A Prospective Post-Marketing Observational Study of Brivaracetam in People With Focal Epilepsy.

We evaluated the effectiveness and tolerability of brivaracetam (BRV), an adjunctive antiseizure medication, as a treatment for focal epilepsy in adults. In this prospective study, we enrolled 51 participants from 3 sites across Canada. At 6 months, 68% (26/38) of participants were still taking BRV, among whom 35% (8/23) attained seizure freedom and 48% (11/23) saw their seizure frequency reduced by over 50%. We did not measure any significant change in irritability, quality of life, depression, and anxiety while treated with BRV. Our findings suggest BRV is effective in reducing seizure frequency among adults with focal epilepsy.

Electroencephalogram measured functional connectivity for delirium detection: a systematic review.

Objective: Delirium is an acute alteration of consciousness marked by confusion, inattention, and changes in cognition. Some speculate that delirium may be a disorder of functional connectivity, but the requirement to lay still may limit measurement with existing functional imaging modalities in this population. Electroencephalography (EEG) may allow for a more feasible approach to the study of potential connectivity disturbances in delirium. We conducted a systematic review to investigate whether there are EEG-measurable differences in brain functional connectivity in the resting state associated with delirium. Methods: Medline, PubMed, PsychInfo, Embase and CINAHL were searched for relevant articles containing original data studying EEG functional connectivity measures in delirium. Results: The search yielded 1,516 records. Following strict inclusion criteria, four studies were included in the review. The studies used a variety of EEG measures including phase lag index, coherence, entropy, shortest path length, minimum spanning tree, and network clustering coefficients to study functional connectivity between scalp electrodes. Across connectivity measures, delirium was associated with decreased brain functional connectivity. All four studies found decreased alpha band connectivity for patients with delirium. None of the studies directly compared the different motor subtypes of delirium. Significance: This systematic review provides converging evidence for disturbances in oscillatory-based functional connectivity in delirium.

Effect of Training on Visual Identification of High Frequency Oscillations-A Delphi-Style Intervention.

OBJECTIVE: We examined the effect of a simple Delphi-method feedback on visual identification of high frequency oscillations (HFOs) in the ripple (80-250 Hz) band, and assessed the impact of this training intervention on the interrater reliability and generalizability of HFO evaluations. METHODS: We employed a morphology detector to identify potential HFOs at two thresholds and presented them to visual reviewers to assess the probability of each epoch containing an HFO. We recruited 19 board-certified epileptologists with various levels of experience to complete a series of HFO evaluations during three sessions. A Delphi-style intervention was used to provide feedback on the performance of each reviewer relative to their peers. A delayed-intervention paradigm was used, in which reviewers received feedback either before or after the second session. ANOVAs were used to assess the effect of the intervention on the reviewers' evaluations. Generalizability theory was used to assess the interrater reliability before and after the intervention. RESULTS: The intervention, regardless of when it occurred, resulted in a significant reduction in the variability between reviewers in both groups (p GroupDI = 0.037, p GroupEI = 0.003). Prior to the delayed-intervention, the group receiving the early intervention showed a significant reduction in variability (p GroupEI = 0.041), but the delayed-intervention group did not (p GroupDI = 0.414). Following the intervention, the projected number of reviewers required to achieve strong generalizability decreased from 35 to 16. SIGNIFICANCE: This study shows a robust effect of a Delphi-style intervention on the interrater variability, reliability, and generalizability of HFO evaluations. The observed decreases in HFO marking discrepancies across 14 of the 15 reviewers are encouraging: they are necessarily associated with an increase in interrater reliability, and therefore with a corresponding decrease in the number of reviewers required to achieve strong generalizability. Indeed, the reliability of all reviewers following the intervention was similar to that of experienced reviewers prior to intervention. Therefore, a Delphi-style intervention could be implemented either to sufficiently train any reviewer, or to further refine the interrater reliability of experienced reviewers. In either case, a Delphi-style intervention would help facilitate the standardization of HFO evaluations and its implementation in clinical care.

Electroencephalogram patterns in critical care: A primer for acute care doctors.

Electroencephalograms are commonly ordered by acute care doctors but not always understood. Other reviews have covered when and how to perform electroencephalograms. This primer has a different, unique, and complementary goal. We review basic electroencephalogram interpretation and terminology for nonexperts. Our goal is to encourage common understanding, facilitate inter specialty collaboration, dispel common misunderstandings, and inform the current and future use of this precious resource. This primer is categorically not to replace the expert neurologist or technician. Quite the contrary, it should help explain how nuanced electroencephalogram can be, and why indiscriminate electroencephalogram is inappropriate. Some might argue not to teach nonexperts lest they overestimate their abilities or reach. We humbly submit that it is even more inappropriate to not know the basics of a test that is ordered frequently and resource intensive. We cover the characteristics of the "normal" electroencephalogram, electroencephalogram slowing, periodic epileptiform discharges (and its subtypes), burst suppression, and electrographic seizures (and its subtypes). Alongside characteristic electroencephalogram findings, we provide clinical pearls. These should further explain what the reporter is communicating and whether additional testing is beneficial. Along with teaching the basics and whetting the appetite of the general clinician, this resource could increase mutual understanding and mutual appreciation between those who order electroencephalograms and those who interpret them. While there is more to electroencephalogram than can be delivered via a single concise primer, it offers a multidisciplinary starting point for those interested in the present and future of this commonly ordered test.

Extreme Delta Brush in Anti-NMDAR Encephalitis Correlates With Poor Functional Outcome and Death.

Objective: To characterize EEG findings in anti-NMDAR encephalitis patients looking for the proportion of EEGs that were abnormal, presence of extreme delta brush (EDB), and to relate EEG findings to clinical outcomes (Glasgow Outcome Scale (GOS) at 6 months, need for ICU admission, and death). Methods: This retrospective cohort single center study included patients with anti-NMDAR encephalitis who had ≥1 EEGs obtained from 2014 to 2021. EEGs were retrospectively analyzed by 2 reviewers. Clinical outcomes of interest were extracted through hospital and clinic chart review. Results: Twenty-one patients with anti-NMDAR encephalitis were included. Sixty-four EEGs were analyzed. Four EEGs (6.3%) were within normal limits. Focal or generalized slowing (without EDB) was seen on 44 EEGs (68.8%). EDB was seen on 16 EEGs (25.0%) in 9 of 21 patients (42.9%). The presence of EDB was significantly associated with need for ICU admission (p = 0.02), poorer outcome at 6 months as per the GOS (p = 0.002), and with death (p=0.02). EDB was present on ≥1 EEG of every patient who died. Conclusions: The presence of EDB on EEG in anti-NMDAR encephalitis patients is associated with increased need for ICU admission, worse functional outcomes at 6 months, and risk of death.

Neurologists' attitudes toward driving among persons with epilepsy in China: A pilot electronic survey.

PURPOSE AND METHODS: Persons with epilepsy (PWE) remain completely and permanently prohibited from driving in China currently. Previous studies have shown that a considerable proportion of PWE with uncontrolled seizures in China continue to drive motor vehicles. Discrepancy between Chinese policy and driving practices for PWE is potentially concerning. We conducted a preliminary online electronic questionnaire (e-questionnaire) survey among neurologists in China aiming to explore neurologists' attitudes toward the issue of driving among PWE. RESULTS: A total of 358 neurologists completed the e-questionnaire with a response rate of 75.8%. 50.3% of neurologists stated that they knew the driving restriction law in China. With respect to reporting of cases to relevant driving authorities, 82.4% of neurologists never directly report PWE, and 90.8% consider that it is PWE's responsibility to report themselves. 87.4% of physicians surveyed indicated that the lack of clearly-articulated guidelines is a major impediment to their routine discussions of driving fitness for PWE. Subgroup analysis indicated that 76.2% of epileptologists were of the opinion that persons with well-controlled epilepsy should be allowed to drive versus 56.2% of general neurologists (P < 0.05). CONCLUSION: Currently, neurologists in China have a low awareness of the legal driving restriction for PWE and have highly varying practices with respect to counseling PWE about driving. According to our preliminary results, a clearly-articulated published national document for medical fitness for driving in China is necessary in order to standardize physicians' practices.

Generalizability of High Frequency Oscillation Evaluations in the Ripple Band.

Objective: We examined the interrater reliability and generalizability of high-frequency oscillation (HFO) visual evaluations in the ripple (80-250 Hz) band, and established a framework for the transition of HFO analysis to routine clinical care. We were interested in the interrater reliability or epoch generalizability to describe how similar the evaluations were between reviewers, and in the reviewer generalizability to represent the consistency of the internal threshold each individual reviewer. Methods: We studied 41 adult epilepsy patients (mean age: 35.6 years) who underwent intracranial electroencephalography. A morphology detector was designed and used to detect candidate HFO events, lower-threshold events, and distractor events. These events were subsequently presented to six expert reviewers, who visually evaluated events for the presence of HFOs. Generalizability theory was used to characterize the epoch generalizability (interrater reliability) and reviewer generalizability (internal threshold consistency) of visual evaluations, as well as to project the numbers of epochs, reviewers, and datasets required to achieve strong generalizability (threshold of 0.8). Results: The reviewer generalizability was almost perfect (0.983), indicating there were sufficient evaluations to determine the internal threshold of each reviewer. However, the interrater reliability for 6 reviewers (0.588) and pairwise interrater reliability (0.322) were both poor, indicating that the agreement of 6 reviewers is insufficient to reliably establish the presence or absence of individual HFOs. Strong interrater reliability (≥0.8) was projected as requiring a minimum of 17 reviewers, while strong reviewer generalizability could be achieved with <30 epoch evaluations per reviewer. Significance: This study reaffirms the poor reliability of using small numbers of reviewers to identify HFOs, and projects the number of reviewers required to overcome this limitation. It also provides a set of tools which may be used for training reviewers, tracking changes to interrater reliability, and for constructing a benchmark set of epochs that can serve as a generalizable gold standard, against which other HFO detection algorithms may be compared. This study represents an important step toward the reconciliation of important but discordant findings from HFO studies undertaken with different sets of HFOs, and ultimately toward transitioning HFO analysis into a meaningful part of the clinical epilepsy workup.

Interrater reliability of visually evaluated high frequency oscillations.

OBJECTIVE: High frequency oscillations (HFOs) and interictal epileptiform discharges (IEDs) have been shown to be markers of epileptogenic regions. However, there is currently no 'gold standard' for identifying HFOs. Accordingly, we aimed to formally characterize the interrater reliability of HFO markings to validate the current practices. METHODS: A morphology detector was implemented to detect events (candidate HFOs, lower-threshold events, and distractors) from the intracranial EEG (iEEG) of ten patients. Six electroencephalographers visually evaluated these events for the presence of HFOs and IEDs. Interrater reliability was calculated using pairwise Cohen's Kappa (κ) and intraclass correlation coefficients (ICC). RESULTS: The HFO evaluation distributions were significantly different for most pairs of reviewers (p<0.05; 11/15 pairs). Interrater reliability was poor for HFOs alone (κmean=0.403; ICC=0.401) and HFO+IEDs (κmean=0.568; ICC=0.570). CONCLUSIONS: The current practice of using two visual reviewers to identify HFOs is prone to bias arising from the poor agreement between reviewers, limiting the extrinsic validity of studies using these markers. SIGNIFICANCE: The poor interrater reliability underlines the need for a framework to reconcile the important findings of existing studies. The present epoched design is an ideal candidate for the implementation of such a framework.

Evaluation of the first seizure patient: Key points in the history and physical examination.

PURPOSE: This review will present the history and physical examination as the launching point of the first seizure evaluation, from the initial characterization of the event, to the exclusion of alternative diagnoses, and then to the determination of specific acute or remote causes. Clinical features that may distinguish seizures from alternative diagnoses are discussed in detail, followed by a discussion of acute and remote first seizure etiologies. METHODS: This review article is based on a discretionary selection of English language articles retrieved by a literature search in the PubMed database, and the authors' clinical experience. RESULTS: The first seizure is a dramatic event with often profound implications for patients and family members. The initial clinical evaluation focuses on an accurate description of the spell to confirm the diagnosis, along with careful scrutiny for previously unrecognized seizures that would change the diagnosis more definitively to one of epilepsy. The first seizure evaluation rests primarily on the clinical history, and to a lesser extent, the physical examination. CONCLUSIONS: Even in the era of digital EEG recording and neuroimaging, the initial clinical evaluation remains essential for the diagnosis, treatment, and prognostication of the first seizure.

Bias in counseling of seizure patients following a transient impairment of consciousness: differential adherence to driver fitness guidelines.

PURPOSE: To determine primary care physicians' counseling as well as patients' driving behaviors following seizure and non-seizure events impairing consciousness in the community. METHODS: Patients attending a rapid-referral first seizure clinic were entered into the study if they were deemed medically-unfit to drive according to national guidelines for driving licensure: had experienced a seizure or an unexplained episode of lost consciousness, and had a valid driver's license at the time of their index event. Risk of physician counseling in the community regarding driving cessation in the interval between initial primary care assessment and neurological consultation was examined as a primary outcome, and patient driving cessation was examined as a secondary outcome. RESULTS: 106 of 192 (55%) patients attending clinic met guideline criteria requiring driver fitness counseling in the primary care community, and 89 patients (46%) were deemed medically-unfit to drive following the initial specialist consultation appointment. Among medically unfit driver cases, 73% were ultimately deemed to have experienced a seizure and 27% had experienced a non-seizure event (e.g. syncope, PNES). Driver fitness counseling was more likely for seizure than non-seizure cases (unadjusted odds ratio: 4.14, p<0.05), as was patient driving cessation (5.10, p<0.05). CONCLUSION: Physician compliance with clinical practice guidelines appears strongly biased when counseling about driving following an episode of transient impairment in consciousness. The failure of the primary care medical community to apply driver fitness counseling equitably to both seizure and non-seizure drivers may have ramifications upon public safety or conversely disease-related quality-of-life.

Counseling at a Seizure Clinic Does Not Ensure Disclosure to the Transportation Registry.

BACKGROUND: The effectiveness of current self-reporting driving laws for medically-unfit potential seizure patients is unknown in Canada. We designed a prospective cohort study of patients' self-reporting practices to the local Transportation Registry (TR) and their driving behaviors following detailed counselling at a seizure clinic in a discretionary physician-reporting jurisdiction. METHODS: Medically unfit drivers, referred to our seizure clinic, who had a valid driver's permit at the time of their episode of impaired consciousness were included. Patients' self-reporting and driving behaviours were assessed using a standardized interview prior to a neurologist's counseling and later at a follow-up visit. RESULTS: Sixty three patients were included; 77% were diagnosed as having had a seizure at the time of their referral. Prior to their seizure clinic visit, 3/63 (5%) had been counseled to self-report to the TR by a non-neurologist physician, and none had done so. Following a neurologist's documented counseling 34/63 (54%) had self-reported themselves at the follow-up seizure clinic visit, and 53/63 (84%) were not driving. CONCLUSION: This prospective study design is the first in North America to examine self-reporting rates for unfit drivers with a seizure disorder. Our findings suggest that self-reporting laws do not ensure high rates of self-reporting behaviors even when patients seen at a seizure clinic are appropriately counseled of their legal obligations. The rate of driving cessation appears greater than the rate of self-reporting to the TR among counseled patients.

Quantification of subfield pathology in hippocampal sclerosis: a systematic review and meta-analysis.

BACKGROUND: The utility of MRI-based hippocampal subfield volumetry as a diagnostic test for hippocampal sclerosis (HS) is based on the hypothesis that specific hippocampal subfields are differentially affected in HS. While qualitative studies suggest selective involvement of certain hippocampal subfields in this condition, whether quantifiable differences exist remains unclear. Neuronal density measurement is the most widely used technique for measuring subfield pathological change in HS. Therefore, a systematic review and meta-analysis of studies reporting neuronal densities in temporal lobe epilepsy was performed in order to quantify subfield pathology in hippocampal sclerosis. METHODS: Studies were identified by searching the Medline and Embase databases using the search terms: cell count, hippocampus, and epilepsy. Of the 192 studies identified by the literature search, seven met all inclusion and exclusion criteria. Random effects meta-analyses were performed, comparing: (i) neuronal densities in control (n=121) versus HS (n=371) groups for subfields CA1-4; and (ii) amount of neuronal loss in HS between subfields CA1-4. RESULTS: Statistically significant neuronal loss was observed comparing HS to control groups in all subfields CA1-4 (p<0.001 for all comparisons). Significantly greater neuronal loss was demonstrated in HS comparing CA1 versus CA2 (p<0.001), CA3 (p=0.005), and CA4 (p=0.003). Greater pyramidal cell loss was also demonstrated in CA3 relative to the CA2 subfield (p=0.003). No significant differences were identified comparing CA2 and CA4 (p=0.39); or comparing CA3 and CA4 (p=0.64). CONCLUSIONS: HS is characterized by pathology in all hippocampal subfields. Quantifiable differences exist in the involvement of specific hippocampal subfields in HS. Neuronal loss is greatest in CA1, intermediate in CA3 and CA4, and least in CA2. Further studies are required to determine if this pattern can be detected using in vivo MRI.

Canadian epileptologists' counseling of drivers amidst guideline inconsistencies.

BACKGROUND: Epilepsy is a common medical condition for which physicians perform driver fitness assessments. The Canadian Medical association (CMA) and the Canadian Council of Motor transportation administrators (CCMTA) publish documents to guide Canadian physicians' driver fitness assessments. OBJECTIVES: We aimed to measure the consistency of driver fitness counseling among epileptologists in Canada, and to determine whether inconsistencies between national guidelines are associated with greater variability in counseling instructions. METHODS: We surveyed 35 epileptologists in Canada (response rate 71%) using a questionnaire that explored physicians' philosophies about driver fitness assessments and counseling practices of seizure patients in common clinical scenarios. Of the nine scenarios, CCMTA and CMA recommendations were concordant for only two. Cumulative agreement for all scenarios was calculated using Kappa statistic. Agreement for concordant (two) vs. discordant (seven) scenarios were split at the median and analyzed using the Wilcoxon signed rank sum test. RESULTS: Overall the agreement between respondents for the clinical scenarios was not acceptable (Kappa=0.28). For the two scenarios where CMa and CCMta guidelines were concordant, specialists had high levels of agreement with recommendations (89% each). A majority of specialists disagreed with CMa recommendations in three of seven discordant scenarios. The lack of consistency in respondents' agreement attained statistical significance (p<0.001). CONCLUSIONS: Canadian epileptologists have variable counseling practices about driving, and this may be attributable to inconsistencies between CMa and CCMta medical fitness guidelines. This study highlights the need to harmonize driving recommendations in order to prevent physician and patient confusion about driving fitness in Canada.

Generalized periodic discharges in the critically ill: a case-control study of 200 patients.

OBJECTIVE: Generalized periodic discharges are increasingly recognized on continuous EEG monitoring, but their relationship to seizures and prognosis remains unclear. METHODS: All adults with generalized periodic discharges from 1996 to 2006 were matched 1:1 to controls by age, etiology, and level of consciousness. Overall, 200 patients with generalized periodic discharges were matched to 200 controls. RESULTS: Mean age was 66 years (range 18-96); 56% were comatose. Presenting illnesses included acute brain injury (44%), acute systemic illness (38%), cardiac arrest (15%), and epilepsy (3%). A total of 46% of patients with generalized periodic discharges had a seizure during their hospital stay (almost half were focal), vs 34% of controls (p = 0.014). Convulsive seizures were seen in a third of both groups. A total of 27% of patients with generalized periodic discharges had nonconvulsive seizures, vs 8% of controls (p < 0.001); 22% of patients with generalized periodic discharges had nonconvulsive status epilepticus, vs 7% of controls (p < 0.001). In both groups, approximately half died or were in a vegetative state, one-third had severe disability, and one-fifth had moderate to no disability. Excluding cardiac arrest patients, generalized periodic discharges were associated with increased mortality on univariate analysis (36.8% vs 26.9%; p = 0.049). Multivariate predictors of worse outcome were cardiac arrest, coma, nonconvulsive status epilepticus, and sepsis, but not generalized periodic discharges. CONCLUSION: Generalized periodic discharges were strongly associated with nonconvulsive seizures and nonconvulsive status epilepticus. While nonconvulsive status epilepticus was independently associated with worse outcome, generalized periodic discharges were not after matching for age, etiology, and level of consciousness.

High frequency oscillations (80-500 Hz) in the preictal period in patients with focal seizures.

PURPOSE: Intracranial depth macroelectrode recordings from patients with focal seizures demonstrate interictal and ictal high frequency oscillations (HFOs, 80-500 Hz). These HFOs are more frequent in the seizure-onset zone (SOZ) and reported to be linked to seizure genesis. We evaluated whether HFO activity changes in a systematic way during the preictal period. METHODS: Fifteen minutes of preictal intracranial electroencephalography (EEG) recordings were evaluated in seven consecutive patients with well-defined SOZ. EEG was filtered at 500 Hz and sampled at 2,000 Hz. Ripples (80-250 Hz) and fast ripples (250-500 Hz) were visually marked, and spectral analysis was performed in seizure-onset as well as nonseizure-onset channels. Linear regressions fitted to the power trends corresponding to intervals of 1, 5, and 15 min before the seizure onset was calculated. RESULTS: Total rates of HFOs were significantly higher in the SOZ than outside. Preictal increases and decreases in HFO rates and band power could be detected in all patients, and they were not limited to the SOZs. These measures were very variable, and no systematic trends were observed when comparing patients or seizures in the same patient. DISCUSSION: High frequencies in the range of 80-500 Hz are present during the preictal period and are more prominent in the SOZ. They do not change in a systematic way before seizure onset for the horizons we tested. The 80-500 Hz band may be used for the localization of seizure-onset areas but may be more difficult to use for seizure prediction purposes.

Functional organization of human visual cortex in occipital polymicrogyria.

Polymicrogyrias (PMG) are cortical malformations resulting from developmental abnormalities. In animal models PMG has been associated with abnormal anatomy, function, and organization. The purpose of this study was to describe the function and organization of human polymicrogyric cortex using functional magnetic resonance imaging. Three patients with epilepsy and bilateral parasagittal occipital polymicrogyri were studied. They all had normal vision as tested by Humphrey visual field perimetry. The functional organization of the visual cortex was reconstructed using phase-encoded retinotopic mapping analysis. This method sequentially stimulates each point in the visual field along the axes of a polar-coordinate system, thereby reconstructing the representation of the visual field on the cortex. We found normal cortical responses and organization of early visual areas (V1, V2, and V3/VP). The locations of these visual areas overlapped substantially with the PMG. In five out of six hemispheres the reconstructed primary visual cortex completely fell within polymicrogyric areas. Our results suggest that human polymicrogyric cortex is not only organized in a normal fashion, but is also actively involved in processing of visual information and contributes to normal visual perception.

Obturator neuropathy complicating elective laparoscopic tubal occlusion.

Isolated obturator neuropathy is rare. We report a woman who developed a severe obturator neuropathy from electrocautery during elective laparoscopic tubal ligation. This complication has not previously been described in association with the procedure, and the potential etiological role of an underrecognized anatomical variant, in which an accessory obturator nerve is present, is discussed.

Neurosyphilis presenting with status epilepticus.

Three patients with neurosyphilis are reported. The first and third patients presented with convulsive status epilepticus and the second with non-convulsive status after penicillin administration. In all cerebrospinal fluid and the serum Venereal Disease Research Laboratory Test (VDRL) and Treponema Pallidum hemagglutination (TPHA) or fluorescent treponemal antibody absorption test (FTA-ABS) were positive, but HIV serology was negative. Their EEGs showed periodic, lateralized, epileptiform discharges (PLEDs) just after SE. The first and third patients had no history of epilepsy. Seizures started as focal motor attacks but then secondarily generalized. The first patient's cranial MRI showed cerebral atrophy and hyperintensity involving bilateral medial and anterior temporal regions, more prominent on the left and which disappeared after penicillin treatment. The second case, after receiving penicillin, had nonconvulsive SE, a clinical presentation suggesting a Jarisch-Herxheimer reaction (JHR). Her cranial MR revealed moderate cortical atrophy and widespread confluent hyperintense foci mainly in both periventricular areas, corona radiata and centrum semiovale. MRI of the third case showed a large, left sylvian, arachnoid cyst without mass effect. Executive dysfunction was observed in follow-up neuropsychological tests in all patients. When investigating status epilepticus, neurosyphilis as a cause must not be forgotten.