Language Lateralization in Patients with Temporal Lobe Epilepsy : A Comparison between Volumetric Analysis and the Wada Test

Objective

Determining language lateralization is important for the presurgical evaluation of patients with medically intractable epilepsy. The Wada test has been the gold standard for lateralization of language dominance before epilepsy surgery. However, it is an invasive test with risk, and have some limitations.

Methods

We compared the volumetric analysis with Wada test, and studied the clinical potential of volumetric analysis to assess language laterality in large surgical candidates with temporal lobe epilepsy (TLE). To examine the efficacy of volumetric analysis to determine language lateralization during presurgical evaluation, we compared the volumetric analysis of the bilateral planum temporale with the results of Wada test in 59 patients with chronic intractable TLE (rTLE, n=32; lTLE, n=27) who underwent epilepsy surgery. We measured the gray matter volumes of planum temporale (PT) of each patients using the VoxelPlus2 program (Mevisys, Daejeon, Korea).

Results

Overall congruence of the volumetric analysis with the Wada test was 97.75% in rTLE patients and 81.5% in lTLE patients. There were more significant leftward asymmetry of the PT in rTLE patients than lTLE patients. In lTLE patients, relatively high proportion (37%) of the patients showed bilateral or right hemispheric language dominance.

Conclusion

These results provide evidence that the volumetric analysis of the PT could be used as an alternatives in language lateralization. Also, the results of the Wada test suggested that there was considerable plasticity of language representation in the brains of patients with intractable TLE and it was associated with an earlier age of brain injury.     

Use of a modified Atkins diet in intractable childhood epilepsy

PURPOSE: To evaluate the efficacy, safety and tolerability of a modified Atkins diet in intractable childhood epilepsy. METHODS: Fourteen children with epilepsy were treated prospectively with a modified Atkins diet. Outcome measures included seizure frequency, adverse reactions and tolerability to the diet; blood beta-hydroxybutyrate and urine ketones were also measured. RESULTS: Six months after diet initiation, seven (50%) remained on the diet, five (36%) had >50% seizure reduction, and three (21%) were seizure free. The diet was well tolerated by 12 (86%) patients. Most complications were transient and were successfully managed by careful follow-up and conservative strategies. A consistently strong ketosis (beta-hydroxybutyrate of >3 mmol/L) seemed to be important for maintaining the efficacy of the diet therapy. CONCLUSIONS: The modified Atkins diet was well tolerated and sometimes a modified Atkins diet can be substituted for the conventional ketogenic diet. Serious complications were rare, but long-term complications remain to be determined.     

Ketogenic diet using a Japanese ketogenic milk for patients with epilepsy: A multi-institutional study

Background

In Japan, Meiji 817-B (M817-B), a powdered ketogenic milk, has been available since the ketogenic diet was introduced to infants and tube-fed children with medication-resistant epilepsy in the 1980s.

Évolution de la prescription du régime cétogène en France chez l’enfant entre 2001 et 2008

Introduction

The ketogenic diet is an adequate treatment for drug-resistant epilepsy and certain inborn metabolic disorders. The efficacy of the ketogenic diet for the treatment of epilepsy is now well established. In France, and more widely in Europe, there is currently no consensus concerning appropriate initiation of the ketogenic diet and subsequent patient management.

Methods

Using the same questionnaire in 2005 and 2008, we retrospectively recorded the practices of child neurology departments of the French university hospitals during three study periods (2001-2002, 2002-2003 and 2005-2008). The aim was to evaluate the number of ketogenic diets started and how the ketogenic diet was initiated.

Results

The ketogenic diet was widely used by pediatric neurologists. The number of patients on a ketogenic diet increased over time. Diet initiation protocols also changed over time, being modified adequately with advances in knowledge of the ketogenic diet.

Conclusion

The French pediatric neurologists appear to have a good understanding of the ketogenic diet.     

Efficacy and tolerability of the modified Atkins diet in adults with pharmacoresistant epilepsy: a prospective observational study

Purpose: Evidence from the pediatric population exists for the efficacy of ketogenic diets in reducing seizure frequency in patients with intractable epilepsy. Recent evidence suggests that a Modified Atkins Diet may be a beneficial form of cotherapy for adult patients with pharmacoresistant epilepsy. Methods: A prospective, open‐label study was performed of adults >18 years of age with pharmacoresistant epilepsy. Carbohydrates were restricted to 20 g/day. Fluids and calories from protein and fat were allowed ad libitum. Key Findings: Eighteen patients, ages 18–55 years, were initially enrolled. Using an intent‐to‐treat analysis, 12% had a >50% seizure reduction after 3 months; 28% after 6 months, and 21% after 12 months. Response at 3 months predicted response at 12 months in 79% of patients. The mean decrease in weight was 10.9 kg and the mean decrease in body mass index (BMI) was 3.8, p = 0.01. Fourteen of 18 patients (78%) completed 12 months of this diet. Patients experienced a decrease in triglycerides from (mean) 1.22 to 0.9 mm (p = 0.02). Significance: The Modified Atkins Diet demonstrates modest efficacy as cotherapy for some adults with pharmacoresistant epilepsy and may be also helpful for weight loss. Financial and logistical barriers were significant factors for those who declined enrollment and for those who discontinued the study.     

Calcified cysticercotic lesions and intractable epilepsy: a cross sectional study of 512 patients

Background

Neurocysticercosis is a major cause of epilepsy in developing countries and is endemic in Brazil. To test the hypothesis that the aetiological profile of patients with intractable epilepsy in Brazil includes neurocysticercosis, we conducted a cross sectional study investigating the aetiology of intractable epilepsy.

Methods

A total of 512 patients evaluated at the outpatient clinic for intractable epilepsy at the Ribeirão Preto School of Medicine were included in the survey. Medical intractability was determined on the basis of seizure incidence and severity, and response to appropriate epilepsy management. Neuroimaging included brain CT with non‐contrasted and contrasted phases and high resolution MRI. Patients were divided into neurocysticercosis and non‐neurocysticercosis groups according to previous diagnostic criteria.

Results

The most common epileptogenic lesions were mesial temporal sclerosis (MTS; 56.0%), malformations of cortical development (12.1%), and brain tumours (9.9%). Neuroimaging was normal in 8.7% of patients. Calcifications were found in 27% of patients and were significantly more common in patients with MTS than in those without MTS (p<0.001). Isolated neurocysticercosis was found in only eight patients (1.56%).

Conclusions

These data suggest that neurocysticercosis is an uncommon cause of intractable epilepsy, even in an endemic region such as Brazil, and that it may only represent a coexistent pathology. However, an analysis of our findings reveals that neurocysticercosis was more common in patients with MTS. This finding could suggest either that there is a cause‐effect relationship between MTS and neurocysticercosis, or that MTS and neurocysticercosis co‐vary with a missing variable, such as socio‐economic status.     

A randomized, crossover comparison of daily carbohydrate limits using the modified Atkins diet

The modified Atkins diet is a dietary therapy for intractable epilepsy that mimics the ketogenic diet, yet does not restrict protein, calories, and fluids. The ideal starting carbohydrate limit is unknown. Twenty children with intractable epilepsy were randomized to either 10 or 20 g of carbohydrates per day for the initial 3 months of the modified Atkins diet, and then crossed over to the opposite amount. A significantly higher likelihood of >50% seizure reduction was noted for children started on 10 g of carbohydrate per day at 3 months: 60% versus 10% (P=0.03). Most parents reported no change in seizure frequency or ketosis between groups, but improved tolerability with 20 g per day. A starting carbohydrate limit of 10 g per day for children starting the modified Atkins diet may be ideal, with a planned increase to a more tolerable 20 g per day after 3 months.     

Magnetoencephalography Interictal Spike Clustering in Relation with Surgical Outcome of Cortical Dysplasia

Objective

The aim of this study was to devise an objective clustering method for magnetoencephalography (MEG) interictal spike sources, and to identify the prognostic value of the new clustering method in adult epilepsy patients with cortical dysplasia (CD).

Methods

We retrospectively analyzed 25 adult patients with histologically proven CD, who underwent MEG examination and surgical resection for intractable epilepsy. The mean postoperative follow-up period was 3.1 years. A hierarchical clustering method was adopted for MEG interictal spike source clustering. Clustered sources were then tested for their prognostic value toward surgical outcome.

Results

Postoperative seizure outcome was Engel class I in 6 (24%), class II in 3 (12%), class III in 12 (48%), and class IV in 4 (16%) patients. With respect to MEG spike clustering, 12 of 25 (48%) patients showed 1 cluster, 2 (8%) showed 2 or more clusters within the same lobe, 10 (40%) showed 2 or more clusters in a different lobe, and 1 (4%) patient had only scattered spikes with no clustering. Patients who showed focal clustering achieved better surgical outcome than distributed cases (p=0.017).

Conclusion

This is the first study that introduces an objective method to classify the distribution of MEG interictal spike sources. By using a hierarchical clustering method, we found that the presence of focal clustered spikes predicts a better postoperative outcome in epilepsy patients with CD.     

Surgical Complications of Epilepsy Surgery Procedures : Experience of 179 Procedures in a Single Institute

Objective

There are a few reports on the complications of surgery for epilepsy. We surveyed our data to present complications of epilepsy surgeries from the neurosurgeon''s point of view and compare our results with other previous reports.

Methods

A total of 179 surgical procedures for intractable epilepsy (41 diagnostic, 138 therapeutic) were performed in 92 consecutive patients (10 adults, 82 children) during the last 9.2 years (February. 1997-April. 2006). Their medical records and radiological findings were reviewed to identify and analyze the surgical complications.

Results

The diagnostic procedures encompassed various combinations of subdural grid, subdural strips, and depth electrodes. Four minor transient complications developed in 41 diagnostic procedures (4/41=9.8%). A total of 138 therapeutic procedures included 28 anterior temporal lobectomies, 21 other lobectomies, 6 lesionectomies, 21 topectomies, 13 callosotomies, 20 vagus nerve stimulations, 13 multiple subpial transections, and 16 hemispherectomies. Twenty-six complications developed in therapeutic procedures (26/138=18.8%). Out of the 26 complications, 21 complications were transient and reversible (minor; 21/138=15.2%), and 5 were serious complications (major; 5/138=3.6%). Five major complications were one visual field defect, two mortality cases and two vegetative states. There were 2 additional mortality cases which were not related to the surgery itself.

Conclusion

Our results indicate that complication rate was higher than previous other reports in minor complications and was comparable in major complications. However, our results show relatively high frequency of mortality cases and severe morbidity case compared to other previous reports. The authors would like to emphasize the importance of acute postoperative care in young pediatric patients as well as meticulous surgical techniques to reduce morbidity and mortality in epilepsy surgery.     

EEG Source Imaging in Partial Epilepsy in Comparison with Presurgical Evaluation and Magnetoencephalography

Background and Purpose

The aim of this study was to determine the usefulness of three-dimensional (3D) scalp EEG source imaging (ESI) in partial epilepsy in comparison with the results of presurgical evaluation, magnetoencephalography (MEG), and electrocorticography (ECoG).

Methods

The epilepsy syndrome of 27 partial epilepsy patients was determined by presurgical evaluations. EEG recordings were made using 70 scalp electrodes, and the 3D coordinates of the electrodes were digitized. ESI images of individual and averaged spikes were analyzed by Curry software with a boundary element method. MEG and ECoG were performed in 23 and 9 patients, respectively.

Results

ESI and MEG source imaging (MSI) results were well concordant with the results of presurgical evaluations (in 96.3% and 100% cases for ESI and MSI, respectively) at the lobar level. However, there were no spikes in the MEG recordings of three patients. The ESI results were well concordant with MSI results in 90.0% of cases. Compared to ECoG, the ESI results tended to be localized deeper than the cortex, whereas the MSI results were generally localized on the cortical surface. ESI was well concordant with ECoG in 8 of 9 (88.9%) cases, and MSI was also well concordant with ECoG in 4 of 5 (80.0%) cases. The EEG single dipoles in one patient with mesial temporal lobe epilepsy were tightly clustered with the averaged dipole when a 3 Hz high-pass filter was used.

Conclusions

The ESI results were well concordant with the results of the presurgical evaluation, MSI, and ECoG. The ESI analysis was found to be useful for localizing the seizure focus and is recommended for the presurgical evaluation of intractable epilepsy patients.     

Comparison between Initial and Recent Surgical Outcome of 15-Year Series of Surgically Remediable Epilepsy

Objective

The aim of this study is to compare the surgical outcome of the initial and recent surgical cases, during our 15-years experience, in terms of the surgical strategies and the prognostic factors for surgically remediable epilepsy.

Methods

We retrospectively reviewed and compared the surgical outcomes between the initial 256 (Group I) and recent 139 (Group II) patients according to the time period of operation for a total of 518 consecutive epilepsy surgeries at our institution since 1992. The patients of the middle intermediate period, which were subjected to changed surgical strategies, were excluded.

Results

The surgical outcome data from the initial and recent groups showed a much improved outcome for patients who underwent temporal lobe epilepsy (TLE) surgery over time. The number of patients with a good outcome (Engel class I-II) was much increased from 87.7% (178 TLE cases of Group I) to 94.8% (79 TLE cases of Group II) and this was statistically significant (p = 0.0324) on univariate analysis. Other remarkable changes were the decreased performance of intracranial invasive studies from 43.5% in Group I to 30.9% in Group II due to the advanced neuroimaging tools. The strip/grid ratio was reduced from 131/32 in Group I to 17/25 in Group II, because of a markedly reduced mesial TLE surgery and an increased extratemporal epilepsy surgery.

Conclusion

Our results show that surgical outcome of epilepsy surgery has improved over time and it has shown to be efficient to control medically intractable epilepsy. Appropriate patient selection, comprehensive preoperative assessments and more extensive resection are associated with good postoperative outcomes.     

Long-Term Outcomes of Hemispheric Disconnection in Pediatric Patients with Intractable Epilepsy

Background and Purpose

Hemispherectomy reportedly produces remarkable results in terms of seizure outcome and quality of life for medically intractable hemispheric epilepsy in children. We reviewed the neuroradiologic findings, pathologic findings, epilepsy characteristics, and clinical long-term outcomes in pediatric patients following a hemispheric disconnection.

Methods

We retrospectively studied 12 children (8 males) who underwent a hemispherectomy at Asan Medical Center between 1997 and 2005. Clinical, EEG, neuroradiological, and surgical data were collected. Long-term outcomes for seizure, motor functions, and cognitive functions were evaluated at a mean follow-up of 12.7 years (range, 7.6-16.2 years) after surgery.

Results

The mean age at epilepsy onset was 3.0 years (range, 0-7.6 years). The following epilepsy syndromes were identified in our cohort: focal symptomatic epilepsy (n=8), West syndrome (n=3), and Rasmussen''s syndrome (n=1). Postoperative histopathology of our study patients revealed malformation of cortical development (n=7), encephalomalacia as a sequela of infarction or trauma (n=3), Sturge-Weber syndrome (n=1), and Rasmussen''s encephalitis (n=1). The mean age at surgery was 6.5 years (range, 0.8-12.3 years). Anatomical or functional hemispherectomy was performed in 8 patients, and hemispherotomy was performed in 4 patients. Eight of our 12 children (66.7%) were seizure-free, but 3 patients with perioperative complications showed persistent seizure. Although all patients had preoperative hemiparesis and developmental delay, none had additional motor or cognitive deficits after surgery, and most achieved independent walking and improvement in daily activities.

Conclusions

The long-term clinical outcomes of hemispherectomy in children with intractable hemispheric epilepsy are good when careful patient selection and skilled surgical approaches are applied.     

High rates of parkinsonism in adults with autism

Background

While it is now recognized that autism spectrum disorder (ASD) is typically a life-long condition, there exist only a handful of systematic studies on middle-aged and older adults with this condition.

Methods

We first performed a structured examination of parkinsonian motor signs in a hypothesis-generating, pilot study (study I) of 19 adults with ASD over 49 years of age. Observing high rates of parkinsonism in those off atypical neuroleptics (2/12, 17 %) in comparison to published population rates for Parkinson’s disease and parkinsonism, we examined a second sample of 37 adults with ASD, over 39 years of age, using a structured neurological assessment for parkinsonism.

Results

Twelve of the 37 subjects (32 %) met the diagnostic criteria for parkinsonism; however, of these, 29 subjects were on atypical neuroleptics, complicating interpretation of the findings. Two of eight (25 %) subjects not taking atypical neuroleptic medications met the criteria for parkinsonism. Combining subjects who were not currently taking atypical neuroleptic medications, across both studies, we conservatively classified 4/20 (20 %) with parkinsonism.

Conclusions

We find a high frequency of parkinsonism among ASD individuals older than 39 years. If high rates of parkinsonism and potentially Parkinson’s disease are confirmed in subsequent studies of ASD, this observation has important implications for understanding the neurobiology of autism and treatment of manifestations in older adults. Given the prevalence of autism in school-age children, the recognition of its life-long natural history, and the recognition of the aging of western societies, these findings also support the importance of further systematic study of other aspects of older adults with autism.     

Ketogenic diet. Update and application

The ketogenic diet is a high-fat, low-carbohydrate, and adequate-protein diet for the treatment of intractable seizures in children, initially introduced in 1921 to mimic the biochemical changes associated with fasting. The diet is individually calculated and rigidly controlled, requiring a comprehensive medical team approach. Although there are adverse, as well as, beneficial effects, several studies have proved its tolerability and efficacy in children with medically refractory epilepsy. Children must be carefully selected, monitored, and followed, and the parents must be committed. The division of Pediatric Neurology at King Faisal Specialist Hospital & Research Center in Jeddah is one of very few centers that provide this treatment option in the Middle East. Over the last 2 years, 8 children with intractable epilepsy were placed on the ketogenic diet in our center. Overall, 38% (3/8) reached accepted efficacy (>50% seizure reduction), which is lower than the 50% efficacy in published literature. Many issues and problems arose in the provision and compliance with the ketogenic diet, many of which were unique to our culture. It is critical that this treatment is provided to highly selected children with committed parents.     

Le régime cétogène et ses variants : certitudes et doutes

The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet that has been employed as a nonpharmacologic therapy for intractable epilepsy. Several multicenter or randomized studies have demonstrated the anticonvulsive properties of the ketogenic diet. The reports on the clinical efficacy have described a greater than 50% reduction in seizure frequency for about 60% of patients on a ketogenic diet. Efficacy has been reported both for child-teenager and adult patients. Patients who were responders to the ketogenic diet exhibited a decrease in seizure frequency within two months of treatment onset. Underlying mechanisms remain unknown. The current hypotheses are: anticonvulsive properties of ketone bodies, variation in excitatory or inhibitory brain neurotransmissions, modulation of cell excitability or implication of polyunsaturated fatty acids. Ketogenic diet is a fastidious and restrictive therapy. Moreover, side effects have been reported. In order to facilitate patient tolerability and palatability, the diet protocols are gradually modified including changes in ratios of the fat versus non fat components, initiation of the diet with or without fasting, fatty acids composition. A modified Atkins diet seems to be a possible alternative diet with a comparable efficacy on intractable epilepsy. This diet induces ketosis without fluid, calorie or protein restriction, nor the requirement for fasting and food weighing. Furthermore, 10 to 20 grams carbohydrates are allowed per day to increase patient tolerability and palatability. New data suggest that ketogenic diet and its variants should not be considered like a “last chance” treatment.     

Trends in Suicide Methods and Rates among Older Adults in South Korea: A Comparison with Japan

Objective

Lethality of the chosen method during a suicide attempt is a strong risk factor for completion of suicide. We examined whether annual changes in the pattern of suicide methods is related to annual changes in suicide rates among older adults in South Korea and Japan.

Methods

We analyzed annual the World Health Organization data on rates and methods of suicide from 2000 to 2011 in South Korea and Japan.

Results

For Korean older adults, there was a significant positive correlation between suicide rate and the rate of hanging or the rate of jumping, and a significant negative correlation between suicide rate and the rate of poisoning. Among older adults in Japan, annual changes in the suicide rate and the pattern of suicide methods were less conspicuous, and no correlation was found between them.

Conclusion

The results of the present study suggest that the increasing use of lethal suicide methods has contributed to the rise in suicide rates among older adults in South Korea. Targeted efforts to reduce the social acceptability and accessibility of lethal suicide methods might lead to lower suicide rate among older adults in South Korea.     

A prospective study of the modified Atkins diet for intractable epilepsy in adults

PURPOSE: The ketogenic diet is not typically offered to adults with epilepsy due to the significant lifestyle alterations needed for its use. The modified Atkins diet has been recently demonstrated to be therapeutic for children without the need for an admission, fasting period, weighing of foods, or fluid, calorie, and protein restriction. METHODS: A prospective, open-label study was performed of adults over 18 years of age, having at least weekly seizures and prior use of at least two anticonvulsants. Carbohydrates were initially restricted to 15 g/day, fats were encouraged, and fluids, protein, and calories were allowed ad lib. RESULTS: Thirty patients, with age ranging from 18 to 53 years, were enrolled. Using an intent-to-treat analysis, 47% had a >50% seizure reduction after 1 and 3 months on the diet; 33% after 6 months. In those with seizure reduction, the median time to improvement was 2 weeks (range: 1-8 weeks). The mean weight loss was 6.8 kg, p < 0.001. Body-mass index (BMI) decrease correlated with efficacy at 3 months, p = 0.03. Ten subjects (30%) discontinued the diet prior to 3 months. Side effects included increased cholesterol (mean 187 to 201 mg/dL), blood urea nitrogen (BUN; 13 to 16 mg/dL), and urine calcium to creatinine ratio (0.14 to 0.19). CONCLUSIONS: A modified Atkins diet appears to demonstrate preliminary efficacy for adults with intractable epilepsy, especially in those who lost weight. Considering the rapid response in those who improved, but somewhat high discontinuation rate, a 2-month trial period may be adequate to assess for efficacy.     

A pilot study of the modified Atkins diet for Sturge-Weber syndrome

The modified Atkins diet (MAD) is a dietary treatment for epilepsy which does not restrict fluids or calories. This theoretically makes the MAD safer than the ketogenic diet for children with Sturge-Weber syndrome (SWS). Five children aged 4-18 years with SWS and at least monthly intractable seizures were started prospectively on the MAD for 6 months. All children had urinary ketosis and seizure improvement, including 3 with > 50% seizure reduction.     

Modified Atkins diet therapy for a case with glucose transporter type 1 deficiency syndrome

Glucose transporter type 1 deficiency syndrome (GLUT-1 DS), giving rise to impaired glucose transport across the blood-brain barrier, is characterized by infantile seizures, complex motor disorders, global developmental delay, acquired microcephaly, and hypoglycorrhachia. GLUT-1 DS can be treated effectively with a ketogenic diet because it can provide an alternative fuel for brain metabolism; however, the excessive restriction of food intake involved frequently makes it difficult for patients to initiate or continue the diet. Recently, the modified Atkins diet, which is much less restrictive in terms of the total calorie and protein intake than the classical ketogenic diet, has been shown to be effective and well tolerated in children with intractable epilepsy. We successfully introduced the modified Atkins diet to a 7-year-old boy with GLUT-1 DS, whose caregivers refused ketogenic diet treatment because of strong concerns over restricting the diet. The modified Atkins diet should be considered for patients with GLUT-1 DS as an alternative to the traditional ketogenic diet.     

Experience in the use of the ketogenic diet as early therapy

The ketogenic diet has traditionally been considered an anticonvulsant therapy of last resort, despite excellent efficacy and limited side effects. We hypothesized that the ketogenic diet would have similar results in patients with new-onset epilepsy. A retrospective study was conducted of patients started on the ketogenic diet since 1994. Thirteen of 460 (2.8%) patients were started on the ketogenic diet as early (zero or one prior anticonvulsant) therapy for seizures. Of those remaining on the diet, 60% (6 of 10) had a > 90% seizure reduction at 6 months and 100% (6 of 6) had a > 90% reduction at 12 months. Patients with infantile spasms were as likely to achieve > 50% seizure reduction at 6 months as patients with other seizure types (75% vs 60%; P = .6). The ketogenic diet can be a valuable therapy before epilepsy becomes intractable. In the 13 patients reported, efficacy without side effects was achieved similarly to that with patients with intractable epilepsy.