Sanjeev V. Kothare

Intravenous Levetiracetam in Children With Epilepsy

Intravenous levetiracetam recently became available for use in patients aged >16 years. There are few data about its safety and efficacy in children. We retrospectively analyzed data from children treated with intravenous levetiracetam. Ten patients (6 female, 4 male), aged 3 weeks to 19 years, were treated with intravenous levetiracetam at a mean dose of 50.5 mg/kg/day for a mean duration of 4.9 days. Four patients received intravenous levetiracetam for acute repetitive seizures/status epilepticus, and three as replacement for oral levetiracetam because administration of oral levetiracetam was temporarily infeasible. One patient each received intravenous levetiracetam for seizure prophylaxis during brain biopsy, as maintenance treatment after acute seizures, and as substitute for sodium valproate. Three of four patients with acute repetitive seizures/status epilepticus became seizure-free; the fourth patient had a partial reduction in seizure frequency. All three patients who received intravenous levetiracetam as substitute for oral levetiracetam tolerated the switch well. The other three patients were seizure-free on intravenous levetiracetam. No serious adverse effects were observed, and all patients completed treatment with intravenous levetiracetam for the intended period. Intravenous levetiracetam may be effective in various clinical situations requiring intravenous administration of an antiepileptic drug.

Spectrum of Polysomnographic Abnormalities in Children With Epilepsy

This study sought to evaluate polysomnographic abnormalities in a cohort of 40 children with epilepsy who underwent a sleep study because of various sleep complaints. Retrospective analyses included polysomnographic variables, antiepileptic drugs, type of epilepsy, and seizure control. The subgroup with epilepsy and obstructive sleep apnea syndrome was compared with 11 children who manifested uncomplicated obstructive sleep apnea syndrome. Thirty-three patients (83%) exhibited snoring (42.5%), sleep-disordered breathing (obstructive hypoventilation, 12.5%; obstructive sleep apnea, 20%; and upper-airway resistance syndrome, 7.5%), or periodic limb movements of sleep (10%). Children with poor seizure control demonstrated significantly lower sleep efficiency, a higher arousal index, and a higher percentage of rapid-eye-movement sleep compared with children who were seizure-free or exhibited good seizure control. Patients with epilepsy and obstructive sleep apnea had significantly a higher body mass index, longer sleep latency, a higher arousal index, and a lower apnea-hypopnea index, but significantly more severe desaturation compared with patients with uncomplicated obstructive sleep apnea. A significant proportion of children with epilepsy referred for polysomnography with diverse sleep problems manifest sleep-disordered breathing, including obstructive sleep apnea syndrome.

Polysomnographic findings in children with headaches.

Although previous studies suggested a relationship between headache and sleep disturbances, polysomnographic findings in children with headache are rarely described. We investigated polysomnographic findings in children with headaches, and correlated them with headache type and severity, body mass index, and medical treatment. Analysis of polysomnographic findings of 90 children with migraine (60), chronic migraine (11), tension headache (6), and nonspecific headache (13) indicated that sleep-disordered breathing was more frequent among children with migraine (56.6%) and nonspecific headache (54%) vs chronic migraine (27%). Tension headache was not associated with sleep-disordered breathing. In the nonspecific headache group, children with sleep-disordered breathing had higher body mass indexes (P = 0.008). Severe migraine and chronic migraine were associated with shorter sleep time, longer sleep latency, and shorter rapid eye movement and slow-wave sleep. Fifty percent of children with tension headache manifested bruxism vs 2.4% of children with nontension headache (odds ratio, 1.95; 95% confidence interval, 1.2-4.34). Our results support an association between migraine and sleep-disordered breathing, and between tension headache and bruxism, in children. Moreover, disrupted sleep architecture with reduced rapid eye movement and slow-wave sleep in severe and chronic migraine headaches may support an intrinsic relationship between sleep and headache disorders.

Vagus nerve stimulation in children with refractory epilepsy: unusual complications and relationship to sleep-disordered breathing

BackgroundVagus nerve stimulation (VNS) is approved for use in patients with refractory epilepsy over the age of 12xa0years. While this procedure is widely used, there is little data on adverse events in young children.Materials and methodsA retrospective chart review was conducted on 26 children who had VNS implantation for refractory epilepsy from 1998 to 2004.ResultsAges ranged from 3 to 17xa0years (16 boys and 10 girls). Seventy-seven percent had moderate to severe mental retardation. Sixty-five percent had more than 30 seizures per month. Symptomatic-generalized epilepsy was the predominant epilepsy syndrome seen in 77% of children. The duration of VNS treatment ranged from 1xa0month to 8xa0years (meanu2009=u20093.5xa0years). Twenty of 26 patients (77%) were on rapid-cycling mode. More than 50% reduction in seizure frequency was noted in 54% with two patients achieving seizure freedom. Twenty-three percent had less than 50% seizure reduction. Four patients were able to terminate seizures with use of the magnet. VNS was removed from one patient because of intractable cough persisting in spite of stimulation being turned off for 1xa0month. Another patient had it removed twice for infection. Obstructive sleep apnea (OSA) was observed in four patients (15%) after placement of VNS.ConclusionVNS appears to be an effective treatment for children with refractory epilepsy. Development of intractable cough in one patient in spite of device being turned off and recurrent infection-related removal in another are unusual complications. Polysomnography before implantation of VNS should be considered to identify patients with pre-existing OSA.

Intrathecal baclofen overdose and withdrawal

Abstract: Intrathecal baclofen (ITB) therapy is being used increasingly to treat medically intractable spasticity in children with cerebral palsy and spinal cord injuries. Baclofen overdose and withdrawal are potentially life-threatening complications of pump and spinal catheter system malfunction. We report a case of a 12-year-old boy, on long-term ITB therapy, who presents to our emergency department with an overdose of ITB, which is followed by withdrawal symptoms. The patient initially presented obtunded and in respiratory arrest. His symptoms of respiratory arrest, obtundation, fixed pupils, and hypotension mimicked other diagnoses, such as head trauma. The history obtained from the family about the pump reservoir being refilled just before the onset of symptoms led to the diagnosis. During hospitalization, as the patient recovered from the overdose, he began to experience symptoms of baclofen withdrawal, including hypertension, hyperthermia, and hallucinations. The pump was found to be disconnected and was revised. The patient was discharged home without permanent sequelae. With increased use of ITB, emergency medicine physicians must be aware of the mechanics of these pumps and the management of baclofen toxicity and withdrawal.

Narcolepsy in Children: A Single-Center Clinical Experience

Although the initial manifestations of narcolepsy in children may differ from those with adult onset, hypersomnia remains the most common presenting sign. This study aimed to (1) describe the clinical and polysomnographic features, and treatment outcomes, of a group of children with narcolepsy, and (2) describe other sleep disorders to be considered in the differential diagnosis of hypersomnia and which may coexist with narcolepsy. A retrospective review of 125 children referred in 1 year for hypersomnia revealed 20 patients (16%) with narcolepsy. Of these, only 15% exhibited cataplexy, 10% experienced hallucinations, and none manifested sleep paralysis. Eighty-five percent of children with narcolepsy had sleep-disordered breathing on polysomnography. Body mass indices of these children were higher than for healthy, age-matched controls subjects. Other polysomnography findings included periodic limb movements of sleep (25%) and parasomnias (5%). The multiple sleep latency test revealed a mean sleep latency of 6.14 minutes, with sleep-onset rapid eye movement periods (median, 2/5 naps). Treatment with modafinil and sodium oxybate provided optimal control of daytime sleepiness. Physicians should routinely screen for hypersomnia in children by obtaining a detailed history and, in appropriate situations, ordering polysomnographic testing to rule out narcolepsy and other causes of hypersomnia.

Sleep Study Abnormalities in Children With Attention Deficit Hyperactivity Disorder

The study objective was to describe polysomnographic findings in children with attention deficit hyperactivity disorder (ADHD) with diverse sleep problems. Polysomnographic data were retrospectively analyzed for 33 children (age 3-16 years) with ADHD who had sleep studies performed for diverse sleep complaints. Eight patients (24%) had obstructive sleep apnea, 10 (30%) had periodic limb movements of sleep, 8 (24%) had upper airway resistance syndrome, and 5 (15%) had obstructive hypoventilation. The ADHD group showed decreased sleep efficiency, increased arousal index, increased wake after sleep onset, decreased oxygen saturation nadir, and increased snoring, compared with control subjects. Compared with ADHD children without sleep disordered breathing, those who had sleep disordered breathing were significantly more obese and had more sleep architectural abnormalities (including increased sleep latency, increased rapid eye movement latency, increased wake after sleep onset, and increased arousal index with more oxygen desaturations), although total sleep time and sleep efficiency were not significantly different. Sleep disordered breathing and periodic limb movements of sleep appear to be common among children with ADHD who have symptoms of disturbed sleep.

Aggravation of Seizures and/or EEG Features in Children Treated with Oxcarbazepine Monotherapy

Purpose: Exacerbation of epilepsy may occur following initiation of therapy with antiepileptic drugs (AEDs). The aim of this study is to analyze the clinical and EEG characteristics of a group of pediatric patients with worsening of seizures and/or EEG deterioration while on oxcarbazepine (OXC).

Efficacy and safety of lamotrigine monotherapy in children and adolescents with epilepsy.

Lamotrigine (LTG) has shown to confer broad-spectrum, well-tolerated control of epilepsy. Monotherapy is preferable over polytherapy because of better compliance, fewer adverse events, less interactions, lower teratogenicity and lower cost. The aim of this study is to evaluate the efficacy and safety of LTG monotherapy on seizure control in a cohort of children and adolescents with epilepsy. We retrospectively reviewed the records of children and adolescents treated with LTG monotherapy at our institution between 2001 and 2006. Data collected included demographics, seizure type, etiology of seizures, age at onset of seizures and at initiation of LTG treatment, number of antiepileptic drugs (AEDs) prior to LTG, dose of LTG, length of follow-up, treatment response, and adverse events. Seventy-two children and adolescents were identified (mean age 12.1 years); 37.5% had mental retardation. Age at onset of epilepsy was 5.7 years (0-16). Twenty three percent had symptomatic focal epilepsy, 15.5% idiopathic focal epilepsy, 19.4% symptomatic generalized epilepsy and 41.6% idiopathic generalized epilepsy. LTG was used as first-line monotherapy in 26.4% of patients and as a second-line monotherapy in 73.6%. Age at initiation of LTG therapy was 10 years (2.8-19). Mean number of AEDs tried prior to LTG was 1.3 (0-6). Mean dose of LTG was 5.5mg/kg/day (1.1-13.7). Mean follow-up period was 33 months (3 weeks to 11.5 years). The degree of seizure reduction was as follows: seizure free in 42%, 75-90% reduction in 17.4%, 50-74% in 11.6%, 25-49% in 10%. Sixteen percent had no change in seizure control and 3% became worse. The most common adverse event was rash (6.9%). Six (8.3%) patients discontinued LTG because of the adverse events. No patient had Stevens-Johnson syndrome. In conclusion, LTG was effective and well-tolerated as monotherapy in children and adolescents for both focal and generalized epilepsies.

Anomalous inhibitory circuits in cortical tubers of human tuberous sclerosis complex associated with refractory epilepsy: aberrant expression of parvalbumin and calbindin-D28k in dysplastic cortex.

Damage or loss of inhibitory cortical γ-aminobutyric acid (GABA)ergic interneurons is associated with impaired inhibitory control of neocortical pyramidal cells, leading to hyperexcitability and epileptogenesis. The calcium binding proteins parvalbumin and calbindin-D28k are expressed in subpopulations of GABAergic local circuit neurons in the neocortex and can serve as neuronotypic markers. Parvalbumin and calbindin-D28k facilitate the neurons ability to sustain firing and provide neuroprotection. The goal of this study was to assess the hitherto unknown status of inhibitory interneurons in cortical tubers of human tuberous sclerosis complex. Surgically excised cortical tubers from three patients with tuberous sclerosis complex were evaluated immunohistochemically with antibodies to parvalbumin and calbindin-D28k. Cortical specimens from young patients with intractable seizures, including microdysgenesis (n = 3), postischemic cortical scarring (n = 1), porencephaly (n = 1), postictal gliosis (n = 3), and low-grade neuronal or glial tumors (n = 5), were also examined for comparison. In cortical tubers, calcium binding protein immunoreactivities (calbindin-D28k > parvalbumin) were present in medium or large-size dysplastic neurons, whereas giant or ballooned cells were parvalbumin or calbindin-D28k negative. In microdysgenesis, a nearly normal number of parvalbumin-positive neurons and a decreased number of calbindin-D28k-positive neurons were present. In peritumoral but more so in gliotic cortex, a coordinate decrease of parvalbumin and calbindin-D28k immunoreactivities was present. Our findings indicate that the expression of parvalbumin or calbindin-D28k by subpopulations of dysplastic neurons in cortical tubers is aberrant and denotes dysfunctional inhibitory circuits inept for excitoprotection.