Joo Hee Seo

Efficacy and Tolerability of the Ketogenic Diet According to Lipid:Nonlipid Ratios—Comparison of 3:1 with 4:1 Diet

Summary:  Purpose: The ketogenic diet (KD) has been considered a highly potent antiepileptic treatment for intractable childhood epilepsy. In this study, we compared the antiepileptic efficacy and diet tolerability of two different diets with lipid:nonlipid ratios of 3:1 and 4:1.

A case of Ohtahara syndrome with mitochondrial respiratory chain complex I deficiency

Ohtahara syndrome (OS) is known as an intractable epileptic syndrome in neonatal and early infantile period, differentiated from early myoclonic encephalopathy (EME) in its etiology. We report a patient with OS associated with mitochondrial respiratory chain complex (MRC) I defect. With ketogenic diet and mitochondrial cocktail therapy, seizures were completely controlled and suppression-burst patterns disappeared 3 months after starting treatment. It is suggested that OS could be caused by specific metabolic disorder such as MRC defect and the intensive therapies including ketogenic diet, vitamin and coenzyme therapy and antioxidant treatment might be helpful for some patients.

Outcome of surgical treatment in non-lesional intractable childhood epilepsy.

PURPOSE The aim of this study is to investigate seizure outcomes following epilepsy surgery in non-lesional neocortical pediatric epilepsy. METHODS We performed a retrospective study on 27 patients with intractable childhood epilepsy who received epilepsy surgery between 1999 and 2006 at Sang-gye Paik Hospital and Severance Childrens Hospital. None of the patients had any detectable lesions on MRI. Surgical outcome was assessed at least 2 years postoperatively; clinical characteristics, surgical outcome, pathologic findings, types of surgery, localizing features on SPECT, FDG-PET, and long-term video-EEG were reviewed. RESULTS Eighteen patients (67%) demonstrated an Engel class I outcome postoperatively. The mean follow-up duration was 4.3 years (range, 2.2-9 years). Eighteen out of 27 cases (67%) showed focal localizing features on ictal SPECT, and 21 of 27 cases (78%) showed abnormal findings on PET. Single lobectomy was the most common procedure, and was performed in 20 patients (74%). Multilobar resection was performed in seven patients (26%). Cortical dysplasia was the most common finding during pathological examination, and was observed in 15 (56%) cases. In addition, gliosis was found in two patients (7%) and non-specific pathological findings were described in 10 patients (37%). CONCLUSIONS In children with intractable epilepsy and a MRI demonstrating no abnormal lesions, epileptic surgery should be strongly considered when cortical pathology can be identified from other studies.

Efficacy and tolerability of adjunctive therapy with zonisamide in childhood intractable epilepsy

PURPOSE This study investigated the efficacy and safety of zonisamide (ZNS) adjunctive therapy in children with intractable epilepsy to existing antiepileptic drugs (AEDs). METHODS A clinical retrospective study was performed from 2003 to 2005 at two tertiary epilepsy centers. We reviewed the data from 163 children (107 boys and 56 girls) who experienced more than four seizures per month, whose seizures were intractable to an initial 2 or more AEDs, and could be followed up for at least 6months after ZNS adjunctive therapy initiation. Efficacy was estimated by seizure reduction rate according to seizure types including infantile spasms, and adverse events were also measured. RESULTS Seventy-nine patients (48.5%) out of 163 patients experienced a reduction in seizure frequency of more than 50%, and 25 patients (15.3%) became seizure-free. The rate of seizure reduction greater than 50% in children with partial seizures was 40.5% (17/42) and in children with generalized seizures was 51.2% (62/121). Of 36 patients who manifested mainly myoclonic seizures, 20 patients (55.6%) showed a seizure reduction of more than 50% and 9 patients (25.0%) were seizure-free. Mean maintenance dosage of drug was 8.2mg/kg/day (range 5.0-16.0mg/kg/day). Adverse events were documented in 15 children (9.2%), including somnolence (8 patients), fatigue, and anorexia, but all were transient and successfully managed. One patient discontinued ZNS therapy due to acute pancreatitis. CONCLUSION ZNS adjunctive therapy is an effective and safe treatment in various childhood intractable epilepsy.

Bilateral intracranial EEG with corpus callosotomy may uncover seizure focus in nonlocalizing focal epilepsy.

PURPOSE To evaluate the value of a new multi-stage surgical procedure using bilateral intracranial electroencephalogram (iEEG) prior and post complete corpus callosotomy (CC) for epileptogenic focus localization. METHOD Thirty patients with drug-resistant epilepsy underwent bilateral iEEG monitoring to localize epileptogenic focus for surgical treatment. Among them, bisynchronous epileptogenic activities were found in 9 pediatric patients. These 9 patients then received complete CC and continued bilateral iEEG monitoring for further seizure localization. Final surgical treatment decisions were made based on the bilateral iEEG findings post complete CC. The entire multi-stage procedure was performed during the same hospital stay. We retrospectively studied the data from the 9 patients. RESULTS Seizure onset was lateralized in 3 patients who later received functional hemispherectomy. In another 4 patients, seizure onset was localized, resulting in resective surgery. Bilateral multiple subpial transection was performed on 1 patient with identified bilateral independent seizure onset. One patient did not have seizures following complete CC leading to removal of electrodes without any further resection. Subsequent follow-up showed favorable outcome in all patients: seizure-free in 7, more than 90% reduction in 2. None of the patients experienced surgery related complications during the procedure and follow-up period. CONCLUSION The multi-stage surgical procedure utilizing iEEG monitoring with CC is a viable option for select patients with catastrophic non-localizing epilepsy. Further study is necessary to find the optimal selection criteria for use of this novel approach.

Cultural challenges in using the ketogenic diet in Asian countries

The ketogenic diet (KD) is a high fat, low carbohydrate diet that has been used for intractable childhood epilepsy since the early 1920s. After the resurgence of the KD since the mid 1990s in the United States, there has been a dramatic increase in its use worldwide. The increasing use of this diet in Asia is not an exception. However, since carbohydrates are considered to be a main dietary composition of Asians, there has been some limitation on the rapid adaptation of KD. This summary will give a brief review on current state, limitations, and efforts to provide a successful KD in Asia.

Identification of Focal Epileptogenic Networks in Generalized Epilepsy Using Brain Functional Connectivity Analysis of Bilateral Intracranial EEG Signals

Simultaneous bilateral onset and bi-synchrony epileptiform discharges in electroencephalogram (EEG) remain hallmarks for generalized seizures. However, the possibility of an epileptogenic focus triggering rapidly generalized epileptiform discharges has been documented in several studies. Previously, a new multi-stage surgical procedure using bilateral intracranial EEG (iEEG) prior to and post complete corpus callosotomy (CC) was developed to uncover seizure focus in non-lateralizing focal epilepsy. Five patients with drug-resistant generalized epilepsy who underwent this procedure were included in the study. Their bilateral iEEG findings prior to complete CC showed generalized epileptiform discharges with no clear lateralization. Nonetheless, the bilateral ictal iEEG findings post complete CC indicated lateralized or localized seizure onset. This study hypothesized that brain functional connectivity analysis, applied to the pre CC bilateral iEEG recordings, could help identify focal epileptogenic networks in generalized epilepsy. The results indicated that despite diffuse epileptiform discharges, focal features can still be observed in apparent generalized seizures through brain connectivity analysis. The seizure onset localization/lateralization from connectivity analysis demonstrated a good agreement with the bilateral iEEG findings post complete CC and final surgical outcomes. Our study supports the role of focal epileptic networks in generalized seizures.

Impact of intraoperative 3-T MRI with diffusion tensor imaging on hemispherectomy

OBJECTIVE Hemispherectomy can produce remarkable seizure control of medically intractable hemispheric epilepsy in children, but some patients continue to have seizures after surgery. A frequent cause of treatment failure is incomplete surgical disconnection of the abnormal hemisphere. This study explores whether intraoperative 3-T MRI with diffusion tensor imaging (DTI) during hemispherectomy can identify areas of incomplete disconnection and allow complete disconnection during a single surgery. METHODS The charts of 32 patients with epilepsy who underwent hemispherectomy between January 2012 and July 2014 at the Florida Hospital for Children were reviewed. Patients were grouped as having had curative or palliative hemispherectomy. To assess the completeness of disconnection when the surgeon considered the operation completed, intraoperative 3-T MRI-DTI was performed. If incomplete disconnection was identified, additional surgery was performed until MRI-DTI sequences confirmed satisfactory disconnection. Seizure outcome data were collected via medical records at last follow-up. RESULTS Of 32 patients who underwent hemispherectomy, 23 had curative hemispherectomy and 9 had palliative hemispherectomy. In 11 of 32 surgeries, the first intraoperative MRI-DTI sequences suggested incomplete disconnection and additional surgery followed by repeat MRI-DTI was performed. Complete disconnection was accomplished in 30 of 32 patients (93.8%). Two of 32 disconnections (6.3%) were incomplete on postoperative imaging. Cross-sectional results showed that 21 of 23 patients (91.3%) who had curative hemispherectomy remained free of seizures (International League Against Epilepsy Class 1) at a median follow-up of 1.7 years (range 0.4-2.9 years). The longitudinal seizure freedom after curative hemispherectomy was 95.2% (SE 0.05) at 6 months, 90.5% (SE 0.06) at 1 year, and 90.5% (SE 0.05) at 2 years. CONCLUSIONS Intraoperative 3-T MRI-DTI sequences can identify incomplete disconnection during hemispherectomy and allow higher rates of complete disconnection in a single surgery. Higher rates of complete disconnection seem to achieve better seizure-free outcome following modified functional hemispherectomy.