Patterns of memory performance in children with controlled epilepsy on the CVLT-C.

Decreased memory skills have been reported in children with epilepsy. However, standardized instruments to evaluate learning and memory in children have been unavailable until recently. The present study was designed to assess memory patterns in children with epilepsy based on the California Verbal Learning Test-Children's Version (CVLT-C). The test was administered to 44 children with complex partial seizures and 21 children with generalized seizures between 8 and 13 years of age. Children in the study had been treated for epilepsy for at least 6 months, had well-controlled seizures on monotherapy, and had no evidence of anticonvulsant toxicity. Children with head injuries, learning disabilities, or hyperactivity were excluded. Test results did not reflect differences in memory performance based on seizure type. Scores for the entire sample indicated intact new learning, decreased intrusions and perseverative responses, and better short-term than long-term delayed recall. Recognition skills were stronger than long-term delayed recall skills and suggested that memory performance may be improved for these children when a multiple-choice format is available in academic settings.

Acute mental status changes and hyperchloremic metabolic acidosis with long-term topiramate therapy.

Mental status changes and metabolic acidosis may occur with topiramate therapy. These adverse events were reported during dosage titration and with high dosages of the drug. A 20-year-old man receiving topiramate, valproic acid, and phenytoin experienced acute-onset mental status changes with hyperchloremic metabolic acidosis. He had been receiving a modest dose of topiramate for 9 months. He was weaned off topiramate over 5 days, and his mental status returned to baseline within 48 hours of discontinuing the agent. This case illustrates the need for close evaluation of patients who experience acute-onset mental status changes during topiramate therapy.

Acute management of hypersensitivity reactions and seizures.

The most crucial step in the management of an antiepileptic drug (AED) hypersensitivity reaction is the recognition of the clinical syndrome and cessation of the presumed offending agent. The severity of the developing reaction will shape the course of treatment because multiple organ systems may become affected. Management of conjunctival involvement and treatment of skin lesions dominate care, with patients whose skin lesions are extensive benefitting from treatment in a structured burn unit. Neutropenia and sepsis are common and potentially fatal complicating factors. The use of steroids remains controversial, as is the utility of immune modulation with other agents such as cyclophosphamide and i.v. immunoglobulin. Acute treatment of seizures should be addressed with i.v. benzodiazepines, given either intermittently or by continuous infusion. Choice of long-term maintenance AEDs should take into consideration the crossreactivity among AEDs that share an arene oxide metabolite.

Cognition and behavior after temporal lobectomy in pediatric patients with intractable epilepsy.

The increased use of surgical intervention for intractable epilepsy during childhood has resulted in a critical need for information concerning possible cognitive and behavioral changes in pediatric patients after surgery. In this pilot study, comprehensive neuropsychologic evaluations were completed on nine children who had a temporal lobectomy for intractable epilepsy before 16 years of age. Performances before and after surgery were compared using cognitive and behavioral measures. Repeated measures analysis of variance did not indicate differences in performance on the basis of laterality of surgery, although the number of left (n = 5) vs right (n = 4) temporal resections was small. Paired comparison t tests, which included all patients, did not suggest marked changes in cognitive functioning after surgery, although decreases in delayed verbal memory were evident. Positive effects on quality of life during the first year after surgical intervention were suggested by reduced internalizing symptoms and increased social interaction. Replication of this study is recommended with a larger number of patients and multicenter collaboration.

Does short-term antiepileptic drug treatment in children result in cognitive or behavioral changes?

PURPOSE: To determine possible cognitive and behavioral effects of antiepileptic drug (AED) therapy by assessing children with newly diagnosed epilepsy before and after initiation of treatment. A comparison group of children with diabetes mellitus (DM) was included to control for the effects of practice, maturation, and chronic illness. METHODS: Baseline neuropsychological assessments were completed for children with epilepsy (n = 37) and children with DM (n = 26) recruited through outpatient clinics at a regional children's hospital. Children were reevaluated 6 months from baseline testing. At follow-up, children with epilepsy had therapeutic AED levels and controlled seizures. Statistical analysis included a between-group repeated measures ANCOVA with pretest scores serving as the covariate. RESULTS: Significant differences between groups were not found for any cognitive or behavioral factors, including attention (p < 0.24), immediate memory (p < 0.24), delayed memory (p < 0.10), complex motor speed (p < 0.19), or behavior problems (p < 0.89). CONCLUSIONS: Changes in performance on cognitive and behavioral measures were not different for children treated with AEDs and controls. Although adverse effects may be associated with prolonged treatment, results would not suggest adverse effects from AED monotherapy during the first 6 months of therapy.

Neuropsychological patterns in pediatric epilepsy.

Results from comprehensive neuropsychological assessments of children diagnosed with epilepsy have rarely been reported. Previous research has generally focused on the measurement of overall intellectual ability and achievement skills. In the present study, neuropsychological evaluations including memory, attention, language, achievement, fine motor, executive function, visual motor integration, and behavior were completed on children (n = 79) diagnosed with epilepsy. Neurocognitive skills were within expectations for measured intelligence with the exception of verbal and visual attention skills, which were significantly below expectations based on measured ability. Behaviorally, children were rated by their parents as demonstrating clinically elevated attentional problems. Differences in cognitive and behavioral function were not found according to seizure type. Findings suggested a more diffuse effect of childhood epilepsy reflected in a pattern of decreased attention skills.

Surgical outcome in patients with epilepsy with occult vascular malformations treated with lesionectomy.

PURPOSE: This retrospective study reports the long-term surgical outcome of patients with medically refractory epilepsy and vascular malformations who were treated with lesionectomy. A detailed analysis of surgical failures had been performed in an attempt to define predictors of surgical success and failure. METHODS: Fifteen patients with medically intractable epilepsy and angiographically occult vascular malformations (AOVMs) were treated surgically with lesionectomy at Duke University Medical Center. Lesionectomy consisted of removal of the AOVM and surrounding hemosiderin-stained brain only, without the use of electrocorticography (ECoG) to guide resection. RESULTS: Eleven (73%) patients are seizure free after lesionectomy. Three showed no significant improvement, and one patient died, presumably after a seizure. Age of onset, duration of seizures, age at resection, and gender did not affect outcome. All patients with neocortical AOVMs in whom EEG findings correlated with the site of the lesion were seizure free after lesional resection. Treatment failures were associated with the presence of multiple intracranial lesions, poorly localized or diffuse EEG findings, discordant positron emission tomography (PET) imaging, or with a lesion in close proximity to the limbic system. CONCLUSIONS: Lesionectomy, with removal of surrounding hemosiderin-stained brain, can be considered the procedure of choice in carefully selected patients with epilepsy with occult vascular malformations.

Bromism: intoxication from a rare anticonvulsant therapy.

Bromide, the first effective therapy for epilepsy, is not commonly prescribed today but has been advocated by some pediatric neurologists for the treatment of intractable seizures in children. We report a 17-year-old female patient with intractable epilepsy who insidiously developed bromism while on treatment with triple bromide elixir. We review the clinical presentation, diagnosis, pathophysiology, and management of bromism.

Dextromethorphan in nonketotic hyperglycinaemia: metabolic variation confounds the dose-response relationship.

Nonketotic hyperglycinaemia (NKH) is an inborn error of the glycine cleavage system resulting in seizures and mental retardation. Two prior reports noted an anticonvulsant effect from high-dose dextromethorphan (DM) in this disorder, although the two reported patients demonstrated widely disparate DM requirements and drug levels. We report two children with NKH who also demonstrated disparate and variable DM metabolism which markedly influenced the dose-concentration-response relationship. Levels of DM and its primary metabolite dextrorphan (DX) were utilized to guide DM therapy and exhibited patterns reflective of the extensive and poor metabolizer phenotypes for CYP2D6, the cytochrome P450 isoform responsible for DM metabolism. In the patient who appeared to represent the extensive metabolizer (EM) phenotype, treatment with the non-specific cytochrome P450 inhibitor cimetidine was required to reduce biotransformation of DM to DX and, thus, to increase DM plasma concentrations. In the patient with the apparent poor metabolizer (PM) phenotype, a change in the DM preparation to a sustained-release form and increase in the dosing interval was required to lower DM plasma concentrations. These cases demonstrate the importance of CYP2D6 phenotype in providing safe and effective DM therapy to patients with NKH.

Mitochondrial encephalomyopathies presenting with features of autonomic and visceral dysfunction.

Three children are reported with mitochondrial encephalomyopathy who presented with autonomic dysfunction. Autonomic dysfunction included gastrointestinal dysmotility, apnea, cardiac arrhythmias, decreased lacrimation, supersensitivity to metacholine, altered sweating, and postural hypotension. These patients illustrate that in some mitochondrial encephalomyopathies autonomic features may be prominent and can mimic the clinical features associated with hereditary sensory and autonomic neuropathies.

Clinical and developmental findings in children with giant interhemispheric cysts and dysgenesis of the corpus callosum.

Giant interhemispheric cysts in association with dysgenesis of the corpus callosum are rare. Clinical and developmental data concerning affected patients are limited, the pathologic basis for these cysts has not been established, and prognosis is uncertain. The purpose of our study was to describe the clinical and developmental findings for 11 children with giant interhemispheric cysts, dysgenesis of the corpus callosum, and ventricular dilatation. Eight of the children required ventriculoperitoneal shunting, eight had normal neurologic examinations, and seven had experienced seizures. Seizure control appeared to correlate with neurodevelopmental function. Cognitively, children ranged from the average to mildly/moderately retarded level. Language delays were frequent, particularly in children with predominantly left hemispheric cysts. Adaptive behavior was mildly delayed with weakness observed in motor skills. Despite the striking neuroimaging abnormalities, our findings suggest the possibility of only mildly delayed neurodevelopmental outcome is good for children with this constellation of neurologic anomalies.

Outcome findings from a multidisciplinary clinic for children with epilepsy.

Children with chronic or intractable epilepsy are at higher risk for medical and social difficulties. A multidisciplinary clinic was established to improve medical management and address psychosocial issues. The purposes of the present study were to describe the multidisciplinary clinic, retrospectively examine the referral patterns for children served by the clinic, and analyze factors significantly predictive of parental satisfaction with the multidisciplinary approach. The Epilepsy Clinic Satisfaction Questionnaire was sent to all patients seen in the clinic over a 2-year period. Outcome findings were based on 136 respondents. A stepwise regression analysis indicated that the best predictor of parental rating of clinic quality was the amount of information given concerning the diagnosis and treatment of epilepsy. Staff attitude was also significantly related to parental satisfaction.

Results of temporal lobectomy for the treatment of partial complex epilepsy.

Epilepsy is the third most common cause of neurologic disability. The disease carries a 15 prevalence and a 3.5% lifetime risk. Seventy percent of patients can achieve good seizure control with medication. The remaining 30%, some 360,000 people across the United States, have intractable epilepsy and would benefit from evaluation at an epilepsy specialty center where surgical intervention is an option. The following report reviews a series of 50 patients referred to the Arkansas Comprehensive Epilepsy Program for treatment of intractable complex partial epilepsy. In this series, we evaluate results of temporal lobectomy, commenting upon factors in the patients' histories which may influence their outcomes.

BAEPs in infants with myelomeningocele and later development of Chiari II malformation-related brainstem dysfunction.

Thirty-seven infants with myelomeningocele received brainstem auditory evoked potentials (BAEPs) at a median age of eight days. No infant had brainstem dysfunction at the time of testing. Median follow-up was at 30 months. Of 12 infants who subsequently developed brainstem dysfunction at a median age of three months, 11 had had abnormal neonatal BAEPs. In contrast, only 10 of 25 infants who did not develop brainstem dysfunction had abnormal BAEPs. The mean average I-V interpeak latencies was greater among those who developed symptoms than among those who did not. Neonatal BAEPs can identify a group of asymptomatic infants with myelomeningocele who need close follow-up for the subsequent development of brainstem dysfunction.

Brachial plexopathy in infants after traumatic delivery: evaluation with MR imaging.

PURPOSE: To determine the value of magnetic resonance (MR) imaging in diagnosing traumatic pseudomeningocele. MATERIAL AND METHODS: Five newborn infants with brachial plexopathy secondary to traumatic delivery underwent MR imaging of the spine and serial neurologic examinations, and the findings were compared. RESULTS: Cervical MR images showed focal collections of cerebrospinal fluid lateral to the spinal cord and extending into the neural foramina. These were believed to represent pseudomeningoceles in four infants, all of whom have persistent major neurologic deficits. The infant with normal cervical MR images has had nearly complete spontaneous recovery. CONCLUSION: Spinal MR images can show pseudomeningoceles, which have been associated with partial or complete nerve root avulsion in infants with birth-related brachial plexopathy.

Hypertrophy of clitoral hood: presenting sign of neurofibromatosis in female child.

Although clitoral involvement with neurofibromatosis is rare, all cases previously reported have described clitoral hypertrophy due to neurofibromas of the clitoral corpora. We report on a patient who had localized enlargement of the prepuce only, with no evidence of neurofibromatous infiltration. In all cases, diagnosis of clitoromegaly requires basic chromosomal and endocrinologic evaluation. However, recognition of its association with neurofibromatosis due to either neurofibromas of the genitalia or localized genital hypertrophy may spare the patient an unnecessary or invasive evaluation. Because of an association with urinary tract neurofibromas, the patient with genital involvement should have cystoscopy. Clitoroplasty with sparing of the neurovascular bundle and glans is the preferred method of management of the enlarged clitoris.

Phenytoin protein binding in pediatric patients with acute traumatic injury.

Phenytoin (DPH) is commonly used to treat seizures associated with acute head injury. Consequent to decreases in DPH protein binding in such patients, the DPH free fraction (DPHff) may increase and thereby produce symptoms compatible with DPH toxicity despite the presence of total serum concentrations within the usually accepted therapeutic range. We examined the effect of acute traumatic injury on DPH protein binding in 13 hospitalized pediatric patients. In addition to total and free DPH serum concentrations, biochemical variables including blood pH, total and direct bilirubin, serum urea nitrogen, creatinine, albumin, gamma glutamyltransferase (GGT), and free fatty acid concentrations were measured serially over 10 days. The DPHff was compared between selected time intervals in hospitalized patients and data obtained in a control population of 27 epileptic outpatients who were maintained on DPH. Additionally, a multiple regression model was used to examine for covariance between the DPHff and the respective biochemical variables in the hospitalized patients. In the study patients, the DPHff progressively increased, attaining a maximum value (8.5 +/- 0.7%) on the fifth hospital day which was significantly greater (6.4 +/- 0.7%, p less than .05) than that on day 1 and also in the control group (6.1 +/- 0.3%; p less than .01). Blood pH, serum albumin, free fatty acids, creatinine and bilirubin concentrations did not change, but GGT did increase significantly over the 10-day sampling period. A significant (r = .51, p less than .0001) linear relationship was found between the DPHff and the serum albumin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)