Nathan Watemberg

Oligohydrosis and hyperthermia: pilot study of a novel topiramate adverse effect.

A 6-year-old boy with partial complex seizures developed recurrent episodes of hyperthermia 2 months after topiramate was introduced into his antiepilepsy drug regimen. Further investigation revealed that the febrile episodes were related to environmental temperature and physical activity. A pilocarpine iontophoresis sweat test showed that the amount of sweat produced by the child was 5% that of age-matched controls. Topiramate discontinuation resulted in the disappearance of febrile episodes and normalization of sweat quantity in repeat sweat testing. Based on this observation and the previous data on zonisamide and isolated case reports on topiramate-related hyperthermia and the effect on sweat production, topiramate was suspected of causing oligohydrosis. A pilot study was carried out involving 13 additional children and young adults (age range 1—37 years) receiving topiramate. All patients were directly questioned regarding symptoms of decreased sweating and heat intolerance, went through a pilocarpine iontophoresis sweat test, and were compared with 14 age-matched controls who went through the sweat test for unrelated reasons. Nine of the patients were found to have reduced sweat quantity on the pilocarpine iontophoresis sweat test (including index case) (mean 0.089 g/30 minutes, SD 0.082; age-matched control: mean 0.21 g/30 minutes, SD 0.06). Eight of them were children (below 16 years). However, only three patients revealed symptoms related to heat intolerance. Topiramate is most likely responsible for decreased sweat production as detected by a pilocarpine iontophoresis sweat test. The effect seems to be more significant in children than in adults. There is a discrepancy between test results and clinical symptoms. Interestingly, oligohydrosis was found to be a relatively common side effect of zonisamide. Both zonisamide and topiramate share a carbonic anhydrase inhibitor activity. The significance of oligohydrosis in hot climates should not be underestimated. Its extent, the role of sweat test prediction, and clinical significance during topiramate treatment should be further estimated. (J Child Neurol 2003;18:254—257).

Neurologic Presentations of Mitochondrial Disorders

This article describes the neurologic presentations of children with mitochondrial disorders. The charts of 42 children with highly suspect mitochondrial disorders were reviewed. Thirty-seven children were diagnosed as having definite mitochondrial disorders based on a suggestive clinical presentation and at least one accepted criteria, while in five patients the diagnosis remained probable. All patients had nervous system involvement, but it was the presenting symptom in 28 of 42. Eighteen children had normal intelligence and 24 had mental retardation or developmental delay at the onset of their disease. Twenty-five patients had either an acute regression or a progressive encephalopathy. The most frequent neurologic manifestations were abnormal tone, seizures, extrapyramidal movements, and autonomic dysfunction. The eyes were involved in 11 children. Nerve deafness was found in seven patients. Myopathy was found in only six patients. In conclusion, a complex neurologic picture, especially with other organ involvement, warrants a full mitochondrial evaluation. (J Child Neurol 2000; 15:44-48).

Significance of microcephaly among children with developmental disabilities.

To assess the clinical impact of microcephaly among children with developmental disabilities, we reviewed the charts of 1393 consecutive patients from birth to 5 years of age referred to our child development center. Comparisons were made between normal and low IQ microcephalic patients and between children with cerebral palsy with and without small head circumference. Microcephaly was detected in 15.4% of patients. Although mental retardation was more common among microcephalic children (P < .001), almost half had normal intelligence. Prematurity (P < .001), perinatal asphyxia (P < .001), small for gestational age (P < .001), respiratory distress syndrome (P < .001), and brain hemorrhage (P < .001) were associated with microcephaly. Hypotonia (P < .001) and spasticity (P < .001) were the most common neurologic findings. Cerebral palsy (P < .001), growth retardation (P < .001), epilepsy (P < .001), and strabismus (P < .001) were the main associated diagnoses found. Mental retardation was significantly more common among microcephalic patients with cerebral palsy than among normocephalic ones (P < .0004). Microcephaly is common among children evaluated for developmental disabilities. Many of these patients have normal or borderline IQ. Of several perinatal conditions associated with later microcephaly, respiratory distress syndrome and intraventricular hemorrhage show the strongest correlation. Mental retardation is not a risk factor for other neurologic complications in microcephalic children. However, in children with cerebral palsy, microcephaly is a risk factor for mental retardation. (J Child Neurol 2002;17:117-122).

Pediatric Refractory Partial Status Epilepticus Responsive to Topiramate

Topiramate was safely administered to two young children with refractory partial status epilepticus via nasogastric tube in rapid titration up to a very high total daily dose. An excellent clinical response occurred in both cases. Reaching high daily doses of topiramate within days allowed for safe discontinuation of other antiepileptic drugs in both patients. Given the high efficacy of rapidly titrated topiramate in our patients, this medication may be useful in some cases of pediatric refractory partial status epilepticus. However, more clinical studies on this therapeutic approach are needed to establish the precise role of topiramate in status epilepticus in children.( J Child Neurol 2005;20:239—241).

Clinical Experience With Open-Label Topiramate Use in Infants Younger Than 2 Years of Age

To assess the efficacy, safety, and tolerability of topiramate in infants younger than 24 months of age, we conducted an open-label, multicenter chart review study of infants who received topiramate. Twenty-eight patients were evaluated. All had refractory epilepsy. The mean age of seizure onset was 3.8 months (range 0—10 months). Refractory infantile spasms were the most common epilepsy syndrome. Among infants without infantile spasms, complex partial seizures were the prominent seizure type in eight, followed by simple partial seizures in six. Topiramate was prescribed as add-on therapy in 25 cases and as monotherapy in 3 cases. Seven of the eight infantile spasms cases improved on topiramate therapy, attaining topiramate monotherapy in three infants. Half of the infants with other seizure types responded to topiramate. The average treatment duration among topiramate responders was 11 months. Topiramate was prescribed after a mean of 3.3 antiepilepsy drugs had been used in these infants. In no case was topiramate the first prescribed antiepilepsy drug. Adverse effects occurred only in five patients, leading to topiramate discontinuation in two patients. Topiramate was efficacious and well tolerated in infants younger than 24 months of age with refractory epilepsy. Prospective data are needed to corroborate this observation. (J Child Neurol 2003;18:258—262).

Comparison of Continuous Drip of Midazolam or Lidocaine in the Treatment of Intractable Neonatal Seizures

Seizures constitute the most common neurological symptom in the neonatal period. Treatment usually involves the administration of intravenous benzodiazepines followed by either phenobarbital or phenytoin. For nonresponsive cases, continuous intravenous drip of either midazolam or lidocaine has been suggested for seizure control. Some reports suggest that seizures themselves may have a deleterious effect on long-term neurological outcome. Therefore, there is a need to find treatment regimens with better efficacy to provide maximum seizure control. The authors compared the effectiveness of lidocaine and midazolam in the treatment of intractable seizures in newborn infants born at or after 36 weeks of gestation who suffered from hypoxic-ischemic encephalopathy and who had their cerebral activity monitored. Thirty infants were included in the study: 22 received lidocaine, and 8 received midazolam. Seventeen (77%) infants had a good or partial response to lidocaine, and 4 (50%) had a partial response to midazolam. Of 20 infants diagnosed with hypoxic-ischemic encephalopathy grade 2, 18 (90%) responded to second-line treatment (14 [93%] of 15 to lidocaine and 4 [80%] of 5 to midazolam). Among 10 infants with hypoxic-ischemic encephalopathy grade 3, only 3 (30%) responded to second-line treatment (all 3 to lidocaine, none to midazolam). The findings suggest that lidocaine may be more effective than midazolam in reducing or controlling refractory neonatal seizures. The lower response rate to midazolam was more evident in infants with severe hypoxic-ischemic encephalopathy (grade 3).

Acute steroid responsive small-fiber sensory neuropathy: a new entity?

Abstractu2003 Small‐fiber neuropathy is often idiopathic and commonly follows a chronic course. Treatment is often effective in treating the core symptom of pain, but it has no effect on the pathologic process. We describe four patients with acute small‐fiber neuropathy who responded dramatically to steroid therapy. All patients had acute onset neuropathic pain, normal nerve conduction studies, and evidence of small‐fiber dysfunction in quantitative sensory testing and skin biopsy. Symptoms were distal and symmetrical in three patients and generalized in one patient. In two cases, the neuropathy presented as an erythromelalgia‐like syndrome. Marked clinical improvement occurred 1–2 weeks after oral prednisone therapy was initiated. Three patients remained symptom free, and one patient experienced recurrence of neuropathy after prednisone was tapered.

Absence Seizures Aggravated by Valproic Acid

Summary: u2002Purpose: To report on pediatric patients with absence epilepsy who experienced absence seizure aggravation while receiving valproic acid (VPA).

Should Autistic Children Be Evaluated for Mitochondrial Disorders

Autism is etiologically heterogeneous; medical conditions are implicated in only a minority of cases, whereas metabolic disorders are even less common. Recently, there have been articles describing the association of autism with mitochondrial abnormalities. We critically review the current literature and conclude that mitochondrial disorders are probably a rare and insignificant cause of pure autism; however, evidence is accumulating that both autosomal recessive and maternally inherited mitochondrial disorders can present with autistic features. Most patients will present with multisystem abnormalities associated with autistic behavior. Finding biochemical or structural mitochondrial abnormalities in an autistic child does not necessarily imply a primary mitochondrial disorder but can also be secondary to technical inaccuracies or another genetic disorder. Clinicians should be careful in diagnosing a mitochondrial disorder in an autistic child because it has important implications for accurate genetic counseling, prognosis, and therapy. (J Child Neurol 2004;19:379-381).

Benign intracranial hypertension associated with budesonide treatment in children with Crohn's disease.

Oral budesonide in adult studies is a potent corticosteroid with decreased systemic bioavailability and an improved adverse effect profile in comparison with prednisone. It has recently been introduced for the treatment of inflammatory bowel disease in Europe, Canada, and Israel. Benign intracranial hypertension has rarely been associated with corticosteroid therapy but has not been reported in association with budesonide therapy. Three adolescents with Crohns disease and poor nutritional status developed benign intracranial hypertension while receiving oral budesonide. All three patients had previously received multiple courses of prednisone during the course of their disease, without developing intracranial hypertension. Benign intracranial hypertension resolved after medication withdrawal and did not recur with subsequent use of prednisone. Evaluation for benign intracranial hypertension should be considered in patients with inflammatory bowel disease who develop headache while receiving oral budesonide. This side effect may be associated with poor nutritional status. (J Child Neurol 2001;16:458-461).