A knowledge synthesis of health research reporting standards relevant to epilepsy surgery.

OBJECTIVE: Numerous studies have examined epilepsy surgery outcomes, yet the variability in the level of detail reported hampers our ability to apply these findings broadly across patient groups. Established reporting standards in other clinical research fields enhance the quality and generalizability of results, ensuring that the insights gained from studying these surgeries can benefit future patients effectively. This study aims to assess current reporting standards for epilepsy surgery research and identify potential gaps and areas for enhancement. METHODS: The Enhancing the Quality and Transparency of Health Research (EQUATOR) repository was accessed from inception to April 27, 2023, yielding 561 available reporting standards. Reporting standards were manually reviewed in duplicate independently for applicability to epilepsy and/or neurosurgery research. The reporting standards had to cover the following aspects in human studies: (1) reporting standards for epilepsy/epilepsy surgery and (2) reporting standards for neurosurgery. Disagreements were resolved by a third author. The top five neurosurgery, neurology, and medicine journals were also identified through Google Scholar's citation index and examined to determine the relevant reporting standards they recommended and whether those were registered with EQUATOR. RESULTS: Of the 561 EQUATOR reporting standards, 181 were pertinent to epilepsy surgery. One was related to epilepsy, six were specific to surgical research, and nine were related to neurological/neurosurgical research. The remaining 165 reporting standards were applicable to research across various disciplines and included but were not limited to CONSORT (Consolidated Standards of Reporting Trails), STROBE (Strengthening the Reporting of Observational Studies in Epidemiology), and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). None of these required reporting factors associated with epilepsy surgery outcomes, such as duration of epilepsy or magnetic resonance imaging findings. SIGNIFICANCE: Reporting standards specific to epilepsy surgery are lacking, reflecting a gap in standards that may affect the quality of publications. Improving this gap with a set of specific reporting standards would ensure that epilepsy surgery studies are more transparent and rigorous in their design.

Responsive Neurostimulation for People With Drug-Resistant Epilepsy and Autism Spectrum Disorder.

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System. METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis. RESULTS: Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a >50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction >90%). For the super responders, two of the four patients had the device implanted for >2 years. The response rate was 70% for those in whom the device was implanted for >2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported. CONCLUSIONS: Based on the authors' experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD-DRE.

Efficacy of Occipital Nerve Stimulation in Trigeminal Autonomic Cephalalgias: A Systematic Review.

BACKGROUND: Trigeminal autonomic cephalalgias (TACs) are a group of highly disabling primary headache disorders. Although pharmacological treatments exist, they are not always effective or well tolerated. Occipital nerve stimulation (ONS) is a potentially effective surgical treatment. OBJECTIVE: To perform a systematic review of the efficacy of ONS in treating TACs. METHODS: A systematic review was performed using Medline, Embase, and Cochrane databases. Primary outcomes were reduction in headache intensity, duration, and frequency. Secondary outcomes included adverse event rate and reduction in medication use. Because of large differences in outcome measures, data for patients suffering from short-lasting, unilateral, and neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and cranial autonomic symptoms (SUNA) were reported separately. Risk of bias was assessed using the NIH Quality Assessment Tools. RESULTS: A total of 417 patients from 14 published papers were included in the analysis, of which 15 patients were in the SUNCT/SUNA cohort. The mean reduction in headache intensity and duration was 26.2% and 31.4%, respectively. There was a mean reduction in headache frequency of 50%, as well as a 61.2% reduction in the use of abortive medications and a 31.1% reduction in the use of prophylactic medications. In the SUNCT/SUNA cohort, the mean decrease in headache intensity and duration was 56.8% and 42.8%. The overall responder rate, defined as a >50% reduction in attack frequency, was 60.8% for the non-SUNCT/non-SUNA cohort and 66.7% for the SUNCT/SUNA cohort. Adverse events requiring repeat surgery were reported in 33% of cases. Risk of bias assessment suggests that articles included in this review had reasonable internal validity. CONCLUSION: ONS may be an effective surgical treatment for approximately two thirds of patients with medically refractory TACs.

Comparing vagus nerve stimulation and resective surgery outcomes in patients with co-occurring autism and epilepsy to patients with epilepsy alone: A population-based study.

Autism and epilepsy commonly co-occur. Understanding trends in healthcare utilization and in-hospital outcomes amongst patients with autism and epilepsy can help optimize care and reduce costs. We compared hospital outcomes amongst patients with autism and epilepsy to those with epilepsy alone undergoing vagus nerve stimulation (VNS) and resective/disconnective surgery. Differences in discharge status, in-hospital mortality, mean length of stay (LOS), cost and surgical/medical complications were examined. Elective surgical admissions amongst patients with epilepsy alone and co-occurring autism and epilepsy were identified in the 2003-14 National Inpatient Sample (NIS) using previously validated ICD-9-CM case definitions. One patient with co-occurring epilepsy and autism was matched to three epilepsy patients for age, sex and (1) VNS and (2) resective/disconnective surgery. Multinomial logistic regressions were performed to examine the outcomes of interest. Data were collected on: (1) VNS-52 (mean age: 12.79 ± 1.03; 19.27% female) hospital admissions in persons with comorbid autism and epilepsy, 156 (mean age: 12.84 ± 0.71; 19.31% female) matched controls with epilepsy alone; (2) resective/disconnective surgery-113 (mean age: 12.99 ± 0.84; 24.55% female) with comorbid autism and epilepsy, 339 (mean age: 13.37 ± 0.68; 23.86% female) matched controls with epilepsy alone. Compared to patients with epilepsy alone, patients with autism and epilepsy who underwent either surgery showed no differences for in-hospital mortality, discharge status, mean LOS, hospitalization cost, and surgical/medical complications. Our study shows the feasibility and safety of epilepsy VNS and resective surgery in those with ASD do not differ with those with epilepsy alone, contrary to the prevalent safety concerns of epilepsy surgery in patients with ASD.

Association of first anti-seizure medication choice with injuries in older adults with newly diagnosed epilepsy.

BACKGROUND: Epilepsy incidence increases exponentially in older adults, who are also at higher risk of adverse drug effects. Anti-seizure medications (ASM) may be associated with sedation and injuries, but discontinuation can result in seizures. We sought to determine whether there was an association between prescribing non-guideline concordant ASM and subsequent injury as this could inform care models. METHODS: Retrospective cohort study of adults 50 years or older with newly-diagnosed epilepsy in 2015-16, sampled from the MarketScan Databases. The outcome of interest was injury within 1-year of ASM prescription (e.g., burns, falls) and the exposure of interest was ASM category (recommended vs. not recommended by clinical guidelines). Descriptive statistics characterized covariates and a multivariable Cox-regression model was built to examine the association between ASM category and subsequent injury. RESULTS: 5,931 people with newly diagnosed epilepsy were prescribed an ASM within 1-year. The three most common ASMs were: levetiracetam (62.86%), gabapentin (11.73%), and phenytoin (4.45%). Multivariable Cox-regression found that medication category was not associated with injury; however, older age (adjusted hazard ratio (AHR) 1.01/year), history of prior injury (AHR 1.77), traumatic brain injury (AHR 1.55) and ASM polypharmacy (AHR 1.32) were associated with increased hazard of injury. CONCLUSIONS: Most older adults appear to be getting appropriate first prescriptions for epilepsy. However, a substantial proportion still receives medication that guidelines suggest avoiding. In addition, we show that ASM polypharmacy is associated with an increased hazard of injury within 1- year. Efforts to improve prescribing in older adults with epilepsy should consider how to reduce. both polypharmacy and exposure to medications that guidelines recommend avoiding.

Seizure onset patterns predict outcome after stereo-electroencephalography-guided laser amygdalohippocampotomy.

OBJECTIVE: Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo-EEG) may miss seizure onset elsewhere. We hypothesized that stereo-EEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the 2-year outcomes of patients who underwent single-fiber SLAH after stereo-EEG and evaluated whether stereo-EEG SOPs predict postoperative seizure freedom. METHODS: This retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent stereo-EEG followed by single-fiber SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. An SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was 2-year Engel I classification or recurrent seizures before then, stratified by SOP category. RESULTS: Fifty-eight patients were included, with a mean follow-up duration of 39 ± 12 months after SLAH. Overall 1-, 2-, and 3-year Engel I seizure freedom probability was 54%, 36%, and 33%, respectively. Patients with SOPs, including low-voltage fast activity or low-frequency repetitive spiking, had a 46% 2-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log-rank test, p = .00015). SIGNIFICANCE: Patients who underwent SLAH after stereo-EEG had a low probability of seizure freedom at 2 years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between hippocampal seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.

Autism Spectrum Disorder and Epilepsy.

Autism spectrum disorder (ASD), was first described in 1943 as a disorder consisting of a triad of qualitative impairments of social interaction, communication and restricted repetitive patterns of behavior, interests, and activities. The relationship between ASD and epilepsy is well documented. Patients with ASD have an increased risk of epilepsy, while those with epilepsy have a higher risk of ASD, as compared with the general population. Diagnosing epilepsy in those with ASD can be challenging. For example, stereotyped behaviors could be mistaken as ASD stereotypies, when in fact, they may be due to seizures. Fortunately, in recent years, we have gained a better understanding of the best antiseizure medications (ASMs) to use in this vulnerable population. However, more studies are needed to understand how best to screen for ASD in epilepsy, what the various ASD phenotypes are in people with epilepsy, especially those due to de novo genes/mutations, as well as factors influencing the fluctuating nature of ASD symptoms (eg, seizure type, frequency, syndromes, ASMs)..

Timing of referral to evaluate for epilepsy surgery: Expert Consensus Recommendations from the Surgical Therapies Commission of the International League Against Epilepsy.

Epilepsy surgery is the treatment of choice for patients with drug-resistant seizures. A timely evaluation for surgical candidacy can be life-saving for patients who are identified as appropriate surgical candidates, and may also enhance the care of nonsurgical candidates through improvement in diagnosis, optimization of therapy, and treatment of comorbidities. Yet, referral for surgical evaluations is often delayed while palliative options are pursued, with significant adverse consequences due to increased morbidity and mortality associated with intractable epilepsy. The Surgical Therapies Commission of the International League Against Epilepsy (ILAE) sought to address these clinical gaps and clarify when to initiate a surgical evaluation. We conducted a Delphi consensus process with 61 epileptologists, epilepsy neurosurgeons, neurologists, neuropsychiatrists, and neuropsychologists with a median of 22 years in practice, from 28 countries in all six ILAE world regions. After three rounds of Delphi surveys, evaluating 51 unique scenarios, we reached the following Expert Consensus Recommendations: (1) Referral for a surgical evaluation should be offered to every patient with drug-resistant epilepsy (up to 70 years of age), as soon as drug resistance is ascertained, regardless of epilepsy duration, sex, socioeconomic status, seizure type, epilepsy type (including epileptic encephalopathies), localization, and comorbidities (including severe psychiatric comorbidity like psychogenic nonepileptic seizures [PNES] or substance abuse) if patients are cooperative with management; (2) A surgical referral should be considered for older patients with drug-resistant epilepsy who have no surgical contraindication, and for patients (adults and children) who are seizure-free on 1-2 antiseizure medications (ASMs) but have a brain lesion in noneloquent cortex; and (3) referral for surgery should not be offered to patients with active substance abuse who are noncooperative with management. We present the Delphi consensus results leading up to these Expert Consensus Recommendations and discuss the data supporting our conclusions. High level evidence will be required to permit creation of clinical practice guidelines.

Incidence and Prevalence of Drug-Resistant Epilepsy: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the incidence and prevalence of drug-resistant epilepsy (DRE) as well as its predictors and correlates, we conducted a systematic review and meta-analysis of observational studies. METHODS: Our protocol was registered with PROSPERO, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology reporting standards were followed. We searched MEDLINE, Embase, and Web of Science. We used a double arcsine transformation and random-effects models to perform our meta-analyses. We performed random-effects meta-regressions using study-level data. RESULTS: Our search strategy identified 10,794 abstracts. Of these, 103 articles met our eligibility criteria. There was high interstudy heterogeneity and risk of bias. The cumulative incidence of DRE was 25.0% (95% confidence interval [CI]: 16.8-34.3) in child studies but 14.6% (95% CI: 8.8-21.6) in adult/mixed age studies. The prevalence of DRE was 13.7% (95% CI: 9.2-19.0) in population/community-based populations but 36.3% (95% CI: 30.4-42.4) in clinic-based cohorts. Meta-regression confirmed that the prevalence of DRE was higher in clinic-based populations and in focal epilepsy. Multiple predictors and correlates of DRE were identified. The most reported of these were having a neurologic deficit, an abnormal EEG, and symptomatic epilepsy. The most reported genetic predictors of DRE were polymorphisms of the ABCB1 gene. CONCLUSIONS: Our observations provide a basis for estimating the incidence and prevalence of DRE, which vary between populations. We identified numerous putative DRE predictors and correlates. These findings are important to plan epilepsy services, including epilepsy surgery, a crucial treatment option for people with disabling seizures and DRE.

Trends in lobectomy/amygdalohippocampectomy over time and the impact of hospital surgical volume on hospitalization outcomes: A population-based study.

OBJECTIVE: Despite national guidelines supporting surgical referral in drug-resistant epilepsy, it is hypothesized that surgery is underutilized. We investigated the volumes of lobectomy/amygdalohippocampectomy surgeries over time and examined differences in outcomes between (1) high-volume (HV), middle-volume (MV), and low-volume (LV) hospitals and (2) Level 4 Centers versus non-Level 4 Centers. METHODS: The 2003-2014 National Inpatient Sample (the largest all-payer hospitalization database, representative of the US population) was utilized. Epilepsy was identified using a previously validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) case definition and surgeries using ICD-9-CM procedure codes. A hospital was considered a Level 4 Center if it performed intracranial electroencephalographic (EEG) monitoring. Tumor surgeries were excluded. Linear regression was used to perform trend tests. Weighted multivariate logistic regression was used to summarize association of surgery with outcomes. RESULTS: A total of 4,487 lobectomy/amygdalohippocampectomy surgeries were performed in children and adults with epilepsy. Lobectomy/amygdalohippocampectomy surgeries significantly decreased over time (slope: -0.24, P < .001). This declining surgical trend was greater for all resective/disconnective surgery (slope: -0.45, P < .001), and greatest when compared to all types of epilepsy surgery, for example, resection/disconnection/radiosurgery/laser interstitial thermal therapy/vagus nerve stimulation/deep brain stimulation/responsive neurostimulation/intracranial EEG (slope: -0.95, P < .001). LV compared to HV hospitals had higher odds of transfer to other facilities (13.60% vs 4.24%, odds ratio [OR] = 2.76, 95% confidence interval [CI] = 1.11-6.82). LV hospitals had higher odds of surgical complications versus MV (12.69% vs 6.80%, OR = 2.20, 95% CI = 1.01-5.09). HV hospitals incurred the least total charges. There were no differences in discharge status, adverse events, length of stay, or cost between Level 4 Centers versus non-Level 4 Centers. SIGNIFICANCE: Lobectomies/amygdalohippocampectomies are decreasing over time, suggesting ongoing underutilization. LV centers are associated with greater complication and transfer rates. Future studies are required to understand the reason for worse outcomes in LV centers and to determine whether a minimum number of surgeries must be performed to meet necessary standards.

Assessment of long-term psychosocial outcomes in anti-NMDA receptor encephalitis.

PURPOSE: The purpose of this study was to assess long-term psychosocial outcomes of anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (anti-NMDARE). METHODS: Adolescents and adults with self-reported anti-NMDARE were invited to complete an online survey distributed by relevant patient organizations. Demographic and clinical information was collected, including the diagnoses initially given for anti-NMDARE symptoms and posthospital care received. Patient-Reported Outcomes Measurement Information System (PROMIS) Psychosocial Impact Illness - Negative short form (Negative PSII) was administered to assess psychosocial outcome of anti-NMDARE. Associations between clinical factors and psychosocial outcomes were evaluated. RESULTS: Sixty-one individuals with anti-NMDARE age 15 years and above participated. Mean age was 33.7 years (standard deviation [SD]: 12.8), and participants were predominantly female (90.2%, n = 55). Mean T-score on PROMIS Negative PSII was 60.7, >1 SD higher (worse psychosocial function) than that of the provided normalized sample enriched for chronic illness (50, SD: 10). Initial misdiagnosis of anti-NMDARE symptoms was associated with decreased odds (odds ratio [OR]: 0.11, p < 0.05), and follow-up with a psychiatrist after hospitalization with increased odds (OR: 8.46, p < 0.05), of return to work/school after illness. Younger age of symptom onset and presence of ongoing neuropsychiatric issues were predictive of worse Negative PSII scores (p < 0.05). CONCLUSION: Individuals with anti-NMDARE demonstrate poor psychosocial outcomes, yet there are no current standards for long-term assessment or management of such symptoms in this population. These findings highlight the need for use of more comprehensive outcome measures that include assessment of psychosocial function and the importance of developing interventions that address this domain for individuals with anti-NMDARE.

Assessment of care transitions and caregiver burden in anti-NMDA receptor encephalitis.

PURPOSE: The purpose of the study was to assess care transitions and caregiver burden among caregivers of individuals with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (anti-NMDARE). METHODS: Caregivers of individuals with anti-NMDARE were recruited via patient organization websites. Demographic and clinical information as well as responses to the Care Transition Measure 15 (CTM-15) and Zarit Burden Interview (ZBI) were collected. Exploratory factor analysis (EFA) was conducted on the ZBI, and underlying constructs were analyzed for associations with the CTM-15 and clinical characteristics. RESULTS: Seventy-six caregivers participated. On the CTM-15, the top items where caregivers disagreed or strongly disagreed were the following: "when the patient left the hospital, I had a readable and easily understood written plan that described how all of their healthcare needs were going to be met" (73%), "when the patient left the hospital, I was confident that I know how to manage their health" (62%), and "when the patient left the hospital, I had all the information I needed to be able to take care of them" (58%). Worse care transitions significantly predicted higher caregiver burden scores. Mean ZBI score was 44, falling in the moderate to severe burden range. Exploratory factor analysis was conducted and found four common underlying factors associated with total score. Factor 1, the impact of caring on caregivers' personal lives (accounting for 51% of total score variance), was selected for further analysis because of its modifiable nature. Higher ZBI scores were associated with lower CTM-15 scores (p < 0.003) and the individual with anti-NMDARE not returning to driving (p < 0.002). CONCLUSION: This study identified specific elements of care transitions and caregiver burden that are not currently being addressed for individuals with anti-NMDARE. Attention to these aspects of care in the development of targeted interventions may improve outcomes in individuals with anti-NMDARE and their caregivers.

Cost-Effectiveness of Advanced Imaging Technologies in the Presurgical Workup of Epilepsy.

The cost-effectiveness and benefit of many diagnostic tests used in the presurgical evaluation for persons with epilepsy is for the most part uncertain as is their influence on decision-making. The options we have at our disposal are ever increasing. Advanced imaging modalities aim to improve surgical candidacy by helping us better define the epileptogenic zone and optimize surgical planning. However, judicious use is important. Randomized controlled trials delineating which mode of investigation is superior are lacking. Presurgical tests do have incremental value by increasing surgical candidacy and refining surgical planning. The yield of additional imaging will increase with complex localization. However, every case must be tailored by hypothesis, cost, and accessibility. Future studies using a quantitative cost-benefit framework are needed to determine the cost-effectiveness of advanced diagnostic tests (beyond magnetic resonance imaging) in the presurgical evaluation of those with epilepsy.

Readmission after neurosurgical intervention in epilepsy: A nationwide cohort analysis.

OBJECTIVE: Hospital readmissions result in increased health care costs and are associated with worse outcomes after neurosurgical intervention. Understanding factors associated with readmissions will inform future studies aimed at improving quality of care in those with epilepsy. METHODS: Patients of all ages with epilepsy who underwent a neurosurgical intervention were identified in the 2014 Nationwide Readmissions Database, a nationally representative dataset containing data from roughly 17 million US hospital discharges. Diagnosis of epilepsy was based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based case definitions. Neurosurgical interventions for epilepsy: resective/disconnective surgery, responsive neurostimulation/deep brain stimulation, vagus nerve stimulation, radiosurgery, and intracranial electroencephalography were identified using ICD-9-CM procedure codes. Primary outcome was all-cause 30-day readmission following discharge from the index hospitalization. RESULTS: There were a total of 2284 index surgical admissions. Overall, 10.83% (n = 251) of patients following an index epilepsy surgery admission were readmitted within 30 days. Factors independently associated with 30-day readmission for all epilepsy surgery admissions were: Medicare insurance (P < .01), discharge disposition that was not home (P < .01), higher Elixhauser comorbidity indexes (P < .01), longer length of stay (P < .01), and adverse events of surgical and medical care during index stay (P = .04). In the multivariate model, Medicare insurance (hazard ratio [HR] 1.81 [1.29-2.53], P < .01) and length of stay (HR 1.02 [1.01-1.04], P < .01) remained significant independent predictors for 30-day readmission. The most common primary reason for readmissions was epilepsy/convulsions accounting for 22.85%. SIGNIFICANCE: Our results suggest that careful management of postoperative seizures and discharge planning after epilepsy surgery may be important to optimize outcomes and reduce the risk of readmission, particularly for patients on Medicare.

Perspectives on the current developments with neuromodulation for the treatment of epilepsy.

Introduction: As deep brain stimulation revolutionized the treatment of movement disorders in the late 80s, neuromodulation in the treatment of epilepsy will undoubtedly undergo transformative changes in the years to come with the exponential growth of technological development moving into mainstream practice; the appearance of companies such as Facebook, Google, Neuralink within the realm of brain-computer interfaces points to this trend.Areas covered: This perspective piece will talk about the history of brain stimulation in epilepsy, current-approved treatments, technical developments and the future of neurostimulation.Expert opinion: Further understanding of the brain alongside machine learning and innovative technology will be the future of neuromodulation for the treatment of epilepsy. All of these innovations and advances should pave the way toward overcoming the vexing underutilization of surgery in the therapeutic armamentarium against medically refractory seizures, given the implicit advantage of a neuromodulatory rather than neurodestructive approach.

Neuro-Behcet Disease Mimicking Lymphoma of the Brain and Coexisting with A Dural Arteriovenous Fistula: A Case Report.

BACKGROUND: Diverse clinical manifestations have characterized reports of central nervous system involvement in Behcet disease. There is a limited number of published case reports of neuro-Behcet disease mimicking brain tumor. CASE DESCRIPTION: We present a rare case of neuro-Behcet disease exhibiting mixed systemic and neurological symptoms mimicking malignant lymphoma. Delayed presentation of oral aphthae and rapid improvement of symptoms with steroid treatment led to a diagnosis of neuro-Behcet disease without brain biopsy. The patient also underwent surgery for the resection of an arterio-venous fistula. CONCLUSIONS: We recommend management of neuro-Behcet disease based on perceived natural history risks, with the understanding that no data exist on this within patients population. A multidisciplinary team approach is always recommended because neuro-Behcet disease is an uncommon condition, especially in neurosurgical practice.

Epilepsy and Neuromodulation-Randomized Controlled Trials.

Neuromodulation is a treatment strategy that is increasingly being utilized in those suffering from drug-resistant epilepsy who are not appropriate for resective surgery. The number of double-blinded RCTs demonstrating the efficacy of neurostimulation in persons with epilepsy is increasing. Although reductions in seizure frequency is common in these trials, obtaining seizure freedom is rare. Invasive neuromodulation procedures (DBS, VNS, and RNS) have been approved as therapeutic measures. However, further investigations are necessary to delineate effective targeting, minimize side effects that are related to chronic implantation and to improve the cost effectiveness of these devices. The RCTs of non-invasive modes of neuromodulation whilst showing much promise (tDCS, eTNS, rTMS), require larger powered studies as well as studies that focus at better targeting techniques. We provide a review of double-blinded randomized clinical trials that have been conducted for neuromodulation in epilepsy.

Basal cell carcinoma of the scalp with destruction and invasion into the calvarium and dura mater: Report of 7 cases and review of literature.

Basal cell carcinoma (BCC) is the most common skin malignancy in humans. Giant BCC is a rarer entity that is characterised by aggressive biological behaviour. Intracranial invasion by a BCC on the scalp is extremely rare. The gold standard treatment of BCCs is represented by surgical excision with a wide variety of reconstructive techniques. In this paper, we describe the largest series to date of recurrent BCCs with intracranial extension involving the dura mater. We report recurrent giant BCC of the scalp with dura mater invasion in 7 patients. All patients in this series previously had more than 2 operations. Gadolinium-enhanced MRI revealed neoplastic invasion of the meninges and brain tissues. All patients had a multi-disciplinary team approach with the surgical margins ranging between 1 and 2 cm depending on the location and the size of the tumour. 5 of the patients underwent reconstruction of the skin defect by antero-lateral thigh flap, 1 patient underwent reconstruction with pedicled myocutaneous (trapezius) flap, and 1 with a pedicled myocutaneous latissimus dorsi flap. There was a mean follow-up of 5.3 years. 2 patients died due to cardio-pulmonary complications in the neuro-intensive care unit. A multi-disciplinary team approach and early aggressive tumour resection followed by sophisticated reconstructive and aesthetic procedures appears to be a reliable and realistic treatment modality for invasive BCC.

Predicting Prognosis of Patients with Chronic Subdural Hematoma: A New Scoring System.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a commonly encountered neurosurgical pathology that frequently requires operative intervention. With an increasing ageing demographic, more elderly and comorbid patients will present with symptomatic CSDH. This study evaluated clinical and radiologic factors to create a scoring system to aid prognostication. METHODS: A cohort of patients undergoing evacuation of CSDH at a single institution was established from 2010 to 2015. Primary endpoint was a dichotomized score on a modified Rankin Scale score at 1-year follow-up (favorable outcome score 0-1; unfavorable outcome score 2-6). Logistic regression analyses were performed to model determinants related to outcome. A prediction rule for diagnosing poor postoperative prognosis with unfavorable modified Rankin Scale score was developed with the obtained results. RESULTS: Logistic regression analyses showed that age >75 years, midline shift >10 mm, and hematoma thickness >30 mm were significantly associated with unfavorable outcome (age >75 years: odds ratio [OR] 0.01, 95% confidence interval [CI] 0.001-0.01; midline shift 11-20 mm: OR 0.18, 95% CI 0.04-0.88; midline shift >20 mm: OR 0.03, 95% CI 0.002-0.41; hematoma thickness >30 mm: OR 0.07, 95% CI 0.01-0.46). A scoring system was designed using the final fitted multivariate model. A minimum score of 3 is feasible, indicating worst prognosis, and maximum score of 13 is feasible, indicating best prognosis. A score of ≥9 showed favorable outcome. Receiver operating characteristic curves were constructed to predict favorable versus unfavorable outcomes with the sensitivity analysis yielding an excellent model discrimination with an area under curve of 0.95, 95% CI 0.92-0.98. CONCLUSIONS: A scoring system has been devised to predict outcome, which can aid in the necessity of surgery in certain patient demographics.

Direct Intracranial Injection of AAVrh8 Encoding Monkey ß-N-Acetylhexosaminidase Causes Neurotoxicity in the Primate Brain.

GM2 gangliosidoses, including Tay-Sachs disease and Sandhoff disease, are lysosomal storage disorders caused by deficiencies in ß-N-acetylhexosaminidase (Hex). Patients are afflicted primarily with progressive central nervous system (CNS) dysfunction. Studies in mice, cats, and sheep have indicated safety and widespread distribution of Hex in the CNS after intracranial vector infusion of AAVrh8 vectors encoding species-specific Hex α- or ß-subunits at a 1:1 ratio. Here, a safety study was conducted in cynomolgus macaques (cm), modeling previous animal studies, with bilateral infusion in the thalamus as well as in left lateral ventricle of AAVrh8 vectors encoding cm Hex α- and ß-subunits. Three doses (3.2 × 1012 vg [n = 3]; 3.2 × 1011 vg [n = 2]; or 1.1 × 1011 vg [n = 2]) were tested, with controls infused with vehicle (n = 1) or transgene empty AAVrh8 vector at the highest dose (n = 2). Most monkeys receiving AAVrh8-cmHexα/ß developed dyskinesias, ataxia, and loss of dexterity, with higher dose animals eventually becoming apathetic. Time to onset of symptoms was dose dependent, with the highest-dose cohort producing symptoms within a month of infusion. One monkey in the lowest-dose cohort was behaviorally asymptomatic but had magnetic resonance imaging abnormalities in the thalami. Histopathology was similar in all monkeys injected with AAVrh8-cmHexα/ß, showing severe white and gray matter necrosis along the injection track, reactive vasculature, and the presence of neurons with granular eosinophilic material. Lesions were minimal to absent in both control cohorts. Despite cellular loss, a dramatic increase in Hex activity was measured in the thalamus, and none of the animals presented with antibody titers against Hex. The high overexpression of Hex protein is likely to blame for this negative outcome, and this study demonstrates the variations in safety profiles of AAVrh8-Hexα/ß intracranial injection among different species, despite encoding for self-proteins.