Comparison between one and three years of treatment in uncomplicated childhood epilepsy: a prospective study. I. Outcome in different seizure types.

PURPOSE: The main purpose of this prospective study was to analyze whether 1 year of treatment was as effective as 3 years with respect to remission rate in children with idiopathic epilepsy. METHODS: Treatment for epileptic seizures was started in 207 children aged 2-16 years. They were randomized to treatment for 1 or 3 years. At the end of the predetermined treatment period, 161 children had been seizure-free for 6 months and the treatment could be gradually withdrawn. RESULTS: The overall remission rate in our group of patients was significantly higher (71%) in the group treated for 3 years than in the group treated for 1 year (53%). However, comparison of remission rates between patients with different seizure types showed statistically significant differences in outcome depending on duration of treatment only in children with complex partial seizures (CPS). CONCLUSIONS: Our results show that 1 year of treatment can be recommended in children with benign partial epilepsy with rolandic spikes (BECT) and in children with simple partial seizures (SPS) but is clearly insufficient in children with CPS. A proper seizure classification is one important tool, although not sufficient, in offering recommendations concerning the duration of treatment in children with idiopathic epilepsy.

Monitoring of phenytoin in epileptic children: value of the single morning sample.

The intra-individual variation in plasma concentration of phenytoin was studied in ten clinically well controlled children on monotherapy. The drug concentration was determined in routine pre-dose samples taken on three to five different mornings. On two of these occasions, plasma phenytoin was also determined at 0.5, 1, 2, 3, 5 and 7 h after the dose. The difference between the highest and lowest morning concentrations in a patient varied between 7.5 and 40 mumol/l (mean 20.1 mumol/l). Half of all morning concentration values were lower than 40 mumol/l. This often-recommended lower limit for good seizure control should therefore be reconsidered. The two concentration versus time curves in each patient during 7 h after administration differed considerably in shape, and the first curve could not be used for prediction of the second curve. The ratio between unbound and total drug was very stable and amounted to 9.4, SD 0.94% (n = 168). It is concluded that the conventional single morning sample is satisfactory for routine monitoring in well-controlled children on monotherapy with phenytoin. In problem patients, and during combination therapy, however, more extensive investigation will be necessary, including repeated morning samples as well as determination of dose-interval curves and protein binding.

Borrelia infection in children.

All children (less than or equal to 15 years) admitted during 1986 to Sachs Children's Hospital and presenting signs of facial palsy and/or meningitis, or with a history of known tick bite followed by headache, fatigue and muscle pain, were investigated for antibodies to Borrelia in serum and cerebrospinal fluid. (The hospital's catchment area has a high incidence of tick-borne Borrelia infections.) Significantly elevated antibody titre was found in 15 of the 33 patients, in three cases only in cerebrospinal fluid. Eight of the 15 children had facial palsy, which was concomitant with meningitis in six cases. Intravenous penicillin was given to all 15 patients with positive antibody titre, and additionally to three severely ill small children with facial palsy and meningitis. Furthermore, two cases of erythema chronicum migrans, which is considered pathognomonic for Borrelia infection, were treated with penicillin perorally. Cases of Borrelia infection occurred throughout the year, but with a peak in August. To emphasize the variety of symptoms, three cases are presented in some detail.

New conjugated urinary metabolites in intermediate type maple syrup urine disease.

N-Lactylvaline, N-lactylleucine, N-lactylisoleucine and the N-2-hydroxyisovaleryl conjugates of glycine, valine, leucine and isoleucine have been identified in urine from a patient with the intermediate type of maple syrup urine disease.

Heredity in febrile convulsions: is it HLA-dependent?

One hundred children consecutively treated for simple febrile convulsions (FC) were investigated with respect to hereditary factors. Twenty-five of the children had parents or siblings with FC. HLA-typing was performed in all available members of ten families with one or two FC children and one FC parent, and in one family with two FC children but no FC parent. There was no clear association with a particular HLA haplotype in any of these families.

Correlation of detrusor vesicae activity to radiologic findings in childhood myelodysplasia.

In selected cases of childhood myelodysplasia associated with incontinence oral anticholinergics, e.g. atropine, may significantly improve the results of continence training programs. At present, the differentiation of patients who may benefit from this kind of pharmacotherapy from those who do not respond calls for laborious recordings of the intravesical pressure. Urography and micturition cystourethrography routinely used for the morphologic evaluation of the urinary tract were compared with the pressure tracings. No useful correlation between findings was obtained, thus excluding the possibility to replace the pressure studies by the much simpler radiologic examinations.

Observations on the internal sphincter mechanism during the filling phase in children with hyperactive neurogenic bladder.

The internal sphincter mechanism in the urinary bladder was investigated in three groups of children. Two groups had neurogenic bladder, one of them with and one without detrusor hyperactivity. The third group had no myelodysplasia and normal detrusor activity in the filling phase. In this group the sphincter contractions were sustained at high pressure level, with superimposed waves of substantial amplitude. Myelodysplasia of segments below L3 was associated with hyperactivity of the detrusor. The general sphincter pattern in this condition was the same as in the normal group, but the behavior of the sphincter was not synchronized with the pressure fluctuations in the bladder. In the children with low thoracic or high lumbar level of lesion ther was no detrusor hyperactivity. Their sphincter mechanism could be characterized as passive, with low mean pressure and low amplitude of superimposed waves. When detrusor hyperactivity is present, it seems to be the main factor in leakage from neurogenic bladder. In the absence of detrusor hyperactivity in neurogenic bladder, passivity of the internal urethral sphincter due to dissociation from the spinal centers is proposed as the explanation of incontinence.

Continence training of children with neurogenic bladder and detrusor hyperactivity: effect of atropine.

Recording of the intravesical pressure throughout the filling phase in children with low lumbar and high sacral levels of myelodysplasia showed detrusor hyperactivity which could be inhibited by anticholinergic medication in a dose-dependent manner under experimental conditions. Atropine as treatment for urinary incontinence during everyday activity was remarkably effective when given parenterally. Orally administered atropine was associated with 50-100% improvement of incontinence in six of 9 patients and 35-45% in the remaining three patients. Successful treatment with anticholinergic drugs requires careful selection of patients, including recording of the filling-phase intravesical pressure. Only in patients with detrusor hyperactivity is a good result of such treatment to be expected.

Diagnosis of detrusor hyperactivity in children with neurogenic bladder.

Detrusor hyperactivity and its reproducibility was investigated in 22 patients with myelodysplasia and neurogenic bladder. The examinations were performed with microtransducers in the bladder, proximal urethra and rectum. Hyperactivity was found in 15 children all belonging to low lumbar and sacral neurological lesion groups. Patients without hyperactivity mostly had their levels of lesion higher in the spinal cord. In 6 children without neurologic disease no hyperactivity was found.

Influence of atropine and isoprenaline on detrusor hyperactivity in children with neurogenic bladder.

Bladder hyperactivity defined as unconscious, involuntary detrusor contractions giving rise to intravesical pressure increase of at least 15 cm H2O and of minimum 15 sec duration, has been examined in 9 children with myelodysplasia and incontinence. The effect of atropine and isoprenaline on the hyperactivity pattern was evaluated. Atropine had a dose-related inhibiting influence on both frequency and amplitude of detrusor contractions whereas isoprenaline was without these favourable effects.

Is beta-receptor blockade of value in continence training of children?

The relaxation of the outlet region of the bladder is subserved by beta-adrenergic receptors. It is conceivable, therefore, that inhibition of beta-adrenergic function should be of value as part of a continence training program in patients with neurogenic bladders. This hypothesis was tested in a series of thirteen children with spinal lesions. A double-blind, cross-over study of alprenolol versus placebo was performed during conventional continence training. The number of "dry periods", however did not differ during the alprenolol and placebo periods. One reason for the lack of clinical effect may be that the drug simultaneously blocked the beta receptors in the corpusfundus of the bladder, thereby decreasing the volume capacity.

Characterization of the adrenergic beta-receptor in the urinary bladder of man and cat.

The corpus-fundus of the urinary bladder of man and cat was studied in vitro with respect to type of beta-adrenergic receptors. In both species beta-adrenergic stimulation produced marked relaxation but species differences were apparent. In the cat bladder only beta1-receptors were found. In the human bladder the beta-receptors had neither beta1- nor beta2-characteristics. It is suggested that the beta-adrenergic receptors in the corpus-fundus of the human bladder are of a third type.

Results of treatment in myelomeningocele.

A follow-up study was made in 48 surviving children with myelomeningocele, the material being derived from a time when all infants were operated upon in the newborn period without primary selection. The follow-up revealed several children with severe physical handicap, whereas relatively few were both physically and intellectually handicapped. The results were compared with two earlier published studies of which one from Sheffield comprised cases where selection had not been applied and the other from Edinburgh in which certain criteria had been set up as contra-indications to early closure of the lesion. The effect of a hypothetical selection applied to the Swedish material is discussed. It is recommended that a uniform system of assessment in grading of handicap is applied to facilitate a comparison between different follow-up investigations.