Develop. Med. Child Neurol. 1980, 22, 502-514

Case Reports

Apparent Cerebral Atrophy in Patients on Treatment with Steroids

Neil Gordon

Introduction Computerised axial tomography is

increasingly used in the investigation of cerebral disease. The technique can give useful information, not only in the case of space-occupying lesions but also in demyelinating disorders (Lane et al. 1978) and when there are structural and atrophic lesions of the brain (Lagenstein et al. 1979~). Cerebral atrophy due to loss of tissue will be irreversible, but similar appearances can be demonstrated by radiological techniques and repeated examinations may show them to have resolved. If hydrocephalus results from raised intracranial pressure and this is relieved, the ventricles and subarachnoid spaces will reduce in size. A much less common example of this reduction is the effect of steroids on the volume of the brain.

A patient is described to illustrate the findings on CAT scan during and after steroid treatment.

Case Report S.R., a girl, developed an upper respiratory

infection at the age of 8% months. During the two weeks following this she had an increasing

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Consultant Neurologist, Booth Hall Children’s Hospital, Charlestown Road, Blackley, Man- Chester M9 2AA.

number of brief attacks in which she made gurgling noises, raised her arms above her head and seemed to bend over to touch her toes. These occurred in groups of 10 to 15 attacks, two to three times a day.

Birth had been induced at 38 weeks because of the mother’s raised blood pressure, but delivery was normal. The child had no significant prior illnesses. The family history was characterised by a high incidence of allergies of various types, and a grandmother had suffered from epilepsy.

Clinical examination on admission to hospital two weeks after the onset of the seizures showed no significant findings, but the EEG was markedly abnormal. There was a generalised increase of high-voltage slow and sharp waves, and a week after admission the record had become so abnormal that i t could be classified as hypsar- rhythmic (Fig. 1). The ‘spasms’ had increased in frequency, so treatment with ACTH, 40 units a day, was started. There was a dramatic improve- ment over the next two weeks, both in the child’s clinical condition and in the EEG. The ACTH was stopped, no doubt prematurely, since the ‘spasms’ returned and ACTH had to be restarted.

During this time the infant’s development appeared to be proceeding normally, although there was slight concern about the rate at which motor skills were being acquired. Apart from some possible irritability, there appeared to be no side-effects from the treatment. Six weeks later, although very occasional myoclonus was occurring, the EEG was normal (Fig. 2) and it was again decided to stop the ACTH and to substitute nitrazepam. In view of the family history of allergy, a milk-free diet was tried but there was no evidence that this helped. Development continued to be satisfactory. At the age of

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14y2 months the child was walking on her own, no seizures were occurring and the EEG was normal.

Apart from the EEG and the CAT scan, results o f other investigations were negative. N o evidence of virus infections or metabolic disorders was tound. The CAT scan taken several weeks after the patient had been started on ACTH showed a normal ventricular system but widening of the basal cisterns, the cerebral sulci and the inter- hemispheric fissure, suggestive of cerebral atrophy (Fig. 3). When the scan was repeated four months after ACTH was stopped it was normal (Fig. 4).

Discussion When the first CAT scan was carried out

on this patient the possibility of a con- dition associated wth epilepsy and leading to cerebral atrophy was considered. An alternative was the effect of treatment with ACTH. In a series of 152 patients with

cerebral atrophy demonstrated by the CAT scan, 15 had been on long-term treatment with corticosteroids. Patients who had also been given cytotoxic drugs were excluded. Most of them had auto-immune disorders of some kind (Bentson et a/. 1978). In another group of more than 40 children with seizures treated with depot ACTH, eight had CAT scans before, during and after therapy, and were found to have enlargement of the ventricles, sulci and cisterns during .ACTH administration, with a return more or less to the pre-treatment picture when it was stopped (Lagenstein et al. 19796).

There are many causes of cerebral atrophy and the etiology of infantile spasms is varied, with a close correlation between this type of epilepsy and cerebral

Fig. 1. Grossly abnormal EEG three weeks after onset of illness.

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Fig. 2. Normal EEG after several weeks on treatment with ACTH.

Fig. 3. C A T scan taken after several weeks o n treatment with ACTH, showing widening of the basal cisterns, the cerebral sulci and the inter- hemispheric fissure.

Fig. 4. Normal CAT scan four months after treatment with ACTH had been stopped.

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insults of a severe degree. The prognosis for mental development of infants with this condition is poor (Jeavons et a/. 1970). I t is therefore not surprising that CAT scans frequently show abnormalities (Gastaut e f al. 1978), but appearances suggestive of cerebral atrophy must be regarded as unreliable if the patient is taking steroids.

Various theories have been suggested to account for the effects of steroids on the brain. Steroid-induced protein catabolism may be significant in Cushing’s disease (Momose et at. 1971). In the case of children having treatment with ACTH, a more likely explanation is a change in brain volume from a loss of water, presumably due either to a reduction of abnormal vascular permeability or to the effects on water andelectrolyte balance. Dexamethasone is most often used in reducing cerebral oedema, but high doses of ACTH may well be a better treatment (Lagenstein et a/. 19796), and the evidence strongly suggests that the mode of action of ACTH is on the cerebral cells themselves and not via the adrenal cotex (Lagenstein et a/. 1979~).

Another explanation for the changes in

CAT scans could be cerebral swelling superimposed on an underlying cerebral atrophy, so that this is unmasked by the treatment (Lyen et a/. 1979). Although this mechanism may occasionally apply, it seems unlikely to explain the majority of reversible abnormalities. Enlargement of the subarachnoid spaces and ventricles can be due to external hydrocephalus but there is no proof that this can be tempor- arily caused by the influence of ACTH on the CSF circulation. Others feel that the changing radiological appearances are the result of the disease process itself, a ‘subacute non-progressive encephalo- pathy’ being seen clinically after its earlier onset (Deonna and Voumard 1979). In view of the fact that the radiological appearances may have different causes, and sometimes not be due to true cerebral atrophy with loss of neurones and neuro- g!ial overgrowth, it does seem important not to use the term ‘cerebral atrophy’ in the reports of radiological findings (Lyen et a/. 1979).

This case is reported to emphasise the need to consider whether changes in the CAT scan suggestive of cerebral atrophy may be reversible.

S U M M A R Y The apparent loss of cerebral tissue sometimes demonstrated by computerised axial

tomography and other radiological techniques is not always irreversible. A report is given of a child with infantile spasms who was treated with ACTH. While on this

treatment, a CAT scan showed findings suggestive of cortical atrophy but when this test was repeated four months after treatment was stopped, i t was normal.

Various theories are discussed to account for the effects of steroids on the brain. The most likely one is a change in brain volume because of loss ofwater. As the radiological appearances can be reversible, they should not be described as cerebral atrophy.

RESUME A trophie cPrPbrale apparente chez les sujets traifks par stiroides

La perte apparente de tissu ciribral quelque fois dimontrie par tomodensitomktrie et autres techniques radiologiques n’est pas toujours irriversible.

Le cas rapporti est celui d’un enfant avec spasme en flexion traiti par ACTH. Au cours du traitement, le scanner pratiqui suggirait I’existence d’une atrophie corticale mais quand I’examen fut r ip i t t quatre mois aprks I’arrtt du traitement, il i tait normal.

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Des thtories varites ont t t t propostes pour expliquer les effets des sttroides sur le cerveau. La plus vraisemblable fait appel A une modification du volume ctrtbral par perte d’eau. Les modifications radiologiques ttant rtversibles, elles ne doivent pas &tre dtcrites comme une atrophie ctrtbrale.

ZUSAMMENFASSUNG Scheinbare cerebrale Atrophie bei Patienten mit Steroidtherapie

Der scheinbare Verlust von cerebralem Gewebe, der manchmal durch axiale Computer- tomographie und andere radiologische Techniken gezeigt wird, ist nicht immer endgultig.

Es wird hier von einem Kind berichtet, das BNs-Krampfe hatte und mit ACTH behandelt wurde. Unter dieser Therapie fanden sich im axialen Computertomogramm Hinweise auf eine cerebrale Atrophie: als jedoch diese Untersuchung vier Wochen nach Absetzen der Behandlung wiederholt wurde, war der Befund normal.

Es werden verschiedene Theorien iiber den EinfluB von Steroiden auf das Gehirn diskutiert. Die wahrscheinlichste besagt, daB die Veranderungen des Hirnvolumens durch einen Wasserverlust hervorgerufen werden. Da die radiologischen Befunde reversibel sein konnen, sollten sie nicht als cerebrale Atrophie beschrieben werden.

RESUMEN A trofia cerebral aparente en pacientes bajo tratamiento con esteroides

La aparente ptrdida de tejido cerebral a veces demonstrada por el scanner y otras ttcnicas radiologicas no siempre es irreversible.

Se aporta el caso de un niiio con espasmos infantiles que fue tratado con ACTH. Mientras dur6 a1 tratamiento una CAT mostrb hallazgos que sugerian una atrofia cortical, pero cuando la prueba fue repetida cuatro meses desputs del tratamiento, la imagen era normal.

Se discuten varias teorias para explicar 10s efectos de 10s esteroides sobre el cerebro. La mas verosimil es un cambio del volumen cerebral por falta de agua. Puesto que la apariencia neurologica puede ser reversible no deberia ser descrita como una atrofia cerebral.

REFERENCES Bentson, J., Reza, M., Winter, J., Wilson, G. (1978) ‘Steroids and apparent cerebral atrophy on computed

tomography scans.’ Journal of Computer Assisted Tomography. 2, 16-23. Deonna. T., Voumard, C. (1979) ‘Reversible cerebral atrophy and corticotrophin.’ Lancet. 2, 207. Gastaut, H.. Gastaut, J . L., Regis, H., Bernard, R.. Pinsard, N., Saint-Jean, M., Roger, J., Dravet, C. (1978)

‘Computerized tomography in the study of Wests’s syndrome.’ Developmental Medicine and Child Neurology, 20, 21-27.

Jeavons, P. M., Harper, J . R., Bower, B. D. (1970) ‘Long-term prognosis in infantile spasms: a follow-up report on I12 cases.’ Developmental Medicine and Child Neurology, 12, 413-421.

Lagenstein, I . , Kiihne, D., Sternowski, H. J., Rothe, M. (19790) ‘Computerized cranial transverse axial tomography (CTAT) in 145 patients with primary and secondary generalised epilepsies: West syndrome, myoclonic-astatic petit mal, absence epilepsy.’ Neuropudiatrie. 10, 15-28.

- Willig, R. P., Kiihne, D. (19794 ‘Reversible cerebral atrophy caused by corticotrophin.’ Lancet. 1,1246. - (1979~) ‘Cranial computed tomography (CCT) findings in children treated with ACTH and dexa-

methasone: first results’. Neuropudiatrie. 10, 370-384. Lane, B., Carroll, B. A., Pedley, T. A. (1978) ‘Computerized cranial tomography in cerebral diseases of

white matter.’ Neurology, 28, 534-544. Lyen, K. R.. Holland, I. M., Lyen, Y. C. (1979) ‘Reversible cerebral atrophy in infantile spasms caused

by corticotrophins.’ Lancet. 7 , 37-38. Momose, K . J., Kjellberg, R. N., Kliman, B. (1971) ‘High incidence of cortical atrophy of the cerebral and

cerebellar hemispheres in Cushing’s disease.’ Radiology, 99, 341-348. 506