From a follow-up series of 24 classical Rett syndrome females (13-59 years of age), side asymmetries of neuroimpairments were systematically investigated. A characteristic right-sided dominance in terms of dysfunction and neurology was revealed. Differences in the perinatal/early postnatal development of finer brain net structures between brain halves are suggested as a possible explanation.

This seventh Swedish population‐based cerebral palsy (CP) report comprises 216 children born between 1987 and 1990. The crude live birth prevalence was 2.36 per 1000, indicating a break in the continuous increase since 1970. Excluding 10 postnatally‐derived cases, gestational‐age specific prevalences were 80 for extremely, 54 for very and 8 for moderately preterms and 1.4 for term children per 1000. Birth weight‐specific prevalences were 57 for birth weights <1000 g, 68 for 1000–1499 g, 14 for 1500–2499 g and 1.4 for ≥2500 g per 1000. The aetiology was considered prenatal in 8%, peri/neonatal in 54% and unclassifiable in 38% of preterms and 33, 28 and 39% of term children. Hemiplegic, diplegic and tetraplegic syndromes accounted for 22, 66 and 7% of preterms and 44, 29 and 10% of term children. Non‐walking, mental retardation, epilepsy, severe visual impairment and infantile hydrocephalus were present in 39, 39, 26, 18 and 23% of preterms; and 38, 44, 36, 14 and 5% of term children, respectively. The entire series of 1408 cases born in 1954–90 revealed three distinct trend eras for preterms, clearly related to changes in perinatal care and shifts in type of CP manifestations.

This seventh Swedish population-based cerebral palsy (CP) report comprises 216 children born between 1987 and 1990. The crude live birth prevalence was 2.36 per 1000, indicating a break in the continuous increase since 1970. Excluding 10 postnatally-derived cases, gestational-age specific prevalences were 80 for extremely, 54 for very and 8 for moderately preterms and 1.4 for term children per 1000. Birth weight-specific prevalences were 57 for birth weights < 1000 g, 68 for 1000-1499 g, 14 for 1500-2499 g and 1.4 for greater than or equal to 2500 g per 1000. The aetiology was considered prenatal in 8%, peri/neonatal in 54% and unclassifiable in 38% of preterms and 33, 28 and 39% of term children. Hemiplegic, diplegic and tetraplegic syndromes accounted for 22, 66 and 7% of preterms and 44, 29 and 10% of term children. Non-walking, mental retardation, epilepsy, severe visual impairment and infantile hydrocephalus were present in 39, 39, 26, 18 and 23% of preterms; and 38, 44, 36, 14 and 5% of term children, respectively. The entire series of 1408 cases born in 1954-90 revealed three distinct trend eras for preterms, clearly related to changes in perinatal care and shifts in type of CP manifestations.

Our Swedish population‐based cerebral palsy (CP) project started 25 years ago and today covers the birth years 1954–1990, with over 1400 CP cases. This large series (1, 2, 3) has opened new perspectives on time trends and aetiological background factors, where two areas of successively increasing knowledge stand out as particularly helpful. One is the growing amount of biological and clinical data from the continuously increasing cohorts of surviving very preterm infants, the other is the rapidly expanding and refined information from neuroimaging. Bilateral spastic CP (BSCP), including spastic and ataxic diplegia, tetraplegia and spastic‐dyskinetic CP, is the most prevalent clinical group of CP syndromes, present in around 75% of preterm and 45% of term CP, and has shown the most significant prevalence changes over time. In this presentation we, therefore, focus on BSCP, also analysed in a collaborative study between southwest Germany and western Sweden and recently presented in a series of four papers (4, 5, 6, 7).

We describe a male patient with late onset globoid cell leukodystrophy (GLD) (Krabbe's disease) still alive at 24 years of age, with a well preserved intellectual and communicative capacity, in contrast to visual failure and severe central pyramidal and extrapyramidal motor disability with spasticity, dystonia, ataxia and peripheral neuropathy. Visual dysfunction began at 4 years of age, limping and balance problems at 8 years and epilepsy at 14 years of age. Neuroimaging at 15 years of age revealed white matter lesions, and nerve conduction velocity examinations showed a slowly developing polyneuropathy. Galactosylceramidase activity was reduced in leukocytes to 0.07μkat/kg protein compared with 0.02 (SD 0.01) μkat/kg protein in infantile GLD.

A previous genealogic study on classical Swedish Rett syndrome (RS) females documented an increased rate of common ancestry, with a high percentage originating generations ago in the same homestead. The present study, an a priori test of the first study, examines an additional 20 RS females, who were consecutively traced. Of these, no fewer than 10/19 (53%) originated from earlier defined "Rett areas": 11/19 (58%) could even be traced to the same homestead. In two clusters, each consisting of three RS females, all six subjects were descendants of the same two couples several generations ago. Consanguineous marriages among grandparents on both sides were found to have occurred in 11% (4/37), i.e. significantly more frequently than in the average Swedish population (1%). The results of this second study confirm all points of the first. A clinical analysis of cases with common ancestral origin underlines the phenotypical variability which is often seen in interrelated RS females. We conclude that RS can appear in either its classical form or as a variant. Our genealogical data may indicate transmission starting with a premutation that over generations can result in a full mutation, probably when the parents have the premutation in a homozygous form.

The broad clinical variety within the Rett syndrome (RS) concept is emphasized. A model recently presented for delineation of atypical Rett variants is reviewed.

The epidemiology of infantile hydrocephalus in the birth years 1973-90 was investigated in west Sweden. The study revealed a significant increase in prevalence from 1973-8 and 1979-82 considered due to the enhanced survival of very and extremely preterm infants. The increase did not continue from 1983-90. This could indicate an improved outcome in preterm survivors as the neonatal survival rate continued to increase. The striking predominance of a perinatal/neonatal aetiology in very preterm hydrocephalic infants could be confirmed: 89% born from 1983-90 had suffered a confirmed postpartum intraventricular haemorrhage. In infants born at term, prenatal origins, mainly maldevelopments, dominated. The outcome in very preterm surviving infants with infantile hydrocephalus was poor: 73% had cerebral palsy, 52% epilepsy, 22% severe visual disability, and 55% were mentally retarded. Despite the increased survival resulting in a majority of healthy infants, there is an accumulating cohort of hydrocephalic children.

A case of mitochondrial encephalomyopathy (Kearns-Sayre syndrome) demonstrating bilateral symmetric metaphyseal dysplasia is reported. This represents a new association with the syndrome.

All Swedish infants with shunt-treated infantile hydrocephalus, born during the period 1979-88 at < or = 34 weeks gestational age and of low birth weight, were studied. Ninety-six infants were born before 32 weeks and 50 at 32-34 weeks. The mean gestational age in the very preterm group gradually decreased from 29.5 to 27.3 weeks. The mean live birth prevalence was 15.9 per 1000 very preterm infants, and 5.1 per 1000 moderately preterm infants. No significant secular prevalence trends were found. The perinatal mortality decreased successively. The slowly decreasing trend in moderately preterm infants may imply better outcome in survivors. The slightly increasing trend in very preterm infants could be explained by more survivors in the low gestational age group. The aetiology was considered perinatal in 94% of the very preterm group and in 56% of the moderately preterm group; prenatal in 1% and 32% of infants, respectively. Additional neuro-impairments were present in 82% of infants, cerebral palsy being the commonest (74%).

The prevalence and origin of cerebral palsy in children born between 1983 and 1986 are reported. The crude live‐birth prevalence was 2.49 per 1000; 1.56 for term births, 0.93 for preterm births. The increasing trend from 1970 persisted and was statistically significant for both groups. The most pronounced increase during 1983–1986 occurred in term cerebral palsy. The increasing use of neuroimaging techniques made the timing of damaging events more reliable. In term cerebral palsy, the origin was convincingly prenatal in 28% of cases and perinatal in 25%. The particular critical period for the brain damage underlying cerebral palsy was considered to be weeks 26–34 of gestation, i.e. when periventricular structures are extraordinarily vulnerable. In term infants, this occurs during late intrauterine life, while in the majority of preterms it occurs in early neonatal life. In total, two‐thirds of cerebral palsy lesions might have been acquired during these decisive months of brain development.

The position at the end of 1990 of clinical experiences and research in the Rett syndrome (RS) is summarized. Aspects on clinical and pathogenetic heterogeneity are given. Supports for RS as a developmental neuronal disconnection condition, with early infantile brain growth arrest, are emphasized. In trying to explain origin a two step process is hypothetically suggested: 1) an age dependent genetic deficiency, or transient dysfunction, as a basic predisposing factor; 2) a superimposed trigger factor which might differ in type and between groups of cases.

On the basis of 29 patients aged 1–48 years, the general clinical manifestations and natural course have been determined of a newly described autosomal recessive multisystem condition with carbohydrate‐deficient glycoproteins, particularly affecting transferrin. The syndrome showed different presentations during different age periods. During infancy and early childhood failure to thrive, liver dysfunction, pericardial effusions, marked developmental delay and stroke‐like episodes were most pronounced. In later childhood and adolescence stationary mental deficiency and ataxia, slowly progressive lower limb neuropathy and pigmentary retinal degeneration, as well as secondary skeletal deformities, were found to be the most disabling constituents. For the purpose of clinical recognition, a four‐stage progression based on age is presented.

The membrane lipids were examined in the cerebellum from five patients who died with Rett syndrome (RS). The major lipids of cerebellar folia and white matter did not show any difference compared with age-matched controls. There were slightly low values for cerebrosides, a biochemical marker for myelin, in cerebellar folia but high values in white matter of corpus medullare. The ganglioside concentration was reduced in one case which had shown marked astrocytosis at histological examination. Astrocyte associated gangliosides were significantly increased in this case, but their proportion was also increased in the four other patients. Lacto series acidic glycosphingolipids, 3′-LM1 and LK1, closely associated with Purkinje cells were reduced in the Rett cases which fits well with neuropathological examination demonstrating the loss of Purkinje cells. The most prominent finding was a decreased proportion of gangliosides GD1a and GT1b in cerebellar folia and white matter. The decreased proportion of GD1a might reflect an abnormality of synaptogenesis in RS and would be compatible with the clinical profile of this disease.

Sural nerve biopsies from nine children with the carbohydrate deficient glycoprotein (CDG) syndrome were examined. The light and electron microscopical findings were consistent with a mild neuropathy of complex pathogenesis in all the children. The most striking finding was an attenuation of myelin sheaths and the presence of multivacuolar myelinoid bodies in the Schwann cells, indicating a change in myelin turnover. Degeneration of scattered unmyelinated fibres suggests that axons may also be primarily affected. Fibrillary‐crystalline cytoplasmic inclusions were found in endo‐and epineurial fibroblasts in all the cases. The neuropathological features support the contention that this syndrome represents a new type of error of macromolecular metabolism.

The Rett syndrome (RS) and infantile neuronal ceroid lipofuscinosis (INCL) are known clinically to present with quite similar manifestations in the very first stages of disease. Ten girls, born 1982-85, from the Swedish series of RS, were compared with 6 children with biopsy-confirmed INCL, deriving from 4 families, as to neurodevelopmental, neurological, ophthalmological, neurophysiological, and CT data. The rapid regression at 1-2 years of age with loss of acquired fine motor skill, learned words, and communication were found to be inseparable between the diseases, as were the successively developing hand and finger stereotypies. Early clues for differential diagnosis were the appearance of transient drop spells, loss of head control, and irregular myoclonias in INCL, flattening of the EEG, early cortical atrophy indicated at CT, and particularly abnormal ERGs. For accurate diagnosis of INCL a biopsy with characteristic EM findings of "snowball" aggregates is a necessity. After 2 3/4-3 years of age, a clinical differentiation was possible in all cases, with visual failure and rapidly decreasing motor ability, head control deterioration, hyperexcitability, and trunk-limb extension tonus being characteristic for INCL.