Heart rate and autonomic biomarkers distinguish convulsive epileptic vs. functional or dissociative seizures.

OBJECTIVE: 20-40% of individuals whose seizures are not controlled by anti-seizure medications exhibit manifestations comparable to epileptic seizures (ES), but there are no EEG correlates. These events are called functional or dissociative seizures (FDS). Due to limited access to EEG-monitoring and inconclusive results, we aimed to develop an alternative diagnostic tool that distinguishes ES vs. FDS. We evaluated the temporal evolution of ECG-based measures of autonomic function (heart rate variability, HRV) to determine whether they distinguish ES vs. FDS. METHODS: The prospective study includes patients admitted to the University of Rochester Epilepsy Monitoring Unit. Participants are 18-65 years old, without therapies or co-morbidities associated with altered autonomics. A habitual ES or FDS is recorded during admission. HRV analysis is performed to evaluate the temporal changes in autonomic function during the peri­ictal period (150-minutes each pre-/post-ictal). We determined if autonomic measures distinguish ES vs. FDS. RESULTS: The study includes 53 ES and 46 FDS. Temporal evolution of HR and autonomics significantly differ surrounding ES vs. FDS. The pre-to-post-ictal change (delta) in HR differs surrounding ES vs. FDS, stratified for convulsive and non-convulsive events. Post-ictal HR, total autonomic (SDNN & Total Power), vagal (RMSSD & HF), and baroreflex (LF) function differ for convulsive ES vs. convulsive FDS. HR distinguishes non-convulsive ES vs. non-convulsive FDS with ROC>0.7, sensitivity>70%, but specificity<50%. HR-delta and post-ictal HR, SDNN, RMSSD, LF, HF, and Total Power each distinguish convulsive ES vs. convulsive FDS (ROC, 0.83-0.98). Models with HR-delta and post-ictal HR provide the highest diagnostic accuracy for convulsive ES vs. convulsive FDS: 92% sensitivity, 94% specificity, ROC 0.99). SIGNIFICANCE: HR and HRV measures accurately distinguish convulsive, but not non-convulsive, events (ES vs. FDS). Results establish the framework for future studies to apply this diagnostic tool to more heterogeneous populations, and on out-of-hospital recordings, particularly for populations without access to epilepsy monitoring units.

Creating a New Set of Milestones for the Clinical Neurophysiology Fellowship.

INTRODUCTION: The Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology first developed milestones for the clinical neurophysiology (CNP) fellowship in 2015. The milestones provide a comprehensive evaluation of the fellow's development based on six domains of competency. Here, we describe the development of a new set of milestones for CNP fellowship with level 1 as the incoming level, level 4 as the goal for graduation, and level 5 as the aspirational level that may not be achieved. METHODS: Committee members were nominated or volunteered to participate in the milestones update. Milestone development began with the creation of a shared mental model of the ideal skills and knowledge a graduating CNP fellow should attain. RESULTS: The CNP committee met virtually 7 times for a total of 14 meeting hours. Nine Patient Care and five Medical Knowledge milestones evolved from the seven Patient Care and six Medical Knowledge milestones that were in the first iteration. The committee incorporated 11 "Harmonized Milestones" into the revision and a supplemental guide was created. CONCLUSIONS: The revised Accreditation Council for Graduate Medical Education milestones for CNP fellowship contain important updates that program directors should review against their curricula to identify any gaps in learning. Program leadership should take note of two new Patient Care milestones for telemedicine and intraoperative monitoring. Clinical neurophysiology fellowships are not designed to provide level 4 competency across all milestones. The revised milestones should be viewed within the context of an individual program's goals.

Improved ictal assessment performance in the epilepsy monitoring unit via standardization.

OBJECTIVE: To determine whether the standardization and implementation of an ictal testing protocol in the Epilepsy Monitoring Unit (EMU) leads to improvements in ictal testing performance. METHODS: Ictal assessments completed in the EMU from a single center were retrospectively reviewed over a two-month period. Each assessment was evaluated to determine whether 8 high-yield aspects of the ictal assessment were performed. Following observation of performance, a standardized ictal testing protocol was developed based on a root cause analysis and review of consensus guidelines. This protocol was disseminated to staff in conjunction with an annual epilepsy education seminar. Ictal assessment performance was re-assessed during the subsequent two months (short-term follow-up) and again during a five- to seven-month period (long-term follow-up) beyond the initial intervention. For sub-group analysis, event characteristics (event type, time of assessment) and patient characteristics (age, gender) were also evaluated and analyzed in relation to ictal testing performance. RESULTS: All eight individual ictal testing elements were more likely to be assessed in short-term and long-term follow-up periods when compared to pre-intervention assessments. The cumulative difference in ictal testing was 20.4% (95% CI 3.7-37.2, p = 0.02) greater for the short-term period and 16.7% (95% CI -0.3% to 33.8%, p = 0.05) greater in the long-term period when compared to baseline testing. CONCLUSIONS: Utilization of a standardized ictal testing battery in conjunction with staff education leads to an objective improvement in ictal assessment performance. Further research is warranted to assess the replicability of our findings.

You never forget your first? Impact of interview timing on institutional rank order.

OBJECTIVE: To analyze the impact of interview date on the applicant rank for Neurology residencies in the United States. METHODS: A multi-institutional retrospective review of interview dates and applicant rank list data for the National Resident Matching Program (NRMP) was conducted for five Neurology programs, totaling 1932 interviewed applicants over a combined total of 31 interview years. For each candidate, the interview date and applicant rank were abstracted along with the total number of interviews for that season. Statistical analyses were completed on the cumulative institution data set as well for each individual institution to assess for a possible relationship between interview date and applicant rank. RESULTS: The cumulative institutional analysis showed that the mean applicant rank decreased as the interview season progressed. Applicants who interviewed on the first day of the interview season were ranked 11.4% higher than those who interviewed on the last interview day. Additionally, applicants interviewed on the first interview day more likely to be ranked higher when compared to all other interview dates. Independent analysis of each program's data identified comparable, statistically significant, differences in mean applicant rank and interview position at three out of the five institutions. CONCLUSIONS: This study evaluated the impact of interview order on the ranking of applicants by Neurology residency programs, noting a temporal relationship with applicant rank and interview date. The primacy bias appreciated in our data merits further evaluation in other medical specialties. Strategies to minimize the impact of this bias should be employed by residency programs who use medical matching services.

Diagnostic accuracy of paroxysmal spells: Clinical history versus observation.

Our goal was to evaluate how accurate neurologists are at differentiating between different paroxysmal events based on clinical history versus observation of the spell in question. Forty-seven neurologists reviewed 12 clinical histories and videos of recorded events of patients admitted in the Epilepsy Monitoring Unit (EMU). They were asked to diagnose events as epileptic seizures, non-epileptic behavioral spells (NEBS), or other physiologic events as well as rate their confidence in their diagnosis. The median diagnostic accuracy for all paroxysmal events was 67% for clinical history and 75% for observation (p=.001). This was largely due to the difference in accuracy within the subgroup of patients with NEBS (67% history vs. 83% observation, p<.001). There were trends for higher diagnostic accuracy and increased inter-rater agreement with higher levels of training. Physicians with higher levels of training were more confident with diagnosis based on observation. In summary, reviewing videos of paroxysmal spells may improve diagnostic accuracy and enhance the evaluation of patients. Neurologists at all levels of training should encourage the recording and review of videos of recurrent spells to aid in medical decision-making especially when there is high concern that the spells in question are NEBS.

The effects of technological advances on outcomes for elderly persons with exudative age-related macular degeneration.

IMPORTANCE Exudative age-related macular degeneration (ARMD) is the major cause of blindness among US elderly. Developing effective therapies for this disease has been difficult. OBJECTIVES To assess the effects of introducing new therapies for treating exudative ARMD on vision of the affected population and other outcomes among Medicare beneficiaries newly diagnosed as having ARMD. DESIGN The study used data from a 5% sample of Medicare claims and enrollment data with a combination of a regression discontinuity design and propensity score matching to assess the effects on the introduction or receipt of new technologies on study outcomes during a 2-year follow-up period. SETTING AND PARTICIPANTS The analysis was based on longitudinal data for the United States, January 1, 1994, to December 31, 2011, for Medicare beneficiaries with fee-for-service coverage. The sample was limited to beneficiaries 68 years or older newly diagnosed as having exudative ARMD as indicated by beneficiaries having no claims with this diagnosis in a 3-year look-back period. EXPOSURES The comparisons with vision outcomes were after vs before the introduction of photodynamic therapy and anti-vascular endothelial growth factor (VEGF) therapy. The comparisons for depression and long-term care facility admission were between beneficiaries newly diagnosed as having exudative ARMD who received photodynamic therapy or anti-VEGF therapy compared with beneficiaries having the diagnosis who received no therapy for this disease. MAIN OUTCOMES AND MEASURES Onset of decrease in vision, vision loss or blindness, depression, and admission to a long-term care facility. RESULTS Among beneficiaries newly diagnosed as having exudative ARMD, the introduction of anti-VEGF therapy reduced vision loss by 41% (95% CI, 52%-68%) and onset of severe vision loss and blindness by 46% (95% CI, 47%-63%). Such beneficiaries who received anti-VEGF therapy and were not admitted to a long-term care facility during the look-back period were 19% (95% CI, 72%-91%) less likely on average to be admitted to a long-term care facility during the follow-up period. CONCLUSIONS AND RELEVANCE This study demonstrates gains in population vision from the introduction of anti-VEGF therapy for patients 68 years or older with an exudative ARMD diagnosis in community-based settings in the United States.

The role of the medial prefrontal cortex in regulating social familiarity-induced anxiolysis.

Overcoming specific fears and subsequent anxiety can be greatly enhanced by the presence of familiar social partners, but the neural circuitry that controls this phenomenon remains unclear. To overcome this, the social interaction (SI) habituation test was developed in this lab to systematically investigate the effects of social familiarity on anxiety-like behavior in rats. Here, we show that social familiarity selectively reduced anxiety-like behaviors induced by an ethological anxiogenic stimulus. The anxiolytic effect of social familiarity could be elicited over multiple training sessions and was specific to both the presence of the anxiogenic stimulus and the familiar social partner. In addition, socially familiar conspecifics served as a safety signal, as anxiety-like responses returned in the absence of the familiar partner. The expression of the social familiarity-induced anxiolysis (SFiA) appears dependent on the prefrontal cortex (PFC), an area associated with cortical regulation of fear and anxiety behaviors. Inhibition of the PFC, with bilateral injections of the GABAA agonist muscimol, selectively blocked the expression of SFiA while having no effect on SI with a novel partner. Finally, the effect of D-cycloserine, a cognitive enhancer that clinically enhances behavioral treatments for anxiety, was investigated with SFiA. D-cycloserine, when paired with familiarity training sessions, selectively enhanced the rate at which SFiA was acquired. Collectively, these outcomes suggest that the PFC has a pivotal role in SFiA, a complex behavior involving the integration of social cues of familiarity with contextual and emotional information to regulate anxiety-like behavior.

Cost offsets to medicare attributable to receipt of hip, knee, and shoulder arthroplasty.

OBJECTIVE: To estimate trends in numbers of and Medicare payments for hip, knee, and shoulder arthroplasties for beneficiaries with osteoarthritis (OA) and potential savings to Medicare from arthroplasty during followup. METHODS: The analysis was based on longitudinal 5% Medicare enrollment and claims data for 1992-2010. The analysis of changes in Medicare payments attributable to total arthroplasty receipt used propensity score matching to obtain beneficiary control groups matched on demographic characteristics, general health, joint pain, and Medicare payments by major condition in the year preceding the index arthroplasty. An average treatment effect on the treated (ATT) overall and for each major condition was calculated for payments for care 7-36 months following the index arthroplasty procedure. RESULTS: Growth in incident OA diagnoses of the hip, knee, and shoulder was substantially higher than growth in real Medicare spending on hip, knee, and shoulder arthroplasties. ATTs showed a mean saving to Medicare of $471/beneficiary/procedure for hip, no difference for knee, and a payment increase of $1,062 for shoulder arthroplasty during followup. For hip arthroplasty, the largest savings was for the circulatory system. For shoulder arthroplasty, increased payments during followup reflected increased payments for musculoskeletal care, especially for hip and knee arthroplasty. Overall, payment differences during followup by major condition were small. CONCLUSIONS: Provision of hip but not knee and shoulder arthroplasty generated savings to Medicare during followup, but even for hip arthroplasty, the cost offset during followup was small relative to the program cost for the procedure itself.

Diffusion of technologies for the care of older adults with exudative age-related macular degeneration.

PURPOSE: To determine patterns of diffusion of diagnostic tests and therapeutic interventions in the United States through 2010 for patients with newly diagnosed exudative macular degeneration (AMD). DESIGN: Retrospective longitudinal cohort analysis. METHODS: SETTING AND PATIENT POPULATION: A total of 23 941 Medicare beneficiaries with exudative AMD newly diagnosed during 1992-2009. OBSERVATION PROCEDURES: Current Procedural Technology (CPT-4) billing codes were used to identify use of diagnostic tests (optical coherence tomography, fluorescein angiography, and fundus photography) and therapeutic interventions (argon laser photocoagulation, photodynamic therapy, intravitreal corticosteroids, and anti-vascular endothelial growth factor [VEGF] agents) used by these beneficiaries during the first year following diagnosis. MAIN OUTCOME MEASURES: Rates of use of study diagnostic and therapeutic procedures. RESULTS: Diffusion was rapid for each successive new diagnostic and treatment modality, with use of newer procedures quickly replacing existing ones. The number of beneficiaries treated with anti-VEGF agents for exudative AMD was considerably greater than for prior innovations, rising from use in 4.0% of beneficiaries in 2004-05 to 62.7% in 2009-10. In each year from first diagnosis years 2006-2009 and in different practice settings, use of bevacizumab exceeded that of ranibizumab (60%-78% vs 33%-47%, respectively). Rates of diffusion of the various therapies were relatively similar in communities throughout the United States irrespective of presence of a major teaching hospital in the vicinity. CONCLUSIONS: Newer, more effective therapeutic interventions for exudative AMD diffused rapidly throughout the United States, quickly replacing older, less effective interventions. Although improving patient outcomes, rapid diffusion raises important public policy issues for Medicare and other payers to consider.

Charles Bonnet syndrome: visual hallucination and multiple sclerosis.

Multiple sclerosis (MS) is a fairly common condition that affects approximately 350,000 people in the United States. It is associated with various neuropsychiatric symptoms including cognitive and behavioral symptoms. However, visual hallucinations are rare in multiple sclerosis without the presence of cognitive deficits. We are describing the case of a 40-year-old married white female with isolated complex visual hallucinations compatible with the Charles Bonnet syndrome (CBS). The patient was successfully treated with the atypical antipsychotic olanzapine.

Light-scattering instrument to detect thromboemboli in blood.

The characteristics and capabilities of a light-scattering microemboli detector (LSMD) are delineated by detailing its state-of-the-art configuration, by discussing the theoretical and empirical aspects of instrument calibration, and by summarizing various experimental studies that have benefited from this instrument. In the past, thromboembolism, which often results when blood contacts medical devices, has eluded scientific scrutiny due to the absence of instruments that could detect and quantify thromboemboli in circulating blood. More recently, the ability of the LSMD to provide continuous, noninvasive detection of thromboemboli in whole blood (meaning that the LSMD probe does not contact the blood) was exploited in various in vitro and ex vivo models to explore thromboembolic phenomena. Through this work, the LSMD evolved as a sensitive and an economical research tool for the study of thromboembolic phenomena.