Febrile convulsions in a national cohort followed up from birth. II--Medical history and intellectual ability at 5 years of age.

Three hundred and three children with febrile convulsions were identified in a national birth cohort of 13 135 children followed up from birth to the age of 5 years. Breech delivery (p less than 0.05) was the only significantly associated prenatal or perinatal factor. There were no associations with socioeconomic factors. Excluding the 13 known to be neurologically abnormal before their first febrile convulsion, children who had had a febrile convulsion did not differ at age 5 from their peers who had not had febrile convulsions in their behaviour, height, head circumference, or performance in simple intellectual tests.     

Febrile convulsions in a national cohort followed up from birth. I--Prevalence and recurrence in the first five years of life.

Of 13 135 children followed up from birth to the age of 5 years, 303 (2.3%) had febrile convulsions. Prior neurological abnormality had been noted in 13. Of the 290 remaining children, 57 (20%) presented with a complex convulsion, and 103 children (35%) went on to have further febrile convulsions. The risk of further febrile convulsions varied with the age at first convulsion and the presence of a history of convulsive disorders in relatives. There were no significant differences between the sexes.     

Primary immunisation and febrile convulsions in Oxford 1972-5.

A three-year study of febrile convulsions in Oxford with comprehensive notification from general practice and hospitals showed a 3% risk for all children of suffering at least one febrile convulsion by the age of 5 years. Children were most at risk between 6 and 27 months, and febrile convulsions were most likely to be prolonged in children aged 9-15 months. The association between febrile convulsions and primary immunisations in the preceding 28 days was compared in case and control children, matched for age and sex. Results suggested that such association was a chance relationship with age. If association was direct, the febrile convulsion rates per 1000 immunisation doses were estimated as follows: diphtheria, pertussis, tetanus--0-09 per 1000; poliomyelitis--0-6 per 1000; and measles--0-9 per 1000. Hence if any of these vaccines had a secific causal relationship with febrile convulsions, these rates would probably have been much higher.     

Failure of phenobarbitone to prevent febrile convulsions.

One-hundred-sixty-five children without known neurological disorder who presented with their first febrile convulsion between the ages of six months and three years were assigned to daily phenobarbitone treatment or to a control group and followed up at a special clinic for six months. One-hundred-and-sixty-one-one children completed the trial, and of the 88 children assigned to phenobarbitone treatment 10 had further convulsions during this period compared with 14 of the 73 control children. Only 49 of those assigned to phenobarbitone took the drug regularly throughout the trial, and four of these had further febrile convulsions, a proportion not significantly different from that in the controls. All four had mean plasma phenobarbitone concentrations over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours of the repeat convulsion. Regular phenobarbitone does not seem to prevent febrile convulsions. Attention should instead be directed to organising emergency services to allow early termination of fevrile convulsions, whether first or subsequent, to prevent irreversible brain damage.     

Outcome of childhood status epilepticus and lengthy febrile convulsions: findings of national cohort study.

OBJECTIVE--To study outcome after lengthy febrile convulsions and status epilepticus in children. DESIGN--Population based birth cohort study. SETTING--The child health and education study (16,004 neonatal survivors born in one week in April 1970). SUBJECTS--Information available for 14,676 children. OUTCOME MEASURES--Clinical information and tests of intellectual performance at five and 10 years after birth. RESULTS--19 children had lengthy febrile convulsions and 18 had status epilepticus. Two children with status epilepticus died (one at 5 years old); neither death was directly due to the status epilepticus. Four of the 19 (21%) developed afebrile seizures after lengthy febrile convulsions compared with 14 of the 17 (82%) survivors after status epilepticus. Measures of intellectual performance were available for 33 of the 35 survivors: 23 were normal and 10 were not normal but eight of them had preceding developmental delay or neurological abnormality. CONCLUSION--The outcome in children after lengthy febrile convulsions and status epilepticus is better than reported from studies of selected groups and seems determined more by the underlying cause than by the seizures themselves.     

Genetic aspects of febrile convulsions

Summary A total of 6706 children 3 years of age (3491 boys, 3215 girls) in a particular geographical area in Fuchu (population approximately 182 000), Tokyo, was investigated. Some 654 children (9.8%; 10.5% for male, 9.0% for female) had had at least one convulsion, and the incidence of febrile convulsions was 6.7% (7.2% for male, 6.2% for female). The 450 FC children with febrile convulsions and 620 randomly selected control children were analyzed on the mode of inheritance.The incidence of the disease among siblings was 21.9% (29.7% after age correction), which rose greatly with increasing numbers of affected family members, and the segregation ratio among siblings was higher (36.5%) with one FC parent, and lower (18.5%) if neither parent had had a seizure. The more severe the illness in FC children, the larger the incidence among siblings.Population and family studies indicated that heredity plays an important role in febrile convulsions and that multifactorial inheritance is most likely.     

Variability in serial CD4 counts and relation to progression of HIV-I infection to AIDS in haemophilic patients. Transfusion Safety Study Group.

OBJECTIVE--To examine the CD4 count and its near term changes relative to progression to AIDS within 30 months and to subsequent CD4 counts. DESIGN--Longitudinal clinical and laboratory study. SETTING--Haemophilia treatment centres in six large American cities. PATIENTS--555 people with congenital clotting disorders who were infected with HIV, initially without AIDS, and seen at follow up for 6-30 months in 1986-9. MAIN OUTCOME MEASURES--Absolute CD4 counts and incidence of AIDS. RESULTS--Outset CD4 count and age were independently related to progression to AIDS (p less than 0.0001 and p less than 0.005 respectively). Patients with CD4 counts of 0.30-0.49 x 10(9) cells/l had an age adjusted risk of AIDS within 30 months of only 9% that of patients with counts less than 0.20 x 10(9)/l. Children under 10 years old had only 16% of the CD4 adjusted risk of AIDS of people aged greater than or equal to 45 years. Analysis of 149 patients'' CD4 counts at the beginning and end of two successive six month intervals showed an average decrease of 11% in each six months regardless of the outset count (greater than or equal to 0.20 x 10(9)/l). For individual patients the decrease in the second six month period was unaffected by the decrease in the first six month period. CONCLUSIONS--Antiviral treatment of asymptomatic people, particularly children, with CD4 counts greater than or equal to 0.3 x 10(9)/l is questionable if predicted on near term progression to AIDS. Because of individual CD4 count variability and the low rate of progression to AIDS near term declines in individual CD4 counts are a poor index for identifying people who will rapidly progress to AIDS.     

Complex segregation analysis of febrile convulsions.

Complex segregation analysis was performed on 467 nuclear families ascertained through febrile-convulsion probands. The probands were identified as having their first febrile convulsion while residents of Rochester, MN, during the years 1935-64. Parents and first- and second-degree relatives of probands were identified through the Olmsted County, MN, record-linkage system. Diagnoses of convulsive activity were made from review of medical records. The genetic models investigated included both single-major-locus and polygenic models, with likelihoods computed jointly on children and parents as well as being conditioned on parental phenotype. Possible heterogeneity was investigated by means of analyses of frequency of febrile convulsions in the proband. Analyses of the entire data set indicated that the single-major-locus models could be rejected. The most parsimonious model for these data was the pure polygenic (or common familial environment) model with a large heritable component (68% +/- 7%). However, when families were partitioned on the basis of frequency of febrile convulsions in the proband, significant heterogeneity was present. Our results indicated that the polygenic model was strongly corroborated in families of probands with a single febrile convulsion. In families of probands with multiple febrile convulsions, evidence was consistent with a single-major-locus model with nearly dominant seizure susceptibility.     

Are all born equal? Incidence of febrile convulsions by seasons of birth.

To test whether the seasons of birth had an effect on subsequent experience of illness, details were obtained of all Sheffield children born between 1973 and 1977 who were admitted to hospital before their second birthday with a first febrile convulsion. Analysis by date of birth in consecutive 28-day cohorts showed that the incidence of febrile convulsions ranged from 2.5 per thousand live births to 30.2 per thousand in different "month" cohorts. Statistically significant variations were noted in the incidence rates in relation to season and year of birth. The implication is that even large scale epidemiological studies which have been confined to children born in a particular week or month may not be representative of the whole child population.     

Successful prophylaxis against febrile convulsions with valproic acid or phenobarbitone.

A total of 184 six-month periods were analysed during which feverish illnesses occurred in children aged 6-42 months with a history of a febrile convulsion. Fits occurred in 34 out of 100 such periods when no treatment was being given, in six out of 45 periods when the serum phenobarbitone concentration was 69.0 mumol/l (1.6 mg/100 ml) or more, and in five out of 39 periods when the plasma valproic acid concentration was 416.4 mumol/l (6.0 mg/100 ml) or more. Thus in adequate dosage both phenobarbitone and valproic acid were significantly better than no treatment in preventing febrile convulsions (p less than 0.02). The two drugs were of comparable efficacy. It is concluded that with improved compliance valproic acid, which is relatively free from side effects, might be an effective prophylactic agent against febrile convulsions.     

GABA-gated chloride ion influx in brains of epileptic El mice

GABA-gated chloride ion influx was measured in brain microsac preparations of epileptic El mice. There was significantly greater sensitivity to GABA in stimulated El mice (which had 14–18 convulsions induced at weekly intervals) than in unstimulated El mice (which had not experienced convulsions) or ddY mice. GABA-gated chloride ion influx was significantly decreased 20 min after a single convulsion, and returned to the preconvulsion level 60 min after a convulsion. These findings suggest that the functional state of GABA-gated chloride channel in El mice is changed secondarily by single or repeated convulsions.     

NERVOUS COMPLICATIONS OF EXANTHEM SUBITUM

For many years it was generally believed that all convulsions associated with exanthem subitum were febrile in origin. More recently several investigators have suggested that the causative agent of this disease has a selective action on brain tissue aside from the effect of high temperature. In support of this concept are a variety of neurological manifestations sometimes observed during the course of exanthem subitum. These include prolonged and repeated convulsions, hemiparesis, headache, vomiting, bulging fontanelle, vertigo, cervical rigidity, extreme irritability and a reversal of the time of sleep. Abnormalities in the spinal fluid have been reported on a few occasions.By chance the authors observed a case of exanthem subitum that began with a prolonged and severe afebrile convulsion and transient left hemiparesis. Serial electroencephalograms showed a focal lesion with suppression and slowing in the right parietal area. Behavior disorders of brief duration were noted. This case is interpreted as additional evidence of the presence of an encephalitic process.The nature of the cerebral lesion remains unknown. The remote possibility of disturbed behavior in later life deserves consideration.     

Serum and cerebrospinal fluid nitrite/nitrate levels in patients with rotavirus gastroenteritis induced convulsion

Nitric oxide (NO) is a highly reactive free radical that is involved in a variety of different biological process. In recent reports, the putative role of NO in the neuropathogenesis of brain inflammation has been demonstrated. And then the relation between neuronal NO and convulsive seizures induced by virus has been suggested. However, there are few reports about NO in vivo under viral neurological infections. In order to evaluate the relation between NO production and neurological disorders induced by viral infection, sixty-six cases including 11 patients with rotavirus gastroenteritis admitted for convulsions were examined in this study. NO metabolites (NOx) levels in both serum and cerebrospinal fluid obtained from rotavirus gastroenteritis patients with convulsion were much higher than in those of patients with purulent meningitis, encephalitis, febrile convulsion or in the control group. There was a relative correlation between IL-6 and NOx in some cases. These results indicated that NO may have a pathophysiological role in convulsions associated by rotavirus infection either through indirect or direct effects of NO. Consequently, NOx inhibitors might be helpful for the treatment of rotavirus encephalopathy.     

Epilepsy in childhood: findings from the National Child Development Study.

By the age of 11 years 1043 children (6.7%) in an unselected national sample had a history of seizures or other episodes of loss of consciousness; 322 (20.8/1000) had a history of febrile convulsions without other epileptic problems. A clear-cut diagnosis of non-febrile epilepsy was established in 64 children (4.1/1000) by the age of 11 on the basis of confirmatory information supplied by family doctors and paediatricians. A further 39 (2.6/1000) were reported as having epilepsy but did not fulfil the study criteria. The progress of 59 of the 64 children with estabished epilepsy was reviewed again when they were aged 16. Of the 37 educated in normal schools eight (22%) had one or more seizures in their 16th year compared with 13 out of 22 (59%) who received special education. A possible cause for epilepsy was found in 17 of the 64 (27%) children, but for the majority there was no obvious reason.     

Serum Trace Element Levels in Febrile Convulsion

Febrile convulsion is the most common disorder in childhood with good prognosis. There are different hypotheses about neurotransmitters and trace element changes in biological fluids which can have a role in pathogenesis of febrile convulsion. In this study, serum selenium, zinc, and copper were measured by atomic absorption spectrometry in the children with febrile convulsion (n?=?30) and in the control group (n?=?30). The age and sex of the subjects were registered. Selenium and zinc were found to be significantly lower in febrile convulsion cases than in the control group (p?<?0.0001 and p?<?0.0001, respectively). There was no significant difference in the value of copper between the two groups (p?=?0.16). While selenium and zinc levels were 44.92?±?10.93 μg/l and 66.13?±?18.97 μg/dl in febrile convulsion, they were found to be 62.98?±?9.80 μg/l and 107.87?±?28.79 μg/dl in healthy children. Meanwhile, copper levels were 146.40?±?23.51 μg/dl in the patients and 137.63?±?24.19 μg/dl in the control group, respectively. This study shows that selenium and zinc play an important role in the pathogenesis of febrile convulsion.     

Comparison of whole-blood eosinophil counts in extrinsic asthmatics with acute and chronic asthma.

Venous whole-blood eosinophil counts were performed on 50 occasions in 42 patients with varying patterns of asthma. None of the patients studied had received systemic corticosteroids during the previous year. Patients with acute severe asthma, as defined by symptomatic airways obstruction with a tachycardia of at least 120 beats/min, showed eosinopenia (21 x 10(9)/l +/- SD 57 x 10(9)/l). Patients with chronic asthma, as defined by symptomatic airways obstruction with a heart rate of less than 100 beats/min, showed appreciable eosinophilia (1048 x 10(9)/l +/- SD 708 x 10(9)/l). Finally, asymptomatic patients had a variable total eosinophil count but with values lower than those of patients with chronic asthma (345 x 10(9)/l +/- SD 431 x 10(9)/l). Eosinophilia may contain chronic asthma, thereby mediating bronchial damage, whereas absence of eosinophils in acute asthma enables vasoactive mediators to enter the systemic circulation, possibly causing circulatory disturbances.     

Pneumococcal bacteraemia: 325 episodes diagnosed at St Thomas's Hospital.

Three hundred and twenty five episodes of pneumococcal bacteraemia occurred at St Thomas''s Hospital during 1970-84, accounting for 13.3% of all episodes of bacteraemia. Twice as many cases occurred in male as in female patients, and common predisposing factors included chronic chest disease, alcoholism, haematological malignancies, cirrhosis, and sickle cell anaemia. Mortality was 28.6% overall but only 11.8% among patients who received antibiotic treatment for at least 24 hours. Most patients (261) had pneumonia, 26 had meningitis, and eight were children with occult bacteraemia. The commonest serotype of pneumococcus in adults was type 3 (39 episodes), and these strains were associated with a high mortality. Other factors determining a fatal outcome included underlying disease (such as cirrhosis, malignancy, and chronic chest disease) and extrapulmonary infection. Almost half the survivors were treated for 10 days or less and became afebrile within 48 hours.     

Relationship Between GABA Concentrations in Cerebrospinal Fluid and Seizure Excitability

Abstract: Various studies suggest that alterations in GABAergic function may be connected to epileptic seizures. Low CSF GABA levels have been reported in epilepsy and also febrile convulsions of children. In this study the pentet-razole seizure threshold of dogs was compared with the concentration of GABA in the CSF and blood plasma. A highly significant positive correlation was found between seizure excitability and CSF GABA level, but not between CSF and plasma GABA concentrations.     

Chronic lymphocytic leukemia and prolymphocytic leukemia: a clinicopathological reappraisal

A series of 300 cases of chronic B-cell leukemia was studied in relation to clinical and laboratory features, and three groups were identified on the basis of the percentage of circulating prolymphocytes (%PROL): typical CLL less than or equal to 10% PROL, 174 cases; PLL greater than 55% PROL, 42 cases; and an intermediate group CLL/PL (11%-55% PROL), 84 cases. Some features of the CLL/PL group resemble those of PLL, such as a disproportionate splenomegaly in relation to the degree of lymphnode involvement. However, membrane markers suggested a closer affinity of CLL/PL with CLL [high percentage of M rosettes, expression of the P67 (T1) antigen, and low reactivity with the McAb FMC7], although high-density SmIg was found in one-third of CLL/PL, as well as in the majority of the PLL cases. Cells volume measurements demonstrated that the prolymphocytes of both PLL and CLL/PL are significantly larger than the homogeneous population of small lymphocytes of typical CLL. Followup studies of the PB picture in CLL and CLL/PL showed that the majority of patients maintain a relatively stable percentage of PROL, but a progressive prolymphocytoid transformation to a PLL-like disease may occur in some cases. On univariate analysis of survival, seven features of disease had a high prognostic values for the whole group of patients: %PROL, absolute number of PROL (ABS PROL), WBC, spleen size, M rosettes, SmIg intensity, and age. However, only ABS PROL (greater than 15 X 10(9)/l) and spleen size (greater than 8 cm) were shown to be independent prognostic features on a multivariate regression analysis. The median survival time of patients with PLL (3 years) was significantly shorter than the median of 8 years for patients with CLL. Within the heterogeneous CLL/PL group, patients with ABS PROL greater than 15 X 10(9)/l (two-thirds) had a median survival time as bad as for PLL patients, whereas the median has not been reached for those with ABS PROL less than 15 X 10(9)/l.     

Effect of 6-hydroxydopamine on brain and blood catecholamine, ammonia, and amino acid metabolism in rats subjected to high pressure oxygen induced convulsions

Effects of 6-hydroxydopamine (6-OHDA) on rat brain and blood adrenaline (A), noradrenaline (NA), ammonia (NH3), gamma-aminobutyric acid (GABA), and amino acid metabolism prior to and after high pressure oxygen (OHP) induced convulsions have been studied. 6-OHDA reduces GABA and glutamate (Glu) rior to OHP exposure in rat brain so that the concentration is even equal to that seen in nondrugged animals after convulsion. Concomitantly, 6-OHDA reduces the latency of OHP-induced convulsion significantly, and increases brain NH3, glutamine, and asparagine significantly. Although 6-OHDA, in increasing dosage, elevates blood A concentration, convulsion produces a significant further increase in A. Blood NA was not significantly changed in drugged, convulsed animals and was much less than blood NA concentrations in nondrugged convulsed animals. Increasing doses of 6-OHDA also increase NH3 in the blood significantly and convulsion increases its concentration further. Latency of convulsion seems to be related to certain monoamine levels since in some drugged animals where A and total catecholamines are still reduced 96 h after the first of two doses of 6-OHDA, NA concentrations are recovered to relatively normal and the convulsion latency time is also increased although it remains significantly abbreviated from undrugged animals' convulsion time. Low brain GABA levels seem to be a prime effector of convulsive activity.