Three Patients of the Early Onset Epileptic Spasms without Hypsarrhythmia.

Epileptic spasms without hypsarrhythmia occur when patients do not display hypsarrhythmia on electroencephalogram (EEG) at the onset and throughout the clinical course. We report three patients of epileptic spasms in patients with early onset, all of whom experienced other types of seizures.We detail three patients (two boys and one girl) of epileptic spasms without hypsarrhythmia, occurring between 1 and 3 months of age, with no abnormalities detected on neurometabolic analysis and brain magnetic resonance imaging. Long-term video-EEG monitoring revealed epileptic spasms with focal onset seizures in two patients, and epileptic spasms followed by generalized tonic-clonic seizures in one patient. Hypsarrhythmia was never observed in repeated EEG examinations. Two patients achieved seizure freedom and improved development through treatment with topiramate alone or in combination with valproate, without requiring hormonal therapies or vigabatrin. The remaining patient achieved seizure freedom following administration of antiseizure medications, including topiramate, after a trial of adrenocorticotropic hormone therapy.We report the cases of three patients with early onset epileptic spasms without hypsarrhythmia. All patients achieved seizure freedom after topiramate treatment. Topiramate may be considered as a relatively effective antiseizure medication for early onset epileptic spasms without hypsarrhythmia.

Surgical aspects using an exoscope for corpus callosotomy: initial experience for epilepsy surgery.

The exoscope is a new form of optic device that has begun to be used in the last decade. The exoscope provides high-quality magnification and illumination at depth, allowing easy manipulation of surgical instruments even in narrow surgical fields. Exoscopic corpus callosotomy (CC) has not been reported. We report herein our initial experience with the utility of exoscopic CC. A 3-year-old boy diagnosed with West syndrome at 4 months old was referred to our hospital. As the seizure spasms were considered to carry a risk of severe traumatic injury, we performed exoscopic CC as palliative therapy. An EX VITOM 3D exoscope and 4K-3D surgical monitor were used during the procedure. No surgical complications that could be related to exoscope use were noted. Operative time for exoscopic CC was comparable to that for microscopic CC, despite a lack of previous experience with the equipment. Stereoscopic vision was easily obtained. The exoscope was perceived as providing higher quality magnification. We report our first clinical experience of exoscopic CC. The exoscope appears useful in the field of epilepsy surgery.

Experience using mTOR inhibitors for subependymal giant cell astrocytoma in tuberous sclerosis complex at a single facility.

BACKGROUND: Subependymal giant cell astrocytoma (SEGA) is occasionally seen in tuberous sclerosis complex (TSC). Two main options are currently available for treating SEGA: surgical resection or pharmacotherapy using mammalian target of rapamycin inhibitors (mTORi). We hypothesized that opportunities for surgical resection of SEGA would have reduced with the advent of mTORi. METHODS: We retrospectively reviewed the charts of patients treated between August 1979 and July 2020, divided into a pre-mTORi era group (Pre-group) of patients treated before November 2012, and a post-mTORi era group (Post-group) comprising patients treated from November 2012, when mTORi became available in Japan for SEGA. We compared groups in terms of treatment with surgery or mTORi. We also reviewed SEGA size, rate of acute hydrocephalus, recurrence of SEGA, malignant transformation and adverse effects of mTORi. RESULTS: In total, 120 patients with TSC visited our facility, including 24 patients with SEGA. Surgical resection was significantly more frequent in the Pre-group (6 of 7 patients, 86 %) than in the Post-group (2 of 17 patients, 12 %; p = 0.001). Acute hydrocephalus was seen in 1 patient (4 %), and no patients showed malignant transformation of SEGA. The group treated using mTORi showed significantly smaller SEGA compared with the group treated under a wait-and-see policy (p = 0.012). Adverse effects of pharmacotherapy were identified in seven (64 %; 6 oral ulcers, 1 irregular menstruation) of the 11 patients receiving mTORi. CONCLUSIONS: The Post-group underwent surgery significantly less often than the Pre-group. Since the treatment option to use mTORi in the treatment of SEGA in TSC became available, opportunities for surgical resection have decreased in our facility.

Possible Role of High-Dose Barbiturates and Early Administration of Parenteral Ketogenic Diet for Reducing Development of Chronic Epilepsy in Febrile Infection-Related Epilepsy Syndrome: A Case Report.

We describe the efficacy of high-dose barbiturates and early administration of a parenteral ketogenic diet (KD) as initial treatments for acute status epilepticus (SE) in an 8-year-old girl with febrile infection-related epilepsy syndrome (FIRES). The patient was admitted to our hospital with refractory focal SE. Abundant epileptic discharges over the left frontal region were observed on electroencephalogram (EEG). Treatment with continuous infusion of thiamylal for 4 hours, increased incrementally to 40 mg/kg/h, successfully ended the clinical SE, and induced a burst-suppression coma. The infusion rate was then gradually decreased to 4 mg/kg/h over the next 12 hours. Parenteral KD was administered from days 6 to 21 of illness. Continuous infusion of thiamylal was switched to midazolam on day 10 without causing seizures or EEG exacerbations. The patient has remained seizure free in the 15 months since hospital discharge. The effectiveness of KD for the treatment of FIRES has attracted attention amongst clinicians, but KD treatment may need to last for 2 to 4 days before it can stop SE, a time period that could cause irreversible brain damage. Considering the severity of SE in our patient and the dose of barbiturates needed to treat it, we consider this case to have had a good clinical outcome. The results suggest that rapid termination of seizure using high-dose barbiturates in conjunction with early administration of parenteral KD could reduce the development of chronic epilepsy in patients with FIRES.

Considering temporality in causal relationship between seizure worsening and psychological stress in patients with epilepsy during the COVID-19 pandemic: A systematic review.

OBJECTIVE: To investigate whether published studies that identified a causal relationship between psychological stress and seizure worsening in patients with epilepsy during the coronavirus disease 2019 (COVID-19) pandemic considered the temporality of Hill's criteria. METHOD: A systematic review approach was used to comprehensively search MEDLINE, CENTRAL, EMBASE, and ClinicalTrials.gov databases for relevant studies. Studies that reported an association between psychological stress and seizure worsening in patients with epilepsy during the COVID-19 pandemic were included accordingly. The quality of assessments in each study was evaluated and an assessment for considering temporality in the causal relationship between the two events in each study was carried out. RESULTS: Seventeen studies were included in the analysis. Most (14/17) were cross-sectional studies and only four out of these 17 studies (23.5%) considered temporality in the causality. Further, these four studies did not consider temporality in the study design, they only described it as a limitation. CONCLUSION: We found that many articles reported a causal relationship between psychological stress and seizure worsening without considering temporality. As both researchers and readers, we need to consider temporality when interpreting the causal relationship between increased psychological stress and seizure worsening in patients with epilepsy during the COVID-19 pandemic.

Higher intelligence may be a risk factor for postoperative transient disturbance of consciousness after corpus callosotomy.

INTRODUCTION: Corpus callosotomy (CC) is an established surgical option for palliative treatment of medically intractable epilepsy, especially for seizures with drop attacks. We postulated that specific risk factors for post-CC transient disturbance of consciousness (pCTDC) are associated with CC. The purpose of this study was to review patients with intractable epilepsy who underwent CC and to statistically analyze risk factors for pCTDC. METHODS: Inclusion criteria for patients who underwent CC between January 2009 and November 2019 were: (1) ≥2 years old and (2) followed up for more than 8 months. The state of consciousness before and after CC was evaluated with the Glasgow coma scale. We statistically assessed predictors for pCTDC as the primary outcome. RESULTS: Fifty-six patients (19 females, 37 males) were enrolled, and the age range was 2-57 years old. Thirty-seven (66.1%) patients developed pCTDC. The mean period from the beginning of the state of pCTDC to recovery to their baseline conscious level was 4.9 days (range: 2-25 days). All three (100%) normal intelligence level patients, 13 (81%) of 16 patients with a moderately impaired level of intelligence, and 21 (57%) of 37 patients with a severely impaired level of intelligence exhibited pCTDC. Univariate (p = 0.044) and multivariate (p = 0.006) logistic regression analyses for predictors of pCTDC showed that intellectual function was statistically significant. CONCLUSION: Two-thirds of patients developed pCTDC. One risk factor for pCTDC may be higher intellectual function.

Epilepsy in patients with focal cortical dysplasia may be associated with autism spectrum disorder.

INTRODUCTION: Patients with epilepsy associated with focal cortical dysplasia (FCD) may be associated with autism spectrum disorder (ASD). Therefore, the purpose of this study was to compare surgically treated patients with epilepsy secondary to FCD and normal volunteers without epilepsy and to review the neuropathological findings of patients with FCD. METHODS: This study involved 38 patients with medically intractable focal onset epileptic seizures who underwent epilepsy surgery (Group 1). All patients had epilepsy associated with FCD. These patients and 38 normal volunteers without epilepsy (Group 2) were administered the autism spectrum quotient (AQ) test, and the groups were compared. RESULTS: The 38 patients in Group 1 included 16 females and 22 males (age range 20-60, mean age, 33.0; standard deviation (SD), 11.8 years). The normal volunteers in Group 2 included 22 females and 16 males (age range 20-57, mean age, 30.6 years; SD, 8.8 years). Total AQ scores were significantly higher in Group 1 than Group 2 (p = 0.027). Patients with FCD I showed a higher AQ score than those with FCD II in the AQ test (p ≤ 0.001). CONCLUSION: Patients with epilepsy secondary to FCD were associated with higher ASD score than normal volunteers. This tendency was seen more strongly in patients with FCD I than FCD II.

Posttraumatic epilepsy may be a state in which underlying epileptogenicity involves focal cortical dysplasia.

INTRODUCTION: The occurrence rate of posttrauma epilepsy ranges widely from 1% to 30%. Little is known about the underlying epileptogenesis of traumatic brain injury (TBI)-related epilepsy (TRE), because no comparison between TRE and TBI without epilepsy has been performed in terms of neuropathology. Therefore, we postulated that different neuropathological factors may be present between TRE and TBI without epilepsy. The purpose of this study was to clarify differences between TRE and TBI without epilepsy. METHODS: We studied patients who experienced severe head trauma and underwent brain surgery. The age range of the patients was 9-71 years old. Patients with medically resistant epilepsy were included in the Epilepsy group, and patients without epilepsy were included in the nonepilepsy group. Pathological findings, age, sex, and cause of head trauma were statistically compared between these two groups. RESULTS: This study involved 10 patients, nine of whom met the inclusion criteria. Pathological findings for all patients in the Epilepsy group included focal cortical dysplasia (FCD) (p = 0.012). CONCLUSION: The difference between TRE and TBI without epilepsy was underlying FCD in patients with TRE.

Seizure focus in the frontal interhemispheric fissure leads to ipsilateral isolated eye deviation.

OBJECTIVE: Few studies have examined the localization of seizures presenting with ictal eye deviation (ED) in the absence of other motor symptoms. We aimed to investigate differences in the localization of the ictal onset zone (IOZ) between patients with isolated ED and those with ED plus head turning (HT) during focal seizures. METHODS: We reviewed intracranial video-EEG data for 931 seizures in 80 patients with focal onset epilepsy in whom the IOZ could be confirmed. The 233 seizures in 49 patients with ED were classified into two semiological groups based on initial ED and the presence/absence of HT: (1) isolated ED (i.e., ED without HT), and (2) ED + HT (i.e., ED with HT). We analyzed the localization and lateralization of IOZs in each semiological group. We performed multivariate logistic regression analysis using a mixed-effects to determine the associations between IOZs and isolated ED/ED + HT. RESULTS: A total of 183 IOZs in 24 patients were included in the isolated ED group, while a total of 143 IOZs in 31 patients were included in the ED + HT group. Sixty-eight IOZs of eight patients in the isolated ED group were located in the ipsilateral frontal interhemispheric fissure (F-IHF). Only ipsilateral F-IHF was significantly associated with isolated ED (odds ratio [OR], 2.43; 95% confidence interval [CI], 0.37-4.49; P = 0.021). The contralateral lateral frontal cortex (latF) (P = 0.007) and ipsilateral mesial temporal region (mT) (P = 0.029) were significantly associated with ED + HT. CONCLUSION: The present study is the first to demonstrate that seizures with an F-IHF focus tend to present with initial ipsilateral isolated ED. This finding may aid in identifying the seizure focus in patients with isolated ED prior to resection.

Postoperative persistent fever may be a risk factor for hydrocephalus in hemispherical disconnection surgery.

INTRODUCTION: Hemispherical disconnection surgery such as hemispherotomy or posterior quadrant disconnection (PQD) surgery sometimes induces hydrocephalus. We postulated that some risk factors for postoperative hydrocephalus can be managed perioperatively. The purpose of this study was to clarify and statistically analyze perioperative risk factors for postoperative progressive hydrocephalus. METHODS: We reviewed patients who underwent hemispherotomy or PQD. We compared patients with and without progressive hydrocephalus with multivariate and univariate logistic regression analysis to identify risk factors for hydrocephalus. RESULTS: Twenty-four patients underwent hemispherectomy or PQD (age: 25 days-45 years old, mean: 13.3 years, median: 8 years, standard deviation: 13.9 years, 14 males). Among them, five patients (21%) required hydrocephalus treatment. Persistent fever was a risk factor for progressive hydrocephalus (multivariate analysis: p = 0.024, univariate analysis: p < 0.001). CONCLUSION: Postoperative persistent fever may be a manageable risk factor for postoperative hydrocephalus in hemispherotomy and PQD surgery.

Epilepsy surgery reduced seizure frequency for patients with severe motor and intellectual disorders.

INTRODUCTION: Little is known about epilepsy surgery for patients with severe motor and intellectual disorders (SMIDs). We hypothesized that epilepsy surgery could reduce epileptic seizure frequency in these patients. The purpose of this study was to compare pre- and postoperative seizure frequency in patients with SMIDs. METHODS: A total of 288 surgeries were performed for pediatric patients, including those with SMIDs, from 2009 to 2018. Inclusion criteria were as follows: Oshima classification 1 (intelligence quotient <20 and bedridden), ≥2 years old, proven ictal events evaluated by long-term video electroencephalography, and ≥1-year follow-up. Seizure frequency and the number of antiseizure medications (ASMs) were compared between pre- and postepilepsy surgery. Patients' respiratory and feeding conditions were also examined to determine comorbidities. RESULTS: Nineteen patients (5 girls, 14 boys; age: 2 to 12 years) fulfilled the inclusion criteria. One patient underwent focus resection, 2 patients underwent total corpus callosotomy, and 16 patients underwent vagus nerve stimulation therapies. Of 19 patients, 16 (84.2%) had daily seizures, and 3 (15.8%) had weekly seizures before surgery. Epilepsy surgery significantly reduced seizure frequency (p = 0.029). Five patients (26.3%) had status epilepticus (SE) before surgery, which disappeared in all but one after surgery (p = 0.046). The number of ASMs did not change between before and after surgery (p = 0.728). CONCLUSION: Epilepsy surgery reduced the frequency of epileptic seizures and improved SE even among patients with compromised respiratory function and compromised food intake.

Association between diffuse cerebral MRI lesions and the occurrence and intractableness of West syndrome in tuberous sclerosis complex.

OBJECTIVE: We aimed to clarify the association between magnetic resonance imaging (MRI)-lesion patterns, including cortices and white matters, and the development, occurrence, and intractableness of West syndrome in patients with tuberous sclerosis complex (TSC), using visual analysis. METHODS: We collected data for 44 patients with TSC who had undergone brain MRI and developmental evaluation after the ages of 2 and 3 years, respectively. Fluid-attenuated inversion recovery (FLAIR) and T1-weighted images were used to analyze the number of cyst-like tubers, the number of cyst-like subcortical lesions, and the presence of diffuse lesions involving the cortices and white matter. RESULTS: Developmental delays were observed in 28 patients. Nineteen patients had a history of West syndrome. Cyst-like tubers (range: 1-10), cyst-like subcortical lesions (range: 1-4), and diffuse lesions (range: 1-6 areas) were observed in 15, 9, and 14 patients, respectively. In the univariate analyses, all MRI findings were associated with development and/or history of West syndrome. However, in the multivariate analyses, only the diffuse lesion was associated with severe development (p = 0.003) and history of West syndrome (p = 0.012). In the subanalysis of patients with West syndrome, the diffuse lesions were also associated with pharmacological intractableness. Patients with diffuse lesions had a history of West syndrome with sensitivity of 68% and specificity of 96%. Patients with two or more areas of diffuse lesions had history of pharmacologically intractable West syndrome with sensitivity of 89% and specificity of 91%. CONCLUSIONS: Diffuse lesions may help to predict the poor neurological outcomes in patients with TSC.

Activities of daily living are associated with outcomes of epilepsy treatment in elderly patients.

AIM: Controlling epileptic seizures in elderly populations is widely considered to be relatively easy, but we hypothesized that the lifestyles of elderly individuals may affect the outcomes of epilepsy treatment. The purpose of this study was to review the activities of daily living (ADL) of elderly individuals with epilepsy and compare them with the outcomes of epilepsy treatment. METHODS: Of the 177 patients ≥65 years old who were referred to our epilepsy centre, epilepsy was diagnosed in 84. ADL and treatment outcomes were then reviewed, with ADL classified into three levels: ADL I, without disability; ADL II, disabled only in some instrumental ADL; and ADL III, disabled in some basic ADL. Epilepsy syndromes and use of anti-seizure drugs were also evaluated. RESULTS: Forty-five patients (53.6%) achieved freedom from seizures, 23 (27.4%) achieved ≥80% but <100% reduction in seizures, 5 (6%) achieved ≥50% but <80% reduction in seizures, and 11 (13.1%) achieved <50% reduction in seizures. Thirty-five patients (81.4%) with ADL I achieved freedom from seizures, compared with seven patients with ADL II (28.0%) and three patients with ADL III (19.0%). A significant difference was evident among the three groups (F = 6.145, P = 0.003). CONCLUSIONS: ADL should be taken into account when an epilepsy treatment is being selected.

Inclusion of general physicians in the multidisciplinary treatment team for epilepsy may lead to an economic benefit.

INTRODUCTION: The purpose of this study was to compare epileptic seizure control and economic impact in patients with epilepsy between when they were seen by general physicians (GPs) versus epilepsy specialists. METHOD: We began distributing a booklet we named the "Epi Passport" to patients with epilepsy in December 2014 to share information within the regional epilepsy network of GPs, epilepsy specialists, and patients (Gep). We compared seizure control and household income levels before and after the introduction of this booklet. RESULTS: There was no significant difference in seizure control between patients who saw specialists or GPs (P = 0.215). Significant increases in household income were seen among 134 patients (36.6%) in the post-Epi Passport period who were primarily seen by GPs (P < 0.001). However, 35 patients (9.6%) showed a decrease in income between periods, and 197 patients (53.8%) showed no change. Age of 20-39 years old was significantly associated with increases in household income (P = 0.0287). CONCLUSION: After the introduction of the Epi Passport, about one-third of the patients with epilepsy who were mainly seen by GPs in their community showed an increase in household income. There was no difference in seizure control among those who saw a GP or a specialist. Inclusion of GPs in the multidisciplinary treatment team for epilepsy may lead to increased patient income because of the fact that patients can manage their epilepsy in their community using their GP.

Corpus callosotomy for drug-resistant spasms associated with tuberous sclerosis complex.

BACKGROUND: Corpus callosotomy (CC) has recently been adopted for the treatment of drug-resistant epileptic spasms and tonic spasms. In the present study, we investigated CC outcomes among patients with drug-resistant epileptic spasms or tonic spasms associated with tuberous sclerosis complex (TSC). METHODS: We retrospectively collected data from seven patients (3 women, 4 men) with diagnosed TSC and who were treated using CC at Seirei Hamamatsu General Hospital in Japan. All patients had experienced drug-resistant epileptic spasms (<3 s of muscular contraction) or tonic spasms (>3 s) prior to CC, which were confirmed via video-electroencephalogram monitoring. RESULTS: All patients exhibited multiple bilateral cortical tubers on brain magnetic resonance imaging. The main seizure types were epileptic spasms in four, tonic spasms in one, and both seizure types in two patients. Patients underwent total CC between the ages of 25 months and 21.5 years. Additional resection or disconnection was performed in two patients. The follow-up period after CC ranged between 9 months and 3.5 years. Three patients achieved remission from spasms following CC alone. Two other patients became free from spasms several months after CC but required an additional focus disconnection or medical treatment. The remaining two patients continued to show spasms or asymmetrical tonic seizures. CONCLUSION: Total CC resulted in freedom from drug-resistant epileptic or tonic spasms in several patients with TSC. Stepwise progression from CC to additional resection or disconnection surgery may aid in the treatment of spasms secondary to TSC.

A case of focal cortical dysplasia type Ib atypically showing reversible intensity changes on magnetic resonance imaging which could be affected by epileptic discharge activity.

Focal cortical dysplasia (FCD) was first described as a distinct neuropathological entity in 1971 by Taylor and colleagues. FCD is thought to be an embryological migration disorder and is thus considered a non-progressive, unchangeable disease throughout life. A 9-year-old right-handed boy was referred from a local hospital for medically intractable epileptic seizures. Serial magnetic resonance images (MRI) showed intensity changes that indicated exacerbation and remission. After presurgical evaluations including intracranial video-electroencephalogram monitoring, we performed a lesionectomy aided by MRI and epileptic focus resection. He has been free from seizures for more than 3 years. Neuropathological findings showed FCD type Ib. We surgically treated a patient with FCD, which showed MRI intensity changes indicating exacerbation and remission. Although FCD type Ib is generally invisible on MRI, in this patient, changes in intensity on MRI made FCD type Ib visible.

Double match of 18F-fluorodeoxyglucose-PET and iomazenil-SPECT improves outcomes of focus resection surgery.

BACKGROUND: When the results of electroencephalography (EEG), magnetic resonance imaging (MRI), and seizure semiology are discordant or no structural lesion is evident on MRI, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are important examinations for lateralization or localization of epileptic regions. We hypothesized that the concordance between interictal 2-[18F]fluoro-2-deoxy-D-glucose (18FDG)-PET and iomazenil (IMZ)-SPECT could suggest the epileptogenic lobe in patients with non-lesional findings on MRI. METHOD: Fifty-nine patients (31 females, 28 males; mean age, 29 years; median age, 27 years; range, 7-56 years) underwent subdural electrode implantation followed by focus resection. All patients underwent 18FDG-PET, IMZ-SPECT, and focus resection surgery. Follow-up was continued for ≥ 2 years. We evaluated surgical outcomes as seizure-free or not and analyzed correlations between outcomes and concordances of low-uptake lobes on PET, SPECT, or both PET and SPECT to the resection lobes. We used uni- and multivariate logistic regression analyses. RESULTS: In univariate analyses, all three concordances correlated significantly with seizure-free outcomes (PET, p = 0.017; SPECT, p = 0.030; both PET and SPECT, p = 0.006). In multivariate analysis, concordance between resection and low-uptake lobes in both PET and SPECT correlated significantly with seizure-free outcomes (p = 0.004). The odds ratio was 6.0. CONCLUSION: Concordance between interictal 18FDG-PET and IMZ-SPECT suggested that the epileptogenic lobe is six times better than each examination alone among patients with non-lesional findings on MRI. IMZ-SPECT and 18FDG-PET are complementary examinations in the assessment of localization-related epilepsy.

[Experience and Solution of Complications of Vagus Nerve Stimulation Therapy in 139 Implant Patients with Medically Refractory Epilepsy].

BACKGROUND: Vagus nerve stimulation(VNS)for patients with intractable epilepsy was approved by the Japan Ministry of Health, Labour and Welfare in 2010. More than 1,500 VNS systems were implanted by the end of August 2016. The aim of the present report is to describe complications we experienced at our department and consider the way to avoid them. METHODS AND PATIENTS: We retrospectively reviewed 139 consecutive patients(122 new implantations and 17 reimplantations)between December 2010 and March 2016. RESULTS: Seven patients demonstrated eight complications. Four patients experienced recurrent nerve paralysis with hoarseness and/or cough that did not require device removal. One patient experienced subsequent aspiration pneumonia. The device was removed in one case due to lead fracture and in three owing to surgical site infection(SSI). CONCLUSION: All recurrent nerve paralysis occurred just after we started VNS implantations. It was presumed that the nerve paralysis was caused by retraction around the vagus nerve. Smaller skin incision and decreased retraction of the surgical field has eliminated this complication. The incidence of infections is reported as 2.2%. Allergic reaction to the VNS device might be one of the causes for SSI in our series. Fracture of the lead was caused by revolving of the pulse generator under the skin. Tight sutures around the pocket or subpectoral placement of a pulse generator is necessary to prevent rotation of the generator depending upon the activity of each patient. This paper provides insight into complications and successful strategies for better outcomes in VNS therapy.