Musicogenic seizures-STXBP1 encephalopathy with reflex seizures.

Mutations in the gene encoding syntaxin binding protein 1 (STXBP1) have been implicated in a wide variety of epileptic encephalopathies. Although the recognized phenotypes of patients with STXBP1 encephalopathies have broadened in recent years, no case of reflex seizures, particularly musicogenic seizures, has been reported in the literature. We present an 18-year-old woman with STXBP1 encephalopathy and seizures that are stereotypically reproducible in response to a variety of audible stimuli. An 18-year-old woman with a history of profound intellectual disability, confirmed STXBP1 genetic defect via genetic testing, and seizures beginning as infantile spasms during childhood, who presented to the epilepsy monitoring unit for seizure characterization. Her mother reported reproducible seizures triggered by a particular cell phone ringtone, music from a certain automobile television commercial and certain beeping alarm sounds. In response, the patient had clinically stereotyped seizures associated with staring, behavioral arrest, followed by eye deviation to the left, tonic stiffening in upper and lower extremities, and labored breathing lasting between 30 s and 2 min. These seizures were reliably reproducible within a few seconds of exposure to the auditory stimulus. During hospitalization, mother played one of the cell phone ringtones known to trigger seizures for the patient, which resulted in induction of a seizure characterized by diffuse electrodecrement, subsequent emergence of frontal-predominant theta which was followed by progressive diffuse attenuation and semi-rhythmic slowing over the right posterior quadrant. This is the first case to describe musicogenic or other reflex seizures in a patient with STXBP1 encephalopathy.

Clinical Neurophysiology Fellowship Program Directors Survey on a Standardized Fellowship Match Process: A Call for Action.

PURPOSE: To survey US Clinical Neurophysiology (CNP) fellowship program directors on the nature of CNP and related training programs, current recruitment cycle, and views for a standardized process. METHODS: A 23-question electronic survey was sent to all 93 US Accreditation Council for Graduate Medical Education-accredited CNP fellowship program directors from December 2020 to January 2021. RESULTS: The response rate was 60%. There was great variability in the number of CNP positions and CNP tracks offered. The following tracks were identified: 48% EEG dominant, 26% EMG dominant, 22% split equally between EEG and EMG, and 2% and 1% were neurophysiologic intraoperative monitoring and autonomic dominant, respectively. Of the responding institutions, 43% offered a second year of training options to CNP fellows, mainly in conjunction with Epilepsy fellowship, which was pursued by 25% of CNP fellows. Many programs indicated flexibility in their design between different CNP tracks or between CNP and other related training programs based on the available candidates. The median percentage of CNP fellowship positions filled over the last 5 years was 80%, and there was great variation in the recruitment timeline across institutions. Overall, 86% of program directors favored a universal timeline and 71% favored a formal match for CNP. The respondents were split between an independent CNP match (39%) and joining the initiatives of affiliate societies on a standardized process (61%). CONCLUSIONS: There is significant heterogeneity in the makeup of the CNP fellowship programs and the recruitment process. The majority of CNP program directors are in favor of standardization of the recruitment process.

Assessment of the Validity of the 2HELPS2B Score for Inpatient Seizure Risk Prediction.

Importance: Seizure risk stratification is needed to boost inpatient seizure detection and to improve continuous electroencephalogram (cEEG) cost-effectiveness. 2HELPS2B can address this need but requires validation. Objective: To use an independent cohort to validate the 2HELPS2B score and develop a practical guide for its use. Design, Setting, and Participants: This multicenter retrospective medical record review analyzed clinical and EEG data from patients 18 years or older with a clinical indication for cEEG and an EEG duration of 12 hours or longer who were receiving consecutive cEEG at 6 centers from January 2012 to January 2019. 2HELPS2B was evaluated with the validation cohort using the mean calibration error (CAL), a measure of the difference between prediction and actual results. A Kaplan-Meier survival analysis was used to determine the duration of EEG monitoring to achieve a seizure risk of less than 5% based on the 2HELPS2B score calculated on first- hour (screening) EEG. Participants undergoing elective epilepsy monitoring and those who had experienced cardiac arrest were excluded. No participants who met the inclusion criteria were excluded. Main Outcomes and Measures: The main outcome was a CAL error of less than 5% in the validation cohort. Results: The study included 2111 participants (median age, 51 years; 1113 men [52.7%]; median EEG duration, 48 hours) and the primary outcome was met with a validation cohort CAL error of 4.0% compared with a CAL of 2.7% in the foundational cohort (P = .13). For the 2HELPS2B score calculated on only the first hour of EEG in those without seizures during that hour, the CAL error remained at less than 5.0% at 4.2% and allowed for stratifying patients into low- (2HELPS2B = 0; <5% risk of seizures), medium- (2HELPS2B = 1; 12% risk of seizures), and high-risk (2HELPS2B, ≥2; risk of seizures, >25%) groups. Each of the categories had an associated minimum recommended duration of EEG monitoring to achieve at least a less than 5% risk of seizures, a 2HELPS2B score of 0 at 1-hour screening EEG, a 2HELPS2B score of 1 at 12 hours, and a 2HELPS2B score of 2 or greater at 24 hours. Conclusions and Relevance: In this study, 2HELPS2B was validated as a clinical tool to aid in seizure detection, clinical communication, and cEEG use in hospitalized patients. In patients without prior clinical seizures, a screening 1-hour EEG that showed no epileptiform findings was an adequate screen. In patients with any highly epileptiform EEG patterns during the first hour of EEG (ie, a 2HELPS2B score of ≥2), at least 24 hours of recording is recommended.

Generalized and Lateralized Rhythmic Patterns.

The relationship between generalized and lateralized rhythmic delta activity (RDA) and seizures is more ambiguous than the relationship between periodic discharges and seizures. Although frontally predominant generalized RDA is not associated with seizures, occipitally predominant RDA may be associated with the absence of seizures. Lateralized RDA seems to be more strongly associated with the presence of seizure activity. Appropriate recognition of generalized RDA and lateralized rhythmic delta activity may be confounded by benign etiologies of RDA, such as phi rhythm, slow alpha variant, subclinical rhythmic electrographic discharges of adults, or hyperventilation-induced high-amplitude rhythmic slowing. Angelman syndrome and NMDA-receptor antibody encephalitis can also produce morphologically distinct patterns of RDA.

Treating Immune-Related Epilepsy.

PURPOSE OF REVIEW: This review explores different treatment modalities for immune-mediated epilepsy, including epilepsy caused by autoantibodies as well as epilepsy in the context of systemic autoimmune disease. RECENT FINDINGS: Autoimmune epilepsy is an increasingly recognized entity. Conventional treatments for epilepsy, such as antiseizure medications and epilepsy surgery, are less successful in treating epilepsy caused by autoimmune disease. Immunomodulatory therapies such as corticosteroids, intravenous immunoglobulin, and plasma exchange are generally more successful in treating immune-mediated epilepsy than conventional epilepsy therapies. Autoimmune epilepsy should be considered as a possible etiology for patients with frequent seizures of unknown etiology. The response to immunotherapies is often promising, particularly in patients with antibodies to neuronal cell surface antigens.

Utility of Clinical Features for the Diagnosis of Seizures in the Intensive Care Unit.

PURPOSE: Seizures in the intensive care unit are often subtle, and may have little or no clinical correlate. This study attempts to determine what clinical features are most strongly associated with the presence of electrographic seizures on continuous EEG (cEEG) monitoring. METHODS: A retrospective review for all patients who underwent cEEG monitoring between January 2003 and March 2009 for either characterization of clinical events or altered mental status was performed. Clinical events were categorized as (1) limb myoclonus/tremor, (2) extremity weakness, (3) eye movement abnormalities, (4) facial/periorbital twitching, and (5) other abnormal movements. The presence of associated dyscognitive event features was also recorded. RESULTS: Records from 626 patients who underwent cEEG were reviewed-154 for event characterization and 472 for altered mental status. Seizures were captured in 48 patients (31.2%) undergoing cEEG monitoring for characterization of clinical events. This was not significantly different from the incidence of seizures in patients undergoing cEEG for altered mental status (N = 133, 28.2%). Patients undergoing cEEG monitoring for facial/periorbital twitching were significantly more likely to have electrographic seizures (78.9%, P < 0.005) than patients undergoing cEEG for altered mental status or characterization of other types of events. CONCLUSIONS: The incidence of seizures in patients in the intensive care unit with clinical events is generally not significantly higher than the incidence of seizures in patients in the intensive care unit with altered mental status. However, the presence of facial/periorbital twitching was associated a higher incidence of electrographic seizures.

Development and Feasibility Testing of a Critical Care EEG Monitoring Database for Standardized Clinical Reporting and Multicenter Collaborative Research.

PURPOSE: The rapid expansion of the use of continuous critical care electroencephalogram (cEEG) monitoring and resulting multicenter research studies through the Critical Care EEG Monitoring Research Consortium has created the need for a collaborative data sharing mechanism and repository. The authors describe the development of a research database incorporating the American Clinical Neurophysiology Society standardized terminology for critical care EEG monitoring. The database includes flexible report generation tools that allow for daily clinical use. METHODS: Key clinical and research variables were incorporated into a Microsoft Access database. To assess its utility for multicenter research data collection, the authors performed a 21-center feasibility study in which each center entered data from 12 consecutive intensive care unit monitoring patients. To assess its utility as a clinical report generating tool, three large volume centers used it to generate daily clinical critical care EEG reports. RESULTS: A total of 280 subjects were enrolled in the multicenter feasibility study. The duration of recording (median, 25.5 hours) varied significantly between the centers. The incidence of seizure (17.6%), periodic/rhythmic discharges (35.7%), and interictal epileptiform discharges (11.8%) was similar to previous studies. The database was used as a clinical reporting tool by 3 centers that entered a total of 3,144 unique patients covering 6,665 recording days. CONCLUSIONS: The Critical Care EEG Monitoring Research Consortium database has been successfully developed and implemented with a dual role as a collaborative research platform and a clinical reporting tool. It is now available for public download to be used as a clinical data repository and report generating tool.

Sleep Features on Continuous Electroencephalography Predict Rehabilitation Outcomes After Severe Traumatic Brain Injury.

OBJECTIVE: Sleep characteristics detected by electroencephalography (EEG) may be predictive of neurological recovery and rehabilitation outcomes after traumatic brain injury (TBI). We sought to determine whether sleep features were associated with greater access to rehabilitation therapies and better functional outcomes after severe TBI. METHODS: We retrospectively reviewed records of patients admitted with severe TBI who underwent 24 or more hours of continuous EEG (cEEG) monitoring within 14 days of injury for sleep elements and ictal activity. Patient outcomes included discharge disposition and modified Rankin Scale (mRS). RESULTS: A total of 64 patients underwent cEEG monitoring for a mean of 50.6 hours. Status epilepticus or electrographic seizures detected by cEEG were associated with poor outcomes (death or discharge to skilled nursing facility). Sleep characteristics were present in 19 (30%) and associated with better outcome (89% discharged to home/acute rehabilitation; P = .0002). Lack of sleep elements on cEEG correlated with a poor outcome or mRS > 4 at hospital discharge (P = .012). Of those patients who were transferred to skilled nursing/acute rehabilitation, sleep architecture on cEEG associated with a shorter inpatient hospital stay (20 days vs 27 days) and earlier participation in therapy (9.8 days vs 13.2 days postinjury). Multivariable analyses indicated that sleep features on cEEG predicted functional outcomes independent of admission Glasgow Coma Scale and ictal-interictal activity. CONCLUSION: The presence of sleep features in the acute period after TBI indicates earlier participation in rehabilitative therapies and a better functional recovery. By contrast, status epilepticus, other ictal activity, or absent sleep architecture may portend a worse prognosis. Whether sleep elements detected by EEG predict long-term prognosis remains to be determined.

New-onset refractory status epilepticus: Etiology, clinical features, and outcome.

OBJECTIVES: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. METHODS: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). RESULTS: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. CONCLUSIONS: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation.

Consensus statement on continuous EEG in critically ill adults and children, part II: personnel, technical specifications, and clinical practice.

INTRODUCTION: Critical Care Continuous EEG (CCEEG) is a common procedure to monitor brain function in patients with altered mental status in intensive care units. There is significant variability in patient populations undergoing CCEEG and in technical specifications for CCEEG performance. METHODS: The Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society developed expert consensus recommendations on the use of CCEEG in critically ill adults and children. RECOMMENDATIONS: The consensus panel describes the qualifications and responsibilities of CCEEG personnel including neurodiagnostic technologists and interpreting physicians. The panel outlines required equipment for CCEEG, including electrodes, EEG machine and amplifier specifications, equipment for polygraphic data acquisition, EEG and video review machines, central monitoring equipment, and network, remote access, and data storage equipment. The consensus panel also describes how CCEEG should be acquired, reviewed and interpreted. The panel suggests methods for patient selection and triage; initiation of CCEEG; daily maintenance of CCEEG; electrode removal and infection control; quantitative EEG techniques; EEG and behavioral monitoring by non-physician personnel; review, interpretation, and reports; and data storage protocols. CONCLUSION: Recommended qualifications for CCEEG personnel and CCEEG technical specifications will facilitate standardization of this emerging technology.

Consensus statement on continuous EEG in critically ill adults and children, part I: indications.

INTRODUCTION: Critical Care Continuous EEG (CCEEG) is a common procedure to monitor brain function in patients with altered mental status in intensive care units. There is significant variability in patient populations undergoing CCEEG and in technical specifications for CCEEG performance. METHODS: The Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society developed expert consensus recommendations on the use of CCEEG in critically ill adults and children. RECOMMENDATIONS: The consensus panel recommends CCEEG for diagnosis of nonconvulsive seizures, nonconvulsive status epilepticus, and other paroxysmal events, and for assessment of the efficacy of therapy for seizures and status epilepticus. The consensus panel suggests CCEEG for identification of ischemia in patients at high risk for cerebral ischemia; for assessment of level of consciousness in patients receiving intravenous sedation or pharmacologically induced coma; and for prognostication in patients after cardiac arrest. For each indication, the consensus panel describes the patient populations for which CCEEG is indicated, evidence supporting use of CCEEG, utility of video and quantitative EEG trends, suggested timing and duration of CCEEG, and suggested frequency of review and interpretation. CONCLUSION: CCEEG has an important role in detection of secondary injuries such as seizures and ischemia in critically ill adults and children with altered mental status.

Therapeutic plasma exchange and immunosuppressive therapy in a patient with anti-GAD antibody-related epilepsy: quantification of the antibody response.

Antibodies to glutamic acid decarboxylase (GAD) have been associated with a host of neurological disorders including stiff person syndrome, cerebellar ataxia, limbic encephalitis, and epilepsy. Whether anti-GAD antibodies have an etiological role in these neurological disorders or simply serve as disease markers is unclear. Here, we report a case of a patient with recurrent seizures, poorly responsive to conventional treatment, associated with anti-GAD antibodies. The patient was experiencing near daily seizures at the time of presentation and had marked improvement while receiving immunosuppressive therapy and therapeutic plasma exchange (TPE). We go on to show that the patient had a substantial reduction of her GAD autoantibody burden following this therapy. Using immunostaining, we further demonstrate a progressive loss of GAD reactivity in the patient's sera to neurons and GAD-expressing HELA cells with successive TPEs. Hence, these data support the concept of an immune-mediated pathogenic component to these autoantibody-associated neurological syndromes.

Natalizumab-induced progressive multifocal leukoencephalopathy.

A 55-year-old woman with known relapsing-remitting multiple sclerosis (RRMS) on natalizumab (Tysabri®) for 3 years was admitted to the hospital with worsening word-finding difficulties and gait instability. Neurologic examination revealed right hemianopia, right arm hemiplegia, right-sided sensory loss, and global aphasia. The patient underwent MRI and PET imaging with concurrent electroencephalogram. She was subsequently diagnosed with natalizumab-induced progressive multifocal leukoencephalopathy (PML) and treated with plasmapheresis, intravenous immunoglobulin, and high-dose intravenous steroids. Steroids were continued over a 3-month hospital course and tapered upon discharge. Speech, arm strength, and ambulation have since improved.

Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis.

OBJECTIVES: To determine continuous EEG (cEEG) patterns that may be unique to anti-NMDA receptor (NMDAR) encephalitis in a series of adult patients with this disorder. METHODS: We evaluated the clinical and EEG data of 23 hospitalized adult patients with anti-NMDAR encephalitis who underwent cEEG monitoring between January 2005 and February 2011 at 2 large academic medical centers. RESULTS: Twenty-three patients with anti-NMDAR encephalitis underwent a median of 7 (range 1-123) days of cEEG monitoring. The median length of hospitalization was 44 (range 2-200) days. Personality or behavioral changes (100%), movement disorders (82.6%), and seizures (78.3%) were the most common symptoms. Seven of 23 patients (30.4%) had a unique electrographic pattern, which we named "extreme delta brush" because of its resemblance to waveforms seen in premature infants. The presence of extreme delta brush was associated with a more prolonged hospitalization (mean 128.3 ± 47.5 vs 43.2 ± 39.0 days, p = 0.008) and increased days of cEEG monitoring (mean 27.6 ± 42.3 vs 6.2 ± 5.6 days, p = 0.012). The modified Rankin Scale score showed a trend toward worse scores in patients with the extreme delta brush pattern (mean 4.0 ± 0.8 vs 3.1 ± 1.1, p = 0.089). CONCLUSIONS: Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.

The frequency and timing of epileptiform activity on continuous electroencephalogram in comatose post-cardiac arrest syndrome patients treated with therapeutic hypothermia.

AIM: The incidence and timing of electrographic seizures and epileptiform activity in comatose, adult, post-cardiac arrest syndrome (PCAS) patients treated with therapeutic hypothermia (TH) have not been extensively investigated. We hypothesized that onset most frequently occurs within the first 24 h post-arrest and is associated with poor neurologic outcome. METHODS: Single-center, retrospective analysis of a cohort of 38 comatose PCAS patients treated with TH and continuous-EEG-monitoring (cEEG), initiated as soon as possible after ICU admission. All raw cEEG waveform records were cleared of annotations and clinical information and classified by two fellowship-trained electroencephalographers. RESULTS: Twenty-three percent (9/38) of patients had electrographic seizures (median onset 19 h post-arrest); 5/9 (56%) had seizure-onset prior to rewarming; 7/9 (78%) had status epilepticus. Forty-five percent (17/38) had evidence of epileptiform activity (electrographic seizures or interictal epileptiform discharges), typically occurring during first 24 h post-arrest. Interictal epileptiform activity was highly associated with later detection of electrographic seizures (6/14, 43%, p=0.001). Ninety-four percent (16/17) of patients with epileptiform activity had poor neurologic outcome or death at discharge (Cerebral Performance Category scale 3-5; p=0.002) as did all (9/9) patients with electrographic seizures (p=0.034). CONCLUSIONS: Electrographic seizures and epileptiform activity are common cEEG findings in comatose, PCAS patients treated with TH. In this preliminary study, most seizures were status epilepticus, had onset prior to rewarming, evolved from prior interictal epileptiform activity, and were associated with short-term mortality and poor neurologic outcome. Larger, prospective studies are needed to further characterize seizure activity in comatose post-arrest patients.

EEG monitoring during therapeutic hypothermia in neonates, children, and adults.

Therapeutic hypothermia is being utilized as a neuroprotective strategy in neonates, children, and adults. The most common indications are hypoxic ischemic encephalopathy in neonates and post cardiac arrest in adults. Electroencephalographic monitoring use is increasing in critical care units, and is sometimes a component of therapeutic hypothermia clinical pathways. Monitoring may detect non-convulsive seizures or non-convulsive status epilepticus, and it may provide prognostic information. We review data regarding indications for therapeutic hypothermia and electroencephalographic monitoring in neonatal, pediatric, and adult critical care units, and discuss technical aspects related to such monitoring.

The neuropathology of Alzheimer disease in African American and white individuals.

BACKGROUND: Data from neuropathologic studies of the frequency of Alzheimer disease (AD) among African American persons conflict as to whether the neuropathologic phenotype of AD is identical in African American and white persons. OBJECTIVES: To examine clinical and neuropathologic phenotypes of AD in African American individuals and to compare AD and vascular burdens between African American and white persons. DESIGN, SETTING, AND PATIENTS: Ten African American decedents who underwent brain autopsy at the Washington University Alzheimer's Disease Research Center were matched for age, sex, and Clinical Dementia Rating with 10 white decedents between January 1, 1990, and January 1, 2000. The presence and degree of neurofibrillary tangles, senile plaques, Lewy bodies, cerebral infarcts, and cerebral amyloid angiopathy were determined. RESULTS: All 20 individuals had a neuropathologic diagnosis of AD. There were no group differences in the presence or number of infarcts, plaques, tangles, Lewy bodies, or amyloid angiopathy. CONCLUSION: In this small sample, we found no substantive differences in the neuropathology of AD among African American and white individuals.