The long-term prognosis of 192 surviving children with the syndrome of infantile spasms was evaluated. The children had been admitted to three paediatric hospitals in Helsinki at the time of initial diagnosis. The aetiological factors of the syndrome were carefully studied in each case. ACTH therapy was employed in 162, usually for about six weeks. The follow-up study 3-19 (mean 10.4) years later was made at the Children's Hospital, University of Helsinki. The rate of mortality was 19.6 per cent. Normal development was seen in 12 per cent and slightly subnormal in 10.4 per cent of the surviving children. Psychiatric disorders were seen in 27.6 per cent of the survivors. Sensory defects were also common. Severe cerebral palsy was seen in 4 per cent. Other seizures after cessation of the infantile spasms were seen in 60 per cent. Serial EEG studies showed that the temporal lobe was the most common site of abnormality. Abnormalities in the temporal lobes were seen frequently in children with symptomatic neonatal hypoglycaemia as a probable cause of the spasms. Prognostically favourable factors were "idiopathic" aetiology, normal development and not other fits prior to the spasms, short treatment lag, good response to ACTH and short duration of the spasms. In this study early treatment seemed to be of great importance even with regard to mental development. The factors connected with a bad outcome were: symptomatic aetiology (especially brain malformations, early infections and tuberous sclerosis), slow development before spasms, other seizures before infantile spasms, early onset of the spasms, long treatment lag, long duration of the spasms and other later occurrence of myoclonic-astatic seizures (Lennox-Gastaut). Large doses of ACTH (120-160 units) were not associated with a better prognosis than the smaller doses (20-40 units). The benefit of long versus short treatment schedules could not be evaluated in this study. The relapse rate here was 32 per cent.

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To our knowledge, ours is the first study to evaluate the outcome of infantile spasms (IS) in adult patients. We analyzed 214 children born between 1960 and 1976 who had been followed for 20-35 years or until death at 3 months to 30 years of age. Mortality was 31% (67 of 214 patients). Thirty-six of the surviving patients (24%) had normal (25 patients) or only slightly impaired (11 patients) intelligence as assessed by their educational abilities. Four had academic occupations. Eight were married or living unmarried with a partner. Five had healthy children. At follow-up, the EEGs of the 25 normal persons were either normal or slightly abnormal, demonstrated focal findings in 9 (36%), and had unspecific changes in 1. Focal abnormalities were not more common in patients with less good outcomes (37%). In patients with normal neurological outcomes, IS had been classified as cryptogenic only in 9 of 25 (36%) cases. Therefore, some patients with IS apparently have normal intelligence and socioeconomic status as adults, including patients whose spasms were either symptomatic or associated with focal EEG findings.

Disturbances in the serotonergic system have been recognized in autism. To investigate the association between serotonin and dopamine transporters and autism, we studied 15 children (14 males, one female; mean age 8y 8mo [SD 3y 10mo]) with autism and 10 non-autistic comparison children (five males, five females; mean age 9y 10mo [SD 2y 8mo]) using single-photon emission computed tomography (SPECT) with [ 123 I] nor-b-CIT. The children, with autism were studied during light sedation. They showed reduced serotonin transporter (SERT) binding capacity in the medial frontal cortex, midbrain, and temporal lobe areas. However, after correction due to the estimated effect of sedation, the difference remained significant only in the medial frontal cortex area (p=0.002). In the individuals with autism dopamine transporter (DAT) binding did not differ from that of the comparison group. The results indicate that SERT binding capacity is disturbed in autism. The reduction is more evident in adolescence than in earlier childhood. The low SERT binding reported here and the low serotonin synthesis capacity shown elsewhere may indicate maturation of a lesser number of serotonergic nerve terminals in individuals with autism.

Neuroligins are cell-adhesion molecules located at the postsynaptic side of the synapse. Neuroligins interact with b-neurexins and this interaction is involved in the formation of functional synapses. Mutations in two X-linked neuroligin genes, NLGN3 and NLGN4, have recently been implicated in pathogenesis of autism. The neuroligin gene family consists of five members (NLGN1 at 3q26, NLGN2 at 17p13, NLGN3 at Xq13, NLGN4 at Xp22, and NLGN4Y at Yq11), of which NLGN1 and NLGN3 are located within the best loci observed in our previous genome-wide scan for autism in the Finnish sample. Here, we report a detailed molecular genetic analysis of NLGN1, NLGN3, NLGN4, and NLNG4Y in the Finnish autism sample. Mutation analysis of 30 probands selected from families producing linkage evidence for Xq13 and/or 3q26 loci revealed several polymorphisms, but none of these seemed to be functional. Family-based association analysis in 100 families with autism spectrum disorders yielded only modest associations at NLGN1 (rs1488545, P ¼ 0.002), NLGN3 (DXS7132, P ¼ 0.014), and NLGN4 (DXS996, P ¼ 0.031). We conclude that neuroligin mutations most probably represent rare causes of autism and that it is unlikely that the allelic variants in these genes would be major risk factors for autism.

SUMMARY 162 children with infantile spasms were treated with ACTH at the Children's Hospital, Helsinki, and at the Aurora Hospital, Helsinki, during 1960-76. In a large proportion (37%) of the children the treatment caused pronounced side effects, and the mortality was 4 9%. The most common complications were infections: septic infections, pneumonias, and urinary and gastrointestinal infections. Other side effects were arterial hypertension (11), osteoporosis (2), hypokalaemic alkalosis (2), and other marked electrolyte disturbances (10). In 2 children necropsy showed fresh intracerebral haemorrhages. Four children developed oliguria and hyperkalaemia during and after withdrawal of ACTH. One of them had tubular necrosis confirmed by renal biopsy. Infections were significantly more common with large doses (120 units) of ACTH than with small ones (40 units). It is concluded that side effects, even severe ones, are more common during this treatment than had been assumed. Careful watch is important before and after treatment. The benefit of very high dosages should also be reconsidered.For 20 years ACTH or corticosteroids has been the treatment of choice in infantile spasms.' Although there are conflicting observations about whether or not it affects intellectual outcome2-8 it usually stops the seizures, and there are fewer relapses than after conventional anticonvulsive drugs. Primarily, spasms will be controlled in 60 to 80 % of the children.9-12

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