Screening for minor changes in the distal part of the human dystrophin gene in Greek DMD/BMD patients.

The distal part of the human dystrophin gene is characterised by particular features and seems to play an important functional role. Additionally in recent years several data have implicated minor mutations in this gene region in some patients with mental retardation (MR). In order to screen for pathogenic mutations at the distal part of the human dystrophin gene we have used single-strand conformation analysis of products amplified by polymerase chain reaction (PCR-SSCA) in 35 unrelated male Greek DMD/BMD patients with no detectable deletions. Seven patients also had severe mental retardation. Direct sequencing of samples demonstrating a shift of SSCA mobility revealed six different and pathogenic minor changes, five in DMD and one in a BMD patient. Four of the mutations were found in DMD patients with severe MR. Three of these mutations were localised in exon 66, which presents an interesting similarity with part of the 3' end of the genome of eastern equine encephalomyelitis virus (EEEV). The present data from Greek DMD/BMD patients give further information about the phenotypic effects consequent on mutations in exons at the distal part of the human dystrophin gene.

Martin-Bell syndrome in Greece, with report of another 47,XXY fragile X patient.

A cytogenetic investigation was carried out among 200 mentally retarded boys in Greece for the detection of the fragile X [fra(X)] syndrome. Thirteen patients were found to carry fra(X) (6.5%). Of those, six boys had a history of familial X-linked mental retardation, two had the phenotype of the Martin-Bell syndrome, four had only mental retardation of unknown etiology, and one was a mentally retarded patient with Klinefelter syndrome. The remaining 187 boys were fra(X) negative. Our findings emphasize the importance of early identification of this syndrome in the diagnosis and prevention, through proper genetic counselling, of mental retardation.

Campylobacter jejuni O:19 serotype-associated Guillain-Barré syndrome in a child: the first case reported from Greece.

We present a case of Guillain-Barré syndrome (GBS) following Campylobacter jejuni HS serotype O:19 infection in a child. Antibodies against C. jejuni and autoantibodies to the peripheral nerve gangliosides GM1 were positive, a pattern correlating well with the existence of an inflammatory neuropathy like GBS. The patient shared the HLA-B35 and HLA-DR8 antigens, which have been found to be increased in GBS patients with previous C. jejuni infection. As this is the first diagnosed C. jejuni-associated GBS case reported from Greece, further clinical and epidemiologic investigations are warranted.

Continuous neostigmine infusion in post-thymectomy juvenile myasthenic crisis.

A 10-year-old boy with myasthenia gravis had severe post-thymectomy myasthenic crisis necessitating reintroduction of mechanical ventilation on the 5th day after thymectomy. He did not respond to therapy with oral pyridostigmine, corticosteroids, or high-dose intravenous immunoglobulin. Finally, in addition to the usual supportive care, he was treated successfully with continuous intravenous infusion of neostigmine. Continuous infusion of neostigmine was used for the first time in post-thymectomy myasthenic crisis in a child to the best of our knowledge.

Idiopathic intracranial hypertension in children.

We studied prospectively the etiology, clinical presentation, and outcome of idiopathic intracranial hypertension in 36 patients (20 boys and 16 girls) aged 3.5 months to 14 years. The etiology was identified in 28 (77.7%) patients. The most common predisposing factor was middle-ear infection, followed by obesity. Of the 36 cases seen, 26 presented with the classic picture of headaches, papilledema, and elevated cerebrospinal fluid pressure; 8 children had intracranial hypertension in the absence of papilledema and 2 had fundoscopic evidence of papilledema with normal cerebrospinal fluid pressure initially. In four children resolution of intracranial hypertension occurred with removal of the causative agent or appropriate treatment of the underlying condition. In 8 of 17 patients intracranial hypertension resolved with acetazolamide therapy and in 22 of 24 patients it resolved with corticosteroids in combination with acetazolamide. Subnormal visual acuity, narrowing of visual fields, or both were present on the initial examination in 10 patients; 2 of them, who presented with loss of vision, have permanent visual impairment. Four additional patients presented a transient, mild impairment of visual acuity during treatment. Our study confirms the wide clinical spectrum and the difficulties encountered in diagnosis of idiopathic intracranial hypertension. A wide variety of etiologic associations should be investigated to provide definitive therapy. Loss of visual function is the only serious complication.

Increased blood lead levels in mentally retarded children in Greece.

In 60 children with mental retardation of unknown etiology, the whole blood lead, as well as the activity of the red cell delta-aminolevulinic acid dehydratase (delta-ALAD), was measured. Thirty normal children and 30 with mental retardation of known etiology were used as controls. The lead values were found significantly higher in the study patients compared with both control groups (P less than 0.001). The delta-ALAD activity in the 14 patients with blood lead levels greater than or equal to 40 microgram/dl, was significantly reduced compared with the normal controls (P less than 0.001) and the mentally retarded controls (P less than 0.01). In more than 20% of the patients with mental retardation of unknown etiology, indications of significant exposure to lead were found. There was no difference in blood lead values between children from cities and those from rural areas. The possible role of lead in the etiology of mental retardation is discussed.

Epilepsy in patients with cerebral palsy.

The incidence of epilepsy in 323 patients with cerebral palsy (CP) was 41.8%. Almost half of the patients with spastic tetraplegia and hemiplegia had epilepsy. The incidence was lower in patients with spastic diplegia. No sex differences were observed. Partial seizures were by far the most common form of epilepsy in spastic hemiplegia, while generalized tonic-clonic episodes predominated in all other forms of CP. A very high incidence of West syndrome was observed in patients with spastic tetraplegia. Most of the patients with spastic tetraplegia had their first seizure in the first year of life. In patients with spastic hemiplegia the onset of epilepsy was often delayed for several years. A high rate of polytherapy was recorded, but two-thirds of the patients remained seizure-free for long periods. In just over one-fifth of the patients successful withdrawal of medication was achieved.

Porencephalic cysts after amniocentesis.

An infant with porencephalic cysts associated with midtrimester amniocentesis is reported. CNS anomalies after amniocentesis have not been reported in live neonates.

Late recurrence of herpes simplex virus meningoencephalitis in two infants.

UNLABELLED: Two infants with recurrence of herpes simplex virus (HSV) encephalitis are reported. Both patients developed HSV encephalitis during their neonatal period and were treated with iv acyclovir. Long-term oral acyclovir prophylaxis was given thereafter. At the age of 8 and 11 months respectively, both babies, while under oral acyclovir prophylaxis, presented a second episode of HSV encephalitis. An inadequate dose of suppressive oral acyclovir therapy may be responsible for the recurrence of encephalitis in these two babies. CONCLUSION: The present observations emphasise the need for very long follow-up of any infant who has suffered from neonatal herpes simplex virus encephalitis and the need for careful prospective controlled studies in order to define the appropriate treatment regimen (initial plus prophylaxis) for neonates with herpes simplex virus infections.

Risk factors for cerebral palsy: a case-control study in Greece.

The purpose of this study was to investigate the relation between a series of maternal, antenatal, perinatal, socioeconomic and environmental variables and the occurrence of cerebral palsy (CP) in a setting different from those in which previous analytic epidemiologic studies had been undertaken. The study was of case-control design and included 103 children with cerebral palsy born between 1984 and 1988 and residents of the Greater Athens area at any time during 1991 and 1992. Controls were chosen among the neighbors of the index case or were healthy siblings of children with neurological diseases other than CP seen by the same neurologists as the children with CP; a total of 254 control children were eventually included. Statistical analysis was done by modeling the data through unconditional logistic regression. Statistically significant (p < 0.05) risk factors of potential causal importance were: twin membership (OR = 10.2), gestational age (OR = 0.5 per 4 weeks), birth weight conditional on gestational age (OR = 0.9 per 100 g), congenital malformations (OR = 7.5), unhealthy placenta (OR = 6.6), placenta previa (6 cases, no controls), abnormal amniotic fluid (OR = 3.6), head circumference more than 36 cm (OR = 9.0), general anesthesia during labor (OR = 4.3), forceps delivery (OR = 6.8), and birth trauma (OR = 11.5). Among children with no identifiable prenatal risk factors there was no excess prevalence of one or more perinatal risk factors in CP cases compared to controls, which implies that the latter factors impart their effect through interactions with co-existing prenatal or other risk factors.

Relapse of herpes simplex encephalitis after acyclovir therapy.

A case of herpes simplex encephalitis in a previously healthy 17-month-old girl relapsing 1 week after completion of a 10-day acyclovir therapy is described. The child responded favourably to a second 10-day course with acyclovir. The time of relapse and the satisfactory response to a second course of acyclovir treatment indicate that the first course of therapy was inadequate for eradication of herpes simplex virus infection.

Birth weight and handedness in boys and girls.

The association between selected demographic variables and birth weight on the one hand and a composite hand preference score based on seven hand tasks (each performed twice) on the other was investigated in a sample of 1387 male and female schoolchildren aged 5 to 10 years old. In multiple regression models left-handedness was significantly more common among boys and among children of better educated mothers and tended to decrease with age. No association was found with respect to urban or rural residence or birth order. Increased birth weight was associated with right-handedness in boys but with left-handedness in girls, and the birth weight by sex interaction term was statistically significant (p = 0.037). The demographic associations in the present study are compatible with those reported previously. The different associations of birth weight with hand preference in boys and girls indicate that the prenatal hormonal factors that affect brain lateralization and handedness are qualitatively or quantitatively different in the two sexes and may be differentially associated with birth weight.

Diet during pregnancy and the risk of cerebral palsy.

The role of maternal diet in the development of the fetal brain has not been adequately explored. Marine n-3 fatty acids have, however, been proposed to be important for brain development. The present case-control study aimed to investigate the relationship between dietary intake during pregnancy and the occurrence of cerebral palsy (CP) in the offspring. Children with CP (n 109), born between 1984 and 1988 to mothers residing in the Greater Athens area, were identified at any time in 1991 or 1992 through institutions delivering care and rehabilitation. Successful nutritional interviews were conducted with ninety-one of these children. Controls were chosen among the neighbours of the CP cases or were healthy siblings of children with neurological diseases other than CP, seen by the same neurologists as the children with CP. A total of 278 control children were chosen, and 246 of them were included in the nutritional study. Guardians of all children were interviewed in person on the basis of a questionnaire covering obstetric, perinatal socioeconomic and environmental variables. A validated semiquantitative food-frequency questionnaire of 111 food items was used to estimate maternal dietary intake during pregnancy. Statistical analysis was done by modelling the data through logistic regression. Food groups controlling for energy intake were alternatively and simultaneously introduced in a core model containing non-nutritional confounding variables. Consumption of cereals (mostly bread) and fish intake were inversely associated with CP (P < 0.05 and P < 0.09 respectively) whereas consumption of meat was associated with increased risk (P < 0.02). A protective effect of fish consumption and a detrimental effect of meat intake have been suggested on the basis of earlier work and appear to be biologically plausible. If corroborated by other studies, these results could contribute to our understanding of the nutritional influences on fetal brain development.

Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.

Episodic ataxia type 1 (EA1) is an autosomal dominant central nervous system potassium channelopathy characterized by brief attacks of cerebellar ataxia and continuous interictal myokymia. Point mutations in the voltage-gated potassium channel gene KCNA1 on chromosome 12p associate with EA1. We have studied 4 families and identified three new and one previously reported heterozygous point mutations in this gene. Affected members in Family A (KCNA1 G724C) exhibit partial epilepsy and myokymia but no ataxic episodes, supporting the suggestion that there is an association between mutations of KCNA1 and epilepsy. Affected members in Family B (KCNA1 C731A) exhibit myokymia alone, suggesting a new phenotype of isolated myokymia. Family C harbors the first truncation to be reported in KCNA1 (C1249T) and exhibits remarkably drug-resistant EA1. Affected members in Family D (KCNA1 G1210A) exhibit attacks typical of EA1. This mutation has recently been reported in an apparently unrelated family, although no functional studies were attempted. Heterologous expression of the proteins encoded by the mutant KCNA1 genes suggest that the four point mutations impair delayed-rectifier type potassium currents by different mechanisms. Increased neuronal excitability is likely to be the common pathophysiological basis for the disease in these families. The degree and nature of the potassium channel dysfunction may be relevant to the new phenotypic observations reported in this study.