth living, and too many restrictions will almost certainly be counter- productive. For example swimming for children with epilepsy can usually be advised as long as there is an adult to keep a personal watch on the child, and it must be remembered that more people with epilepsy die in the bath than in the swimming pool. Such problems reach a peak in adolescence, which is a difficult enough period of life without the further complication of epilepsy. Also, among those children whose epilepsy is a symptom of brain damage, other symptoms may include a lower threshold to emotional disturbances and a variety of behavioural disorders resulting from an interaction of the disability and the environment.

At school, children with epilepsy may become outsiders, shunned by their peers and sometimes ridiculed. Teachers may be unsympathetic and make it plain that they do not want such a child in their class. Obviously the teacher can play a vital r61e in helping the child with epilepsy and if the occurrence of a fit in the classroom is dealt with in a matter-of-fact way the other children are likely to take their cue from this. Often, too, there are learning disabilities: if the epilepsy is a symptom of brain damage there may be defects of memory and language development in the case of dominant hemisphere lesions, and of perceptual motor function if the non-dominant hemisphere is affected5. There is also the problem of the child’s treatment and its side-effects, such as the drowsiness caused

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ANNOTATIONS

by barbiturates. No wonder such children are often under excessive strains at school, and if these can be modified there may be a reduction in the frequency of fits which have not responded to drug treatment. All this must not mean that the child is over-protected, or he will never reach his full potential.

Ifbrain damage has occurred, or isoccurring,seizures will almost certainly bemoredifficult to control. This can be shown even in the context of febrile convulsions6. Such a situation will warrant full investigation for structural and biochemical disorders. For example, it is well known that epilepsy can exist for years before there is other evidence of an infiltrating glioma’. I t is now possible to screen for a wide variety of metabolic, infective and structural disorders by the use of such investigations as chomatographic techniques, the estimation of white-cell enzymes, studies for unusual viral encephalitides like SSPE, and the use of the computerized axial tomography. However, there is a significant number of children in whom such tests are negative, yet the seizures continue and there is progressive deterioration of the physical state.

Intractable epilepsy in the context of a deterioration of the child’s physical and mental state obviously poses special problems. Is this due to the occurence of frequent severe seizures themselves or to an undiagnosed disease? Admitting that there is still much to learn about chronic degenerative diseases in childhood, it will at this stage be necessary to consider such rarities as Alper’s disease or poliodystrophia cerebri*, progressive myoclonus epilepsy or Lafora’sdisease if these ‘bodies’ are present9’10, infantile neuroaxonal dystrophy or Seitelberger’s disease”, and perhaps most frequently, Batten’s disease or neuronal ceroid lipofuscinosisI2. I t may be possible to establish the diagnosis of the last two conditions by characteristic findings on electronmicroscopy of biopsies. Skin and rectal biopsies are used, and particular attention is now being paid to conjunctival biopsies because of their rich content of nerves.I3.

Occasionally it may be possible to help children with intractable epilepsy of unknown or irremedial cause by surgical treatment, particularly in the case of focal fits. If it becomes apparent that medical treatment is failing, it does seem reasonable to consider operation at a fairly early ageI4. If the child’s seizures can be reduced or stopped by removal of a cortical focus or by interruption of association tracts, and the child even enabled to discontinue anti-epileptic treatment while there are still a few years of schooling left rather than waiting until the patient is too old for adequate further education, so much the better.

Inevitably there will be a small number of children whose fits, for no adequate reason, cannot be well controlled by treatment. The number will be reduced by a meticulous attention to the details of management. One reason for a poor response to treatment is a wrong diagnosis; for example the child is not suffering from epilepsy but from reflex anoxic seizuresi5. Occasionally older children, particularly if they or members of their family suffer from undoubted epileptic seizures, may simulate attacks in order to manipulate the environment to their advantage. The correct diagnosis may be difficult to make, but prolonged EEG recordings, video-monitoring and EEG telemetry can helpi6. The exact type of epilepsy may not have been identified, e.g. absence seizures from focal temporal-lobe fits, and therefore the wrong type of treatment given. The underlying cause of the fits, for example a metabolic disorder such as hypoglycaemia, with the attacks only occurring after a prolonged fast, may not have been recognised. Or again, it may not have been realised how much stress the child may be experiencing at home and at school and what unhappiness this has caused. Learning difficulties may not have been diagnosed, and

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other frustrations can easily arise, for example the failure of an adolescent to fulfil his ambitions-from riding a bicycle to undertaking the job training of his choice.

If all these medical and social factors have been carefully checked and the fits continue, even after seeing if treatment can be stopped or observing the patient's progress for a few months in a suitable residential unit, the situation will have to be accepted, as is the case with many chronic disabilities. Then there will be an even greater need than usual to keep the patient's progress under careful observation, to help try and solve as many of the social and educational problems as possible, and to contain the anti-epileptic treatment within reasonable bounds. It is rarely justifiable to use more than two drugs at the same time, having learnt from experience in the specific case which drugs appear to reduce seizure frequency to thelowest level without causingunacceptableside-effects; the hope being that this treatment will at least give the patient some protection against worse happenings such as status epilepticus. Monitoring of serum drug levels and folic acid and vitamin B 12 levels, and checking for evidence of disorders of calcium metabolism, will need special attention. A delicate balance will have to be maintained between exposure to unacceptable risks and over-protection, between remedial help at school and not putting any pressures on the child to learn, and between too little and too much medical treatment.

The ultimate hope is that in the absence of any progressive cerebral disease the child's liability to seizures will decrease with increasing age as a result of maturation of protective mechanisms.

Booth Hall Children's Hospital, Blackley, Manchester M9 2AA.

N E I L GORDON

REFERENCES I . Aicardi. J . , Chevrie, J . J . (1971) 'Myoclonic epilepsies of childhood.' Neuropudiatrie, 3, 177-190. 2. Troupin. A. S., Ojemann, L . M. ( l Y 7 5 ) 'Paradoxical intoxication-a complication ot anticonvulsant

3. Hanson. R. A,, Menkes, J. H . (1972) 'A new anticonvulsant in the management of minor motor

4. Hansson. 0.. Sillanpaa. M . (1976) 'Pyridoxine and serum concentration of phenytoin and pheno-

5. Stores, G. (1978) 'Schoolchildren with epilepsy at risk for learning and behaviour problems.'

6. Wallace, S. L. (1977) 'Spontaneous fits after convulsions with fever.' Archives qf'Disease in Childhood,

7. Page, L. K.. Lombroso, C. T.. Matson, D. D. (1969) 'Childhood epilepsy with late detection of cerebral glioma.' Journal of' Neurosurger,v. 31, 253-26 I .

8. Blackwood, W., Buxton, P. H. , Cumings. J . N.. Robertson, D. J.. Tucker, S. M. (1963) 'Diffuse cerebral degeneration in infancy (Alper's disease).' Archives of Disease in Childhood, 38, 193-204.

9. Schwarz. G . A, , Yanoff, M. (1965) 'Latora's disease.' Archives o/.Neurology, 12, 172-188. 10. Koskiniemi, K., Donner, M.. Majuri, H., Haltia, H., Norio. R. (1974) 'Progressive myoclonus

epilepsy.' Acro Neurologica Scanriinavica. 50, 307-332. I I , Gordon. N. (1978) 'Infantile neuroaxonal dystrophy and related disorders.'Developmental Medicine and

Child Neurology, 20, 497-500. 12. Gordon, N. S., Marsden, H. B., Noronha, M. J . (1972) 'Neuronal ceroid lipofuscinosis (Batten's

disease).' Archives of Disease in Childhood, 47, 285-29 I . 13. Libert, J . , Martin, J . J., Evrard, P., Verougstraete, C., Danis, P. (1977) 'Les ckroide-lipofuscinoses.

Ultrastructure oculaire et diagnostic par biopsie conjunctivale.' Archives d'Ophtalmologie (Paris), 37,

14. Davidson, S., Falconer, M. A. (1975) 'Outcome of surgery in 40 children with temporal-lobe epilepsy.' Lancer. 1, 126b1263.

15. Stephenson, J . B. P. (1978)'Retlexselzures("white breath-holding") anoxic nonepileptic vagal attacks.' Archives of Disease in Childhood, 53, 193-200.

16. Hopkins, A. ( 1979) 'Uncontrolled epilepsy.' British Journal of' Hospital Medicine. 22, 265-266.

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