Who is willing to participate in research? A screening model for an anxiety and depression trial in the epilepsy clinic.

OBJECTIVE: Anxiety and depression in epilepsy are prevalent, associated with poor outcomes, underrecognized, undertreated, and thus a key area of need for treatment research. The objective of this study was to assess factors associated with research participation among epilepsy clinic patients who screened positive for anxiety or depression. This was accomplished by characterizing clinical and psychiatric factors among patients seen in an epilepsy clinic and evaluating which factors were associated with consent for potential research participation, via a combined clinical and research screening model. METHODS: In a pragmatic trial of anxiety and depression treatment in epilepsy, individuals with a positive screen for anxiety and/or depression at a routine epilepsy clinic visit were invited to opt-in (via brief electronic consent) to further eligibility assessment for a randomized treatment study. Information on psychiatric symptoms and treatment characteristics were collected for dual clinical care and research screening purposes. Cross-sectional association of demographic, clinical, and psychiatric factors with opting-in to research was analyzed by multiple logistic regression. RESULTS: Among N = 199 unique adults with a first positive screen for anxiety and/or depression among 786 total screening events, 154 (77.4%) opted-in to further potential research assessment. Higher depression scores and current treatment with an antidepressant were independently associated with opting-in to research (depression odds ratio (OR) = 1.13 per 1-point increase in Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) score, p = 0.028, 95% confidence interval (CI): 1.01-1.26; antidepressant OR = 2.37, p = 0.041, CI: 1.04-5.41). Nearly half of the 199 individuals (43.7%) with anxiety and/or depression symptoms were already being treated with an antidepressant, and 46.7% were receiving neither antidepressant therapy nor mental health specialty care. One-quarter (24.1%) reported a past psychiatric hospitalization, yet only half of these individuals were receiving mental health specialty care. SIGNIFICANCE: Our results demonstrate a high willingness to participate in research using a brief electronic consent approach at a routine clinic visit. Adults with persistent anxiety or depression symptoms despite antidepressant therapy and those with higher depression scores were more willing to consider a randomized treatment study. This has implications for future study design, as individuals already on treatment or those with more severe symptoms are often excluded from traditional research designs. We also found a high burden of psychiatric disease and high prevalence of persistent symptoms despite ongoing antidepressant treatment.

Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial.

OBJECTIVE: To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. METHODS: Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up. RESULTS: All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was -37.9% in the active and -17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. SIGNIFICANCE: Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures.

Positive anxiety or depression screen despite ongoing antidepressant prescription in people with epilepsy: A large cross-sectional analysis.

Purpose: While antidepressants are recommended to manage anxiety or depression in epilepsy, limited effectiveness data exist in real-world epilepsy samples, and prior work indicated frequent positive screens despite antidepressant prescription. In response, this study evaluates factors associated with positive anxiety or depression screen during ongoing antidepressant prescription. Methods: Clinical and sociodemographic characteristics were collected among consecutive adult epilepsy clinic patients completing validated anxiety and depression instruments. The sample was divided by presence vs absence of existing antidepressant prescription at time of screening. Among those on an antidepressant, multivariable logistic regression was performed on pre-selected characteristics to evaluate for association with positive anxiety and/or depression screen. Pre-selected characteristics included: antidepressant dose, antidepressant prescriber specialty, antiseizure medications (number, potential psychotropic effects), seizure frequency, employment, visit no-shows, and medical insurance. Results: Of 563 people with epilepsy, 152 had evidence of antidepressant prescription at time of screening and 73/152(48%) had positive anxiety and/or depression screen. Multivariable modeling demonstrated low antidepressant dose and no-show visit(s) were associated with positive screens (adjusted OR 2.29, CI 1.00-5.48 and 3.11, 1.26-8.22 respectively). Conclusion: Low antidepressant dose and factors potentially associated with adherence (visit no-shows) may contribute to persistent anxiety and/or depression among epilepsy patients on an antidepressant.

Chronic levetiracetam (Keppra®) treatment increases the reinforcing strength of cocaine in rhesus monkeys.

BACKGROUND: Drugs that increase inhibitory neuronal activity in the brain have been proposed as potential medications for stimulant use disorders. OBJECTIVE: The present study assessed the ability of chronically administered levetiracetam (Keppra®), a clinically available anticonvulsant drug that increases GABA by binding to synaptic vesicle glycoprotein 2A, to modulate the reinforcing strength of cocaine in monkeys. METHODS: Three adult male rhesus monkeys (Macaca mulatta) self-administered cocaine intravenously each day under a progressive-ratio (PR) schedule of reinforcement. Two monkeys also responded to receive food pellets under a 50-response fixed-ratio schedule (FR 50) each morning. After determining a cocaine dose-response curve (0.001-0.3 mg/kg per injection, i.v.) in the evening, levetiracetam (5-75 mg/kg, p.o., b.i.d.) was administered for 12-16 days per dose. To model a treatment setting, cocaine self-administration sessions were conducted using the PR schedule every 4 days during levetiracetam treatment. After tapering the dose of levetiracetam over two weeks in the absence of cocaine sessions, cocaine dose-effect curves were re-determined. RESULTS: Lower doses of levetiracetam produced non-systematic fluctuations in numbers of cocaine injections received in each subject, whereas the highest tested dose significantly increased the reinforcing strength of cocaine; no effects on food-maintained responding were observed. After termination of levetiracetam treatment, dose-effect curves for cocaine self-administration were shifted to the left in two monkeys. CONCLUSION: These data suggest that levetiracetam is not likely to be an efficacious pharmacotherapy for cocaine dependence. Rather, sensitivity to cocaine may be increased during and after levetiracetam treatment.

Adherence to levetiracetam for management of epilepsy: Assessment with electronic monitors.

INTRODUCTION: Anti-seizure medications are used to manage epilepsy and require long-term adherence to maintain therapeutic drug levels. We assessed adherence to levetiracetam and the use of a digital intervention to improve adherence in patients with epilepsy. METHODS: 30 participants with epilepsy were randomized 1:1 either to a digital email adherence intervention or control group. All patients were provided levetiracetam equipped with electronic monitoring caps to assess patient adherence to medication. Patients were followed for 6 months, with return visits at 1 month, 3 months, and 6 months. RESULTS: Subjects randomized to the control arm (n = 15) took 66% of the prescribed doses compared to the intervention group, who took 65% of prescribed doses (n = 15). Nine participants did not complete the study. Of the twenty-one participants that completed the study, the overall rate of adherence was 72% of prescribed doses taken. Two subjects in the control group and three subjects in the intervention group were adherent every month of the study-taking at least 80% of prescribed doses. Those randomized to the control group took the correct number of doses 44% of days in the study, and those in the intervention group took the correct number of doses 37% of days. DISCUSSION: Poor adherence to levetiracetam is common. An internet-based email survey intervention did not improve adherence to levetiracetam in epilepsy patients. Further advances in adherence are needed to help patients receive the maximum benefit of their medical treatments.

Organizational strategies to reduce physician burnout and improve professional fulfillment.

Burnout is highly prevalent among physicians and has been associated with negative outcomes for physicians, patients, staff, and health-care organizations. Reducing physician burnout and increasing physician well-being is a priority. Systematic reviews suggest that organization-based interventions are more effective in reducing physician burnout than interventions targeted at individual physicians. This consensus review by leaders in the field across multiple institutions presents emerging trends and exemplary evidence-based strategies to improve professional fulfillment and reduce physician burnout using Stanford's tripartite model of physician professional fulfillment as an organizing framework: practice efficiency, culture, and personal resilience to support physician well-being. These strategies include leadership traits, latitude of control and autonomy, collegiality, diversity, teamwork, top-of-license workflows, electronic health record (EHR) usability, peer support, confidential mental health services, work-life integration and reducing barriers to practicing a healthy lifestyle. The review concludes with evidence-based recommendations on establishing an effective physician wellness program.

Analysis of NAMCS data for multiple sclerosis, 1998-2004.

BACKGROUND: To our knowledge, no study to date has investigated the prescribing patterns of immunomodulatory agents (IMAs) in an outpatient setting in the United States. To address this issue, we performed retrospective data analyses on National Ambulatory Medical Care Survey (NAMCS) data for MS patient visits between 1998 and 2004. METHODS: NAMCS data are a weighted estimate of the nationwide frequency of patients' outpatient clinic visits. We analyzed NAMCS data in the following categories: (1) the proportion of MS patient visits to neurologists, family practitioners or internists, (2) age/gender/race/geographical distribution patterns in patient visits, and (3) the proportion of patients on IMA treatment among established MS patients. RESULTS: There were an estimated 6.7 million multiple sclerosis (MS) patient visits to the clinics between 1998-2004. Neurologists recorded the most patient visits, 50.7%. Patient visits were mostly in the fourth and fifth decade age group (57.9%). The male to female ratio was 1:4. No statistical evidence was observed for a decline or increase in IMA usage. About 62% patients visiting neurologists and 92% seen by family practitioners/internists were not using IMAs. Our results suggest that between the years 1998-2003, the use of interferon-1a tended to decline while the use of interferon-1b and glatiramer acetate, increased. CONCLUSION: Strategies that lead to improved use of IMAs in the management of MS in the outpatient setting are needed.

Focal akinetic seizures as the only clinical manifestation of partial epilepsy.

Episodic hemipareis is usually thought to have a vascular etiology. Ictal paresis during seizures usually occurs with other clinical signs. The exact mechanism by which weakness occurs during seizures is difficult to determine as positive and negative motor phenomenona occur in rapid succession. This case describes a girl with episodic ictal hemiparesis since infancy as the only clinical seizure manifestation with VEEG suggesting mesial frontal ictal onset.

Burnout, career satisfaction, and well-being among US neurology residents and fellows in 2016.

OBJECTIVE: To study prevalence of and factors contributing to burnout, career satisfaction, and well-being in US neurology residents and fellows. METHODS: A total of 938 US American Academy of Neurology member neurology residents and fellows were surveyed using standardized measures of burnout, career satisfaction, and well-being from January 19 to March 21, 2016. RESULTS: Response rate was 37.7% (354/938); about 2/3 of responders were residents and 1/3 were fellows. Median age of participants was 32 years and 51.1% were female. Seventy-three percent of residents and 55% of fellows had at least one symptom of burnout, the difference largely related to higher scores for depersonalization among residents. For residents, greater satisfaction with work-life balance, meaning in work, and older age were associated with lower risk of burnout; for fellows, greater satisfaction with work-life balance and effective support staff were associated with lower risk of burnout. Trainees experiencing burnout were less likely to report career satisfaction. Career satisfaction was more likely among those reporting meaning in work and more likely for those working in the Midwest compared with the Northeast region. CONCLUSIONS: Burnout is common in neurology residents and fellows. Lack of work-life balance and lack of meaning in work were associated with reduced career satisfaction and increased risk of burnout. These results should inform approaches to reduce burnout and promote career satisfaction and well-being in US neurology trainees.

Transcranial Doppler ultrasound: a new method of monitoring hemispheric anesthetization during the intracarotid amobarbital procedure.

BACKGROUND: Electroencephalography (EEG) is traditionally used to assess the duration of hemispheric anesthetization and to monitor return of function in the anesthetized hemisphere during the intracarotid amobarbital procedure (IAP), but EEG changes are not consistently seen. The authors evaluated the role of continuous transcranial Doppler (TCD) monitoring as an alternative to EEG. METHODS: The authors performed both continuous TCD monitoring and EEG during the IAP in 10 patients with medically intractable partial epilepsy. Mean velocities were monitored continuously in both middle cerebral arteries (MCAs), and changes in MCA velocities on continuous TCD monitoring were time locked with the EEG changes. RESULTS: The average mean MCA velocities were within normal limits bilaterally (50-85 cm/s) in all patients at baseline. Mean MCA velocites increased in all patients to 95-115 cm/s at the start of the test when the patients were asked to raise their hands and start counting. After injection of sodium amobarbital, mean MCA velocities in all patients dropped dramatically on the ipsilateral side to values of 12-39 cm/s and returned to the baseline average value when the hemiparesis recovered. In 8 patients, the duration of delta activity on EEG coincided with the time interval during which the mean MCA velocities were low on TCD monitoring. In 2 patients, despite the presence of hemiparesis clinically and a drop in mean MCA velocities on the ipsilateral side on continuous TCD monitoring, EEG remained normal on the ipsilateral side. CONCLUSIONS: Continuous TCD monitoring may be a more sensitive method than EEG in determining the duration of hemispheric anesthetization during IAP. Because the items for assessment of memory are presented during the period of hemispheric anesthetization, TCD may be useful in more precisely defining the time window for memory testing.

Localization of interictal epileptiform activity using magnetoencephalography with synthetic aperture magnetometry in patients with a vagus nerve stimulator.

Magnetoencephalography (MEG) provides useful and non-redundant information in the evaluation of patients with epilepsy, and in particular, during the pre-surgical evaluation of pharmaco-resistant epilepsy. Vagus nerve stimulation (VNS) is a common treatment for pharmaco-resistant epilepsy. However, interpretation of MEG recordings from patients with a VNS is challenging due to the severe magnetic artifacts produced by the VNS. We used synthetic aperture magnetometry (g2) [SAM(g2)], an adaptive beamformer that maps the excessive kurtosis, to map interictal spikes to the coregistered MRI image, despite the presence of contaminating VNS artifact. We present a series of eight patients with a VNS who underwent MEG recording. Localization of interictal epileptiform activity by SAM(g2) is compared to invasive electrophysiologic monitoring and other localizing approaches. While the raw MEG recordings were uninterpretable, analysis of the recordings with SAM(g2) identified foci of peak kurtosis and source signal activity that was unaffected by the VNS artifact. SAM(g2) analysis of MEG recordings in patients with a VNS produces interpretable results and expands the use of MEG for the pre-surgical evaluation of epilepsy.

Successful ECT treatment for medically refractory nonconvulsive status epilepticus in pediatric patient.

Status epilepticus is a life threatening condition with a high mortality rate in spite of aggressive treatment. There is little consensus on third and fourth line approaches in refractory cases. While electroconvulsive therapy (ECT) has been employed successfully as a treatment for refractory epilepsy and status epilepticus (SE) after exhausting conventional therapy, its use for pediatric patients is limited. We describe a 7-year-old pediatric case in which ECT was used successfully to treat medically refractory nonconvulsive status epilepticus (NCSE) without complete withdrawal of antiepileptic drugs (AED).

Outcome of patients with sleep complaints and normal polysomnograms.

STUDY OBJECTIVE: To determine the outcome in patients with sleep complaints and normal polysomnograms (PSG). BACKGROUND: PSG is used in the evaluation of persons with sleep complaints. There is a small amount of literature available on patients with sleep complaints and normal PSGs. METHODS: PSGs interpreted as normal at the sleep laboratory at Wake Forest University Baptist Medical Center over a 3-year period were considered for inclusion. All PSG requests were screened for appropriateness. Follow-up data were obtained by structured telephone interview (within a period of 5 months of PSG) and chart review. This interview requested: (1) main sleep complaint, (2) diagnosis given by the ordering physician, (3) treatment for the sleep complaint, (4) further studies, and (5) overall satisfaction. RESULTS: Forty-six patients were identified with a normal PSG, and 27 (58%) were successfully contacted for the telephone interview. Of these 27 patients, 8 were men and 19 were women. Fifty-two percent of patients were not given a diagnosis by the referring physician after their normal PSG to explain their sleep symptoms. Eight patients (29%) were offered treatment for their sleep complaints despite their normal PSGs. Twenty patients (74%) reported no change in their sleep quality since the PSG. Most patients (66%) did not find the PSG helpful. CONCLUSIONS: The majority of patients with sleep complaints and normal PSG were not given a clear diagnosis by the referring physician, and sleep complaints persist after a normal PSG. Further evaluation by a sleep specialist may be appropriate.

Gabapentin-induced myoclonus in end-stage renal disease.

PURPOSE: We analyzed the occurrence and clinical features of myoclonus in patients with end-stage renal disease (ESRD) who were treated with gabapentin (GBP). METHODS: We reviewed the medical records of patients with ESRD who were treated with GBP and hospitalized during an 18-month period and analyzed clinical details such as type of myoclonus, doses of GBP, electroencephalographic (EEG) findings, and relation of symptoms to GBP exposure and dosage. RESULTS: Three of 71 patients had myoclonus with GBP doses ranging from 9 mg/kg to 20 mg/kg and within 4 months of treatment onset. Myoclonus was characterized as multifocal, involving all extremities in the three patients. EEG did not show epileptiform discharges with the myoclonus. Myoclonus resolved in the three individuals within 4-15 days after GBP was discontinued. CONCLUSIONS: GBP increases the risk of myoclonus in ESRD. Myoclonus in these individuals was more disabling than that in patients with normal renal function, and discontinuation of GBP is required to restore normal function.