Yu-Tze Ng

Endoscopic resection of hypothalamic hamartomas for refractory symptomatic epilepsy.

Background: Hypothalamic hamartomas (HHs), rare developmental abnormalities of the inferior hypothalamus, often cause refractory, symptomatic, mixed epilepsy, including gelastic seizures. We present 37 patients with HH who underwent transcortical transventricular endoscopic resection. Methods: Between October 2003 and April 2005, 42 consecutive patients with refractory epilepsy who underwent endoscopic resection of HH were studied prospectively. The endoscope was held by an articulated pneumatic arm and tracked with a frameless stereotactic neuronavigation system. Data collection and follow-up were performed by personal interview. Five patients were excluded. The remaining 37 patients (22 males, 15 females; median age 11.8 years; range 8 months to 55 years) had frequent and usually multiple types of seizures. Results: Postoperative MRI confirmed 100% resection of the HH from the hypothalamus in 12 patients. At last follow-up (median 21 months; range 13–28 months), 18 (48.6%) patients were seizure free. Seizures were reduced more than 90% in 26 patients (70.3%) and by 50% to 90% in 8 patients (21.6%). Overall, the mean postoperative stay was shorter in the endoscopic patients compared with our previously reported patients who underwent transcallosal resection (mean 4.1 days vs 7.7 days, respectively; p = 0.0006). The main complications were permanent short-term memory loss in 3 patients and small thalamic infarcts in 11 patients (asymptomatic in 9). Conclusions: Endoscopic resection of hypothalamic hamartoma (HH) is a safe and effective treatment for seizures. Its efficacy seems to be comparable to that of transcallosal resection of HH, but postoperative recovery time is significantly shorter.

Clobazam in the treatment of Lennox-Gastaut syndrome

Purpose:  This randomized, double‐blind, dose‐ranging study evaluated safety and efficacy of clobazam (CLB) as adjunctive therapy for drop seizures in patients with Lennox‐Gastaut syndrome (LGS).

Interobserver agreement in the interpretation of EEG patterns in critically ill adults.

Summary: The significance of rhythmic and periodic EEG patterns in critically ill patients is unclear. A universal terminology is needed to facilitate study of these patterns, and consistent observer agreement should be demonstrated in its use. The authors evaluated inter- and intraobserver agreement using the standardized terminology (Hirsch et al., J Clin Neurophysiol 2005;22:128–135) recently proposed by the American Clinical Neurophysiology Society. Trained electroencephalographers viewed a series of 10-second EEG samples from critically ill adults (phase I), a set of ≥20-minute EEGs from the same patient cohort (phase II), and then reevaluated the first sample set (phase III). The readers used the proposed terminology to “score” each EEG. For each possible term, interobserver agreement (phases I and II) and intraobserver agreement (phase III) were calculated using pairwise kappa (&kgr;) values. Moderate agreement beyond chance was seen for the presence/absence of rhythmic or periodic patterns and for localization of these patterns. Agreement for other terms was slight to fair. Inter- and intraobserver agreement were consistently lower for optional terms than mandatory terms. Even when standardized terminology is used, the description of rhythmic and periodic EEG patterns varies significantly. Further refinement of the proposed terminology is required to improve inter- and intraobserver agreement.

The Histopathology of Hypothalamic Hamartomas: Study of 57 Cases

Hypothalamic hamartomas (HHs) are rare developmental tumors that cause seizures or pituitary axis dysfunction, usually beginning in childhood. We analyzed HH tissue from 57 patients whose tumors were resected through recently developed transcallosal interforniceal and transventricular endoscopic surgical approaches. All cases were composed of abnormally distributed but cytologically normal neurons and glia, including fibrillary astrocytes and oligodendrocytes. Neuronal elements predominated in most cases, but a relative increase in astrocytic elements was seen with increasing age. All had various sized nodular foci of neurons as well as areas of diffusely distributed neurons with interspersed glial cells. Smaller neurons predominated, and most cases had only a few interspersed large ganglion cells. Immunohistochemistry demonstrated extensive production of synapse-associated proteins. Immunohistochemistry for phosphorylated and nonphosphorylated neurofilament and &agr;-internexin demonstrated staining patterns consistent with mature neurons. In contrast to cortical dysplasia, atypical large ganglion-like balloon cells were almost never seen. In summary, although their number and distribution vary, mature smaller neurons were the most prominent and most consistent histologic feature of HH. Nodules of these small neurons were a universal feature of the microarchitecture of HH lesions associated with epilepsy. Characterization of these neurons may aid in understanding the mechanism of seizure development in HH.

Efficacy of the ketogenic diet in Lennox–Gastaut syndrome: a retrospective review of one institution’s experience and summary of the literature

Aim  To determine the efficacy of the ketogenic diet for children with Lennox–Gastaut syndrome (LGS) at our institution and in the literature.

Treatment of refractory status epilepticus with hemispherectomy.

Summary:  A 7‐year‐old boy with left hemiparesis secondary to right hemispheric cortical dysplasia was admitted to the hospital with increasing numbers of seizures. Magnetic resonance imaging showed a small dysplastic right hemisphere with abnormally thickened gyri and an apparently normal left hemisphere. Previous video‐electroencephalogram (EEG) monitoring showed bilateral independent spikes and generalized slow spike‐and‐wave episodes on EEG and [18F]fluorodeoxyglucose (FDG) positron emission tomography scan demonstrated scattered areas of regional hypometabolism bilaterally; therefore hemispherectomy was not undertaken at that time. During this hospital stay, nonconvulsive status epilepticus developed and was refractory to multiple medical therapies including pentobarbital (PTB) coma. Burst‐suppression pattern during PTB coma appeared to be generalized spike and wave, but when EEG was reviewed with increased time resolution spikes suggested a right hemisphere origin. The patient underwent bilateral intracarotid amobarbital spike‐suppression test that showed only minimal suppression of epileptiform discharges with injection of the left carotid, but complete suppression of spike activity after right‐sided carotid injection. A right hemispherectomy was performed with complete cessation of status epilepticus. Postoperative EEG showed no epileptiform discharges. Patient follow‐up was limited to 12 months after surgery. The patient had regained the ability to walk unaided and was seizure free with a single antiepileptic medication. This case illustrates a potentially life‐saving procedure for refractory status epilepticus and several techniques including a spike‐suppression test to aid in prediction of cessation of seizures after hemispherectomy.

Successful Neurosurgical Treatment of Childhood Complex Partial Status Epilepticus with Focal Resection

Summary: The treatment of complex partial status epilepticus continues to be controversial, especially with regard to the intensity of the treatment. Medical therapy and drug‐induced coma are sometimes required. Rarely this may not be effective. A healthy 4‐year old girl was first seen in complex partial status epilepticus. She had a 1‐year history of cryptogenic partial‐onset seizures. Detailed magnetic resonance imaging (MRI) studies were normal. Her course was refractory to multiple medical therapies and multiple subpial transection (MST). An urgent epilepsy surgery evaluation resulted in a focal cortical resection being performed over the right mesial parietal region with resultant seizure freedom and no significant neurologic deficit 2 years later. This patient illustrates the need to consider occult focal cortical dysplasia as a cause of nonconvulsive status epilepticus (NCSE) in children, and if it is not responsive to medical management, the utility of performing an urgent epilepsy surgery evaluation.

Lacosamide in Refractory Mixed Pediatric Epilepsy: A Prospective Add-on Study

Lacosamide is a new antiepileptic drug that is currently approved by the US Food and Drug Administration (FDA) for adults 17 years or older for partial-onset seizures. The authors reviewed 21 pediatric patients (<17 years) with various seizure types who were started on oral lacosamide as part of a prospective add-on study as adjunctive therapy for refractory epilepsy. Five patients were excluded due to less than 3 months of meaningful follow-up. Maintenance dosages used ranged from 2.4 to 19.4 mg/kg/d. Eight of 16 (50%) patients had greater than 50% reduction in seizure frequency with adjunctive lacosamide therapy. Eight (50%) patients had generalized epilepsy including 4 with Lennox-Gastaut syndrome. Lacosamide was effective therapy for most seizure types but was particularly effective for partial-onset seizures. Lacosamide was effective in treating 5 of 8 (62.5%) localization-related epilepsies but only 2 of 8 (25%) generalized epilepsies, both Lennox-Gastaut syndrome patients with greater than 90% seizure reduction. None of these very refractory patients remained seizure free.

Intravenous Levetiracetam In Children With Seizures: A Prospective Safety Study

In 2006, intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy, 16 years or older. We have established the safety, tolerability, and dosage of intravenous levetiracetam in children. This prospective study included 30 children (6 months to <15 years of age). Patients were administered a single dose of intravenous levetiracetam (50 mg/kg, maximal dose 2500 mg) over 15 minutes. A blood level of levetiracetam was performed 10 minutes after the infusion. The treated children’s average age was 6.3 years (range 0.5-14.8 years). The mean levetiracetam level was 83.3 µg/mL (range 47-128 µg/mL). There were no serious adverse reactions. Minor reactions included sleepiness, fatigue, and restlessness. An apparent decrease in seizure frequency across all seizure types was noted. The dose of 50 mg/kg was well tolerated by the patients and is a safe, appropriate loading dose.

Update on the Management of Lennox-Gastaut Syndrome

Lennox-Gastaut syndrome is a severe childhood epilepsy disorder characterized by encephalopathy and multiple, often intractable, seizure types. The drop attack is the most frequently recognizable seizure type in this patient population, and is also the most dangerous physically, thus severely limiting quality of life. The diagnosis is confirmed by electroencephalography, for which the classic pattern is a slow 2.5 Hz generalized spike-and-wave. Newer pharmacologic treatments include rufinimide and clobazam. However, antiepileptic drugs are often exhausted in pursuit of seizure control requiring nonpharmacologic interventions. These include dietary therapies, vagus nerve stimulation, and epilepsy surgery, including corpus callosotomy and focal curative resection. Although large lobar resections are often required, very localized, discrete resections may be possible, as in symptomatic Lennox-Gastaut syndrome (specifically, hypothalamic hamartoma). We review the history of the disease and current management options.