Retained Intracerebral Depth Electrode after Stereotactic Electroencephalography Monitoring: A Case Report.

Stereotactic electroencephalography (SEEG) is an increasingly popular surgical modality for localizing the epileptogenic zone. Robot-guided stereotactic electrode placement has been covered in Japan by National Health Insurance since 2020. However, several surgical devices, such as the anchor bolt (a thin, hollow, metal shaft that serves as a guide screw or fixing for each electrode), have not been approved. A 14-year-old female who underwent SEEG for intractable epilepsy and required additional surgery to remove a retained depth electrode from the skull after the SEEG monitoring was finished. She had uncontrolled focal seizures consisting of nausea and laryngeal constriction at the onset. After a comprehensive presurgical evaluation, robot-guided stereotactic electrode implantation was performed to evaluate her seizures by SEEG. Nine depth electrodes were implanted through the twist drill hole. The electrodes were sutured to her skin for fixation without anchor bolts. When we attempted to remove the electrodes after 8 days of SEEG monitoring, one of the electrodes was retained. The retained electrode was removed through an additional skin incision and a small craniectomy under general anesthesia. We confirmed narrowing of the twist drill hole pathway in the internal table of the skull due to osteogenesis, which locked the electrode. This complication might be avoided if an anchor bolt had been used. This case report prompts the approval of the anchor bolts to avoid difficulty in electrode removal. Moreover, approval of a depth electrode with a thinner diameter and more consistent hardness is needed.

[Preoperative Simulation in Epilepsy Surgery].

In patients with intractable epilepsy, seizure focus resection can yield favorable seizure outcomes. First, the localization of the seizure focus is estimated by noninvasive methods such as magnetic resonance imaging(MRI), video-electroencephalography(EEG)monitoring, nuclear medicine examinations, magnetoencephalography, and neuropsychological tests. A subgroup of patients may require additional information obtained from the intracranial EEG. There are two major methods for intracranial EEG: intracranial EEG with subdural grid electrodes(SDG)and stereotactic electroencephalography. If the estimated seizure focus overlaps with the eloquent area in noninvasive studies, the margin and extent of the resection are determined by the results of intracranial EEG and functional mapping by electrical cortical stimulation. Herein, we present a case of lobe epilepsy with subtle MRI lesions in the superior temporal sulcus of the language-dominant hemisphere. The results of the SDG and functional mapping showed that the seizure onset zone overlapped with the language area. Resection of the middle and inferior temporal gyri and multiple transections of the language area resulted in Engel IIB seizure outcomes. In such cases, a thorough preoperative simulation is required to determine the best resection margin for seizure control and functional preservation.

Paradoxical effects of levetiracetam in people with epilepsy with rhythmic epileptiform discharges.

OBJECTIVE: To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects. METHODS: We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors. RESULTS: In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01-28.21) were independently associated with paradoxical LEV effects. CONCLUSIONS: Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.

Identifying the Carcinogenic Mechanism of Malignant Struma Ovarii Using Whole-Exome Sequencing and DNA Methylation Analysis.

BACKGROUND: Since malignant struma ovarii is a very rare disease, its carcinogenic mechanism has not been elucidated. Here, we sought to identify the genetic lesions that may have led to the carcinogenesis of a rare case of malignant struma ovarii (follicular carcinoma) with peritoneal dissemination. METHODS: DNA was extracted from the paraffin-embedded sections of normal uterine tissues and malignant struma ovarii for genetic analysis. Whole-exome sequencing and DNA methylation analysis were then performed. RESULTS: Germline variants of RECQL4, CNTNAP2, and PRDM2, which are tumor-suppressor genes, were detected by whole-exome sequencing. Somatic uniparental disomy (UPD) was also observed in these three genes. Additionally, the methylation of FRMD6-AS2, SESN3, CYTL1, MIR4429, HIF3A, and ATP1B2, which are associated with tumor growth suppression, was detected by DNA methylation analysis. CONCLUSIONS: Somatic UPD and DNA methylation in tumor suppressor genes may be associated with the pathogenesis of malignant struma ovarii. To our knowledge, this is the first report of whole-exome sequencing and DNA methylation analysis in malignant struma ovarii. Genetic and DNA methylation analysis may help elucidate the mechanism of carcinogenesis in rare diseases and guide treatment decisions.

Hippocampal volumetry to determine the resection side in patients with intractable non-lesional bilateral temporal lobe epilepsy.

Bilateral Temporal lobe epilepsy (BTLE) cases may result in poor surgical outcomes due to the difficulty in determining/localizing the epileptogenic zone. In this study, we investigated whether hippocampal volume (HV) would be useful for the determination of the best resection side in BTLE. Eighteen cases of BTLE determined by a scalp video electroencephalogram (SVEEG) underwent resection via intracranial electroencephalography (IVEEG). Patients with lesions or semiologically determined focus lateralization were excluded. In addition to SVEEG, an epilepsy protocol magnetic resonance imaging (MRI) including hippocampus fluid-attenuated inversion recovery (FLAIR) and HV, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), single-photon emission computed tomography with 123I-iomazenil (IMZ-SPECT), and magnetoencephalography (MEG) were performed for the preoperative evaluation of the lateralization. The resection side was determined based on the IVEEG results, and the seizure outcome at two years postoperatively was classified as either a well-controlled seizure outcome (Engel class I), or residual (classes II-V). We used a Fisher's exact test to compare the concordance between the determination of the epileptic focus by each modality and the resected side where patients achieved a well-controlled seizure outcome. Seizures were well controlled in 9/18 patients after surgery. Eight out of 11 patients (72.7%), in whom the HV results (strongly atrophic side) and the resection side were matched, had well-controlled seizure outcomes (P = 0.0498). The concordance of other presurgical evaluations with the resection side was not significantly related to a well-controlled seizure outcome. HV may be a useful method to determine the optimal resection side of the epileptic focus/foci in cases of suspected BTLE.

[Diagnosis of Epilepsy: Clinical Definition, Seizure Semiology, and Differentiation from Acute Symptomatic Seizure(Provoked Seizure)].

Recently, a practical clinical definition has been proposed by the International League Against Epilepsy(ILAE). Management of an unprovoked first seizure in adults has also been reported with risk factors of recurrence relevant to epilepsy diagnosis by the American Academy of Neurology. The term "unprovoked" implies the absence of a temporary or reversible factor lowering the threshold and producing a seizure at that point in time. A seizure immediately after a stroke or head injury would exemplify a provoked seizure, as called acute symptomatic(or early)seizure, that would not lead to a diagnosis of epilepsy. The underlying mechanisms that cause the early seizure are considered to be different from those of epileptogenesis associated with recurrent epileptic seizures. Psychogenic non-epileptic seizure(PNES)or syncope resembles epileptic seizures and are often misdiagnosed. Some clinical features can help distinguish PNES or syncope from epileptic seizure. Clinicians should be familiarized with seizure semiology presumable to epilepsy. The incidence of epilepsy increases steadily after 50 years of age. As in younger people, the diagnosis of epilepsy is a clinical decision; however, in older people this can be more challenging. Many disorders, common in older people may confuse epilepsy seizures which should be differentiated by appropriate investigations.

Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors.

BACKGROUND: While immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs, the prevalence of irAEs and potential risk factors have not been clarified. We identified irAE predictive factors and examined the relationship between the effect of ICIs and irAEs for patients with malignancies. METHODS: A total of 533 cases treated with ICIs, including programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), for various malignancies were included retrospectively. We recorded irAEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 5. Prevalence and predictive factors associated with immune-related liver injury and the relationship between irAE and treatment response were analyzed. RESULTS: During a median of 10 (1-103) cycles with a median follow-up after several ICI initiations of 384 (21-1715) days, irAEs with all grades and with grade ≥ 3 developed in 144 (27.0%) and 57 (10.7%) cases. Cumulative irAE development rates were 21.9, 33.5, and 43.0% in all grades and 8.8, 14.9, and 20.7% in grade ≥ 3 at 5, 10, and 20 cycles, respectively. Patients who received anti-CTLA4 therapy were more likely to develop irAEs compared to those who received anti-PD-1 or anti-PD-L1 monotherapy. Liver injury was the most common irAE. Multivariate analysis identified the combination of PD-1 and anti-CTL-4 antibodies (hazard ratio [HR], 17.04; P < 0.0001) and baseline eosinophil count ≥130/µL (HR, 3.01 for < 130; P = 0.012) as independent risk factors for the incidence of immune-related liver injury with grade ≥ 2. Patients who developed irAEs had a higher disease control rate (P < 0.0001) and an increased overall survival rate compared to those without irAEs (P < 0.0001). CONCLUSION: Combination therapy with anti-PD-1 and anti-CTL-4 antibodies resulted in higher a frequency of irAEs. Baseline absolute eosinophil count was found to be a predictive factor for immune-related liver injury. Occurrence of irAEs may be associated with higher efficacy of ICI treatment and longer survival among patients who receive ICI therapy.

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

Isolated Neurohypophysial Sarcoidosis Involving the Cavernous Sinus Mimicking a Malignant Tumor.

Because of nonspecific clinical and radiological findings, it is difficult to diagnose isolated neurosarcoidosis without histological examination. Distinguishing neurosarcoidosis from neoplasm, infectious disease, or granulomatous disease can be challenging. In this study, we present a case of a 61-year-old female who presented with unilateral blindness. Magnetic resonance imaging (MRI) revealed a large invasive mass lesion located in the neurohypophysis with homogeneous enhancement after the injection of gadolinium. The lesion involved the bilateral cavernous sinus, which extended along the dura of the skull base with leptomeningeal lesions. Contrast-enhanced computed tomography (CT) and fluorodeoxyglucose positron emission tomography/CT of the entire body showed no other lesions. Biochemical examinations showed no useful data, including angiotensin-converting enzyme, ß-glucan, soluble interleukin-2 receptor, and T-SPOT. Cerebrospinal fluid examination revealed only the elevation of total protein. Under the preoperative diagnosis of a malignant tumor or metastatic tumor, followed by tuberculosis, fungal infection, or granulomatous disease, a biopsy was performed to immediately determine the appropriate therapy, which revealed the histological diagnosis of sarcoidosis. After steroid therapy, the lesions had markedly shrunk as observed on MRI, and the eyesight of the patient's right eye was completely restored. In this case, without a biopsy, discriminating between sarcoidosis and a malignant tumor was difficult. We believe that a prompt histological diagnosis of an invasive isolated neurohypophysial mass lesion involving the bilateral cavernous sinus, which is similar to a malignant tumor, is essential for selecting the appropriate therapy.

Mechanisms underlying the prokinetic effects of endogenous glucagon-like peptide-1 in the rat proximal colon.

Glucagon-like peptide-1 (GLP-1), a well-known insulin secretagogue, is released from enteroendocrine L cells both luminally and basolaterally to exert different effects. Basolaterally released GLP-1 increases epithelial ion transport by activating CGRP-containing enteric afferent neurons. Although bath-applied GLP-1 reduced the contractility of colonic segments, GLP-1-induced stimulation of afferent neurons could also accelerate peristaltic contractions. Here, the roles of endogenous GLP-1 in regulating colonic peristalsis were investigated using isolated colonic segments. Isolated segments of rat proximal colon were placed in an organ bath, serosally perfused with oxygenated physiological salt solution, and luminally perfused with degassed 0.9% saline. Colonic wall motion was recorded using a video camera and converted into spatiotemporal maps. Intraluminal administration of GLP-1 (100 nM) stimulating the secretion of GLP-1 from L cells increased the frequency of oro-aboral propagating peristaltic contractions. The acceleratory effect of GLP-1 was blocked by luminally applied exendin-3 (9-39) (100 nM), a GLP-1 receptor antagonist. GLP-1-induced acceleration of peristaltic contractions was also prevented by bath-applied BIBN4069 (1 µM), a CGRP receptor antagonist. In colonic segments that had been exposed to bath-applied capsaicin (100 nM) that desensitizes extrinsic afferents, GLP-1 was still capable of exerting its prokinetic effect. Stimulation of endogenous GLP-1 secretion with a luminally applied cocktail of short-chain fatty acids (1 mM) increased the frequency of peristaltic waves in an exendin-3 (9-39)-sensitive manner. Thus, GLP-1 activates CGRP-expressing intrinsic afferents to accelerate peristalsis in the proximal colon. Short-chain fatty acids appear to stimulate endogenous GLP-1 secretion from L cells resulting in the acceleration of colonic peristalsis.NEW & NOTEWORTHY Glucagon-like peptide-1 (GLP-1) activates CGRP-containing intrinsic afferent neurons resulting in the acceleration of colonic peristalsis. Short-chain fatty acids stimulate the secretion of endogenous GLP-1 from L cells that accelerates colonic peristalsis. Thus, besides the well-known humoral insulinotropic action, GLP-1 exerts a local action via the activation of the enteric nervous system to accelerate colonic motility. Such a prokinetic action of GLP-1 could underlie the mechanisms causing diarrhea in patients with type-2 diabetes treated with GLP-1 analogs.

A case of repetitive seizures following immune checkpoint inhibitor therapy as a feature of autoimmune encephalitis.

Pembrolizumab, an immune-checkpoint inhibitor (ICI), is a humanized monoclonal antibody that binds to programmed cell death-1 receptor (PD-1) and thereby inhibits binding to its ligand, which inhibits the suppression of activated T cells by cancer cells, resulting in enhancing antitumour immunity. Although several cases of encephalitis have been reported as immune-related adverse effects of ICIs, epilepsy has not been reported following ICI treatment. We describe the case of an elderly woman with bladder carcinoma who experienced two episodes of generalized seizures after treatment with pembrolizumab. The episodes were atypical of encephalitis, because the seizures were completely responsive to AEDs and the CSF parameters normalized completely without immunotherapy. Since interictal EEG revealed persistent epileptic discharges after the seizures, pembrolizumab was considered to have induced a chronic state of epileptogenicity as the possible pathology, with a clinical picture similar to that of autoimmune epilepsy. The possibility that ICIs may cause an immune-related adverse effect, such as a chronic epileptic condition, should be considered, since ICIs are used widely.

Comparison of seizure outcomes and ADL recovery period after total or anterior corpus callosotomy in adolescent and young adults with drop attacks and severe mental retardation.

PURPOSE: The aim of this study was to evaluate seizure outcomes and postoperative neurologic complications, with an emphasis on the recovery period of activities of daily living (ADL) between anterior partial corpus callosotomy (ACC) and total corpus callosotomy (TCC) in adolescent and young adults with drop attacks and severe mental retardation. METHODS: We retrospectively reviewed the clinical records of consecutive patients with intractable epilepsy who underwent corpus callosotomy (CC) for drop attacks between 2010 and 2019 in the Department of Neurosurgery, Hiroshima University hospital, with a minimum follow-up of one year. Inclusion criteria of this study were 1) age at surgery: 11-39 years, 2) preoperative intelligence quotient <35, and 3) preoperative Barthel index (BI) ≥30. Postoperative full ADL recovery was defined as complete recovery to the preoperative BI score. We compared the postoperative days required for 1) recovery of oral intake ability, 2) discharge from our hospital, 3) returning home from any hospital, 4) returning home with full ADL recovery, and 5) seizure outcomes in patients with ACC versus those with one-stage TCC. RESULTS: Ten patients with ACC and 14 patients with one-stage TCC met the inclusion criteria. The period for returning home with full ADL recovery was a median of 15 days (range 9-45 days) after ACC, while the median was 21.5 days (range 10-62 days) after one-stage TCC (p = 0.2904). Although there was a tendency for the ADL recovery period to be longer after one-stage TCC, there were no statistically significant differences in any category of ADL recovery period. Eleven of 14 (78.6 %) patients who received a one-stage TCC showed favorable seizure outcomes, with drop attack cessation, which was significantly better than 1 of 10 (10 %) patients with ACC (p = 0.0009). CONCLUSIONS: From the viewpoint of postoperative seizure outcomes and ADL recovery period, one-stage TCC is preferred to ACC for adolescent and young adults with severe mental retardation.

Initiating an epilepsy surgery program with limited resources in Indonesia.

To share the experiences of organizing the epilepsy surgery program in Indonesia. This study was divided into two periods based on the presurgical evaluation method: the first period (1999-2004), when interictal electroencephalogram (EEG) and magnetic resonance imaging (MRI) were used mainly for confirmation, and the second period (2005-2017), when long-term non-invasive and invasive video-EEG was involved in the evaluation. Long-term outcomes were recorded up to December 2019 based on the Engel scale. All 65 surgical recruits in the first period possessed temporal lobe epilepsy (TLE), while 524 patients were treated in the second period. In the first period, 76.8%, 16.1%, and 7.1% of patients with TLE achieved Classes I, II, and III, respectively, and in the second period, 89.4%, 5.5%, and 4.9% achieved Classes I, II, and III, respectively, alongside Class IV, at 0.3%. The overall median survival times for patients with focal impaired awareness seizures (FIAS), focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures were 9, 11 and 11 years (95% CI: 8.170-9.830, 10.170-11.830, and 7.265-14.735), respectively, with p = 0.04. The utilization of stringent and selective criteria to reserve surgeries is important for a successful epilepsy program with limited resources.

[Ictal electroencephalography (EEG) activity and cerebral blood flow dynamics as potential pathological indicators: a case of anti-leucine-rich glioma-inactivated 1 protein (LGI1) encephalitis].

A 29 year-old, right-handed woman was admitted to our hospital due to her headache with fever elevation lasting for two months followed by a prolonged loss of awareness with an involuntary movement in her left hand and mouth. This movement appeared very frequently, and the duration was very short, so called "faciobrachial dystonic seizures (FBDS)". Some of FBDS were followed by prolonged loss of awareness. Brain MRI fluid attenuated inversion recovery (FLAIR) image revealed high intensity lesion in the left mesial temporal lobe. Arterial spin labeling (ASL) image indicated hyper perfusion in this lesion and also the lateral temporal region. No ictal electroencephalography (EEG) change was observed before the onset of FBDS. FBDS was often followed by focal impaired awareness seizure (FIAS) in which ictal EEG showed rhythmic alpha activity arising from left mid-temporal region. This EEG seizure pattern was clearly visible in the time-frequency analysis. Given these clinical findings, along with an evidence of serum anti-leucine-rich glioma-inactivated 1 (LGI1) antibody positive, she was diagnosed with anti-LGI1 encephalitis. Immunotherapy (methylpredonisolone and intravenous immunoglobulin) with a multiple anti-epileptic drugs therapy (lacosamide, perampanel, and lamotrigine) was highly responsible to her symptoms. Although the high intensity lesion in FLAIR image still remained after the treatment, findings of ASL and EEG showed clear correlation to her cognitive function and seizures, respectively. Temporal change in ASL imaging suggested that the hyper perfusion in ASL during the acute stage could be provided by inflammation of the encephalitis its self and also the seizures activities (FBDS and FIAS). The pathophysiological indication of anti-LGI1 encephalitis was limited in terms of the therapeutic strategy, however, our findings collectively suggested that the combination analysis of EEG activity and cerebral blood flow dynamics (ASL) could be the potential candidate.

Preoperative sensory aura predicts risk for seizure in temporal lobe epilepsy surgery.

BACKGROUND: Patients with temporal lobe epilepsy (TLE) often report viscerosensory and experiential auras, with substantial epilepsy localization. However, few previous studies have investigated the epileptic preoperative aura, particularly with regard to its effect on surgical outcomes in patients with drug-resistant epilepsy. OBJECTIVE: This study investigated the potential role of preoperative aura in predicting outcomes after surgery for TLE. MATERIAL AND METHODS: This study included consecutive patients diagnosed with TLE who underwent anterior temporal lobectomy (ATL) for drug-resistant TLE during the period from January 1999 to December 2017. Data pertaining to patient age at the time of surgery, sex, age at initial seizure onset, duration of epilepsy, presence of preoperative aura, comprehensive clinical semiology, side of surgery, and type of pathology were analyzed. Preoperative auras were classified as autonomic, sensory, mental and affective, or multiple manifestations. Patients were followed at 3 and 12 months after surgery and at regular intervals thereafter. RESULTS AND CONCLUSIONS: A total of 498 patients were included in the study. Positive preoperative aura was observed in 386 patients (77.51%). The correlation of each variable with seizure outcomes was analyzed, and the only variable found to correlate with seizure outcome was the presence of preoperative aura. Compared with those with negative preoperative aura, those with positive preoperative aura were 1.74-fold more likely to be seizure-free after surgery for TLE. The analysis of patient data suggested a later onset of initial seizure in those with positive preoperative aura, compared with those without (p = 0.04, 95% confidence interval (CI): 0.55-3.24). Patients with a shorter duration of disease prior to TLE surgery were more likely to achieve seizure-free status postoperatively. Preoperative sensory aura was a good predictor that a patient would be seizure-free during follow-up (p = 0.022).

Surgery for Radiologically Normal-Appearing Temporal Lobe Epilepsy in a Centre with Limited Resources.

Approximately 26-30% of temporal lobe epilepsy (TLE) cases display a normal-appearing magnetic resonance image (MRI) leading to difficulty in determining the epileptogenic focus. This causes challenges in surgical management, especially in countries with limited resources. The medical records of 154 patients with normal-appearing MRI TLE who underwent epilepsy surgery between July 1999 and July 2019 in our epilepsy centre in Indonesia were examined. The primary outcome was the Engel classification of seizures. Anterior temporal lobectomy was performed in 85.1% of the 154 patients, followed by selective amygdalo-hippocampectomy and resection surgery. Of 82 patients (53.2%), Engel Class I result was reported in 69.5% and Class II in 25.6%. The median seizure-free period was 13 (95% CI,12.550-13.450) years, while the seizure-free rate at 5 and 12 years follow-up was 96.3% and 69.0%, respectively. Patients with a sensory aura had better seizure-free outcome 15 (11.575-18.425) years. Anterior temporal lobectomy and selective amygdala-hippocampectomy gave the same favourable outcome. Despite the challenges of surgical procedures for normal MRI TLE, our outcome has been favourable. This study suggests that epilepsy surgery in normal MRI TLE can be performed in centres with limited resources.

Preservation of Memory Despite Unresected Contralateral Hippocampal Volume Loss After Resection of Hippocampal Sclerosis in Seizure-Free Patients.

OBJECTIVE: To determine postoperative long-term changes of hippocampal volume (HV) correlating with cognitive functions in patients who underwent surgery for hippocampal sclerosis with postoperative freedom from seizures. METHODS: We studied 1.5T magnetic resonance imaging before and after surgery in 24 patients (mean ± SD age, 36.9 ± 11.0 years) with hippocampal sclerosis. We performed serial magnetic resonance imaging at 6 months to 1 year, 1-2 years, 2-3 years, and 3-5 years postoperatively. We compared HVs of 24 patients with HVs of 14 age-matched control subjects. We analyzed correlations between consecutive HVs and seizure duration and age at surgery. We compared consecutive changes in HVs between dominant and nondominant hemispheres with concurrent cognitive functions. RESULTS: Preoperative HVs of unresected contralateral hippocampus were significantly smaller than HVs of control subjects (P < 0.01). Unresected contralateral HV changes compared with preoperative HVs were -3.6% ± 6.9%, -2.3% ± 8.5%, -3.6% ± 10.2% (P < 0.05), and -5.0% ± 9.5% (P < 0.05) at consecutive postoperative periods. Largest change in HVs at 3-5 years was significantly correlated with older age at surgery (P < 0.05). Unresected contralateral dominant 14 HVs remained consistently smaller than nondominant 10 HVs up to 5 years with statistical significance (P < 0.05). Verbal memory was preserved in 14 patients with unresected contralateral smaller dominant hippocampus. CONCLUSIONS: In seizure-free patients after hippocampal sclerosis resection , unresected contralateral HV significantly declined with older age at surgery. Visual memory was preserved regardless of side and volume loss. Despite significantly reduced HVs, verbal memory was preserved with the unresected contralateral dominant hippocampus. Earlier surgical intervention may have lower potential risk for memory decline secondary to postoperative HV loss.

Anti-seizure effect and neuronal activity change in the genetic-epileptic model rat with acute and chronic vagus nerve stimulation.

BACKGROUND: VNS showed time-dependent anti-seizure effect. However, the precise mechanism of VNS in acute and chronic anti-seizure effect has not been fully elucidated. Noda epileptic rat (NER) is genetic epilepsy model rat which exhibits spontaneous generalized tonic-clonic seizure (GTC) approximately once per 30 h and frequent dialeptic seizure (DS). We performed acute and chronic VNS on NER to focus on the acute and chronic anti-epileptic effect and neuronal activity change by VNS. METHODS: We performed acute VNS (2 h) on 22 NERs (VNS, n = 11, control, n = 11), then subsequently administered chronic (4 weeks) VNS on 10 of 22 NERs (VNS n = 5, control n = 5). We evaluated the acute and chronic anti-seizure effects of VNS on GTC and DS by behavioral and electroencephalographical observation (2 h every week). We carried out double immunofluorescence for biomarkers of short-term (c-Fos) and long-term (ΔFosB) neuronal activation to map regions in the brain that were activated by acute (VNS n = 6, control n = 6) or chronic VNS (VNS n = 5, control n = 5). Furthermore, we performed chronic VNS (4 w) on 12 NERs (VNS n = 6, control n = 6) with long-term observation (8 h a day, 5d per week) to obtain an adequate number of GTCs to elucidate the time dependent anti-epileptic effect on GTC. RESULTS: Acute VNS treatment reduced GTC seizure frequency and total duration of the DS. Chronic VNS resulted in a time-dependent reduction of DS frequency and duration. However, chronic VNS did not show time-dependent reduction of GTC frequency. There were significant c-Fos expressions in the central medial nucleus (CM), mediodorsal thalamic nucleus (MDM), locus coeruleus (LC), and nucleus of solitary tract (NTS) after acute VNS. And there were significant ΔFosB expressions in the lateral septal nucleus (LSV), medial septal nucleus (MSV), MDM, and pontine reticular nucleus caudal (PnC) after chronic VNS. Any decrease in frequency of GTCs by chronic VNS could not be confirmed even with long-term observation. CONCLUSION: We confirmed acute VNS significantly reduced the frequency of GTC and duration of DS. Chronic VNS decreased the frequency and duration of DS in a time-dependent manner. The brainstem and midline thalamus were activated after acute and chronic VNS. The forebrain was activated only after chronic VNS.

Comparative Evaluation of Angioscopy and Intravascular Ultrasound for Assessing Plaque Protrusion During Carotid Artery Stenting Procedures.

BACKGROUND: Evaluation of plaque protrusion after carotid artery stenting (CAS) is important for predicting periprocedural ischemic complications. In contrast to intravascular ultrasound (IVUS), angioscopy allows direct visualization of the plaque. The aim of this study was to evaluate utility and safety of angioscopy during CAS and compare it with IVUS. METHODS: The study included 13 carotid artery stenosis lesions in 11 consecutive patients (mean age 70.5 years; 10 men) at a single center. During CAS procedure, poststenting plaque protrusion was evaluated with angioscopy and IVUS. RESULTS: Mean level of internal carotid artery stenosis was 79.2%. Eight lesions were symptomatic, and 5 lesions were predicted to have vulnerable plaque by preprocedural magnetic resonance imaging. A carotid WALLSTENT was placed in all cases. After stenting, angioscopy provided good visualization in all cases. Plaque protrusions were observed in 1 case by IVUS and in 8 cases by angioscopy. Diffusion-weighted imaging showed positive lesions in 3 cases (23%). For 2 of these lesions, plaque protrusions were observed by angioscopy but not by IVUS. All lesions associated with positive diffusion-weighted imaging findings were observed to have yellow plaque on angioscopy. CONCLUSIONS: Angioscopy provided direct visualization of stent lumens after CAS. Angioscopy detected more plaque protrusion than IVUS and allowed clearer observation of plaque characteristics. Angioscopy may be more useful than IVUS for examination of plaque protrusion and plaque evaluation after CAS, especially for plaque identified as potentially vulnerable by preprocedural examination.

High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients.

The frequency of KRAS/BRAF mutations associated with low-grade serous ovarian carcinoma (LGSC)/serous borderline tumors (SBTs) in Japan is unknown. We aimed to identify genetic variations in KRAS, BRAF, PIK3CA, and ERBB2 in LGSC/SBT/serous cystadenomas (SCAs) in a Japanese population. We performed a mutation analysis (by Sanger sequencing) of 33 cases of LGSC/SBT/SCA and 4 cases of LGSC with synchronous SBTs using microdissected paraffin-embedded sections. Immunohistochemistry of p53 and ARID1A was also performed. The frequency of oncogenic mutations in PIK3CA was 60.0% (6/10) in LGSCs, 63.6% (7/11) in SBTs, and 8.3% (1/12) in SCAs. All cases harbored wild-type KRAS. The frequency of BRAF mutations was 20.0% (2/10) in LGSCs, whereas all SBTs and SCAs harbored the wild-type allele. The frequency of ERBB2 mutations was 30.0% (3/10) in LGSCs, 0.0% (0/11) in SBTs, and 16.7% (2/12) in SCAs. ARID1A staining was positive in all cases. p53 staining was positive in 0% (0/10) LGSCs, 9.1% (1/11) SBTs, and 0.0% (0/12) SCAs. One LGSC case had two PIK3CA mutations (G1633A and G3149A) in both LGSC and SBT lesions, but a BRAF mutation was detected only in an LGSC lesion. These results suggest that, compared with the values in Western populations (16-54%), the KRAS mutation frequency in LGSCs/SBTs is lower and that of PIK3CA mutations in LGSCs/SBTs is much higher in Japanese populations. Therefore, the main carcinogenesis signaling pathways may be different between Japanese and Western LGSCs. Molecular therapies targeting the PIK3CA/AKT pathway may be effective in LGSCs in Japan.