Determinants of epileptogenic zone identification and seizure outcome in children with refractory epilepsy undergoing stereoelectroencephalography.

OBJECTIVE: The objective of this paper was to investigate the factors associated with successful epileptogenic zone (EZ) identification and postsurgical seizure freedom in pediatric patients with drug-resistant epilepsy who underwent first-time stereoelectroencephalography (SEEG). METHODS: The authors conducted a retrospective cohort study of all consecutive patients younger than 18 years of age at the time of recommendation for invasive evaluation with SEEG who were treated from July 2009 to June 2020. The authors excluded patients who had undergone failed prior resective epilepsy surgery or prior intracranial electrode evaluation for seizure localization. For their primary outcome, the authors evaluated the relationship between clinical and radiographic factors and successful identification of a putative EZ. For their secondary outcome, the authors investigated whether these factors had a significant relationship with seizure freedom (according to the Engel classification) at last follow-up. RESULTS: The authors included 101 patients in this study. SEEG was safe, with no major morbidity or mortality experienced. The population was complex, with an MRI lesion present in less than 40% of patients and patients as young as 2.9 years included. A proposed EZ was identified in 88 (87%) patients. Patients with an older onset of epilepsy (OR 1.20/year, p = 0.04) or epilepsy etiology suspected to be due to a developmental lesion (OR 8.38, p = 0.02) were more likely to have proposed EZ identification. Patients with a preimplantation bilateral seizure-onset hypothesis (OR 0.29, p = 0.047) and those who underwent longer periods of monitoring (OR 0.86/day, p = 0.006) were somewhat less likely to have proposed EZ identification. The presence of an MRI lesion was a positive factor on secondary analyses (OR 4.18, p = 0.049; 1-tailed test). Fifty percent of patients who underwent surgical treatment with resection or laser ablation achieved Engel class I outcomes, in contrast to 0% of patients who underwent neuromodulation. Patients with a preimplantation hypothesis in the frontal/parietal lobes had increased odds of seizure freedom compared with patients with a hypothesis in other locations (OR 3.64, p = 0.01). CONCLUSIONS: Pediatric SEEG is safe and often identifies a proposed resectable EZ. These results suggest that SEEG is effective in patients with frontal/parietal preimplantation hypothesis, with or without identified lesions on MRI.

Secondary Stroke Risk Reduction in Black Adults: a Systematic Review.

OBJECTIVE: To address the fact that Black adults (BAs) experience significantly greater stroke burden than the general population, we conducted a systematic literature review which described evidence-based interventions targeting secondary stroke risk reduction in BAs. DATA SOURCE: Publications were selected from PubMed, Ovid, Cochrane, and Web of Science databases. We included peer-reviewed, longitudinal, English-language studies performed in the USA which reported results for BAs separately and had adult participants who had experienced stroke-related events. RESULTS: Six of the 7 studies employed behavioral interventions which promoted education on stroke risk factors, problem-solving skills, and healthy-coping strategies. These studies demonstrated improvements in one or more biologic outcomes including cholesterol control and systolic blood pressure. CONCLUSIONS: Existing interventions on secondary stroke risk reduction approaches are effective in reducing secondary stroke risk among BAs, especially in individuals with poorly controlled blood pressure at baseline. However, additional research is needed because the current approaches may limit generalizability.

Seizure Outcomes and Reoperation in Surgical Rasmussen Encephalitis Patients.

BACKGROUND: Rasmussen encephalitis (RE) is a rare inflammatory disease affecting one hemisphere, causing progressive neurological deficits and intractable seizures. OBJECTIVE: To report long-term seizure outcomes, reoperations, and functional outcomes in patients with RE who underwent hemispherectomy at our institution. METHODS: Retrospective review was performed for all patients with RE who had surgery between 1998 and 2020. We collected seizure history, postoperative outcomes, and functional data. Imaging was independently reviewed in a blinded fashion by 2 neurosurgeons and a neuroradiologist. RESULTS: We analyzed 30 patients with RE who underwent 35 hemispherectomies (5 reoperations). Using Kaplan-Meier analysis, seizure-freedom rate was 81.5%, 63.6%, and 55.6% at 1, 5, and 10 years after surgery, respectively. Patients with shorter duration of hemiparesis preoperatively were less likely to be seizure-free at follow-up (P = .011) and more likely to undergo reoperation (P = .004). Shorter duration of epilepsy (P = .026) and preoperative bilateral MRI abnormalities (P = .011) were associated with increased risk of reoperation. Complete disconnection of diseased hemisphere on postoperative MRI after the first operation improved seizure-freedom (P = .021) and resulted in fewer reoperations (P = .034), and reoperation resulted in seizure freedom in every case. CONCLUSION: Obtaining complete disconnection is critical for favorable seizure outcomes from hemispherectomy, and neurosurgeons should have a low threshold to reoperate in patients with RE with recurrent seizures. Rapid progression of motor deficits and bilateral MRI abnormalities may indicate a subpopulation of patients with RE with increased risk of needing reoperation. Overall, we believe that hemispherectomy is a curative surgery for the majority of patients with RE, with excellent long-term seizure outcome.

Top 100 cited studies in periacetabular osteotomy for acetabular dysplasia: do lower levels of evidence guide clinical practice?

As no prior study has examined the citations profile of key articles related to periacetabular osteotomy (PAO), our analysis utilized the Web of Science database to (1) identify the most-cited clinical studies relating to PAO in the management of acetabular dysplasia and (2) assess any trends over time with respect to the quality of literature. The top 100 highest-cited studies related to PAO had a mean of 49 citations (range, 6-666 per study). With respect to the level of evidence, most studies had level IV evidence (58%); 1% level I, 16% level II, 28% level III and 2% level V. Most studies were retrospective ( n = 86); there were 14 prospective studies (including one randomized study). The most common study designs were case series ( n = 58) and cohort ( n = 16), followed by matched-cohort ( n = 13) and case-control ( n = 6). The mean ± SD Newcastle-Ottawa Scale score was 6.48 ± 1.31. A total of 59 and 41 of the included articles were classified as high risk and high quality, respectively. No studies were classified as very high risk. As a whole, our analysis demonstrated that currently available PAO literature is still of low quality and of low level of evidence. While PAO has been well-documented as a durable procedure for addressing acetabular dysplasia, future research must focus on higher quality, randomized and prospective data to answer key clinical or technique-related topics.

The Clinical Utility of Surgical Histopathology in Predicting Seizure Outcomes in Patients with Rasmussen Encephalitis Undergoing Hemispherectomy.

OBJECTIVE: The objectives of this study were to determine the relationship between the severity of pathology and seizure outcomes in patients who underwent hemispherectomy for Rasmussen encephalitis (RE) and to investigate which clinical factors correlated with severity of pathology. METHODS: In this retrospective cohort study, we collected and reviewed pathology and clinical variables. We ascertained seizure outcomes using Engel's classification, and Pardo stages were used to grade pathology. RESULTS: We included 29 unique patients who underwent 34 hemispherectomy procedures for analysis. There was no statistically significant correlation between Pardo stage and seizure outcome (P = 1). Increasing duration of epilepsy (ß = 0.011, P = 0.02) and duration of hemiparesis (ß = 0.024, P = 0.01) were significantly associated with a more severe Pardo stage. In contrast, the presence of epilepsia partialis continua had a negative relationship with Pardo stage (ß = -0.49, P = 0.04). Twenty-six (89.75%) patients were Engel class I at the last follow-up, including all 5 patients who underwent redo hemispherectomy in our cohort. CONCLUSIONS: Consistent with the progressive nature of RE, more severe pathology was associated with a longer duration of epilepsy and longer duration of hemiparesis, while the presence of epilepsia partialis continua was associated with less severe pathology. Results from this series suggest the degree of cortical involvement with RE as assessed on surgical histopathology does not correlate with seizure outcome after hemispherectomy, which appears to be more dependent on surgical technique/complete disconnection.

A systematic literature review of health disparities among rural people with epilepsy (RPWE) in the United States and Canada.

BACKGROUND: Epilepsy is a leading cause of global disease burden, with people with epilepsy (PWE) experiencing adverse health outcomes related to the psychiatric comorbidities and socioeconomic consequences of the disorder. Rural populations are more likely to be impoverished or uninsured, which could impact health outcomes for rural-dwelling PWE (RPWE). AIMS: This systematic literature review identified original research studying health disparities and outcomes among RPWE in the United States and Canada to (1) characterize the disparities faced by RPWE and (2) elucidate the effects of these disparities upon clinical outcomes. METHODS: We performed a systematic search of six electronic databases: Pubmed, Cochrane, PsychInfo, Web of Science, Scopus, and Ovid. Articles considered were original research reports conducted in Canada or the United States before August 2020. A modified Newcastle Ottawa Scale was used to assess the quality of the included studies. RESULTS: Our search returned 2093 articles that examined the health disparities of RPWE, of which six met criteria for this review. Outcome measures of health disparity included in these papers were mortality (2; 33%), use of health resources (2; 33%), and epilepsy prevalence (2; 33%). Only one paper (16%) concluded that RPWE experienced worse health outcomes relative to urban-dwelling PWE, while 5 (84%) found no difference. CONCLUSION: Our study did not find sufficient evidence that RPWE in the US and Canada experience significant health disparities compared to similar urban populations of PWE. More research using prospective studies and datasets allowing better characterization of rurality is required.

Systematic Literature Review of Psychiatric Comorbidities in Adults with Epilepsy.

BACKGROUND AND PURPOSE: Mental illness is disproportionately common in people with epilepsy (PWE). This systematic literature review identified original research articles that reported the prevalence of psychiatric comorbidities based upon clinical assessments in a sample of PWE and assessed the clinical features of the populations found in studies included in our review of mental health comorbidity. METHODS: The included articles were written in English and published from 2008 to 2018, and focused on adults aged ≥18 years who had psychiatric diagnoses determined in clinical assessments, such as those found in medical records, clinician psychiatric evaluations, structured diagnostic interviews, and mental health screening questionnaires specific for a psychiatric disorder. The primary outcome was the prevalence of psychiatric comorbidities as a percentage of the total sample of PWE. Additional data included the overall sample size, mean age, epilepsy type, study design, and method of diagnosis. A modified Newcastle Ottawa Scale was used to assess the quality of the studies. All 23 articles that were consistent with the inclusion criteria were related to observational studies. RESULTS: Mood disorders and anxiety disorders were the most common psychiatric comorbidities, with prevalence rates of 35.0% and 25.6%, respectively. Major depressive disorder was the most common mood disorder, with a prevalence of 24.2%. Post-traumatic stress disorder (PTSD) had the highest reported prevalence among anxiety disorders, at 14.2%, followed by general anxiety disorder at 11.1%. Other comorbidities included psychosis (5.7%), obsessivecompulsive disorder (3.8%), schizophrenia (1.7%), bipolar disorder (6.2%), and substance abuse (7.9%). The pooled prevalence of suicidality, as reported for two studies, was 9.3%. Temporal lobe epilepsy (TLE) was associated with higher levels of psychiatric comorbidity. Two (8.7%) of the 23 studies compared psychiatric comorbidities in TLE with that of extratemporal lobe epilepsy (ETLE), and one of these two studies found that depression was more common in TLE (53.8%) than in ETLE (25%). Regarding seizure types, partial seizures were associated with a higher prevalence of depression vs generalized seizures. CONCLUSIONS: This systematic literature review of recent original research found a relatively high prevalence of mental health comorbidities in PWE. Mood and anxiety disorders are the most common comorbidities, while psychotic spectrum conditions such as schizophrenia and bipolar disorder are much rarer. The prevalence of comorbidity may vary with the epilepsy type and treatment responsiveness. These findings suggest that screening tools for depression and anxiety should be included as part of the training for epilepsy care, while resources for other relatively common conditions such as PTSD and substance abuse disorders should be readily available to neurology specialists who treat PWE.

A systematic literature review of recommendations for referral to specialty care for patients with epilepsy.

OBJECTIVE: In epilepsy, patients who receive appropriate care receive treatment that differs substantially from those that do not. Given the need for a more detailed assessment of the role of specialty referral in the care of patients with epilepsy, this systematic literature review identified epilepsy care guidelines and recommendations that specifically address when and why people with epilepsy should be referred to specialty care. METHODS: This study identified recent (in the last 10 years) publications that made best-practice recommendations for referring people with epilepsy to a neurologist or epileptologist. We searched six databases in December 2018: MEDLINE (PubMed), Cochrane Library, ProQuest, Web of Science, CINAHL (Ebsco), Scopus (Elsevier). Search terms included "Epilepsy" OR "Seizures," "Guideline" OR "Practice Parameter," and "Referral." RESULTS: The 15 full-text articles identified included formal guidelines, summaries of these guidelines, or professional commentary that builds upon existing guidelines. Most of these publications came from the U.K and its National Institute for Health and Care Excellence. Overall, the included recommendations for referral varied considerably both for new-onset and refractory epilepsy. Although these recommendations were not consistent, it is reasonable to refer patients following the failure of 2 anti-seizure medication (ASM) trials. SIGNIFICANCE: Guidelines and informal recommendations are not consistent regarding best practices for specialty care referral for patients with epilepsy. These guidelines and recommendations should consider the context of care in real-world settings and suggest pragmatic approaches that optimize seizure control and functioning.

Ethnicity and health outcomes among people with epilepsy participating in an epilepsy self-management RCT.

People with epilepsy (PWE) may experience negative health events (NHEs) such as seizures, emergency room visits, and hospitalizations, with ethnic and racial minorities disproportionately affected. Epilepsy self-management may reduce NHEs; however, few reports examine self-management outcomes in racial minorities. Using data from a longitudinal 6-month randomized controlled trial (RCT) of 120 PWE, this analysis compared African-American and Whites at baseline, 10 weeks and 24 weeks after receiving the "Self-management for people with epilepsy (SMART) and a history of NHEs" self-management program. The primary RCT outcome was number of NHEs. At baseline, compared to Whites, African-Americans had less education (p = 0.02) and greater depressive severity (p = 0.04). Both African-American and Whites generally improved with SMART, and there were no racial differences in NHE counts or other outcomes' responses. Given known racial disparities in epilepsy care, it may be particularly important to reach out to minority PWE with self-management programs.

Hotspots of dendritic spine turnover facilitate clustered spine addition and learning and memory.

Modeling studies suggest that clustered structural plasticity of dendritic spines is an efficient mechanism of information storage in cortical circuits. However, why new clustered spines occur in specific locations and how their formation relates to learning and memory (L&M) remain unclear. Using in vivo two-photon microscopy, we track spine dynamics in retrosplenial cortex before, during, and after two forms of episodic-like learning and find that spine turnover before learning predicts future L&M performance, as well as the localization and rates of spine clustering. Consistent with the idea that these measures are causally related, a genetic manipulation that enhances spine turnover also enhances both L&M and spine clustering. Biophysically inspired modeling suggests turnover increases clustering, network sparsity, and memory capacity. These results support a hotspot model where spine turnover is the driver for localization of clustered spine formation, which serves to modulate network function, thus influencing storage capacity and L&M.

Development of a fuzzy logic based intelligent system for autonomous guidance of post-stroke rehabilitation exercise.

This paper presents preliminary studies in developing a fuzzy logic based intelligent system for autonomous post-stroke upper-limb rehabilitation exercise. The intelligent system autonomously varies control parameters to generate different haptic effects on the robotic device. The robotic device is able to apply both resistive and assistive forces for guiding the patient during the exercise. The fuzzy logic based decision-making system estimates muscle fatigue of the patient using exercise performance and generates a combination of resistive and assistive forces so that the stroke survivor can exercise for longer durations with increasing control. The fuzzy logic based system is initially developed using a study with healthy subjects and preliminary results are also presented to validate the developed system with healthy subjects. The next stage of this work will collect data from stroke survivors for further development of the system.

The development of an upper limb stroke rehabilitation robot: identification of clinical practices and design requirements through a survey of therapists.

PURPOSE. Timely and adequate rehabilitation after a stroke is crucial to maximising recovery. A way of increasing treatment access could be through robots, which would aid therapists in providing post-stroke rehabilitation. This research sought to discover the needs and preferences of therapists with respect to a robot that focuses on upper limb rehabilitation. Understanding requirements for devices could help to increase integration into clinical practice. METHODS. An international online survey was distributed through professional organisations and e-mail list services to therapists. The survey contained 85 items covering topics such as therapist background and treatment approach, rehabilitation aims and robotic rehabilitation device attributes. RESULTS. Data were analysed for 233 respondents, most of whom were physiotherapists and occupational therapists from Australia, Canada and USA. Top attributes included: facilitating a variety of arm movements, being usable while seated, giving biofeedback to clients, having virtual activities specific to daily living, being useful in-home and having resistance adjustable to client needs. In addition, the device should cost under 6000 USD. CONCLUSIONS. Findings from this survey provide guidance for technology developers regarding therapists' specifications for a robotic device for upper limb rehabilitation. In addition, findings offer a better understanding of how acceptance of such devices may be facilitated.

Habituation of the C-start response in larval zebrafish exhibits several distinct phases and sensitivity to NMDA receptor blockade.

The zebrafish larva has been a valuable model system for genetic and molecular studies of development. More recently, biologists have begun to exploit the surprisingly rich behavioral repertoire of zebrafish larvae to investigate behavior. One prominent behavior exhibited by zebrafish early in development is a rapid escape reflex (the C-start). This reflex is mediated by a relatively simple neural circuit, and is therefore an attractive model behavior for neurobiological investigations of simple forms of learning and memory. Here, we describe two forms of short-lived habituation of the C-start in response to brief pulses of auditory stimuli. A rapid form, persisting for ≥1 min but <15 min, was induced by 120 pulses delivered at 0.5-2.0 Hz. A more extended form (termed "short-term habituation" here), which persisted for ≥25 min but <1 h, was induced by spaced training. The spaced training consisted of 10 blocks of auditory pulses delivered at 1 Hz (5 min interblock interval, 900 pulses per block). We found that these two temporally distinguishable forms of habituation are mediated by different cellular mechanisms. The short-term form depends on activation of N-methyl-d-aspartate receptors (NMDARs), whereas the rapid form does not.