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.

A Single-center Analysis of Three Japanese Patients with Mahjong-related Seizures.

Mahjong is one of the most popular Chinese tile games played in Japan. Mahjong-related seizures (MRS) are rare praxis-induced seizures. We identified three patients with MRS from February 2000 to February 2021. All cases were men, with a middle-age onset, generalized convulsive seizures, and lack of non-provoked, myoclonic, and absence seizures. All patients had no or non-specific neuroimaging or electroencephalogram abnormalities. They did not have features linked to idiopathic generalized epilepsy. All patients were seizure-free after behavioral adjustments, although one patient required anti-seizure medication and avoided long duration games. These changes may help other patients with MRS continue playing Mahjong.

Therapeutic Monitoring of Lacosamide in Japanese Patients With Epilepsy: Clinical Response, Tolerability, and Optimal Therapeutic Range.

BACKGROUND: Lacosamide is a novel anticonvulsant that acts by enhancing sodium channel slow inactivation. The aims of this study were to evaluate the influence of concomitant antiepileptic drugs (AEDs) on serum lacosamide concentration and explore the relationship between lacosamide serum concentration and both clinical response and adverse effects. METHODS: The authors analyzed 649 serum samples from 426 Japanese patients with epilepsy. The concentration-to-dose (CD) ratio of lacosamide was compared among patients on various AED regimens. Clinical information about seizure frequency and adverse events was obtained from clinical records. RESULTS: In patients who did not receive enzyme-inducing AEDs, the CD ratio (mean ± SD) of lacosamide was 1.84 ± 0.68. By contrast, the CD ratio in patients who received phenytoin, carbamazepine, and phenobarbital was 1.42 ± 0.66 (22.8% lower), 1.46 ± 0.40 (20.7% lower), and 1.36 ± 0.38 (26.1% lower), respectively. Seventy-four patients (17.3%) achieved >50% seizure reduction. The median lacosamide concentration in patients who received and did not receive a sodium channel blocker was 6.6 mcg/mL (26.4 µmol/L) and 8.4 mcg/mL (33.6 µmol/L), respectively. Adverse events, including dizziness, somnolence, diplopia, and anorexia, were reported by 70 patients (16.4%). The incidence rate in patients treated with sodium channel blockers was significantly higher than that in patients not treated with these drugs (21.1% vs. 10.3%; P < 0.005), and the median lacosamide concentration in these patient groups was 5.1 (20.4 µmol/L) and 7.5 mcg/mL (30 µmol/L), respectively. CONCLUSIONS: Therapeutic drug monitoring of lacosamide is clinically useful because it allows physicians to estimate the extent of drug interactions and adjust the dose in individual AED regimens.

Semiology of hyperkinetic seizures of frontal versus temporal lobe origin.

Hyperkinetic seizures are usually associated with frontal lobe epilepsy. However, some patients have hyperkinetic seizures of temporal lobe origin. The semiological differences in hyperkinetic seizures between frontal and temporal lobe epilepsy have not been well studied. Here, we retrospectively assessed ictal semiology in order to distinguish between hyperkinetic seizures of frontal lobe origin and those of temporal lobe origin. We retrospectively reviewed data on patients who had undergone surgery for hyperkinetic seizures of temporal or frontal lobe origin and achieved favourable seizure outcomes (Engel Class I) with a minimum postoperative follow-up of 24 months. We reviewed seizure histories, imaging reports, video-EEG monitoring data, operative records, and pathological findings. We analysed and compared the hyperkinetic semiology of video-recorded seizures of temporal lobe origin and those of frontal lobe origin. Forty hyperkinetic seizures in eight patients (seven adult patients and one 12-year-old patient) with temporal lobe epilepsy and 45 hyperkinetic seizures in nine patients (eight adult patients and one 16-year-old patient) with frontal lobe epilepsy were analysed. Emotional facial expressions (such as fear, laughing, or anger), bilateral forceful elbow flexion, bilateral forceful grasping, facial flushing, and bilateral facial contraction were observed significantly more frequently in seizures of frontal lobe origin. Oroalimentary automatisms, seizures during wakefulness, salivation, and bilateral drop of the corners of the mouth were observed significantly more frequently in seizures of temporal lobe origin. Observation of a number of signs during hyperkinetic manifestations may help to predict whether a seizure originates from the frontal lobe or the temporal lobe.

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.

Bidirectional neural connectivity between basal temporal and posterior language areas in humans.

OBJECTIVE: The basal temporal language area (BTL) is known to be involved in the semantic processing of language. To investigate the neural connectivity between BTL and the posterior language area (PL), we used cortico-cortical evoked potential (CCEP) technique. METHODS: Four patients with intractable epilepsy who underwent presurgical evaluation with subdural electrodes were examined. All patients were right-handed and left language dominance by Wada test. We directly stimulated 20 pairs of electrodes placed on BTL in patient 1-3, putative BTL in patient 4, and PL in patient 1-4. In patient 4, all electrodes on the left temporal basal area were stimulated. RESULTS: We could record 132 CCEP responses including 40 responses by the left basal temporal stimulation in patient 4. The waveforms from PL to BTL were triphasic, while those from BTL to PL were biphasic. The mean latency of the first negative peak (N1) was shorter at BTL (31.8-41.0ms; mean 35.1ms) than at PL (39.6-73.2ms; mean 52.3ms). CONCLUSIONS: We revealed the uneven bidirectional connection between BTL and PL. SIGNIFICANCE: We speculated that the two language areas are connected mainly through subcortical fibers from PL to BTL and through cortico-cortical fibers from BTL to PL, mediated by multisynaptic transmissions.

Sixty six-month follow-up of muscle power and respiratory function in a case with adult-type Pompe disease treated with enzyme replacement therapy.

We report a patient with adult-type Pompe disease treated with enzyme replacement therapy (ERT) for 5.5 years. We evaluated pulmonary function and muscle strength using 6-minute walk test, manual muscle test, and dynamometer-based measurement. The long-term ERT resulted in a substantial improvement in the pulmonary function and a possible stabilization followed by mild deterioration in muscle power measured by dynamometer and 6-minute walk test. Our data may rationalize the long-term use of ERT for adult-type Pompe disease in terms of maintaining pulmonary function.

Mesial temporal lobe epilepsy with no specific histological abnormality: a distinct surgically remediable syndrome.

PURPOSE: The purposes of the study were twofold: to clarify the clinical features and surgical outcome of mesial temporal lobe epilepsy (MTLE) with no specific histological abnormality and to determine the optimal surgical strategy. METHODS: Twelve patients who met the following criteria were included: (1) normal preoperative MRI; (2) intracranial EEG findings consistent with mesial temporal onset of seizures; (3) selective amygdalohippocampectomy (AHE) was performed, and the patient was followed for more than 2years postoperatively; and (4) hippocampal histopathology was nonspecific. Clinical characteristics, intracranial EEG findings, and postoperative seizure outcome were examined. These twelve patients were compared with twenty-one patients with MTLE with unilateral hippocampal sclerosis (HS) on MRI who underwent intracranial EEG before resection (control group). RESULTS: In patients with MTLE with no specific histological abnormality, the age at onset was significantly higher, the history of febrile seizures was significantly less frequent, and preoperative IQ score was significantly higher than that in the control group. The proportion of patients with bitemporal independent and/or nonlateralizing seizure onset on intracranial EEG was 50% in patients with MTLE with nonspecific histopathology and was significantly higher than that in the control group. Seizure outcome was classified as Engel class I in seven patients, class II in three, class III in one, and class IV in one. Seizure outcome was favorable even in three patients with seizures originating more frequently from the side contralateral to the resected side. CONCLUSIONS: Mesial temporal lobe epilepsy with no specific histological abnormality is a clinical entity distinctly different from MTLE with HS. Bitemporal independent and/or nonlateralizing seizure onset on intracranial EEG is very common. Although the presence of lateral temporal and/or extratemporal epileptogenicity should always be kept in mind, postoperative seizure outcome after AHE is favorable even in cases with bitemporal independent and/or nonlateralizing seizure onset.

Month of birth in multiple sclerosis with and without longitudinally extensive spinal cord lesions: a study of a Japanese national survey.

OBJECTIVES: Month of birth has been associated with the environmental factors for multiple sclerosis (MS). This study aimed to investigate whether individuals with MS had significantly different frequencies of birth in a particular month of the year, and whether month-of-birth patterns were influenced by the longitudinally extensive spinal cord lesions (LESCL) status relative to the general population in the same Japanese birth cohort. METHODS: In this study, performed as a part of the fourth Japanese nationwide survey of MS, patients were divided into two groups according to the presence (n=307) or absence (n=906) of LESCLs that were diagnosed on the basis of magnetic resonance imaging findings. The number of births in every month was counted for both groups. Control data were obtained from birth records of the Japanese general population of the median years of birth of each group. Differences in the month-of-birth distributions between the patients and the general population were assessed using the chi-square test. RESULTS: In MS patients without LESCLs, significantly more patients were born in January and June, whereas significantly fewer patients were born in May, compared to the general population. The seasonal patterns of birth were not in association with those of ambient ultraviolet (UV) radiation. No significant differences were found for the month-of-birth distributions between MS patients with LESCLs and the general population. CONCLUSIONS: A different distribution of month of birth in Japanese MS patients without LESCLs from the general population, but not in those with LESCLs, suggests some role for environmental factors in the pathogenesis of the former group. Environmental factors other than UV radiation should be further elucidated in Japanese and other Asian MS cohorts.

[A case of subacute myelitis with anti-aquaporin 4 antibody after thymectomy for myasthenia gravis: review of autoimmune diseases after thymectomy].

We report the case of a 60-year-old woman with myasthenia gravis (MG) and Basedow's disease who seven years after thymectomy developed subacute myelitis, a limited form of neuromyelitis optica (NMO). The patient presented with a centrally located long spinal cord lesion (LCL) on cervical cord MRI, anti-aquaporin 4 (AQP4) antibody in serum, and HLA DPB1*0501. Brain MRI showed no specific findings of classic multiple sclerosis (MS). CSF study showed elevated protein (67 mg/dl) but a normal IgG index (0.63) and no oligoclonal IgG bands. After repeated methylprednisolone pulse and immunoadsorption therapies, the T2-high signal lesion shrunk and tetraparesis improved. We reviewed the English and Japanese literature and found reports of 30 patients showing MS including NMO complicated with MG; 27 had been diagnosed as MS after thymectomy. Among these 27, 16 of 17 who were examined by spinal cord MRI and for anti-AQP4 antibodies were NMO. Only one patient with signs and symptoms localized to the optic nerves and spinal cord showed no LCL and was not examined for anti-AQP4 antibodies. In autoimmune disorders of the central nervous system after thymectomy in patients with MG, NMO is more predominant than classic MS.