LETTERS TO THE EDITOR - Delayed Eruption of Secondary Dentition associated with Phenytoin Therapy

Sir-Gingival hypertrophy is a recognised side-effect of treatment with phenytoin‘. =. Delayed eruption of primary dentition3 and a decreased crown-root ratio4 have also been reported in patients with epilepsy receiving phenytoin and other anti- convulsants. There have been no reports of delayed eruption of secondary or permanent dentition.

A 13-year-old boy had developed generalised tonic-clonic seizures at the age of seven years. Seizure control was eventually achieved using phenytoin monotherapy from the age of 10 years, with drug levels within the ‘therapeutic range’. He demonstrated minimal overgrowth of the gums, but no other abnormality. The patient’s primary dentition had appeared between six and nine months of age and dental caries had not been a problem. None of the permanent teeth had erupted by 13 years of age. Dental radiography confirmed the presence of the permanent teeth, and the crown-root ratios appeared to be normal. There was no clinical or biochemical evidence of hypothyroidism, hypopituitarism, syphilis, rickets or other bone disorder.

There was no relevant family history. Attempts to withdraw the phenytoin resulted in loss of seizure control.

Gum hypertrophy occurs in most patients receiving phenytoin, but is usually mild. Severe gingival overgrowth may result in ectopically erupting dentition, with poor occlusal development or even delayed eruption of primary teeth3. Short dental roots have also been described (unrelated to the degree of gingival overgrowth), but whether this influences the timing of eruption is unclear. Secondary dentition usually commences by the age of seven to eight years with eruption of the central and lateral incisors. Although our patient had not erupted any of his permanent teeth by I 0 years of age, and before taking phenytoin, it is possible that the drug resulted in a further delay in eruption. We have reported this as a possible adverse reaction to the Committee on Safety of Medicines.

RICHARD E. APPLETON Consultant Paediatric Neurologist

HELEN LEACH Research Pharmacist

Royal Liverpool Children’s Hospital, Alder Hey, Eaton Road, Liverpool L12 2AP.

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y1 8 References * c) 1. Kapor, R. N., Girgis, S., Little, T. M., Masotti, 2 R. E. (1973) ‘Diphenylhydantoin-induced

gingival hyperplasia: its relationship to dose and serum level.’ Developmental Medicine and Child Neurology, 15, 483-487.

2. Jones, J. E., Weddell, J. A., McKown, C. G. (1988) ‘Incidence and indications for surgical management of phenytoin-induced gingiva! overgrowth in a cerebral palsy population. Journal of Oral and Maxillofacial Surgery, 46,

3. Church, L. F., Brandt, S. K. (1984) ‘Phenytoin- induced gingival overgrowth resulting in delayed eruption of the primary dentition.’ Journal of Periodontology, 55, 19-21.

4. Girgis, S. S., Staple, P. H., Miller, W. A., Sedransk, N., Thompson, T. (1980) ‘Dental root abnormalities and gingival overgrowth in epilepti: patients receiving anticonvulsant therapy. Journal of Periodontology, 51, 474-482.

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Failure to Thrive on Chloride-deficient Formula

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SIR-The report by Kaleita et al. (DMCN, 33, 626-635) on 13 children who failed to thrive as infants because they received a chloride-deficient formula raises some questions. Since the children failed in normal school studies, spoke poorly and were clumsy, there seems to be little doubt that they suffered from neurological dysfunction. This is a far cry, however, from the authors’ claim that the children had ‘a distinctive constellation of cognitive and motor deficits’ or ‘a specific developmental aphasia ’.

Two of the children were severely retarded and could not respond to detailed neuropsychological testing. The authors examined auditory comprehension, naming ability, verbal fluency and sentence memory in the other 11. Performances for all functions for the most part, were one to two standard deviations below published norms. They examined one visual-motor test and found a similar level of performance. Clinically they judged the children to be clumsy, to have defective speech, to suffer from typical attention deficit hyperactivity disorder, and at the same time to be suffering from ‘a distinctive overfocused pattern of attention deficit [which] could be distinguished from typical attention deficit . . . with 100 per cent reliability’. I submit that this is an embarrassment

of riches. If every function examined

was affected, and all to much the same degree, what is specific about the neuropsychological findings? Are we to believe that all unexamined functions were normal? And i f motor and visual- motor functions are as affected as speech and language, why should this be regarded as a specific developmental aphasia rather than a general cognitive and motor deficit?

These questions are not necessarily unanswerable, but the validity of the answers depends greatly on the study’s methodology, which itself gives rise to additional questions. The authors’ belief that they are describing a specific neuropsychological syndrome probably is based partly on the apparent discrepancy between the ‘normal’ Wechsler, Binet and Peabody IQs and the other tests. In the absence of a control group, I believe it risky to assume that the IQs were any more normal than the other tests. Two of the children were grossly retarded, while the latest IQs of the remaining I1 had a median of 98. This would be near- average only in the year the psychometric tests were standardized. The known upward drift of the IQ standardization curve with time would make an IQ of 98 close to one standard deviation below the normal population mean if 10- to 15-year-old tests were used, as they probably were. In general, drawing psychoneurological conclusions from such a small sample ordinarily would require the concurrent examination of a control group with all the tests used.

The significance of these questions extends beyond this specific article. It is not yet certain that neuropsychological profiles in childhood, as presently measured, are stable with time, or that they are correlated with aetiology, or even that knowing them improves the results of remedial teaching. There are indeed findings which suggest that the main long-term neuropsychological deficit following diffuse brain-injury early in life (such as trauma or malnutrition) is simply a decrease in the intelligence quotient, and that the touted tests of specialized functions are informative only during the period

immediately following injury’. =. A t this time, when the exact contribution of neuropsychology to child neurology is still undefined, any exaggerated claims of unproven syndromes may be counterproductive to its progress.

HANAN COSTEFF, M.D. Director, Neuropediatric Unit, Loewenstein Hospital Rehabilitation

Center and Sackler Faculty of Medicine,

Tel-A viv University, P. 0. Box 3, Ra ’anana, Israel.

References 1 . Costeff, H., Abraham, E., Brenner, T.,

Horowitz, I. , Apter, N., Sadan, N., Najenson, T. (1988) ‘Late neuropsychologic status after childhood head trauma.’ Brain and Develop- ment, 10, 371-374.

2 . Davison, L. A. (1974) ‘Current status of clinical neuropsychology.’ In Reitan, R. M., Davison, L. A. (Eds.) Clinical Neuropsychology: Current Status and Applications. New York: Wiley. pp. 330-331.

The authors have replied as follows:

SIR-Zn his letter, Costeff raises one important question: namely whether there is any evidence that brain injury in infancy or early childhood can induce specific neuropsychological deficits or whether it simply produces a generalized reduction in all aspects of intellectual function, and with it a reduction in the intelligence quotient.

We believe that both types of injury can occur, and that the more severe the insult and the earlier in cerebral ontogeny it occurs, the more likely it is that all aspects of intelligence will be affected. (See cases 10 and 13.) The neuropsychological consequences of postnatal exposure to a low-chloride formula are therefore of considerable theoretical importance.

To start with, we should emphasize that a biological marker of this syndrome was the deceleration of growth of head circumference which accompanied the ingestion of the formula, and resumption of a normal rate of growth after the deficient formula was discontinued. In addition,

symptoms of developmenal dysplasia were a prominent component of the syndrome; more apparent in the general functioning of the child than in the neuropsychological test data presented in our article, which focused on quantitative aspects of language functioning. Further details of our data, such as the WISC-R subtest scaled scores (not published in our paper) support our findings of attention deficit disorder, whereas they indicate above- average non-verbal reasoning abilities in five of seven children tested. As a further indication of uneven cognitive development, the mean decile scores of the picture completion and picture assembly su btests, indices of visual- motor function, were I * 0 and 2.2 deciles higher, respectively, than the mean verbal I Q scores. In addition, subsequent tests indicated language development to be more severely affected than academic achievement and motor co-ordination. The above considerations rein force our conclusions that early chloride deficiency can cause a specific syndrome of cognitive deficit.

We do agree with Costeff that longitudinal studies are necessary to ascertain definitively whether or not these disabilities are permanent. However, cases I , 4 and I1 were all still impaired on retest.

We should also point out that children who have sustained other forms of diffuse metabolic brain-injury in early lue, e.g. children with phenylketonuria whose low phenylalanine diet was initiated after the first month or two of lue, may show a permanent circumscribed impairment in cognitive skills’.

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THOMAS A. KALEITA, Ph.D. MARCEL KINSBOURNE, M.D., Ph.D.*

JOHN H. MENKES, M.D. UCLA School of Medicine and

*Boston University School of Medicine.

Reference 1 . Koff, E., Boyle, P., Pueschal, S. M. (1977)

‘Perceptual-motor functioning in children with phenylketonuria.’ American Journal of Diseases of Children, 131, 1084-1087. I119

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Congenital Varicella Infection

SIR-Apropos our paper on congenital varicella infection (DMCN, 33, 916920), it has been brought to our attention that there have been three previous reports linking maternal varicella infection with severe neurological consequences to the fetal nervous system. These have been well summarised in a paper by Harding and Baumer’, who added a further case con firmed by a rising titre of varicella zoster-specific IgM. Death occurred at eight days and neuropathology showed a destructive lesion with polymicrogyria.

Our case report adds weight to the

occasional seriousness of intra-uterine varicella infections.

MICHAEL BARAITSER, F.R.C.P. Consultant in Clinical Genetics

EDWARD M. BRETT,

Consultant Paediatric Neurologist M.A., D.M., F.R.C.P.

The Hospitals for Sick Children, Great Ormond Street, London WClN 3JH.

References 1. Harding, B., Baumer, J. A. (1988) ‘Congenital

varicella-zoster: a serologically proven case with necrotising encephalitis and malfor- mation.’ Acta Neuropathologica, 76, 31 1-315.

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