TUBEROUS SCLEROSIS: A SURVEY OF 97 CASES, I : SEIZURES, PERTUSSIS IMMUNISATION AND HANDICAP

346

Ann Hunt

This study was undertaken in order t o ascertain the effects of tuberous sclerosis on affected individuals and their families. The results are presented in three parts: I seizures, pertussis immunisation and handicap; I1 physical findings; and 111 family aspects.

There has been considerable publicity about brain damage following immunis- ation with pertussis vaccine (Geffen 198 1). Before data for this study were gathered, several parents with children affected by tuberous sclerosis had mentioned that their children began to have epileptic seizures soon after pertussis vaccinations, and that ‘vaccine damage’ had been the original diagnosis. Tuberous sclerosis was diagnosed subsequently, often many years later, but in the parents’ minds their children still had been ‘vaccine damaged’. Of particular concern in part I of this study, therefore, was the association between time of vaccination and onset of seizures.

Method A questionnaire was sent to 150 families contacted through the Tuberous Sclerosis Association of Great Britain, whose membership includes parents of severely affected children and carriers of the gene who are themselves neurologically un- affected. The questionnaire covered a wide range of problems, from epilepsy and

physical stigmata to developmental mile- stones, behaviour and genetic counselling.

Information was received o n 97 indi- viduals, a response rate of 65 per cent. There were 47 males and 50 females, ranging in age from less than one year to 5 1 years; of these, 15 had never had seizures (Table I).

The remaining 82 were divided into four groups according t o their immunisation status a t the time of their first seizure. Group I(20) were never immunised; group I1 (27) were immunised after the first seizure; group 111 (17) were immunised less than a month before the first seizure; and group IV (18) were immunised more than a month before the first seizure (Table 11).

The degree of mental handicap cannot be measured from a questionnaire but a

TABLE I

Age range and seizure status

Age range Seizure status (srs) With Wiihour Total

0- 2 7 3- 5 21 6-10 29 2

11-15 14 16-20 9 21-30 2 5 3 1-40 6 41-51 2 Total 82 15

7 21 31 14 9 7 6 2

97

rough estimate was obtained from the answers to questions about schooling, walking, talking and continence. The most profound handicap was defined oper- ationally as a child over the age of five who could neither walk nor talk. It was possible, therefore, to consider this pro- found handicap in relation to the onset of seizures and to whether the child had been immunised, particularly with pertussis

TABLE I1

Cases with epilepsy, grouped according to immunisation status at first seizure

Group No. Immunisation Status at,firsr seizure ~~

I 20 Not irnmunised

irnrnunisation

irnmunisation

irnmunisation

I1 27 Seizures began before

111 17 Seizures began < I mth after

IV 18 Seizures began > I mth after

TABLE 111

Educational placement in relation to immunisation status at first seizure

IV 2 15 ( I ) 1

Toral 7 64 (14) 10 I

TABLE IV

Age at first seizure and immunisation status

First .seizure Group (mth.s) I and II 111 and IV (Prqfounco Toral

< I 6 ( 2 ) 6 I 8 2 7 (4) 7 3 I I 5 (4 ) I6 4 3 3 6 5 5 3 6 3 9 ( I ) 12 7 2 2 8 4 4 9 3 3

l o t 2 8 10 9 3

l o t 2 8 3

10 Total 47 35 (14) 82

vaccine. If the handicap were related to severe lesions already present, profoundly retarded children would have earlier onset of seizures, which would predate immunis- ation (groups I and 11); however, if the vaccine were the cause of brain damage, the majority of profoundly affected children would have been vaccinated (groups 111 and IV).

Results Onset of seizures Infantile spasms often were the first serious presenting symptom, occurring in 66 of the 82 cases. Mothers'descriptions of these early spasms-a scream and drawing up of the legs-often led to a diagnosis of colic. However, most of the children were treated for infantile spasms within three months of the initial seizures, but nine had the condition for six months before it was recognised and seven others waited between seven and 17 months before their spasms were diagnosed.

Parents reported that the infantile spasms gradually changed to other forms of myoclonic or temporal lobe epilepsy in 65 cases. 42 also experienced grand ma1 seizures, and in 1 1 cases these were the first form ofattack. Prolonged statusepilepticus occurred in 16, and two have died as a result of prolonged seizures. Four children had required operations for brain tumours, and a further two who had died from inoperable tumours were identical twins.

Mental handicap Seven children were below two years of age. Of the remaining 75 with seizures, only one attended a normal school. The other 74 attended special schools, 10 schools for the moderately retarded and 64 schools for the severely retarded (Table 111). Of these 64, 14 (indicated paren- thetically in Tables I11 and IV) were judged to be profoundly retarded.

Seizures and immunisation The ages at which seizures first occurred are shown in Table IV.

All the profoundly handicapped child- ren had begun to have seizures before seven months of age, and there were more of these children in groups I and 11-those who had never been immunised and those immunised after their first seizure. Thus

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both profound handicap and early onset of seizures were the result of severe congenital tuberous sclerosis.

Because some parents believed that pertussis vaccination had damaged their children, the severity of handicap was reviewed for all four groups. Group 111, whose fits began less than a month after immunisation, included 10 children whose parents blamed the vaccinations for the brain damage. Eight o f the 17 in this group had been vaccinated before 1968, when the antigenic content of the pertussis vaccine was changed. Parents of six of these older children specifically reported major re- actions, such as screaming or fits, within 48 hours of the injections, and five received n o further immunisations. Information was sought from these children’s family doctors; their records revealed that adverse reactions within 48 hours had been recorded for only two children.

There wereonly two profoundly retarded individuals in group 111. a far lower number than would be expected had the brain damage been the immediate result of pertussis vaccine. The highest incidence o f profound handicap was in group 11, children immunised after the fits had begun, but i t had to be considered that vaccine damage may have compounded existing brain damage due to tuberous sclerosis. Therefore group I1 was divided into the 14 who received the triple diphtheria-pertussis-tetanus (DPT) vaccine and the 13 who had been immunised without pertussis vaccine ( DT). The common age for immunisation is between three and six months, and if seizures have occurred before that age consideration should be given to the wisdom of vaccinating the child, in accordance with the recommendations of the Joint Com- mittee on Vaccination and lmmunisation (Great Britain: DHSS 1981).

If the pertussis vaccine had caused further damage, more cases with profound handicap would be in the IIPT’ group. I n fact the reverse was found: six o f the 13 L) I - vaccinated individuals were profoundly handicapped, compared with two of the 14 in the DPTgroup. Therefore the severity of handicap among children with tuberous sclerosis appears to be related to factors other than pertussis vaccine.

348 Analysis of the relationship between

TABLI: V

Number of drugs being taken

8 27 35 10 -

2

onset of seizures and the date of the first ur’i‘ immunisation was a further method of determining whether there was any found- ation for the parents’ belief that their children’s problems began with the im- munisations. Sufficient information was available for only 37 cases, eight of whom had seizures before the immunisation and 29 after. Of the latter group, 14 had their first seizure within a month of being vaccinated, and this coincidence could have reinforced the parents’ conviction that immunisation was the cause of damage.

Meriica tion Epilepsy often is difficult to control in individuals with tuberous sclerosis, and many anticonvulsants may be tried, singly or in combination. Other problems, such as sleeplessness and hyperactivity, may lead to the prescription of further drugs. The number of different drugs being prescribed for the 82 people with seizures are shown in Table V. Two people were taking five drugs: in one case phenytoin, nitrazepam, thioridazine (‘Melleril’), hy- droxyzine hydrochloride (‘Atarax’) and trimeprazine tartrate (‘Vallergan forte’); in the other case clonazepam, carbamazepine, primidone, thioridazine and pyridoxine. In neither case were the seizures under control.

Discussion Tuberous sclerosis produces congenital brain-lesions. Gomez ( 1979) reported that 88 per cent of his tuberous sclerosis sample had seizures and 56 per cent had some degree of mental retardation. In the present sample of 97 individuals with tuberous sclerosis, 82 (85 per cent) had seizures, infantile spasms being the pres-

enting symptom in 68 per cent of cases. This is virtually identical with the 69 per cent reported by Pampiglione and Moynahan (1976).

Many mothers reported that they had had difficulty in persuading their family doctors that their baby had more than colic. Often babies with tuberous sclerosis are large and appear to be thriving, and it is only when they become increasingly irritable and withdrawn that the screaming and leg-jerks are given another diagnosis. In general, Pampiglione and Pugh (1975) report that between 20 and 25 per cent of cases of infantile spasms ultimately are diagnosed as having tuberous sclerosis. When the spasms occur in a baby with depigmented skin patches this diagnosis must be considered.

No evidence was found in this study that pertussis vaccine caused additional brain damage t o children with tuberous sclerosis. Those with early and severe fits were most likely not to have been immunised or to have been given only DT vaccine. The profoundly handicapped children who neither walked or talked by five years suffered their first seizure before seven

months of age, which suggests that severe lesions already were present at birth. Gomez (1979) considers that there is a good correlation between psychomotor development and the age at onset of seizures among patients with tuberous sclerosis: not only does early onset suggest more pronounced abnormality of the central nervous system, but also the seizures may interfere with its functional organisation.

Because so many seizures began close to the time of immunisation, parents associ- ated the two events. It may well be that immunisation acted as a trigger for the seizures that herald the diagnosis of epilepsy, but teething, high temperature, and polio, smallpox and BG vaccines have also been suspected by parents. Without these various triggers, some children with tuberous sclerosis, although predisposed to seizures, might have had later onset and fewer subsequent deleterious effects on their development.

Authors' Appointmiwt A n n Hunt , B . A . , Research Worker. Human Develop- ment Research Unit, Park Hospital for Children. Old Road. Headington, Oxford OX3 7LQ.

SUMMARY The relationship between the ontet of wirures, inirnunisation dates and degree 01' mental handicap was reviewed among children with IUberOuS sclerosis. Profound handicap occurred i n those children who had an early onset of seizures. There was n o evidence that pertussis vaccine caused additional brain-damage.

RPSUMI-: .ScIBro.\e /ubPrrusr: Ptutle ile 97 i'u\. 1. CI La relation entre le debut des crises. lea etudiee c h w des enfants prksentant uiie sclkrose tuhkreuse. Le\ handicaps Ies plus skvkres survenaient chez Ies enlant j ayant u n debut prkcoce de criw. I I n'est pas apparu que le vaccin contre l e pertussis ait entrain6 une aggravation des domniages cCrkbraux.

%USA M M E N M S S IJN <i Tir/wij\c SX k r o \i': rin 1 ' t J d I / i c ' h i ihiv 9 7 I ?ill(J. 1: Kriitnp/c. I'rrru \ \I\-lnipfuti,q irnd Bchini/cvun,q R K I Kindern niit tubertiser Sklerose wurde untcr5ucht. uelctic Beiiehung [wischen den1 Beginn v o n Krampfen, Impfdaten und dern Grad der Behinderung besteht. Schwerwiegende Behinderungen traten bei den Kindern auf. die friihtritig Kr in ipfc bekommcn I iat ten. lJ\ gab keinen ITinweis dafur. daR dcr Keuchliusteninipl\ totl~ einen rusiitzlichcn Hirnschadcn Lcrursachtc.

i~nmunitutron i.onrw li) pi'1114\ \:i\ ('1 huntlii~up s d'immunisation et I'importance du handicap mental a i t &

ESlJMEN \( If,ro.\i\ /uhiw~tu: wvi\ion rle 97 ('u\o\. I : ( 'onwl \ ion i ' \ , inn?unizuc.ron i OIII I 'U lu 10.5 ferinu I' hunclicup 1 revisa la relacion entre el inicio de l i i s convulsioiics, el grado de minusvalia mental y las lechas de

immunizacion en niiios con esclrro\is tubercm. IJn handicap grave tuvo lugar en 10s nifios con ataques de aparici6n precoi. N o h u h o evidencia de q u e la vacuna antipertussis c a u u r a una alteracicin cerebral adicional.

Rc:fi.rmt~i~ \

Geffen, T. (1981) 'Vaccination against whooping cough.' I f c d t h T r e n d , 13. 44-45.

Conic/. M. R. (1979) 'Clinical exper ience at the Mayo Clinic.' In G o m e i , M. R. (Ed.) ~ U h m J U \ Sclcro\i.\:. New York: Raven Press. pp. 16-20.

Great Britain, DHSS (1981) Whooprn<q C'iqqh. Reports from /he Commr / re~ on Sufer,~ of Miviicrnc\ and the .Joint C'ommrrtet~ on Vaccination and

/mmuni:urion. London: HMSO. Paiiipiglionr. 6,. Pugh, 1.. (1975) 'Intantile spasms

and \ub\equent appearance o l tuberous sclerosis syidrome.' Luncct, 2, 1046. - Mo>nahan. E. J . (1976) 'The tuberou\

sclero\ih s>ndroine: clinical and E E C studies in 100 ch I Id reii . ' .lournu1 o f Ni~ur.olo,qi.. .Yi,i4ro \ur,qi'rj' und 1'1 I ' t h / l / r r l ' . 39. 666-673.

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