The Brain Health Imperative in the 21st Century-A Call to Action: The AAN Brain Health Platform and Position Statement.

Brain health is crucial to optimizing both the function and well-being of every person at each stage of life and is key to both individual and social progress. As a concept, brain health is complex and requires a multidisciplinary collaborative approach between many professional and public organizations to bring into effect meaningful change. Neurologists are uniquely positioned to serve as specialists in brain health and to advance the newly evolving field of preventive neurology, which aims to identify individuals at high risk of brain disorders and other neurologic conditions and offer strategies to mitigate disease emergence or progression. For decades, the American Academy of Neurology (AAN) has demonstrated a commitment to brain health through its public outreach and advocacy. The AAN's Brain Health Initiative launched in 2022 with a strategic plan prioritizing brain health as a key aspect of public engagement and positioning the AAN and neurologists as champions of brain health in collaboration with a broad range of other brain health providers. In this study, we present (1) the new definition of brain health developed by the AAN for neurologists, patients, partners in health care, and the public; (2) the strategic objectives of the AAN Brain Health Initiative; and (3) the AAN Brain Health Platform and Action Plan framework, including key positions on brain health, its 3 ambitious goals, and a national brain health vision. The top-line priorities of the AAN Brain Health Action Plan highlight the need for research, education, public policy, and direct-to-public messaging across the individual's life span and will serve as a catalyst for future cross-disciplinary collaborations within each epoch and longitudinally. The AAN Brain Health Platform is designed to communicate the AAN's vision for brain health and provide a blueprint toward achieving the future of optimal brain health across the life span for all. Through this position statement, we call upon neurologists and other stakeholders in brain health to join our collective efforts to accomplish the ultimate goal of transforming the current trajectory of public health of an increasing burden of neurologic disorders-from both illness and injury-to achieving optimal brain health for all.

Pearls & Oy-sters: Whole-Genome Sequencing in Critically Ill Neurologic Patient Leads to Diagnosis With Treatment Implications.

Many adult patients with a history of seizures and global developmental delay do not have an identified etiology for their epilepsy. Rapid whole-genome sequencing (rWGS) can be used to identify a genetic etiology in critically ill patients to provide actionable interventions. In this case, a 27-year-old patient with a history of epilepsy, global developmental delay, and intellectual disability presented with altered mental status and new abnormal movements. The patient acutely declined over the course of 24-48 hours of presentation, including nonconvulsive status epilepticus leading to intubation for airway protection, 2 episodes of ventricular tachycardia requiring synchronized cardioversion, and 1 episode of supraventricular tachycardia. The patient was found to be in metabolic crisis. Metabolic workup and rapid whole-genome sequencing were sent. Patient was treated with 10% dextrose in normal saline and a mitochondrial cocktail. She received treatment with ammonia scavengers and hemodialysis with resolution of metabolic crisis. rWGS found a homozygous pathogenic variant in TANGO2 and a de novo pathogenic variant in KCNQ1, ultimately leading to the creation of a metabolic emergency protocol and implantable cardioverter defibrillator placement. This case highlights the use of rWGS in an acutely ill patient leading to actionable interventions. It also highlights the utility and importance of genetic sequencing in reevaluation of adult neurologic patients.

Inpatient long-term video-electroencephalographic monitoring event capture audiovisual diagnostic quality.

OBJECTIVES: Long-term video-electroencephalographic monitoring (LTVEM) represents the gold-standard method to evaluate whether events represent electrographic seizures, but limited work has evaluated the quality of inpatient event capture. We evaluated the frequency of audiovisual factors impairing the ideal electroclinical correlation of seizure-like episodes during LTVEM. METHODS: We retrospectively reviewed consecutive inpatient LTVEM studies (11/2019-12/2019) from three academic epilepsy centers. We evaluated all pushbutton events for audiovisual characteristics such as whether the event was narrated, whether the patient was blocked on camera, and what diagnostic challenges impaired the electroencephalographer's ability to understand either the reason the event button was pushed or clinical semiology ("electroclinical correlation"). We determined the percent of events and studies with each outcome. RESULTS: There were 154 studies with 520 pushbutton events. The pushbutton was most commonly activated by patients (41%), followed by nurses (31%) or family (17%). Twenty-nine percent of events represented electrographic seizures, and 78% occurred in the Epilepsy Monitoring Unit. The reason for the push was not stated in 45% of events, and inadequate narration impaired electroclinical correlation in 19% of events. At least one relevant part of the patient's body was blocked during 12% of events, but this impaired electroclinical correlation in only 1% of events. There was at least one factor impairing electroclinical correlation in 21% of events, most commonly due to incomplete narration (N = 99), lights off (N = 15), or blankets covering the patient (N = 15). At least one factor impaired electroclinical correlation for any event in 36% of studies. CONCLUSION: Audiovisual factors impairing the electroencephalographer's ability to render an electroclinical correlation were common, particularly related to inadequate narration from bedside observers to explain the reason for pushing the button or event semiology. Future efforts to develop targeted countermeasures should address narration challenges and improve inpatient seizure monitoring quality metrics.

The impact of a depression self-management intervention on seizure activity.

PURPOSE: Seizures have a variety of significant physical, cognitive, and social effects upon the individual. Depression has been linked to an increase in seizure activity, and Project Using Practice and Learning to Increase Favorable Thoughts (UPLIFT) was shown to reduce depressive symptoms. Project UPLIFT, based upon mindfulness-based cognitive therapy (MBCT), provides distance delivery of depression management skills to groups of people with epilepsy. Because Project UPLIFT reduces depression and depression is linked to seizure activity, the current analysis was designed to determine the impact of Project UPLIFT upon seizure frequency and severity. METHOD: Participants (n = 107) were adults ages 21-70 with epilepsy and mild-to-moderate depressive symptoms from the states of Georgia, Michigan, Texas, and Washington. The eight-session Project UPLIFT intervention was group-delivered weekly via the web or telephone. Participants were randomly assigned to condition (i.e., Project UPLIFT or a treatment-as-usual [TAU] waitlist) and assessed at baseline, and after intervening in the Project UPLIFT group (~10 weeks). Assessments included valid self-report measures of seizure frequency and severity and depression. RESULTS: Mediation analysis found that there was a significant negative direct relationship between condition and number of seizures at posttest; the mean number of seizures decreased by 3.2 in the Project UPLIFT group, but increased by 2.3 in the TAU group. The indirect path from condition to number of seizures through change in depression was not significant. Conversely, there was no significant negative direct relationship between condition and seizure severity at posttest, although the seizure severity decreased by 2.2 points in the UPLIFT group and increased by 2.7 points in the TAU group. The indirect path from condition to seizure severity through depression was significant, however, demonstrating that change in depression mediated the effect of Project UPLIFT on seizure severity. CONCLUSIONS: This study found that participating in Project UPLIFT directly reduced the number of seizures experienced by participants with epilepsy. This was not mediated by the change in depression. Participation in Project UPLIFT also reduced their perceived seizure severity indirectly, through reducing their depressive symptoms. This suggests Project UPLIFT may have the potential to impact the health, healthcare costs, and well-being of people with epilepsy.

Seizure semiology of anti-LGI1 antibody encephalitis.

Limbic encephalitis associated with anti-LGI1 antibody (LGI1 encephalitis) presents with a variety of features, the most prominent of which include seizures and progressive disturbance of memory and behaviour. Although varied in semiology, recognition of the pattern of seizures in LGI1 encephalitis is important, as early diagnosis and definitive treatment may prevent subsequent development of cognitive impairment. We present a patient with LGI1 encephalitis and "faciobrachial dystonic seizures-plus", which began as classic faciobrachial dystonic seizures and progressed to focal seizures with impaired awareness, dacrystic/gelastic-like outbursts, ictal speech, manual automatisms, and autonomic signs (tachycardia). Recognition of the broad range of seizure types associated with LGI1 encephalitis is crucial for early diagnosis and definitive treatment. [Published with video sequence on www.epilepticdisorders.com].

Mentored peer review of standardized manuscripts as a teaching tool for residents: a pilot randomized controlled multi-center study.

BACKGROUND: There is increasing need for peer reviewers as the scientific literature grows. Formal education in biostatistics and research methodology during residency training is lacking. In this pilot study, we addressed these issues by evaluating a novel method of teaching residents about biostatistics and research methodology using peer review of standardized manuscripts. We hypothesized that mentored peer review would improve resident knowledge and perception of these concepts more than non-mentored peer review, while improving review quality. METHODS: A partially blinded, randomized, controlled multi-center study was performed. Seventy-eight neurology residents from nine US neurology programs were randomized to receive mentoring from a local faculty member or not. Within a year, residents reviewed a baseline manuscript and four subsequent manuscripts, all with introduced errors designed to teach fundamental review concepts. In the mentored group, mentors discussed completed reviews with residents. Primary outcome measure was change in knowledge score between pre- and post-tests, measuring epidemiology and biostatistics knowledge. Secondary outcome measures included level of confidence in the use and interpretation of statistical concepts before and after intervention, and RQI score for baseline and final manuscripts. RESULTS: Sixty-four residents (82%) completed initial review with gradual decline in completion on subsequent reviews. Change in primary outcome, the difference between pre- and post-test knowledge scores, did not differ between mentored (-8.5%) and non-mentored (-13.9%) residents (p = 0.48). Significant differences in secondary outcomes (using 5-point Likert scale, 5 = strongly agree) included mentored residents reporting enhanced understanding of research methodology (3.69 vs 2.61; p = 0.001), understanding of manuscripts (3.73 vs 2.87; p = 0.006), and application of study results to clinical practice (3.65 vs 2.78; p = 0.005) compared to non-mentored residents. There was no difference between groups in level of interest in peer review (3.00 vs 3.09; p = 0.72) or the quality of manuscript review assessed by the Review Quality Instrument (RQI) (3.25 vs 3.06; p = 0.50). CONCLUSIONS: We used mentored peer review of standardized manuscripts to teach biostatistics and research methodology and introduce the peer review process to residents. Though knowledge level did not change, mentored residents had enhanced perception in their abilities to understand research methodology and manuscripts and apply study results to clinical practice.

Expanding the efficacy of Project UPLIFT: Distance delivery of mindfulness-based depression prevention to people with epilepsy.

OBJECTIVE: Depression affects about 16% of the U.S. population over a lifetime. People with chronic diseases have especially high rates of comorbid depression; 32% to 48% of people with epilepsy experience depression. This study evaluated the efficacy of a mindfulness-based cognitive therapy intervention for preventing major depressive disorder (MDD) episodes in people with epilepsy. METHOD: Participants (n = 128) were adults from Georgia, Michigan, Texas, and Washington with epilepsy and mild/moderate depressive symptoms. The 8-session weekly Project UPLIFT intervention, based on mindfulness-based cognitive therapy, was group-delivered via Web or telephone. Using a randomized, controlled crossover design, participants were assigned to Project UPLIFT or a treatment-as-usual (TAU) waitlist and assessed at baseline, and after intervening in the intervention group (∼10 weeks) and in the TAU group (∼20 weeks). Assessments included valid self-report measures of depression and MDD, knowledge/skills, and satisfaction with life. RESULTS: The incidence of MDD episodes (new or relapse) from baseline to interim assessment was significantly lower in the intervention condition (0.0%) than in TAU (10.7%). Depressive symptoms decreased significantly more in the intervention condition than in TAU; Web and telephone did not differ. Change in knowledge/skills mediated the effect, which persisted over the 10 weeks of follow-up. Knowledge/skills and life satisfaction increased significantly more in the intervention condition than in TAU. CONCLUSIONS: Distance delivery of group mindfulness-based cognitive therapy can prevent episodes of MDD, reduce symptoms of depression, and increase life satisfaction in people with epilepsy. This intervention is easily modified for persons with other chronic diseases and other disparity populations. (PsycINFO Database Record

Sleep staging and respiratory events in refractory epilepsy patients: Is there a first night effect?

PURPOSE: We performed this analysis of possible first night effects (FNEs) on sleep and respiratory parameters in order to evaluate the need for two serial night polysomnograms (PSGs) to diagnose obstructive sleep apnea (OSA) in epilepsy patients. METHODS: As part of a pilot multicenter clinical trial investigating the effects of treating sleep apnea in epilepsy, two nights of PSG recording were performed for 40 patients with refractory epilepsy and OSA symptoms. Sleep architecture was examined in detail, along with respiratory parameters including apnea/hypopnea index (AHI) and minimum oxygen saturation. Analysis included two-tailed t-tests, Wilcox sign rank analysis, and Bland Altman measures of agreement. RESULTS: Total sleep time differed between the two nights (night 1,363.8 min + 59.4 vs. 386.3 min + 68.6, p = 0.05). Rapid eye movement (REM) sleep and percentage of REM sleep were increased during night two (night 1: 12.3% + 5.9 vs. night 2: 15.5% + 6.2, p = 0.007), and the total minutes of slow-wave sleep (SWS) were increased (night 1: 35.6 + 60.7 vs. night 2: 46.4 + 68.1, p = 0.01). No other sleep or respiratory variables differed between the two nights. Given an AHI inclusion criterion of five apneas per hour, the first PSG identified all but one patient with OSA. DISCUSSION: Respiratory parameters showed little variability between the first and second nights. Sleep architecture was mildly different between the first and second PSG night. Performing two consecutive baseline PSGs to diagnose OSA may not be routinely necessary in this population.

What should psychiatry residents be taught about neurology?: A survey of psychiatry residency directors.

OBJECTIVES: To improve our ability to teach psychiatry residents during their required 2 months on neurology rotations, we investigated the perceived needs of psychiatry program training directors. METHODS: We contacted the program directors organization of the American Psychiatric Association and disseminated a web-based survey to all program directors. The survey asked questions about the format and content of neurology training desired for psychiatry residents. The survey was sent a second time to increase response rate. RESULTS: Sixty (32%) training directors responded. Overall satisfaction with neurologic education was rated at 3.6 out of 5 (standard deviation +/- 0.96). The specific content areas which elicited the most interest for focused training modules were differential diagnosis and biologic substrates of dementia, evaluation and treatment of drug-related and spontaneous movement disorders, evaluation and management of sleep disorders, cognitive and mood effects of stroke, and inherited disorders. Many program directors commented on perceived weaknesses of inpatient-based exposure to neurology; 78% of responders favored outpatient and consultation settings. CONCLUSIONS: In an era of deliberation about neurobehavioral integration and cross-training of neurologists and psychiatrists, neurologists should strive to provide the best possible multidisciplinary education to psychiatry trainees.

Analysis of the first night effect and sleep parameters in medically refractory epilepsy patients.

OBJECTIVES: To assess the first night effect (FNE) and compare sleep stage proportions to normative values in a sample of medically refractory epilepsy patients. PATIENTS AND METHODS: Sleep parameters of 53 epilepsy patients, ages (18-56, mean: 34+/-12, 25 females 28 men), who underwent two consecutive nights of polysomnography (PSG) were compared. Non-rapid eye movement (NREM) stage 3 and NREM stage 4 were combined as slow wave sleep (SWS). Sleep efficiency, sleep latency, rapid eye movement (REM) latency, number of stage shifts, total minutes and proportion of total sleep time for stage 1, stage 2, SWS, and REM sleep were compared between the 2 nights. RESULTS: SWS was the only parameter that differed between nights 1 and 2 for both total minutes (P=0.02) and proportion of total sleep time (P=0.01), although the means for both nights were within the normative range. Comparing sleep proportions to normative values indicates that our patients had increased NREM stage 1 and decreased REM sleep. CONCLUSIONS: We observed a minimal FNE in this sample of epilepsy patients manifested by reduced SWS. Multiple PSGs to accommodate the FNE may not be necessary in this population.

Lessons in mentoring.

Mentoring is an essential catalyst for a successful medical career in science or clinical practice. In recent years, tools have been developed to measure the impact of mentoring on career achievements, and numerous models have been developed to improve mentor training. Sid Gilman, M.D., F.R.C.P., Chair of Neurology for 26 years at the University of Michigan, is well-recognized as a role model for mentors in neurology across the country. We report the result of a survey of his former trainees on the valuable aspects of his mentoring style. A review of the current mentoring literature, including suggested training programs for mentors, is also provided.

Long-term outcome of nonsurgical candidates with medically refractory localization-related epilepsy.

PURPOSE: Epilepsy surgery can result in complete seizure remission rates of upto 80% in patients with mesial temporal sclerosis and unilateral seizures. The seizure-free rate after surgery for patients with extratemporal nonlesional epilepsy has ranged between 30% and 40%. Some patients with medically refractory localization-related epilepsy cannot be offered surgical resection because of inadequate localization of the epileptogenic zone, documentation of bilateral ictal onsets, or functionally important areas of cortex that prohibit resection. The short-term rate of complete remission with medications in temporal lobe epilepsy is poor. Less is known about remission rates in patients who are not surgical candidates. In this study, we evaluated the outcome of medical treatment in patients with medically refractory partial epilepsy who were evaluated for possible epilepsy surgery but deemed to be inadequate surgical candidates. METHODS: A retrospective chart review and telephone survey with a self-rating questionnaire were completed for all patients who underwent epilepsy surgery evaluation but were not ultimately offered surgical treatment at the University of Michigan from 1990 through 1998. We assessed changes in seizure frequency and type, imaging characteristics, ictal recordings, interim medication history, and subjective changes in quality of life. RESULTS: Thirty-four subjects were available for follow-up study, at an average of >4 years after surgical evaluation. A significant reduction in seizure frequency was noted at the time of follow-up compared with that at the time of surgical evaluation. Of patients, 21% achieved seizure remission and remained seizure free for an average of 2.5 years. Four of the seven seizure-free patients attributed their remission to new antiepileptic drugs (AEDs). On a global self-rating item, 15 of 34, or 44%, felt more or much more satisfied with their lives, and 41% felt their quality of life was stable. CONCLUSIONS: A surprisingly large number of patients we surveyed, with refractory partial epilepsy not eligible for surgical management, reported reduced seizure frequency at follow-up, and 21% were seizure free. Our findings suggest that the long-term prognosis in patients with refractory partial epilepsy who are not surgical candidates may be more positive than might be generally expected.

Seizure disorders in the elderly.

Seizure disorders become increasingly common after the age of 60 years and can have a significant impact on functional status. The goal of antiepileptic drug therapy is to control seizures but preserve quality of life. If possible, seizure control should be achieved with one agent given in the lowest effective dosage. Clinical response, rather than drug levels, should guide dosage changes. All antiepileptic drugs can cause dose-dependent sedation and cognitive impairment. Although the newer agents may have theoretical advantages over standard antiepileptic agents, higher cost may limit their use. Drugs for first-line monotherapy of seizures in elderly patients include carbamazepine, valproic acid, oxcarbazepine, gabapentin, and lamotrigine.

Sodium methohexital (brevital) as an anesthetic in the Wada test.

PURPOSES: We report our experience with sodium methohexital (Brevital) as an anesthetic used in the Wada test for language and memory in 86 epilepsy surgery patients (173 procedures). METHODS: The methods are compared with those of the more commonly used anesthetic sodium amobarbital (Amytal). RESULTS: Despite differences between the methohexital and amobarbital test protocols, the behavioral and neurologic effects of the two anesthetics are similar. Because of the brief duration of methohexital, two successive injections are made on each side rather than one, to lengthen the time available for testing both language and memory. Behavioral and EEG indices return to baseline more quickly and more completely with methohexital than with amobarbital, allowing several repetitions of the procedure without incremental drowsiness, and the total time taken for the procedure is less with methohexital than with amobarbital. CONCLUSIONS: The results of language and memory testing in the Wada test are equivalent for amobarbital and methohexital, except that methohexital has a briefer duration of action and is associated with less sedation.