Central nervous system involvement in nephropathic cystinosis.

Nephropathic cystinosis, an autosomal recessive lysosomal storage disorder due to impaired cystine transport, causes damage to multiple organs that results in end-stage renal disease, hypothyroidism, and retinopathy, usually in childhood. Dialysis and renal transplantation now frequently enable patients with cystinosis to live into adulthood. Examinations at autopsy of a 28-year-old man who died of complications of this disease showed deposits of cystine crystals in multiple organs. There was severe cerebral involvement with multifocal cystic necrosis, dystrophic calcification, spongy change, and vacuolization that had produced profound neurologic deficits. Electron microscopy of the brain documented cytoplasmic deposition of cystine crystals in membrane bound vacuoles within the cytoplasm of pericytes and within parenchymal cells of the white matter. While affected patients who have received renal transplants may no longer die from renal failure, serious, potentially life-threatening, neurologic complications of this disorder may supervene.

Myoclonic, atonic, and absence seizures following institution of carbamazepine therapy in children.

Five children, aged 3 to 11 years, treated with carbamazepine for epilepsy, had an acute aberrant reaction characterized by the onset of myoclonic, atypical absence and/or atonic (minor motor) seizures within a few days. When the carbamazepine was discontinued, two of the children returned to their former state very quickly, two had the minor motor seizures resolve in 3 and 6 months, and one had the seizures persist. The child in whom the seizures persisted was later found to have ceroid lipofuscinosis. The other children are doing well on other anticonvulsants.

Torticollis in three children with syringomyelia and spinal cord tumor.

There are numerous well-known causes of acquired torticollis. However, an extensive review of the literature reveals only a rare, brief remark that associates torticollis with syringomyelia. We present three children found to have syringomyelia and spinal cord tumor, with torticollis as an early finding in each.

Randomized trial of vigabatrin in patients with infantile spasms.

BACKGROUND: Infantile spasms are a rare but devastating pediatric epilepsy that, outside the United States, is often treated with vigabatrin. The authors evaluated the efficacy and safety of vigabatrin in children with recent-onset infantile spasms. METHODS: This 2-week, randomized, single-masked, multicenter study with a 3- year, open-label, dose-ranging follow-up study included patients who were younger than 2 years of age, had a diagnosed duration of infantile spasms of no more than 3 months, and had not previously been treated with adrenocorticotropic hormone, prednisone, or valproic acid. Patients were randomly assigned to receive low-dose (18-36 mg/kg/day) or high-dose (100-148 mg/kg/day) vigabatrin. Treatment responders were those who were free of infantile spasm for 7 consecutive days beginning within the first 14 days of vigabatrin therapy. Time to response to therapy was evaluated during the first 3 months, and safety was evaluated for the entire study period. RESULTS: Overall, 32 of 142 patients who were able to be evaluated for efficacy were treatment responders (8/75 receiving low-dose vigabatrin vs 24/67 receiving high doses, p < 0.001). Response increased dramatically after approximately 2 weeks of vigabatrin therapy and continued to increase over the 3-month follow-up period. Time to response was shorter in those receiving high-dose versus low-dose vigabatrin (p = 0.04) and in those with tuberous sclerosis versus other etiologies (p < 0.001). Vigabatrin was well tolerated and safe; only nine patients discontinued therapy because of adverse events. CONCLUSIONS: These results confirm previous reports of the efficacy and safety of vigabatrin in patients with infantile spasms, particularly among those with spasms secondary to tuberous sclerosis.

Amantadine in the treatment of refractory epilepsy in childhood: an open trial in 10 patients.

Amantadine HCl was given to 10 children with medically refractory seizures; other anticonvulsant medications were continued unchanged through the 12- to 16-week trial. Several patients noted improvement in control of myoclonic or atypical absence seizures. Tonic seizures were controlled in one patient, but worsened in another. Tonic-clonic and atonic seizures remained unchanged or worsened. Amantadine may be useful as an adjunctive anticonvulsant in some children with refractory atypical absence or myoclonic seizures.

Surgical treatment of intractable neonatal-onset seizures: the role of positron emission tomography.

We have performed positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D-glucose (FDG) in eight infants and children (aged 18 days to 5 years) with medically refractory epilepsy of neonatal onset. It was hypothesized that in at least some of these infants a surgical approach (focal resection, cerebral hemispherectomy) might be of benefit in achieving seizure control, and that PET might assist in surgical selection. In three of the eight subjects, interictal PET revealed unilateral diffuse hypometabolism; following cerebral hemispherectomy in these three patients, all seizures ceased and there were no adverse effects. In one child, ictal PET showed hypermetabolism in the left frontal cortex, left striatum, and right cerebellum; a partial left cerebral hemispherectomy guided by intraoperative electrocorticography was performed, following which all seizures ceased. One infant had relative hypermetabolism in the right temporal and occipital lobes, right thalamus, and left frontal lobe on ictal PET, and EEG telemetry revealed a right occipitotemporal epileptic focus; this infant died from anesthetic complications following right occipitotemporal cortical resection. Of the three unoperated patients, one is a potential candidate for right frontal lobectomy, but the other two were not considered to be surgical candidates due to bilateral epileptogenicity. Neuropathologic correlation in our series revealed that PET is a sensitive test capable of detecting cytoarchitectural disturbances whereas CT and MRI failed in this regard. In addition, PET provides a very unique and important assessment of the functional integrity of brain regions outside the area of potential resection.

Fibromuscular dysplasia as a cause of stroke in infancy and childhood.

Two children had abrupt onset of hemiplegia due to childhood fibromuscular dysplasia (FMD). Although FMD is a recognized cause of strokes in adults, the disorder has not, to our knowledge, been reported previously in children. Our report reviews the pathology and diagnosis of FMD and discusses the complexities of its treatment.

Normal neurodevelopment in four young children treated with bone marrow transplantation for acute leukemia or aplastic anemia.

Longitudinal neurodevelopmental studies of four consecutive young children treated by bone marrow transplantation for acute leukemia or aplastic anemia are presented. The children, the only four children less than 2 years of age who have received bone marrow transplants for these diseases at UCLA Medical Center, ranged in age from 36 weeks to 24 months at the time of transplantation. Conditioning involved high-dose cyclophosphamide treatment; three also had total body irradiation prior to bone marrow transplantation. Their respective outcomes after follow-up times of 28 months to 71 months posttransplantation are remarkable for normal somatic growth and normal development of intelligence, language, perception, and motor coordination. These findings indicate that future therapeutic studies of infants and young children with acute leukemia or aplastic anemia using total body irradiation, cyclophosphamide, and bone marrow transplantation are not contraindicated by risks of debilitating neurodevelopmental sequelae.

Infants and children with convulsions and hypotonic-hyporesponsive episodes following diphtheria-tetanus-pertussis immunization: follow-up evaluation.

In a prior prospective study, we evaluated the nature and rates of adverse reactions occurring within 48 hours following 15,752 diphtheria-tetanus-pertussis (DTP) immunizations. Nine children had convulsions, and nine had hypotonic-hyporesponsive episodes. After an interval of 6 to 7 years, we were successful in contacting the families of 16 of these children to determine whether any had evidence of neurologic impairment too subtle to have been detected at the time of initial evaluation. All 16 were considered normal by their parents and were doing well in school. A complete neurologic and psychometric evaluation was performed on 13 of these children. No child had significant neurologic deficit, although four had minor neurologic abnormalities. Psychometric testing revealed normal performance IQ scores (104.3 +/- 15.8) but low verbal IQ scores (91.8 +/- 18.4); however, these lower verbal IQ scores can be explained by the proportion of Hispanic and bilingual children in this sample. Therefore, there is no evidence that any of these 16 children have any serious neurologic damage as a result of a convulsion or a hypotonic-hyporesponsive episode temporally associated with a prior diphtheria-tetanus-pertussis immunization.

Correlation of ominous fetal heart rate patterns and brain-specific creatine kinase.

Creatine kinase isoenzyme analysis was performed on the cord blood of 125 infants who had undergone at least 30 minutes of intrapartum electronic fetal monitoring. The tracings were scored blindly according to severity of abnormal patterns, and the infants were grouped into ominous, intermediate, and normal scores. No differences were seen in creatine kinase MM or creatine kinase MB levels among the three groups. However, infants with ominous fetal heart rate patterns had higher creatine kinase BB levels and poorer outcome than infants with normal patterns.

Middle childhood onset of interictal psychosis.

The authors describe three children (mean age = 7.8 years) with complex partial epilepsy, left temporal lobe involvement, and interictal schizophrenia-like psychosis. As described in adults with complex partial epilepsy, these children met DSM-III criteria for schizophrenia, their affect was intact, and they demonstrated no negative signs of schizophrenia. Unlike adult epileptic patients, these children demonstrated psychotic symptomatology despite inadequate seizure control and after a short latency period. The possible role of early onset seizures, temporal lobe lesions, and kindling on the developing brain are discussed.

Communication deficits in children undergoing temporal lobectomy.

OBJECTIVE: To examine formal thought disorder and discourse (cohesive) devices that make speech coherent prospectively in seven children, aged 5.7 to 16.7 years, before and after temporal lobectomy for intractable cut points determined from sensitivity and specificity analyses of formal thought disorder and discourse measures in 22 children with complex partial seizure disorder and 45 normal children. RESULTS: Before surgery, the mean illogical thinking and discourse scores of the surgical candidates were in the pathological range. After a mean postoperative follow-up period of 15.1 months, their illogical thinking (but not their discourse scores) decreased significantly to the normal range. CONCLUSIONS: These preliminary findings are discussed in terms of the possible role of postsurgical changes in seizure control, behavior, antiepileptic drugs, cognition, and prefrontal function.

Formal thought disorder and psychopathology in pediatric primary generalized and complex partial epilepsy.

OBJECTIVE: To examine whether formal thought disorder and psychopathology occurred in children with complex partial seizures (CPS) rather than children with primary generalized epilepsy with absences (PGE) or nonepileptic children. METHOD: Formal thought disorder was coded in 30 children with CPS, 24 children with PGE, and 61 nonepileptic children, and structured interview-based psychiatric diagnoses were obtained for the epileptic subjects. RESULTS: The CPS subjects had significantly more illogical thinking than the PGE and nonepileptic children. The severity of their illogical thinking was related to global cognitive dysfunction and a schizophrenia-like psychosis. Age of onset and seizure control, however, were significantly associated with the severity of illogical thinking in the PGE group. One or more psychiatric diagnoses were found in 63% of the CPS and 54% of the PGE patients, particularly if they had global cognitive deficits. CONCLUSION: Illogical thinking, associated with cognitive dysfunction or schizophrenia-like symptoms, might be a feature of pediatric CPS. Psychopathology might be related to global cognitive dysfunction in pediatric CPS and PGE.

Measures of psychopathology in children with complex partial seizures and primary generalized epilepsy with absence.

OBJECTIVE: This investigation examined psychopathology in 48 children with complex partial seizures (CPS), 39 children with primary generalized epilepsy with absence (PGE), and 59 nonepileptic children, aged 5 to 16 years, by comparing the Child Behavior Checklist (CBCL) and the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). METHOD: The CBCL was completed by parents and the K-SADS was administered to both parent and child. RESULTS: The CBCL identified psychopathology in 26% and the K-SADS in 51% of the CPS and PGE patients (kappa = 0.32). The CPS and PGE groups had significantly higher mean CBCL scores, as well as higher rates of psychiatric diagnoses and symptoms of psychopathology, compared with the nonepileptic group. However, the CPS and PGE groups did not differ in these measures. Within each patient group, Full Scale IQ, but not seizure control, was associated with these measures of psychopathology. CONCLUSION: These findings suggest that the K-SADS identifies more children with psychopathology than the CBCL in children with CPS and PGE.

Ganaxolone for treating intractable infantile spasms: a multicenter, open-label, add-on trial.

This is a multicenter, open-label, add-on trial, investigating the safety and efficacy of ganaxolone (GNX) in a population of children with refractory infantile spasms, or with continuing seizures after a prior history of infantile spasms. A total of 20 children aged 7 months to 7 years were enrolled in this dose-escalation study, after baseline seizure frequencies were established. Concomitant antiepilepsy drugs were maintained throughout the study period. The dose of GNX was progressively increased to 36 mg/kg/d (or to the maximally tolerated dose) over a period of 4 weeks, then maintained for 8 weeks before tapering and discontinuation. Seizure diaries were maintained by the families, and spasm frequency was compared with the baseline period. The occurrence of adverse events was clinically monitored, and global evaluations of seizure severity and response to treatment were obtained. A total of 16 of the 20 subjects completed the study, 15 of whom had refractory infantile spasms at the time of study enrollment. Spasm frequency was reduced by at least 50% in 33% of these subjects, with an additional 33% experiencing some improvement (25-50% reduction in spasm frequency). Ganaxolone was well tolerated, and adverse events attributed to GNX were generally mild. Ganaxolone was safe and effective in treating this group of refractory infantile spasms patients in an open-label, add-on trial. Further investigation with randomized, controlled study design is warranted.

Vigabatrin.

Vigabatrin is a structural analogue of gamma amino butyric acid (GABA), which binds irreversibly to GABA-transaminase causing increased brain levels of GABA. It is an important advance in the medical management of children with epilepsy. It appears to be particularly effective in the treatment of infantile spasms, especially when caused by tuberous sclerosis. It is also effective in the treatment of partial seizures and some generalized seizures including those of the Lennox-Gastaut syndrome. However, myoclonic seizures may be made worse by vigabatrin. It is not yet approved for use in the United States but it is approved throughout most of the rest of the world including Canada and Mexico. Release in the United States is expected in the near future.

Risk factors of respiratory failure in children with Guillain-Barré syndrome.

Recently it was found that plasmapheresis and intravenous immunoglobulins are effective in treating patients with Guillain-Barré syndrome (GBS). However, these treatments are expensive and not without possible adverse effects. Because signs and symptoms predictive for respiratory failure in GBS would be helpful in targeting the treatment, risk factors for respiratory failure were evaluated in 120 children with GBS. Twenty children required assisted ventilation. None of the children without any of the following risk factors had respiratory failure. If the symptoms of GBS began within 8 days after a preceding infection, the odds ratio (OR) for respiratory failure was 4.9 [95% confidence intervals (CI): 1.3-18.5]. Cranial nerve involvement was more common in children who required assisted ventilation (15/20 versus 32/100, OR: 6.4, 95% CI: 2.1-19.1). A cerebrospinal protein level > 800 mg/L during the first week had an OR for assisted ventilation of 3.1 (95% CI of OR: 1.04-9.0). In the logistic multivariate model, all of these risk factors were associated with the need for assisted ventilation. On the basis of our findings, preventive treatment with either plasmapheresis or intravenous immunoglobulins could be directed to those children with any of the risk factors; for those patients without the risk factors, clinical monitoring would be satisfactory.

Acute necrotizing ulcerative gingivitis. A study of some of the contributing factors and their validity in an Army population.

A study of some of the possible contributing factors in ANUG were evaluated by a comparison of ANUG patients with a random patient sample. This paper supports the role of stress and smoking in the pathogenesis of ANUG.

Status epilepticus.

Status epilepticus generally is considered to be a medical emergency requiring immediate intervention to prevent permanent injury to the brain. Tonic-clonic status epilepticus is a very frightening event; the inexperienced parents invariably believe that their child is dying. Emergent management is imperative for convulsive tonic-clonic (grand mal) status epilepticus, but there are nonconvulsive types of status epilepticus in which the problem is more one of correct diagnosis than emergent management. This article reviews aspects of status epilepticus, particularly the classification and treatment of the various types of status.

Surgery for epilepsy. Special pediatric considerations.

Children with epilepsy require special consideration because the nature of their seizures is different from those in adults, the effects of intractable epilepsy may be more serious in children, and younger children may have greater potential for recovery than adults. This article reviews the unique problems and approaches to resective surgery for pediatric epilepsy.