Neuropsychological outcome after frontal surgery for pediatric-onset epilepsy with focal cortical dysplasia in adolescent and young adult.

OBJECTIVE: We investigated neuropsychological outcome in patients with pharmacoresistant pediatric-onset epilepsy caused by focal cortical dysplasia (FCD), who underwent frontal lobe resection during adolescence and young adulthood. METHODS: Twenty-seven patients were studied, comprising 15 patients who underwent language-dominant side resection (LDR) and 12 patients who had languagenondominant side resection (n-LDR). We evaluated intelligence (language function, arithmetic ability, working memory, processing speed, visuo-spatial reasoning), executive function, and memory in these patients before and two years after resection surgery. We analyzed the relationship between neuropsychological outcome and resected regions (side of language dominance and location). RESULTS: Although 75% of the patients showed improvement or no change in individual neuropsychological tests after surgical intervention, 25% showed decline. The cognitive tests that showed improvement or decline varied between LDR and n-LDR. In patients who had LDR, decline was observed in Vocabulary and Phonemic Fluency (both 5/15 patients), especially after resection of ventrolateral frontal cortex, and improvement was observed in WCST-Category (7/14 patients), Block Design (6/15 patients), Digit Symbol (4/15 patients), and Delayed Recall (3/9 patients). In patients who underwent n-LDR, improvement was observed in Vocabulary (3/12 patients), but decline was observed in Block Design (2/9 patients), and WCST-Category (2/9 patients) after resection of dorsolateral frontal cortex; and Arithmetic (3/10 patients) declined after resection of dorsolateral frontal cortex or ventrolateral frontal cortex. General Memory (3/8 patients), Visual Memory (3/8 patients), Delayed Recall (3/8 patients), Verbal Memory (2/9 patients), and Digit Symbol (3/12 patients) also declined after n-LDR. CONCLUSION: Postoperative changes in cognitive function varied depending on the location and side of the resection. For precise presurgical prediction of neuropsychological outcome after surgery, further prospective studies are needed to accumulate data of cognitive changes in relation to the resection site.

Localized focal cortical dysplasia type II: seizure freedom with lesionectomy guided by MRI and FDG-PET.

OBJECTIVE: The authors perform thorough, noninvasive presurgical evaluations for intractable epilepsy at their center and avoid unnecessary intracranial EEG when possible. The purpose of this study was to clarify the appropriateness of their lesion-oriented surgical strategy for localized focal cortical dysplasia (FCD) type II. METHODS: Fifty-one patients with pathologically proven localized FCD type II who were followed for at least 1 year after surgery were included. Patients with FCD type II with lobar or multilobar distribution were excluded. The results of presurgical evaluations, including thin-slice 3-T MRI, FDG-PET, and ictal SPECT, as well as surgical procedures and postoperative seizure and functional outcomes, were examined retrospectively. RESULTS: MRI was positive in 46 (90%) of 51 patients, and FDG-PET revealed localized hypo- or hypermetabolism in 47 (92%) of 51 patients. Ictal SPECT revealed concordant hyperperfusion in 37 of 42 patients examined. Intracranial EEG was used in only 13 patients (25%), including 5 with negative MRI results and 4 with subtle MRI findings. Of the 15 patients with FCD in the vicinity of eloquent (sensorimotor and language) areas, intracranial EEG was used in 4. Lesionectomy was performed in all 51 patients. Intraoperative electrocorticography (ECoG) was performed in 8 patients, but the findings were not used to tailor the extent of resection. Postoperative seizure outcomes were Engel class I in 47 patients (92%) and Ia in 45 (88%). In the 15 patients with FCD in the vicinity of eloquent areas, 13 (87%) achieved a class I outcome. Predictive factors for favorable seizure outcome were complete resection of the MRI lesion (p = 0.006) and frontal lobe surgery (p = 0.012). Postoperative neurological deficits were noted in only 4 (27%) of 15 patients with FCD in the vicinity of eloquent areas. All 5 MRI-negative patients achieved an Engel class I outcome. CONCLUSIONS: In most of the patients with localized FCD type II, MRI and/or FDG-PET detected the localized abnormality. Lesionectomy without intracranial EEG led to seizure freedom in most cases. Even when lesions were in the vicinity of eloquent areas, seizure and functional outcomes were favorable. Intraoperative ECoG may thus be unnecessary. Complete resection of the lesion is essential for favorable seizure outcome in MRI-positive patients. In MRI-negative patients, surgery with intracranial EEG guided by FDG-PET provided seizure-free outcomes.

Mesial temporal lobe epilepsy with amygdalar hamartoma-like lesion: Is it a distinct syndrome?

INTRODUCTION: We examined the clinical, semiological, scalp electroencephalographic (EEG), and neuropsychological features of patients with amygdalar hamartoma-like lesion (AHL) without hippocampal sclerosis (HS). METHODS: This retrospective study included 9 patients with mesial temporal lobe epilepsy (MTLE) who had an amygdalar lesion on preoperative MRI; underwent mesial temporal resection; were diagnosed with amygdalar hamartoma-like lesion (AHL) without hippocampal sclerosis (HS); were followed up for at least 2 years after surgery; and had a favourable postoperative seizure outcome (Engel Class I). There were 5 women and 4 men, and age at surgery ranged from 19 to 54 (mean, 36.6) years. Clinical characteristics, auras, video-recorded seizure semiology, interictal and ictal EEG, and preoperative neuropsychological data were reviewed. Twenty patients with MTLE with HS who had favourable postoperative seizure outcomes (Engel Class I) were selected as controls. RESULTS: Age at seizure onset was significantly higher in patients with AHL without HS than in those with HS. Fear was more frequently seen in patients with AHL (44 %) than in those with HS (5 %) (P = 0.022). There were no significant differences in interictal epileptiform discharges or ictal EEG pattern. Preoperative full-scale IQ score was significantly higher in the AHL group than in the HS group (mean, 92.9 v. 74.8, P = 0.004), as was preoperative memory quotient score (mean 100.7 v. 85.1, P = 0.028). CONCLUSION: We clarified the clinical, semiological, and neuropsychological features of patients with MTLE-AHL. These findings may be useful for preoperative evaluation, especially of patients with suspected MTLE but without apparent HS on preoperative MRI.

Localizing and Lateralizing Value of Seizure Onset Pattern on Surface EEG in FCD Type II.

BACKGROUND: Surface ictal electroencephalographic (EEG) monitoring has an important role in the presurgical evaluation of patients with focal cortical dysplasia (FCD). This study aimed to examine the characteristics of seizure onset pattern (SOP) on surface ictal EEG. This information will be useful for invasive monitoring planning. METHODS: We reviewed 290 seizures from 31 patients with intractable seizures related to FCD type II (6 patients with FCD IIa and 25 patients with FCD IIb). We categorized the SOPs into five patterns and evaluated the relationships between the SOPs and the location and pathology of the FCD II subtype. RESULTS: The most common SOP was no apparent change (39.0%), followed by rhythmic slow wave and repetitive spikes/sharp waves. The SOP of rhythmic slow wave was associated with FCD II in the temporal lobe (P < 0.001), and the SOP of no apparent change was associated with FCD II in the occipital lobe (P = 0.012). The SOPs of rhythmic slow waves and fast activity were most common in FCD IIa, P < 0.001 and 0.031, respectively. The repetitive spikes/sharp waves SOP was the most common pattern in FCD IIb (P < 0.001). The surface SOPs provided correct localization and lateralization of epileptic foci in FCD in 62.1% and 62.7%, respectively. In 61.3% of the patients, over 50% of the SOPs in each patient indicated accurate localization. CONCLUSIONS: SOPs in surface EEG monitoring are beneficial for presurgical evaluation and lead to localization of epileptic foci and pathologic subtypes of FCD.

Retained absolute pitch after selective amygdalohippocampectomy.

This study assessed the pre-operative chronic condition and effect of epilepsy surgery in a 21-year-old Japanese woman with drug-resistant right temporal lobe epilepsy (TLE). For this patient, it was crucially important to preserve language and her music capabilities, including absolute pitch (AP), which is found in the general population at less than 0.1%. The patient became seizure free, and her AP capability was preserved after selective amygdalohippocampectomy in the non-dominant right hemisphere. Most of the neuropsychological test (WAIS-III and WMS-R) scores remained in the normal range, except for low scores in verbal memory and markedly improved attention/concentration index. The patient's pre- and postoperative brain function related to language and music capabilities were investigated using functional magnetic resonance imaging (fMRI) based on two language tasks and a music task (listening to melodies). While task performance was similar in pre- and postoperative examinations, her brain activation patterns markedly differed. The most striking difference was during the music task: areas with significant activation existed in the bilateral frontal and temporal lobes before surgery, whereas postoperative activation was confined to a very limited region in the left angular gyrus. The authors speculate that the surgery triggered some change in functional organization in the brain, which contributed to preserving her capabilities.

Is additional mesial temporal resection necessary for intractable epilepsy with cavernous malformations in the temporal neocortex?

PURPOSE: Cavernous malformation (CM) in the temporal neocortex causes intractable epilepsy. Whether to resect additional mesial temporal structures in addition to the lesionectomy is a still controversial issue. To clarify the need for the procedure, we retrospectively analyzed pre- and postoperative clinical data of patients with surgically removed CM. SUBJECTS AND METHODS: We included data from 18 patients with CM in the temporal neocortex who presented with intractable epilepsy. Eleven patients of our early series were treated with extended resection, i.e., lesionectomy and the resection of additional mesial temporal structures. Seven patients underwent lesionectomy, i.e., removal of the CM and of hemosiderin-stained surrounding brain tissue. Pathological assessments of the resected hippocampus were performed. Chronic intracranial electroencephalography (EEG) recordings were obtained in 6 patients. We performed perioperative neuropsychological assessments in all patients. RESULTS: The seizure outcome was recorded as Engel class I in 17 patients (94.4%); Ia = 12 (66.7%) Ib = 2 (11.1%), Ic = 1 (5.6%), Id = 2 (11.1%), and class IIb in one patient (5.6%). Adding resection of the mesial temporal structures to lesionectomy did not alter the seizure outcome. Pathology of hippocampus revealed limited neuronal loss in CA4. Ictal onsets in the ipsilateral lateral cortex were detected in all 6 patients who underwent intracranial EEG. In 4 patients each, we also detected ictal onsets from the ipsilateral mesial temporal structures and from the contralateral temporal lobe. Postoperatively, in the patients where their CM was located in the language-dominant hemisphere (n = 10), the full-scale intelligence quotient (IQ) and the performance IQ increased (p < 0.05), whereas the verbal memory (WMS-R) deteriorated in two of 5 patients. CONCLUSION: Excellent seizure outcomes were obtained even the lesionectomy alone. To confirm appropriate surgical strategy for lateral temporal CM with intractable epilepsy, further studies in large sample size are needed.

Risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia.

OBJECTIVE: The purpose of this study was to identify the risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia (FCD). METHODS: 77 patients with histopathologically confirmed FCD were studied. The statistical relationship between cognition levels and clinical factors at presurgical evaluation was analyzed. Cognitive function was evaluated by development quotient or intelligence quotient (DQ-IQ). RESULTS: Ages at seizure onset were younger than 15 years (mean ±â€¯SD; 5.0 ±â€¯4.2 years). Mean disease duration was 14.5 ±â€¯8.5 years. Mean age at pre-surgical DQ-IQ evaluation was 34.8 ±â€¯10.7 years. Mean DQ-IQ was 60.5 ±â€¯20.5, and 41 of 77 (53.2%) patients had mental retardation (DQ-IQ < 70). Younger seizure onset and seizure clustering were significantly associated with lower DQ-IQ (p < 0.001). A multiple regression study identified higher seizure frequency pattern, a history of epileptic spasm and status epilepticus as aggravating factors of DQ-IQ decline (R2 = 0.63, p < 0.001). On the other hand, the risk was decreased in patients with habitual focal aware seizure and transient seizure-free periods up to 6 months in the course of epilepsy. FCD location (FCD site, extent of radiological lesion and laterality) and histopathology of FCD did not affect DQ-IQ. CONCLUSIONS: Our study suggests that seizure characteristics including higher seizure frequency pattern, a history of epileptic spasm, status epilepticus, seizure clustering and early onset of seizure are risk factors of cognitive impairment in FCD patients.

Working memory deficit in drug-resistant epilepsy with an amygdala lesion.

This study compared temporal lobe epilepsy (TLE) patients with amygdala lesion (AL) without hippocampal sclerosis (HS) (TLE-AL) with patients with TLE and HS without AL (TLE-HS). Both subtypes of TLE arose from the right hemisphere. The TLE-AL group exhibited a lower Working Memory Index (WMI) on the Wechsler Adult Intelligence Scale, third edition (WAIS-III), indicating that the amygdala in the right hemisphere is involved in memory-related function. [18F]fluorodeoxyglucose positron emission topography (FDG-PET) showed glucose hypometabolism limited to the right uncus for the TLE-AL group. The results suggest the importance of considering cognitive functions in the non-dominant hemisphere to prevent impairment after surgery.

A classification system for verifying the long-term efficacy of resective surgery for drug-resistant seizures.

OBJECTIVE: To verify the long-term efficacy of resective surgery, we created a classification system in which strictly defined patterns of postoperative seizure emergence are incorporated as basic components and the seizure states throughout the entire follow-up period are assessed comprehensively. METHODS: In our system, Class I has three subclasses (A-C); subclasses A and B are identical to Engel I-A and I-B, respectively. Subclass C comprises patients whose disabling seizures remit within the first 2 years postoperatively. Patients in Class II have only 1-3 days with disabling seizures throughout follow-up after the first 2 years. Patients in Class III have a maximum of 3 seizure days annually, and those in Class IV have ≥4 seizure days annually after the first 2 years. Classes II-IV each have 2 subclasses (A and B): subclass A, late recurrence (i.e., the first seizure occurs after 2 years postoperatively); and subclass B, early recurrence (i.e., first seizure within 2 years). In 646 patients who underwent resective surgery (temporal lobe resection, 74.6%) and were followed for at least 8 years (mean, 14.6 years), we analyzed three patterns of postoperative seizures: early remission, late recurrence, and occasional seizures. In addition, we investigated the differences between the long-term seizure outcomes of the cohort as determined according to our system and the Engel scale. RESULTS: Overall, 52.9% of the cohort experienced at least one disabling seizure postoperatively throughout the follow-up period; in 1/3 of these patients, the first seizure occurred after 2 years. In 73.8% of the 80 patients who manifested the running-down phenomenon, seizure remission occurred within the first 2 years. In addition, 36.7% of the 283 patients who had disabling seizures after 2 years experienced only 1-3 seizure days. Engel Class I-C included about 30% of the patients who had ≥4 seizure days after 2 years. The long-term seizure outcomes, determined according to our system, were: Class I, 56.2% (C, 9.1%) of the overall cohort; Class II, 16.1% (A, 11.0%); and Class III/IV, 27.7% (A, 6.6%). CONCLUSION: Our system clarifies the actual effect of resective surgery more precisely than the Engel scale and thus may be useful for comparing outcomes between different surgical procedures or for identifying potential risk factors predicting unfavorable outcome.

Functional neuroimaging in Rasmussen syndrome.

PURPOSE: For a diagnosis of Rasmussen syndrome (RS), clinical course together with electroencephalography (EEG) and magnetic resonance imaging (MRI) findings are considered important, but there are few reports on functional neuroimaging. This study investigated cerebral blood flow (CBF)-single photon emission computed tomography (SPECT), central benzodiazepine receptor (BZR)-SPECT, and fluorine-18 fluorodeoxy glucose-positron emission tomography (FDG-PET) in RS patients, and correlated neuroimaging results with MRI and pathological findings. METHODS: Twenty-three patients diagnosed with RS according to Bien's (2005) diagnostic criteria (including 12 patients with a histological diagnosis) were studied. CBF-SPECT, BZR-SPECT and FDG-PET images were visually evaluated, and the findings correlated with MRI and histological findings. RESULTS: Hypoperfusion areas were observed in 16 of 22 patients by interictal CBF-SPECT. Hyperperfusion areas were observed in 10 of 12 patients by ictal CBF-SPECT, which correlated with ictal onset area by ictal EEG (IOAE). In the limited data of BZR-SPECT in nine patients, lowered uptake was detected in all nine patients, including two with no MRI abnormalities. Lowered glucose metabolism was observed in affected areas in all five patients by FDG-PET. Histological examination revealed findings of chronic encephalitis in all 12 patients examined, concomitant with focal cortical dysplasia in five patients. CONCLUSION: In RS patients, functional neuroimaging reveals clear abnormal findings, even before the appearance of MRI abnormalities. BZR-SPECT and FDG-PET could detect the IOAE efficiently even in the absence of MRI abnormalities, while interictal CBF-SPECT occasionally failed to detect IOAE if MRI was normal. Based on BZR-SPECT, refractory epileptic seizures in RS may suggest possible impairment of inhibitory neurons.

Ictal single photon emission computed tomographic study of myoclonic absence seizures.

BACKGROUND: Epilepsy with myoclonic absences (EMAs) is a rare epileptic disorder characterized by a predominant type of seizures, myoclonic absences (MAs). The pathophysiology of MAs in patients with EMAs remains unknown. Here, we report the first characterization of the ictal phase of MAs by single photon emission computed tomography (SPECT). METHODS: We evaluated 1 male (Patient 1) and 1 female (Patient 2) patient with EMAs, aged 8 and 4years at first SPECT investigation, respectively. We performed ictal and interictal 99 mTc-ethyl cysteinate dimer (ECD) SPECT. We then generated images of subtraction ictal SPECT co-registered to MRI (SISCOM) from the interictal and ictal data to evaluate topographic changes in cerebral blood flow (CBF) during MAs as compared to the interictal state. RESULTS: In Patient 1, the CBF increased in the perirolandic areas, thalamus, caudate nucleus, and precuneus, and decreased in the middle frontal gyrus and bilateral orbitofrontal regions. In Patient 2, CBF increased in the thalamus, putamen, and globus pallidus. In contrast to the CBF in Patient 1, CBF was decreased in the precuneus. CONCLUSIONS: Using SPECT, we showed that, in addition to the thalamus and basal ganglia, the perirolandic cortical motor area is involved in MAs. We hypothesize that in MAs the blood perfusion in the perirolandic cortical motor area might have changed under the influence of the cortico-thalamic network oscillation features. The CBF properties observed by means of our SPECT procedure may represent key features of the pathophysiological mechanisms underlying MAs.

Characteristics of EEG Seizure-Onset Patterns Recorded From Subdural Electrodes Over MRI-Visible Frontal Focal Cortical Dysplasia Type IIb Lesions.

PURPOSE: Focal cortical dysplasia (FCD) is intrinsically epileptogenic, and an MRI-visible lesion typically constitutes the core part of the epileptogenic zone. We aimed to identify ictal EEG patterns that represent the epileptogenic zone by using subdural electrodes placed over the MRI-visible FCD lesion. METHODS: We selected seven patients with frontal lobe epilepsy caused by pathologically proven FCD type IIb who underwent preoperative intracranial EEG evaluation with subdural electrodes followed by resection surgery with seizure-free outcome. The characteristics of ictal EEG patterns, interictal/ictal high-frequency oscillations, and ictal direct current shifts from intracranial electrodes placed over the MRI-visible lesion were analyzed. RESULTS: Two seizure-onset patterns (low voltage fast activity and fast spike activity) were identified. Low voltage fast activity was seen in all patients with a lateral frontal lesion, and it was always preceded by preictal spikes. Fast spike activity occurred only in patients with a mesial frontal lesion. Interictal/ictal high-frequency oscillations and ictal direct current shifts were seen in all patients. CONCLUSIONS: The epileptogenic zone of frontal FCD type IIb may be characterized by EEG seizure-onset patterns consisting of low voltage fast activity and fast spike activity accompanied by ictal high-frequency oscillations and ictal direct current shifts. Further study is needed to determine whether other seizure-onset patterns exist in patients with FCD type IIb.

Long-term outcomes of epilepsy surgery in 85 pediatric patients followed up for over 10 years: a retrospective survey.

OBJECTIVE The aim of this study was to investigate the treatment outcomes and social engagement of patients who had undergone pediatric epilepsy surgery more than 10 years earlier. METHODS Between 1983 and 2005, 110 patients younger than 16 years underwent epilepsy surgery at the National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders. The authors sent a questionnaire to 103 patients who had undergone follow-up for more than 10 years after surgery; 85 patients (82.5%) responded. The survey contained 4 categories: seizure outcome, use of antiepileptic drugs, social participation, and general satisfaction with the surgical treatment (resection of the epileptic focus, including 4 hemispherectomies). The mean patient age at the time of surgery was 9.8 ± 4.2 (SD) years, and the mean duration of postoperative follow-up was 15.4 ± 5.0 years. Of the 85 patients, 79 (92.9%) presented with a lesional pathology, such as medial temporal sclerosis, developmental/neoplastic lesions, focal cortical dysplasia, and gliosis in a single lobe. RESULTS For 65 of the 85 responders (76.5%), the outcome was recorded as Engel Class I (including 15 [93.8%] of 16 patients with medial temporal sclerosis, 20 [80.0%] of 25 with developmental/neoplastic lesions, and 27 [73.0%] of 37 with focal cortical dysplasia). Of these, 29 (44.6%) were not taking antiepileptic drugs at the time of our survey, 29 (44.6%) held full-time jobs, and 33 of 59 patients (55.9%) eligible to drive had a driver's license. Among 73 patients who reported their degree of satisfaction, 58 (79.5%) were very satisfied with the treatment outcome. CONCLUSIONS The seizure outcome in patients who underwent resective surgery in childhood and underwent followup for more than 10 years was good. Of 85 respondents, 65 (76.5%) were classified in Engel Class I. The degree of social engagement was relatively high, and the satisfaction level with the treatment outcome was also high. From the perspective of seizure control and social adaptation, resective surgery yielded longitudinal benefits in children with intractable epilepsy, especially those with a lesional pathology in a single lobe.

Seizures with tonic posturing: Semiologic difference between supplementary sensorimotor area (SSMA) origin and extra-SSMA origin.

In seizures with tonic posturing, differentiation of seizures originating in SSMA from seizures originating in cortices other than SSMA and spreading to SSMA has not been previously attempted. Twenty-two patients were studied with intractable focal epilepsy with tonic limb posturing as the most prominent semiology, who underwent resective surgery and obtained favorable postoperative seizure outcomes. These 22 patients were divided into an SSMA group (N = 12) and an extra-SSMA group (N = 10), according to the location of resection. Resection area in the extra-SSMA group was located in the dorsolateral frontal or prefrontal area in four patients, the frontal operculum (insula) in two, the parietal cortex in three, and the temporoparietal cortex in one patient. Video-recorded seizures were carefully reviewed. Tonic posturing characteristics and the presence or absence of accompanying symptoms were compared between groups. Incidence of preservation of consciousness was significantly higher in the SSMA group (p < 0.001). Patients in the SSMA group demonstrated a propensity for having unilateral or bilateral asymmetrical tonic limb posturing. In contrast, patients in the extra-SSMA group had a statistically significantly higher incidence of bilateral symmetrical tonic limb posturing (p < 0.05). These findings may be helpful in identifying seizure origin.

Semiological and electroencephalographic features of epilepsy with amygdalar lesion.

OBJECTIVE: To identify semiological and scalp/sphenoidal electroencephalographic (EEG) features of epilepsy with amygdalar lesion (AL). METHODS: This study included 17 patients with epilepsy and distinct AL on MRI, who underwent resective surgery. There were nine female and eight male patients with ages at surgery ranging from 8 to 48 (mean 26.3) years. Postoperative seizure outcome was Engel class I or seizure-free in 12 patients, class II in four, and class III in one. Pathological examination revealed dysembryoplastic neuroepithelial tumor in eight cases, astrocytoma in two, mixed oligoastrocytoma in three, ganglioglioma in two, localized encephalitis in one, and cortical dysplasia in one. Semiology and scalp/sphenoidal EEG findings of these patients (AL group) were compared with those of 20 mesial temporal lobe epilepsy patients with hippocampal sclerosis (HS) who underwent resective surgery with favorable seizure outcome (Engel class I) (control group). RESULTS: Increased tonic components during seizure were more frequently seen in AL group (58.8%) than in control group (20%). Interictal unitemporal slow waves were more frequently found in AL group (58.8%) than in control group (20%). Ictal EEG revealed generalized (not only bitemporal) onset in six patients in AL group (35.3%), but none in control group. The generalized EEG onset patterns in AL group included spike and wave complexes, rhythmic spikes, and delta waves. CONCLUSION: Patients with AL had increased tonic components during seizure and generalized ictal EEG onset more frequently than patients with HS. These findings suggest widespread epileptic network involving subcortical structures such as the thalamus and the brainstem in patients with AL.

An analysis of epileptic negative myoclonus by magnetoencephalography.

PURPOSE: To clarify the neurophysiologic mechanism of epileptic negative myoclonus (ENM), we analyzed the magnetoencephalography (MEG) of a patient with ENM. METHODS: The 52-year-old right-handed male had frequent ENM in the right upper limb during awake and monthly seizures with sudden tonic stiffening of the right forearm during sleep. MRI demonstrated a focal cortical dysplasia in the cortex of the posterior portion of the left superior frontal sulcus. Whole-head type MEG, electroencephalography and electromyography were simultaneously recorded during ENM. Single equivalent currents dipoles (ECDs) were calculated for each spike component followed by silent period (SP) in the right deltoid muscle. These MEG spike components were averaged with respect to their peaks, and single ECD was also calculated for the averaged spike component. Furthermore, we analyzed the MEG with the silent-period-locked-averaging (SPLA) method. Twenty MEG signal data were averaged with respect to the onset of SP. Twenty epochs in each of five separate periods of recording were repeatedly averaged. ECDs were calculated for spike components observed in each averaged epoch. RESULTS: ECDs of each spike followed by SP were clustered near the cortex of the left central sulcus. In MEG spike averaging and SPLA method, ECDs at the peak of spike components were located near the right shoulder division of the primary sensorimotor cortex reproducibly. ECDs on the ascending phase before the peak were located lateral to the above ECD location in MEG spike averaging method. CONCLUSIONS: ENM was produced by an inhibitory action on the primary sensorimotor cortex corresponding to the body segment in which ENM occurs.

Developmental outcome after surgery in focal cortical dysplasia patients with early-onset epilepsy.

The purpose of this study was to investigate the developmental outcome after surgery for early-onset epilepsy in patients with focal cortical dysplasia (FCD). Among 108 patients with histopathologically confirmed FCD operated between 1985 and 2008, we selected 17 patients with epilepsy onset up to 3 years of age. Development was evaluated by the developmental quotient or intelligence quotient (DQ-IQ) and mental age was measured by the Mother-Child Counseling baby test or the Tanaka-Binet scale of intelligence. Postsurgical development outcome was evaluated by the changes in DQ-IQ and mental age as well as rate of increase in mental age (RIMA) after surgery. RIMA was calculated as the increase in mental age per chronological year (months/year; normal average rate: 12 months/year). Age at epilepsy onset of 17 patients ranged from 15 days to 36 months (mean±SD, 11.0±10.0 months). Age at surgery ranged from 18 to 145 months (75.1±32.4 months). Evaluation just before surgery showed that 13 of 17 (76.4%) patients had DQ-IQ below 70. Ten patients (58.8%) were seizure-free throughout the postsurgical follow-up period. After surgery, DQ-IQ was maintained within 10 points of the presurgical level in 13 patients (76.4%), and increased by more than 10 points in one patient (5.9%). After surgery, RIMA in patients with Engel's class I (7.5±3.8) was higher than patients with Engel's class II-IV (2.6±3.4) (unpaired t-test with Welch's correction, t=2.99, df=15, p=0.0092). RIMA was particularly low in two patients with spasm. In four patients with presurgical DQ-IQ<70, seizure-free after surgery and without spasm, DQ-IQ did not increase but RIMA improved from 3.6±2.8 before surgery to 6.9±2.5 months/year after surgery. RIMA became better from 2 years after surgery. In four patients with presurgical DQ-IQ≥70 and no spasm, two showed the same or higher RIMA than normal average after surgery. In 58.8% of FCD patients with early onset epilepsy, epilepsy surgery effectively controlled seizures, and in 82.3% of patients, epilepsy surgery preserved or improved development. Residual seizures after surgery and lower DQ-IQ before surgery might be potential risk factors for poor development after surgery. In patients of Engel's class I with lower presurgical DQ-IQ, catch-up increase in mental age was observed after two years following surgery.

Statistical parametric mapping of interictal 123I-iomazenil SPECT in temporal lobe epilepsy surgery.

Brain single photon emission computed tomography (SPECT) for epilepsy is divided into two types (using three radionuclide tracers)-perfusion SPECT (123I-IMP or 99 mTc-ECD), identifying epileptogenic foci by detecting abnormality in regional cerebral blood flow, and 123I-iomazenil SPECT, identifying epileptogenic foci based on distribution of central benzodiazepine receptors. This study aimed to statistically evaluate and compare the SPECT effectiveness for the three tracers. Statistical parametric mapping (SPM) analysis was performed on 30 mesial temporal lobe epilepsy (mTLE) patients. The radionuclide and patient data were categorized as follows: abnormality in the medial temporal lobe on the operated hemisphere (AAA), in the entire temporal lobe on the operated hemisphere (AA), in the dominantly affected temporal lobe on the operated hemisphere (A), in bilateral temporal lobes (B), with no abnormalities in bilateral temporal lobes (C), and with abnormality in the temporal lobe on the nonoperated hemisphere (D). For analyses of (AAA), (AA), and (A), examining the hemisphere containing epileptogenic foci, IMP-SPECT was significantly superior to ECD-SPECT (P<0.05). For (AAA), indicating localization, IMZ-SPECT was significantly superior to the other two (P<0.05). IMP-SPECT was superior for lateralizing and IMZ-SPECT was useful for localizing epileptogenic foci in mTLE patients though the applicability of the results in extratemporal lobe epilepsy is unknown.

Immunomodulatory therapy versus surgery for Rasmussen syndrome in early childhood.

We examined seizure, cognitive, and motor outcomes in patients with Rasmussen syndrome or Rasmussen encephalitis (RS), after recent initiation of immunomodulatory therapies. Among 53 patients with a diagnosis of RS referred from all over Japan, 49 patients (male 22, female 27) with symptoms and findings characteristic of RS were evaluated. Regular intravenous immunoglobulin (IVIg) therapy was administered at a dose of 100mg/kg/day, etc. Regular steroid pulse therapy was conducted with methylprednisolone at a dose of 30mg/kg/day (children) or 1000mg/day (adults) for 3days. Tacrolimus was given at an initial dose of 0.1mg/kg/day (children). Mean onset age was 8.7±10.5years. Seizure-free rate was 71% after treatment by functional hemispherectomy (FH), and response rate for seizures was 81% by regular steroid pulse therapy, 42% by tacrolimus therapy, and 23% by regular IVIg therapy. Rate of patients with IQ higher than 80 (R80) was 50% by regular steroid pulse therapy, 43% by regular IVIg therapy, 29% by tacrolimus therapy, and 0% by FH. R80 after regular steroid pulse therapy was 100% in patients without MRI lesions, and 37% in those with advanced MRI lesions. Improvement of motor function (paresis) was observed only by immunomodulatory therapy. Motor function was aggravated in 100% of patients treated by FH, 62% by regular IVIg, and 10% by regular steroid pulse therapy. We suggest a new treatment strategy for RS using early immunomodulatory therapy: initiation of regular steroid pulse therapy after early diagnosis indicated by biomarkers, then switching to tacrolimus therapy after several months.

KCC2 was downregulated in small neurons localized in epileptogenic human focal cortical dysplasia.

Focal cortical dysplasia (FCD), which is characterized histologically by disorganized cortical lamination and large abnormal cells, is one of the major causes of intractable epilepsies. γ-aminobutyric acid (GABA)(A) receptor-mediated synchronous depolarizing potentials have been observed in FCD tissue. Since alterations in Cl(-) homeostasis might underlie these depolarizing actions of GABA, cation-Cl(-) cotransporters could play critical roles in the generation of these abnormal actions. We examined the expression patterns of NKCC1 and KCC2 by in situ hybridization histochemistry and immunohistochemistry in FCD tissue obtained by surgery from patients with intractable epilepsy. KCC2 mRNA and protein were expressed not only in non-dysplastic neurons in histologically normal portions located in the periphery of the excised cortex, but also in dysplastic cells in FCD tissue. The levels of KCC2 mRNA and protein were significantly decreased in the neurons around large abnormal neurons (giant neurons), but not in giant neurons, compared with non-dysplastic neurons. The neurons localized only around giant neurons significantly smaller than non-dysplastic neurons. However NKCC1 expression did not differ among these cell types. These results suggest that the intracellular Cl(-) concentration ([Cl(-)](i)) of small neurons might increase, so that depolarizing GABA actions could occur in the FCD tissue of epileptic foci.