Pyridoxine dependent epilepsy: Is late onset a predictor for favorable outcome?

AIM: In pyridoxine dependent epilepsy (PDE), patients usually present with neonatal seizures. A small subgroup is characterized by late-onset beyond 2 months of age. We aim to analyze the observation of relatively good cognitive outcome in this subgroup of late-onset PDE patients. METHODS: We retrospectively analyzed data from four metabolically and genetically confirmed late-onset patients with PDE due to antiquitin (ALDH7A1) deficiency. Data were analyzed regarding ALDH7A1 mutations, alpha-Aminoadipic semialdehyde (α-AASA) and pipecolic acid (PA) levels, medication during pregnancy, delivery, treatment delay, amount of seizures, pyridoxine dose, adjuvant therapy and findings on brain MRI. RESULTS: Results showed that three patients had relatively good outcome (IQ 80-97), while one patient did not undergo formal testing and was considered mildly delayed. We were unable to find a clear association between the above-mentioned variables and cognitive outcome, although a less severe genotype may be present in three patients, and maternal medication could be accountable for better outcome in two patients. INTERPRETATION: We suggest that favorable outcome in late onset PDE might be explained by a combination of factors. A yet unknown protective factor, different genetic variations, functional variation and secondarily variation in treatment regimens and absence of neonatal seizure induced brain damage.

Epileptic phenotypes, electroclinical features and clinical characteristics in 17 children with anti-NMDAR encephalitis.

BACKGROUND: Anti-N-methyl d-aspartate receptor (NMDAR) encephalitis is a rare disorder characterized by seizures, neuropsychiatric symptoms, dyskinesia and autonomic instability. OBJECTIVE: Aim of the present study was to evaluate the seizure phenotypes and electroencephalogram (EEG) features in children with anti-NMDAR encephalitis. METHODS: Seizure types, electroclinical features and clinical characteristics of 17 children with anti-NMDAR encephalitis were analysed in a retrospective case series from nine centres in Europe. RESULTS: Nearly half (8/17) of the children presented with psychiatric symptoms, whereas in 4/17 patients seizures were the first symptom and in 5/17 both symptoms occurred at the same time. During the following course seizures were reported in 16/17 children. The first EEG detected generalized slowing in 11/17 patients, focal slowing in 3/17 and normal background activity in only 3/17 children. The extreme delta brush (EDB) pattern was detected in 9/17 (53%) patients. CONCLUSION: In addition to psychiatric symptoms, children with anti-NMDAR encephalitis often show generalized slowing in EEG with or without seizures at initial presentation. EDB is present in half of all children and is potentially a helpful tool for early detection of this immune-mediated disease.

Severe bleeding complications during antiepileptic treatment with valproic acid in children.

Valproic acid (VPA) is an antiepileptic drug frequently used in children. Although VPA can cause a variety of laboratory abnormalities affecting haemostasis, controversy exists about the clinical relevance of such haematological abnormalities. We report on 4 children with severe bleeding complications while on VPA therapy; two presented with intracranial bleeding, while two suffered from severe bleeding postoperatively. Diagnostic and therapeutic measures are discussed that help to avoid severe bleeding complications in children with VPA treatment.

Neurological outcome in comatose children with bilateral loss of cortical somatosensory evoked potentials.

Bilateral loss of median nerve cortical somatosensory evoked potentials (SEP) in comatose patients is reported to be one of the most discriminating predictors of poor outcome. We reviewed 53 children with bilateral absent cortical SEP with respect to their outcome and their follow-up SEP. Brain injury was caused by global cerebral ischaemia in 18 children, severe head trauma (SHT) in 13, nervous system infections in 10, and other aetiologies in 12 children. Thirty of 53 children died within the first 4 weeks and another 8 children within 4 years after the event. Two children (both ischaemia) survived in a persistent vegetative state, 9 children (1 ischaemia, 2 SHT, 3 nervous system infections, 3 other aetiologies) survived with severe deficits and 4 children (all SHT) with mild or moderate deficits. In 30 children SEP were repeated and in 8 children (5 SHT, 2 nervous system infection, 1 other aetiology) unilateral or bilateral cortical responses reappeared. Although bilateral loss of cortical SEP predicted an unfavourable outcome in most patients, a few comatose children with SHT showed an outcome with mild or moderate neurological deficits.

Visual field constriction is not limited to children treated with vigabatrin.

Vigabatrin (GVG) is widely used in the treatment of complex partial seizures and infantile spasms. Persistent visual field constriction associated with GVG therapy in adults was reported as a rare but serious side-effect. Visual field examination in children is more difficult because of a lack of cooperation among very young or mentally handicapped patients. We performed Goldmann perimetry in 12 of 153 patients treated with GVG as mono- or as add-on therapy. The others would not cooperate, and two adolescents refused the examination. For comparison, we examined 12 age-matched patients with complex partial or generalized epilepsy who had never taken GVG. In five of 12 GVG-treated patients, and in one of the control group, we found a concentric visual field constriction. All patients were subjectively asymptomatic. The GVG-treated patients had taken the drug in combination with valproic acid (VPA) or oxcarbazepine (OCB). In four patients, GVG treatment was already stopped at the time of the ophthalmologic examination. Three patients had intracerebral lesions that could not account for the pathologic perimetric findings. The single patient from the control group with concentric visual field constriction had an absence epilepsy, treatment being performed with VPA and lamotrigine (LTG). In conclusion, GVG has a causal but not unique connection with visual field constriction in pediatric patients.

Unusual presentations of neuroborreliosis (Lyme disease) in childhood.

Two children with atypical neuroborreliosis (cranial polyneuritis and acute transverse myelitis) are presented. The diagnosis was confirmed by the determination of specific antibodies against Borrelia burgdorferi in both serum and CSF. Neuroimaging findings were nonspecific, indicating, however, that neuroborreliosis should be included in the differential diagnosis of cases with cranial polyneuritis and acute transverse myelitis in childhood.

Adverse effects of vigabatrin in Angelman syndrome.

New antiepileptic drugs designed for enhancing GABAergic inhibition, such as vigabatrin (VGB) may be effective in Angelman syndrome (AS), because associated convulsions could be related to a reduced GABA-receptor density or receptor abnormality. From our preliminary experiences in four children with AS treated with VGB, we conclude that it may induce and increase seizures in patients with AS.

Electroencephalogram changes during inhalation with nitric oxide in the pediatric intensive care patient--a preliminary report.

OBJECTIVES: Although endogenous nitric oxide (NO) is an excitatory mediator in the central nervous system, inhaled NO is not considered to cause neurologic side effects because of its short half-life. This study was motivated by a recent case report about neurologic symptoms and our own observation of severe electroencephalogram (EEG) abnormalities during NO inhalation. DESIGN: Blind, retrospective analyses of EEGs which were registered before, during, and after NO inhalation. EEG was classified in a 5-point rating system by an independent electroencephalographer who was blinded to the patients' clinical histories. Comparisons were made with the previous evaluation documented at recording. Other EEG-influencing parameters such as oxygen saturation, hemodynamics, electrolytes, and pH were evaluated. SETTING: Pediatric intensive care unit of a tertiary care university children's hospital. PATIENTS: Eleven ventilated, long-term paralyzed, sedated children (1 mo to 14 yrs) who had EEG or clinical assessment before NO treatment and EEG during NO inhalation. They were divided into two groups according to the NO-indication (e.g., congenital heart defect, acute respiratory distress syndrome). MEASUREMENTS AND MAIN RESULTS: All 11 patients had an abnormal EEG during NO inhalation. EEG-controls without NO showed remarkable improvement. EEG abnormalities were background slowing, low voltage, suppression burst (n = 2), and sharp waves (n = 2) independent of patients' age, NO-indication, and other EEG-influencing parameters. CONCLUSIONS: These preliminary data suggest the occurrence of EEG-abnormalities after application of inhaled NO in critically ill children. We found no correlation with other potential EEG-influencing parameters, although clinical state, medication, or hypoxemia might contribute. Comprehensive, prospective, clinical assessment regarding a causal relationship between NO-inhalation and EEG-abnormalities and their clinical importance is needed.

Vigabatrin as a first-line drug in West syndrome: clinical and electroencephalographic outcome.

The cessation of infantile spasms and the disappearance of hypsarrhythmia in sleep EEG are the criteria for successful treatment in West syndrome. In a prospective study at the Children's University Hospital, 28 children with West syndrome (17 symptomatic, 7 cryptogenic, 4 idiopathic) were treated with vigabatrin monotherapy for at least 2 weeks. Seven children received vigabatrin 150 mg/kg/day, and 21 children received 65-75 mg/kg/day. Patients were classified as responders, when infantile spasms and hypsarrhythmia in sleep EEG disappeared within 2 weeks. After 2 weeks, 18 patients were seizure-free, 14 without hypsarrhythmia. Fourteen children were responders (8 symptomatic, 3 cryptogenic, 3 idiopathic), and 14 non-responders. The follow-up encompassed 6 months to 5.3 years (mean 20.3 months). In the responder group, 12/14 patients (6 symptomatic, 3 cryptogenic and 3 idopathic) remained seizure-free, no relapse of West syndrome occurred. In the non-responder group, ACTH was efficient in 11, valproic acid in 2 children and clonazepam in 1 child. Relapse occurred in 4 children after discontinuation of ACTH. At last visit EEG was normal in 8/14 responders and 1/14 non-responders. The efficacy of vigabatrin monotherapy was comparable to ACTH and occurred within 2 weeks.

The effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan on perioperative brain injury in children undergoing cardiac surgery with cardiopulmonary bypass: results of a pilot study.

Experimental evidence indicates a role of the N-methyl-D-aspartate receptor in the pathogenesis of brain injury occurring during cardiac surgery with cardiopulmonary bypass (CPB). Dextromethorphan is a noncompetitive antagonist of this receptor with a favorable safety profile. Thirteen children age 3-36 months undergoing cardiac surgery with expected CPB of 60 minutes or more were randomly assigned to treatment with dextromethorphan (36-38 mg/kg/day) or placebo administered by naso-gastric tube. Dextromethorphan was absorbed well and reached putative therapeutic levels in blood and cerebrospinal fluid. Adverse effects were not observed. Mild hemiparesis developed after operation in one child of each group, and severe encephalopathy in one of the placebo group. Sharp waves were recorded in postoperative continuous electroencephalography in all placebo (n = 7) but only in 2/6 dextromethorphan treated children (p = 0.02). Pre- and postoperative cranial magnetic resonance imaging (MRI) revealed less pronounced ventricular enlargement in the dextromethorphan group (not significant). An increase of periventricular white matter lesions was visible in two placebo-treated children only. No elevations of cerebrospinal fluid enzymes were observed in either group. Although children with dextromethorphan showed less abnormalities in electroencephalography and MRI, dissimilarities of the treatment groups by chance diminished conclusions to possible protective effects of dextromethorphan at this time.

Benign focal epileptiform discharges in children after severe head trauma: prognostic value and clinical course.

PURPOSE: To assess the occurrence and prognosis of benign focal epileptiform discharges (BFED) in EEG after severe head trauma (SHT) in children. METHODS: Between January 1987 and December 1994, 47 of 828 children with anamnestic SHT showed a single or dominant epileptic focus in EEG. Spike wave localization and morphology were either suggestive for BFED (group I, 21 children) or were suspected to be symptomatic (group II, 26 children). We analyzed the course of epilepsy and epileptic discharges in EEG, neuroradiologic findings, neurologic outcome, and school adjustment. RESULTS: After SHT, spike waves appeared immediately (within 72 h) or delayed (maximum 7 years) and disappeared between ages 3 and 14 years in 14 children of group I and between ages 8 and 23 years in 10 of group II. Children with persistent spike waves in group I were all younger than 14 years; in group II, seven were older than 15 years. Computed tomographic (CT) lesions, ipsilateral to the epileptic focus, were seen in 10 children of group I and 15 of group II. Early seizures occurred in nine children of group I and eight of group II and late-onset seizures in one of group I and nine of group II (p = 0.028). Epilepsy developed in three children of group I and 12 of group II and was drug refractory in six children of group II, all with persistent epileptic foci. Regular schools were attended by 14 (67%) children in group I and 12 (48%) of group II. CONCLUSIONS: Benign focal epileptiform discharges in posttraumatic EEGs have the same favorable prognosis as in benign focal epilepsy and should be handled as recommended for classic benign focal epilepsy.

Psychiatric, neuropediatric, and neuropsychological symptoms in a case of hypomelanosis of Ito.

This case report presents a thirteen year-old boy who was diagnosed as having Hypomelanosis of Ito. The developmental history includes severe failure to thrive, and moderate atypical autism as well as diverse clinical and neuropsychological symptoms are present. The pattern of neuropsychological functioning, which can be partially related to the neurophysiological findings, is discussed within the context of existing neuropsychological theories about autistic disorders.