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Background Residency application patterns by gender and race/ethnicity offer important insights about diversity in residency recruitment. It is unknown how the COVID-19 pandemic and virtual interviewing affected these patterns. Objective We hypothesized that the introduction of virtual interviews caused an increase in applications submitted per applicant and that there may be differences by gender and race/ethnicity. Methods We extracted publicly reported Electronic Residency Application Service application data from 2018 to 2022 for 14 residency specialties with 1000 or more applicants in 2022 by self-reported gender and underrepresented in medicine (UIM) status. We compared patterns before and after virtual interviews were introduced in 2021. Results Among 401 480 residency applicants, the average number of applications submitted per applicant increased for all specialties between 2018 and 2022 across gender and race/ethnicity. Across all years, women applied to more programs than men in 5 specialties (dermatology, neurology, obstetrics/gynecology, pediatrics, and surgery), whereas men applied to more programs than women in 3 (anesthesia, family medicine, and physical medicine and rehabilitation). Across all years, non-UIM applicants applied to more programs than UIM applicants in all 14 specialties. There were no clear changes in application patterns by gender and race/ethnicity during in-person versus virtual interview years. Conclusions The average number of applications submitted per applicant increased over time across gender and race/ethnicity. In some specialties, women applied to more programs than men, and in others vice-versa, whereas non-UIM applicants applied to more programs than UIM applicants in all specialties. Virtual interviews did not change these patterns.

Autoimmune glial fibrillar acidic protein (GFAP) astrocytopathy is a rare autoimmune neuroinflammatory disorder that affects the central nervous system. We present a case of GFAP astrocytopathy in a middle-aged male who presented with constitutional symptoms, encephalopathy and lower extremity weakness and numbness. Initially MRI of the spine was normal, but he subsequently developed longitudinally extensive myelitis and meningoencephalitis. Workup for infectious aetiologies was negative and the patient's clinical course worsened despite broad antimicrobial coverage. Ultimately, he was found to have anti-GFAP antibodies in his cerebral spinal fluid consistent with GFAP astrocytopathy. He was treated with steroids and plasmapheresis with clinical and radiographic improvement. This case demonstrates the temporal evolution of myelitis on MRI in a case of steroid-refractory GFAP astrocytopathy.

BackgroundUnplanned readmission is one of many measures of the quality of care of pediatric patients with neurological conditions. In this multicenter study, we searched for novel risk factors of readmission of patients with neurological conditions.MethodsWe retrieved hospitalization data of patients less than 18 years with one or more neurological conditions. This resulted in a total of 105,834 encounters from 18 hospitals. We included data on patient demographics, prior healthcare resource utilization, neurological conditions, number of other conditions/diagnoses, number of medications, and number of surgical procedures performed. We developed a random intercept logistic regression model using stepwise minimization of Akaike Information Criteria for variable selection.ResultsThe most important neurological conditions associated with unplanned pediatric readmissions include hydrocephalus, inflammatory diseases of the central nervous system, sleep disorders, disease of myoneural junction and muscle, other central nervous system disorder, other spinal cord conditions (such as vascular myelopathies, and cord compression), and nerve, nerve root and plexus disorders. Current and prior healthcare resource utilization variables, number of medications, other diagnoses, and certain inpatient surgical procedures were associated with changes in odds of readmission. The area under the receiver operator characteristic curve (AUROC) on the independent test set is 0.733 (0.722, 0.743).ConclusionsPediatric patients with certain neurological conditions are more likely to be readmitted than others. However, current and prior healthcare resource utilization remain some of the strongest indicators of readmission within this population as in the general pediatric population.

BackgroundParents of neonates with seizures are at risk of mental health symptoms due to the impact of illness on family life, prognostic uncertainty, and the emotional toll of hospitalization. A family-centered approach is the preferred model to mitigate these challenges. We aimed to identify strategies to promote family-centered care through an analysis of parent-offered advice to clinicians caring for neonates with seizures.MethodsThis prospective, observational, and multicenter (Neonatal Seizure Registry) study enrolled parents of neonates with acute symptomatic seizures. Parents completed surveys about family well-being at 12, 18, and 24 months corrected gestational age. Parents were asked open-ended questions eliciting their advice to clinicians caring for neonates with seizures. Responses were analyzed using a conventional content analysis approach.ResultsAmong the 310 parents who completed surveys, 118 (38%) shared advice for clinicians. These parents were predominantly mothers (n = 103, 87%). Three overarching themes were identified. (1) Communicate information effectively: parents appreciate when clinicians offer transparent and balanced information in an accessible way. (2) Understand and validate parent experience: parents value clinicians who display empathy, compassion, and a commitment to parent-partnered clinical care. (3) Providesupportand resources: parents benefit from emotional support, education, connection with peers, and help navigating the health care system.ConclusionsParents caring for neonates with seizures appreciate a family-centered approach in health care encounters, including skilled communication, understanding and validation of the parent experience, and provision of support and resources. Future interventions should focus on building structures to reinforce these priorities.

Fosphenytoin (FOS) and its active form, phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA) are commonly used second-line treatments of status epilepticus. However, limited information is available regarding LEV and VPA concentrations following high intravenous doses, particularly in young children. The Established Status Epilepticus Treatment Trial, a blinded, comparative effectiveness study of FOS, LEV, and VPA for benzodiazepine-refractory status epilepticus provided an opportunity to investigate early drug concentrations. Patients aged ≥2 years who continued to seizure despite receiving adequate doses of benzodiazepines were randomly assigned to FOS, LEV, or VPA infused over 10 minutes. A sparse blood-sampling approach was used, with up to 2 samples collected per patient within 2 hours following drug administration. The objective of this work was to report early drug exposure of PHT, LEV, and VPA and plasma protein binding of PHT and VPA. Twenty-seven children with median (interquartile range) age of 4 (2.5-6.5) years were enrolled. The total plasma concentrations ranged from 69 to 151.3 μg/mL for LEV, 11.3 to 26.7 μg/mL for PHT and 126 to 223 μg/mL for VPA. Free fraction ranged from 4% to 19% for PHT and 17% to 51% for VPA. This is the first report in young children of LEV concentrations with convulsive status epilepticus as well as VPA concentrations after a 40 mg/kg dose. Several challenges limited patient enrollment and blood sampling. Additional studies with a larger sample size are required to evaluate the exposure-response relationships in this emergent condition.

BackgroundThe nucleotide binding protein-like (NUBPL) gene was first reported as a cause of mitochondrial complex I deficiency (MIM 613621, 618242) in 2010. To date, only eight patients have been reported with this mitochondrial disorder. Five other patients were recently reported to have NUBPL disease but their clinical picture was different from the first eight patients. Here, we report clinical and genetic findings in five additional patients (four families).MethodsWhole exome sequencing was used to identify patients with compound heterozygous NUBPL variants. Functional studies included RNA-Seq transcript analyses, missense variant biochemical analyses in a yeast model (Yarrowia lipolytica) and mitochondrial respiration experiments on patient fibroblasts.ResultsThe previously reported c.815-27T>C branch-site mutation was found in all four families. In prior patients, c.166G>A [p.G56R] was always found in cis with c.815-27T>C, but only two of four families had both variants. The second variant found in trans with c.815-27T>C in each family was: c.311T>C [p.L104P] in three patients, c.693+1G>A in one patient and c.545T>C [p.V182A] in one patient. Complex I function in the yeast model was impacted by p.L104P but not p.V182A. Clinical features include onset of neurological symptoms at 3-18 months, global developmental delay, cerebellar dysfunction (including ataxia, dysarthria, nystagmus and tremor) and spasticity. Brain MRI showed cerebellar atrophy. Mitochondrial function studies on patient fibroblasts showed significantly reduced spare respiratory capacity.ConclusionWe report on five new patients with NUBPL disease, adding to the number and phenotypic variability of patients diagnosed worldwide, and review prior reported patients with pathogenic NUBPL variants.

IntroductionWomen have historically been under-represented in randomised controlled trials (RCTs), including many landmark RCTs that established standards of care. In light of this fact, some modern researchers are calling for replication of earlier landmark trials with women only. This approach is ethically concerning, in that it would require some enrolled women to be deprived of treatments that are currently considered standard of care.ObjectiveIn an attempt to better understand the justification of a women-only approach to designing clinical trials, this study looks to systematically categorise the number of women-only RCTs for conditions that affect both men and women and the reasons given within the medical and philosophical literatures to perform them.MethodologyThis scoping review of the literature will search, screen and select articles based on predetermined inclusion/exclusion criteria, after which a grounded theory approach will be used to synthesise the data. It is expected that there will be a variety of reasons given for why a women-only trial may be justified. Electronic databases that will be searched include MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov, Philosopher's Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE and the National Reference Centre for Bioethics.SignificanceThe scope of this study is to determine published rationales used to justify women-only randomised trials, both in the case of new trials and in the repetition of landmark trials.Ethics and disseminationResearch ethics board approval is not required for this study as there is no participant involvement. Results will be published as a stand-alone manuscript and will inform a larger project related to the ethics of a women-only RCT of carotid intervention for women with symptomatic high-grade carotid stenosis.

BackgroundSmartphone technology is ubiquitous throughout neurologic practices, and numerous apps relevant to a neurologist's clinical practice are now available. Data from other medical specialties suggest high utilization of smartphones in routine clinical care. However, the ways in which these devices are used by neurologists for patient care-related activities are not well defined.ObjectiveThis paper aims to characterize current patterns of smartphone use and perceptions of the utility of smartphones for patient care-related activities among academic neurology trainees and attending physicians. We also seek to characterize areas of need for future app development.MethodsWe developed a 31-item electronic questionnaire to address these questions and invited neurology trainees and attendings of all residency programs based in the United States to participate. We summarized descriptive statistics for respondents and specifically compared responses between trainees and attending physicians.ResultsWe received 213 responses, including 112 trainee and 87 attending neurologist responses. Neurology trainees reported more frequent use of their smartphone for patient care-related activities than attending neurologists (several times per day: 84/112, 75.0% of trainees; 52/87, 59.8% of attendings; P=.03). The most frequently reported activities were internet use, calendar use, communication with other physicians, personal education, and health care-specific app use. Both groups also reported regular smartphone use for the physical examination, with trainees again reporting more frequent usage compared with attendings (more than once per week: 35/96, 36.5% of trainees; 8/58, 13.8% of attendings; P=.03). Respondents used their devices most commonly for the vision, cranial nerve, and language portions of the neurologic examination. The majority of respondents in both groups reported their smartphones as "very useful" or "essential" for the completion of patient care-related activities (81/108, 75.0% of trainees; 50/83, 60.2% of attendings; P=.12). Neurology trainees reported a greater likelihood of using their smartphones in the future than attending neurologists ("very likely": 73/102, 71.6% of trainees; 40/82, 48.8% of attendings; P=.005). The groups differed in their frequencies of device usage for specific patient care-related activities, with trainees reporting higher usage for most activities. Despite high levels of use, only 12 of 184 (6.5%) respondents reported ever having had any training on how to use their device for clinical care. Regarding future app development, respondents rated vision, language, mental status, and cranial nerve testing as potentially being the most useful to aid in the performance of the neurologic examination.ConclusionsSmartphones are used frequently and are subjectively perceived to be highly useful by academic neurologists. Trainees tended to use their devices more frequently than attendings. Our results suggest specific avenues for future technological development to improve smartphone use for patient care-related activities. They also suggest an unmet need for education on effectively using smartphone technology for clinical care.

BACKGROUND: Neonatal seizures are associated with death and neurological morbidity; however, little is known about how neonates with seizures die. METHODS: This was a prospective, observational cohort study of neonates with seizures treated at seven sites of the Neonatal Seizure Registry. We characterized the mode of death, evaluated the association between infant characteristics and mode of death, and evaluated predictors of death or transfer to hospice. RESULTS: We enrolled 611 consecutive neonates with seizures, and 90 neonates (15%) died before hospital discharge at a median age of 11 days (range: 1 to 163 days); 32 (36%) died in the first postnatal week. An additional 19 neonates (3%) were transferred to hospice. The most common mode of in-hospital death was death after extubation amidst concerns for poor neurological prognosis, in the absence of life-threatening physiologic instability (n = 43, 48%). Only one infant died while actively receiving cardiopulmonary resuscitation. In an adjusted analysis, premature birth (odds ratio: 3.06, 95% confidence interval 1.59 to 5.90) and high seizure burden (odds ratio: 4.33, 95% confidence interval 1.88 to 9.95) were associated with increased odds of death or transfer to hospice. CONCLUSION: In a cohort of neonates with seizures, death occurred predominantly after decisions to withdraw or withhold life-sustaining intervention(s). Future work should characterize how these decisions occur and develop optimized approaches to support families and clinicians caring for newborns with seizures.

OBJECTIVE:Neonates with seizures have a high risk of mortality and neurological morbidity. We aimed to describe the experience of parents caring for neonates with seizures. DESIGN:This prospective, observational and multicentre (Neonatal Seizure Registry) study enrolled parents of neonates with acute symptomatic seizures. At the time of hospital discharge, parents answered six open-ended response questions that targeted their experience. Responses were analysed using a conventional content analysis approach. RESULTS:144 parents completed the open-ended questions (732 total comments). Four themes were identified. Sources of strength: families valued medical team consensus, opportunities to contribute to their child's care and bonding with their infant. Uncertainty: parents reported three primary types of uncertainty, all of which caused distress: (1) the daily uncertainty of the intensive care experience; (2) concerns about their child's uncertain future and (3) lack of consensus between members of the medical team. Adapting family life: parents described the many ways in which they anticipated their infant's condition would lead to adaptations in their family life, including adjusting their family's lifestyle, parenting approach and routine. Many parents described financial and work challenges due to caring for a child with medical needs. Emotional and physical toll: parents reported experiencing anxiety, fear, stress, helplessness and loss of sleep. CONCLUSIONS:Parents of neonates with seizures face challenges as they adapt to and find meaning in their role as a parent of a child with medical needs. Future interventions should target facilitating parent involvement in clinical and developmental care, improving team consensus and reducing the burden associated with prognostic uncertainty.

BackgroundSidewinder gait in horses is poorly understood and characterized by walking with the trunk and pelvic limbs drifting to 1 side.Hypothesis/objectivesTo report causes, clinical and diagnostic features.AnimalsHorses examined at 2 institutions.Materials and methodsRetrospective study (2000-2019). Cases with sidewinder gait, neurological and orthopedic examination, and diagnostic work up or postmortem evaluation were included. Descriptive statistics were performed.ResultsTwenty-four horses (mean age 18.9 years) of various breeds and both sexes were included. Onset was acute (N = 10), subacute (N = 6), and insidious (N = 8). Electromyography and muscle biopsy supported neurologic disease and further aided in localizing site of lesion (N = 9/9). Neurologic causes included dynamic thoracolumbar spinal cord compression (N = 5), equine protozoal myeloencephalitis (N = 4, confirmed and presumed [2 each]), thoracic myelopathy of unknown etiology (N = 4), gliosis (N = 2), and thrombosis of thoracic spinal cord segments (N = 1). Non-neurologic causes included osteoarthritis of the coxofemoral joint (N = 4), multiple displaced pelvic fractures (N = 2), bilateral rupture of the ligamentum capitis ossis femoris (N = 1), and severe myonecrosis of multiple pelvic limb muscles (N = 1). Case fatality was 79%.Conclusion and clinical importanceSidewinder gait is usually observed in older horses and can have neurologic or musculoskeletal etiologies. Electromyography can be used as a diagnostic aid to determine neurologic versus non-neurologic disease and further localize those of neurologic origin. The condition often has a poor prognosis for function and life.

Radiotherapy, surgery and the chemotherapeutic agent temozolomide (TMZ) are frontline treatments for glioblastoma multiforme (GBM). However beneficial, GBM treatments nevertheless cause anxiety or depression in nearly 50% of patients. To further understand the basis of these neurological complications, we investigated the effects of combined radiotherapy and TMZ chemotherapy (combined treatment) on neurological impairments using a mouse model. Five weeks after combined treatment, mice displayed anxiety-like behaviors, and at 15 weeks both anxiety- and depression-like behaviors were observed. Relevant to the known roles of the serotonin axis in mood disorders, we found that 5HT1A serotonin receptor levels were decreased by ∼50% in the hippocampus at both early and late time points, and a 37% decrease in serotonin levels was observed at 15 weeks postirradiation. Furthermore, chronic treatment with the selective serotonin reuptake inhibitor fluoxetine was sufficient for reversing combined treatment-induced depression-like behaviors. Combined treatment also elicited a transient early increase in activated microglia in the hippocampus, suggesting therapy-induced neuroinflammation that subsided by 15 weeks. Together, the results of this study suggest that interventions targeting the serotonin axis may help ameliorate certain neurological side effects associated with the clinical management of GBM to improve the overall quality of life for cancer patients.

Between 2016 and 2017, several U.S. Diplomats in Havana, Cuba, experienced perplexing vestibular and neurological symptoms attributed to an unknown source. They presented with significant vestibular and headache symptoms similar to individuals who experience vestibular migraine (VM). As such, we hypothesize that VM may be a possible explanation for the Havana cohort's presenting symptoms. To evaluate this hypothesis, we compared symptoms reported by the affected individuals in Havana, Cuba, to symptoms reported by corresponding patients from a tertiary academic neurotology clinic with a chief complaint of vertigo or disequilibrium, who met the International Classification of Headache Disorders criteria for VM. The prevalence of the Havana subjects experiencing various symptomatic domains was compared with the VM cohort, leading to 26 unique domains and statistical comparisons between the cohorts. Of the 26 domains compared between the two cohorts, 18 were not significantly different. This included the two most important components of meeting criteria for VM, namely the co-existence of headache and vestibular symptoms. On regression analysis, the only feature which kept its significant difference between the two cohorts was acute intense head pressure (P = 0.007). The domains with similar occurrence ratios included dizziness, headache, light sensitivity, hearing reduction, and tinnitus. In other words, multiple headache and vestibular symptoms, consistent with VM criteria, were similar between the two cohorts. The considerable similarities across various domains between VM patients and Havana subjects could be due to migraine as a possible common etiology for both groups. We propose VM as a potential etiology for the symptomatology in the U.S. diplomats in Cuba.

BackgroundMedical comorbidities accumulate in older persons living with HIV (PLWH), causing disability and reduced quality of life. Sensory neuropathy and polypharmacy may contribute to balance difficulties and falls. The contribution of neuropathy is understudied.ObjectiveTo evaluate the contribution of chronic distal sensory polyneuropathy (cDSPN) to balance disturbances among PLWH.MethodsAmbulatory PLWH and HIV- adults (N = 3379) were prospectively studied. All participants underwent a neurologic examination to document objective abnormality diagnostic of cDSPN and reported neuropathy symptoms including pain, paresthesias, and numbness. Participants provided detailed information regarding balance disturbance and falls over the previous 10 years. Balance disturbances were coded as minimal or none and mild-to-moderate. Covariates included age, HIV disease, and treatment characteristics and medications (sedatives, opioids, and antihypertensives).ResultsEleven percent of participants reported balance disturbances at some time during the last 10 years; the rate in PLWH participants exceeding that for HIV- [odds ratio 2.59, 95% confidence interval: 1.85 to 3.64]. Fifty-two percent met criteria for cDSPN. Balance problems were more common in those with cDSPN [odds ratio = 3.3 (2.6-4.3)]. Adjusting for relevant covariates, balance disturbances attributable to cDSPN were more frequent among HIV+ than HIV- (interaction P = 0.001). Among individuals with cDSPN, older participants were much more likely to report balance disturbances than younger ones.ConclusionscDSPN contributes to balance problems in PLWH. Assessments of cDSPN in older PLWH should be a clinical priority to identify those at risk and to aid in fall prevention and the ensuing consequences, including bone fractures, subdural hematoma, hospital admissions, and fatal injury.

ObjectiveTo evaluate feasibility and acceptability of a health professional resilience skills training program with neurology residents.MethodsThe curriculum consists of five 1-hour-long modules that included the following skills: reflective narrative practices, emotion regulation, communication with highly distressed individuals, boundary management, and the identification of depression and trauma. Using a web-based survey tool, we administered the Brief Resilience Scale (BRS) and Abbreviated Maslach Burnout Inventory (aMBI) at baseline, in addition to a pre- and post-survey assessing change in beliefs and self-efficacy, as well as satisfaction with the intervention. Means were compared using the Wilcoxon rank-sum and signed rank tests.ResultsTwenty-two residents representing each year of training completed the pre-survey; 41% were women. Subscale scores on the aMBI revealed that 50% had moderate or high emotional exhaustion, 41% had moderate depersonalization, and 37% had moderate or low personal accomplishment, though 77.3% reported high career satisfaction. Female residents had lower scores on the BRS (mean 3.26 vs 3.88, p < 0.05), though scores on aMBI subscales did not differ by sex. Scores did not differ by year of training. Sixteen residents completed both the pre- and post-survey. Significant increases were detected in 4 of 9 self-efficacy statements. Seventy-one percent of residents were satisfied or extremely satisfied with the training.ConclusionsResidents were satisfied with the curriculum and reported improved ability to identify and cope with work-related stress. Further study is needed to evaluate the influence of skills adoption and practice on resilience and burnout.

BackgroundSeveral lines of research support associations between sleep and cognition in older adults. However, there is a paucity of data regarding sleep and cognition in nonagenarians and centenarians.AimsThe current study examined self-reported sleep quantity and sleep quality in relation to hippocampal volume and cognition in adults aged 90 and older.MethodsA total of 144 participants of The 90+ Study completed The Medical Outcomes Study sleep questionnaire. Participants reported subjective sleep duration in hours and three sleep quality factors: sleep problems, adequacy, and somnolence. Neuropsychological assessments of memory, global cognition, language, and executive function were completed, on average, 61 days from the questionnaire. Hippocampal volume on 3 T MRI, adjusted for intracranial volume, was obtained in 82 participants. We performed multiple linear regressions, controlling for age, sex, education, sleep medication, and depression, to examine sleep characteristics in relation to hippocampal volume and cognitive performance in all the subjects and then stratified by cognition.ResultsSleep duration > 8 h was associated with lower scores in tests of global cognition, memory, and executive function compared to sleep duration of 7-8 h when collapsing across cognitive status, but only with memory in cognitively impaired subjects, and not in cognitively normal subjects.Conclusions and discussionLong-sleep duration is associated with poorer global cognition, memory, and executive function in the oldest-old, and is only associated with memory in cognitively impaired oldest-old. Additional research is necessary to determine if sleep duration is a risk factor or a result of poor cognition in advanced age.

We present a protocol designed to measure the neural correlates of reward in children. The protocol allows researchers to measure both reward anticipation and processing. Its purpose is to create a reward task that is appropriate for young children with and without autism while controlling reward properties between two conditions: social and nonsocial. The current protocol allows for comparisons of brain activity between social and nonsocial reward conditions while keeping the reward itself identical between conditions. Using this protocol, we found evidence that neurotypical children demonstrate enhanced anticipatory brain activity during the social condition. Furthermore, we found that neurotypical children anticipate social reward more robustly than children with autism diagnoses. As the task uses snacks as a reward, it is most appropriate for young children. However, the protocol may be adapted for use with adolescent or adult populations if snacks are replaced by monetary incentives. The protocol is designed to measure electrophysiological events (event-related potentials), but it may be customized for use with eye-tracking or fMRI.

Background Epilepsy is a common complication of pediatric stroke. Aim In this study, we aim to measure the association between epilepsy and neurologic outcome after childhood arterial ischemic stroke. Methods Prospective cohort study of children (29 days-19 years) enrolled after an acute arterial ischemic stroke at 21 international pediatric stroke centers and followed to identify epilepsy. One year post-stroke, outcomes were scored using the examination-based Pediatric Stroke Outcome Measure (range = 0-10); higher values reflect greater disability. Ordinal logistic regression was used to measure the association of Pediatric Stroke Outcome Measure scores (categorized as 0-1, 1.5-3, 3.5-6, 6.5-10) with epilepsy. Results Investigators enrolled 86 children (median age = 6.1 years, interquartile range (IQR) = 1.4-12.2 years) with acute stroke. At 1 year, 18/80 (23%) remained on an anticonvulsant including 8/80 (10%) with epilepsy. Among the 70 with Pediatric Stroke Outcome Measure scored, the median was 0.5 (IQR = 0-1.5) for children without epilepsy ( n = 63), and 6 (IQR = 0.5-10) for children with epilepsy ( n = 7). In univariable analyses, poorer 1-year outcome was associated with middle cerebral artery stroke, cortical infarcts, hemorrhagic transformation, hospital disposition not to home, and epilepsy. In multivariable analysis, middle cerebral artery stroke (odds ratio (OR) = 4.9, 95% confidence intervals (CI) = 1.1-21.3) and epilepsy (OR = 24.1, CI = 1.5-380) remained associated with poorer outcome. Conclusions Children who developed epilepsy during the first year post-stroke had poorer neurologic outcomes than those without epilepsy.

BACKGROUND AND PURPOSE:In Orange County, California, patients with suspected acute stroke are taken to stroke neurology receiving centers that are designated by County Emergency Medical Services authorities as either hubs or spokes based on endovascular treatment capability. We examined relationships between stroke details, reperfusion therapies, hospital transfers, and their change over time. METHODS:All patients from January 1, 2013, to December 31, 2015, for whom 911 was called within 7 hours of onset in whom Emergency Medical Services personnel suspected acute stroke were evaluated. RESULTS:Among 6132 patients, 3924 (64%) had confirmed diagnosis of stroke (74% ischemic/26% hemorrhagic), yielding diagnostic precision of 64% in the field. Of the 2892 patients with acute ischemic stroke, acute reperfusion therapy was given to 29.2% (21.7% intravenous tPA [tissue-type plasminogen activator] only and 7.5% endovascular treatment). Rates of endovascular treatment of patients with ischemic stroke increased over time, more than doubling from 5.6% in 2013 to 12.5% (odds ratio per 3-month quarter=1.09; 95% confidence interval, 1.04-1.14; P

OBJECTIVE:To study and provide an update on the state of clinical research in neurology in the United States. METHODS:US American Academy of Neurology members and chairs of departments of neurology were surveyed regarding clinical research in 2016. NIH data on the neuroscience pipeline and extramural grant funding were also collected. RESULTS:The response rate was 32% (n = 254) for nonchair researchers and 58% (n = 67) for department chairs. Researcher respondents were on average 50 years old, 66% were men, and 81% were actively conducting clinical research, with phase II/III clinical trials and outcome measure studies being the most common type of research conducted. Time to conduct research, recruitment, and administrative burden were the major barriers reported. According to department chairs, funding and training opportunities in patient-oriented research have increased over the last 10 years. Overall, applicants to neuroscience-specific NIH institutes for extramural funding have decreased over the same time period. CONCLUSIONS:The state of clinical research in neurology has remained relatively stable over the last 10 years, but neurologists still have barriers in conducting clinical research. There has been an interval decrease in neuroscience applicants for NIH funding, which raises concerns about the pipeline and future of clinical research in neurology. These results will serve as a reference for the development of solutions to these issues.

Neurofibromatosis type 1 (NF1)-related lung disease is a rare but increasingly recognised, high morbidity associated feature of the condition. We present a 48-year-old male patient with NF1, who was initially admitted for a subarachnoid haemorrhage requiring aneurysmal coil embolisation. During his recovery, he developed a left-sided pneumothorax requiring chest tube placement followed by concerns for re-expansion pulmonary oedema requiring intubation. Subsequently, the patient also developed a right-sided pneumothorax requiring additional chest tube placement but did not develop right-sided pulmonary oedema. During his hospitalisation, the patient also exemplified other important NF1-related pathophysiology including pheochromocytoma, cerebrovascular abnormalities and cardiovascular manifestations. Due to his multiple comorbidities and poor prognosis, we held a goals of care discussion with the patient's mother, and with her agreement, the patient underwent compassionate withdrawal of artificial life support.

In brain PET/MRI, the major challenge of zero-echo-time (ZTE)-based attenuation correction (ZTAC) is the misclassification of air/tissue/bone mixtures or their boundaries. Our study aimed to evaluate a sinus/edge-corrected (SEC) ZTAC (ZTACSEC), relative to an uncorrected (UC) ZTAC (ZTACUC) and a CT atlas-based attenuation correction (ATAC). Methods: Whole-body 18F-FDG PET/MRI scans were obtained for 12 patients after PET/CT scans. Only data acquired at a bed station that included the head were used for this study. Using PET data from PET/MRI, we applied ZTACUC, ZTACSEC, ATAC, and reference CT-based attenuation correction (CTAC) to PET attenuation correction. For ZTACUC, the bias-corrected and normalized ZTE was converted to pseudo-CT with air (-1,000 HU for ZTE < 0.2), soft-tissue (42 HU for ZTE > 0.75), and bone (-2,000 × [ZTE - 1] + 42 HU for 0.2 ≤ ZTE ≤ 0.75). Afterward, in the pseudo-CT, sinus/edges were automatically estimated as a binary mask through morphologic processing and edge detection. In the binary mask, the overestimated values were rescaled below 42 HU for ZTACSEC For ATAC, the atlas deformed to MR in-phase was segmented to air, inner air, soft tissue, and continuous bone. For the quantitative evaluation, PET mean uptake values were measured in twenty 1-mL volumes of interest distributed throughout brain tissues. The PET uptake was compared using a paired t test. An error histogram was used to show the distribution of voxel-based PET uptake differences. Results: Compared with CTAC, ZTACSEC achieved the overall PET quantification accuracy (0.2% ± 2.4%, P = 0.23) similar to CTAC, in comparison with ZTACUC (5.6% ± 3.5%, P < 0.01) and ATAC (-0.9% ± 5.0%, P = 0.03). Specifically, a substantial improvement with ZTACSEC (0.6% ± 2.7%, P < 0.01) was found in the cerebellum, in comparison with ZTACUC (8.1% ± 3.5%, P < 0.01) and ATAC (-4.1% ± 4.3%, P < 0.01). The histogram of voxel-based uptake differences demonstrated that ZTACSEC reduced the magnitude and variation of errors substantially, compared with ZTACUC and ATAC. Conclusion: ZTACSEC can provide an accurate PET quantification in brain PET/MRI, comparable to the accuracy achieved by CTAC, particularly in the cerebellum.

Language mapping is a key goal in neurosurgical planning. fMRI mapping typically proceeds with a focus on Broca's and Wernicke's areas, although multiple other language-critical areas are now well-known. We evaluated whether clinicians could use a novel approach, including clinician-driven individualized thresholding, to reliably identify six language regions, including Broca's Area, Wernicke's Area (inferior, superior), Exner's Area, Supplementary Speech Area, Angular Gyrus, and Basal Temporal Language Area. We studied 22 epilepsy and tumor patients who received Wada and fMRI (age 36.4[12.5]; Wada language left/right/mixed in 18/3/1). fMRI tasks (two × three tasks) were analyzed by two clinical neuropsychologists who flexibly thresholded and combined these to identify the six regions. The resulting maps were compared to fixed threshold maps. Clinicians generated maps that overlapped significantly, and were highly consistent, when at least one task came from the same set. Cases diverged when clinicians prioritized different language regions or addressed noise differently. Language laterality closely mirrored Wada data (85% accuracy). Activation consistent with all six language regions was consistently identified. In blind review, three external, independent clinicians rated the individualized fMRI language maps as superior to fixed threshold maps; identified the majority of regions significantly more frequently; and judged language laterality to mirror Wada lateralization more often. These data provide initial validation of a novel, clinician-based approach to localizing language cortex. They also demonstrate clinical fMRI is superior when analyzed by an experienced clinician and that when fMRI data is of low quality judgments of laterality are unreliable and should be withheld. Hum Brain Mapp 38:4239-4255, 2017. © 2017 Wiley Periodicals, Inc.

Sex is a biological variable that contributes to individual variability in brain structure and behavior. Neuroimaging studies of population‐based samples have identified normative differences in brain structure between males and females, many of which are exacerbated in psychiatric and neurological conditions. Still, sex differences in MRI outcomes are understudied, particularly in clinical samples with known sex differences in disease risk, prevalence, and expression of clinical symptoms. Here we review the existing literature on sex differences in adult brain structure in normative samples and in 14 distinct psychiatric and neurological disorders. We discuss commonalities and sources of variance in study designs, analysis procedures, disease subtype effects, and the impact of these factors on MRI interpretation. Lastly, we identify key problems in the neuroimaging literature on sex differences and offer potential recommendations to address current barriers and optimize rigor and reproducibility. In particular, we emphasize the importance of large‐scale neuroimaging initiatives such as the Enhancing NeuroImaging Genetics through Meta‐Analyses consortium, the UK Biobank, Human Connectome Project, and others to provide unprecedented power to evaluate sex‐specific phenotypes in major brain diseases. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the evidence basis of single-domain cognitive tests frequently used by behavioral neurologists in an effort to improve the quality of clinical cognitive assessment.MethodsBehavioral Neurology Section members of the American Academy of Neurology were surveyed about how they conduct clinical cognitive testing, with a particular focus on the Neurobehavioral Status Exam (NBSE). In contrast to general screening cognitive tests, an NBSE consists of tests of individual cognitive domains (e.g., memory or language) that provide a more comprehensive diagnostic assessment. Workgroups for each of 5 cognitive domains (attention, executive function, memory, language, and spatial cognition) conducted evidence-based reviews of frequently used tests. Reviews focused on suitability for office-based clinical practice, including test administration time, accessibility of normative data, disease populations studied, and availability in the public domain.ResultsDemographic and clinical practice data were obtained from 200 respondents who reported using a wide range of cognitive tests. Based on survey data and ancillary information, between 5 and 15 tests in each cognitive domain were reviewed. Within each domain, several tests are highlighted as being well-suited for an NBSE.ConclusionsWe identified frequently used single-domain cognitive tests that are suitable for an NBSE to help make informed choices about clinical cognitive assessment. Some frequently used tests have limited normative data or have not been well-studied in common neurologic disorders. Utilizing standardized cognitive tests, particularly those with normative data based on the individual's age and educational level, can enhance the rigor and utility of clinical cognitive assessment.

A sophisticated mechanistic understanding of physiology and disease requires knowledge of how sex-biasing factors cause sex differences in phenotype. In therian mammals, all sex differences are downstream of the unequal effects of XX vs. XY sex chromosomes. Three major categories of sex-biasing factors are activational and organizational effects of gonadal hormones, and sex chromosome effects operating outside of the gonads. These three types of effects can be discriminated from each other with established experimental designs and animal models. Two important mouse models, which allow conclusions regarding the sex-biasing effects of sex chromosome complement, interacting with gonadal hormone effects, are the Four Core Genotypes model and the XY* model. Chromosome Y consomic strains give information about the role of the Y chromosome. An important recent change in sexual differentiation theory is the increasing realization that sex-biasing factors can counteract the effects of each other, reducing rather than producing sex differences in phenotype. This change in viewpoint rationalizes a change in experimental strategies for dissecting sex chromosome effects. The overall goal is to understand the sexome, defined as the sum of effects of sex-biasing factors on gene systems and networks.

PurposeThe increasing use of amyloid PET in Alzheimer's disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the (11)C radiotracer Pittsburgh Compound B (PiB) and that of two (18)F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two (18)F tracers.MethodsOne group of 40 subjects underwent PiB and flutemetamol imaging sessions and a separate group of 32 subjects underwent PiB and florbetapir imaging sessions. We compared cortical and white matter retention for each (18)F tracer relative to that of PiB, as well as retention in several reference regions and image analysis methods. Correlations between tracer pairs were used to convert tracer-specific threshold values for amyloid positivity between tracers.ResultsCortical retention for each pair of tracers was strongly correlated regardless of reference region (PiB-flutemetamol, ρ = 0.84-0.99; PiB-florbetapir, ρ = 0.83-0.97) and analysis method (ρ = 0.90-0.99). Compared to PiB, flutemetamol had higher white matter retention, while florbetapir had lower cortical retention. Two previously established independent thresholds for amyloid positivity were highly consistent when values were converted between tracer pairs.ConclusionDespite differing white and grey matter retention characteristics, cortical retention for each (18)F tracer was highly correlated with that of PiB, enabling conversion of thresholds across tracer measurement scales with a high level of internal consistency. Standardization of analysis methods and measurement scales may facilitate the comparison of amyloid PET data obtained using different tracers.

ObjectiveTo assess the strengths and weaknesses of neurology resident education using survey methodology.MethodsA 27-question survey was sent to all neurology residents completing residency training in the United States in 2011.ResultsOf eligible respondents, 49.8% of residents returned the survey. Most residents believed previously instituted duty hour restrictions had a positive impact on resident quality of life without impacting patient care. Most residents rated their faculty and clinical didactics favorably. However, many residents reported suboptimal preparation in basic neuroscience and practice management issues. Most residents (71%) noted that the Residency In-service Training Examination (RITE) assisted in self-study. A minority of residents (14%) reported that the RITE scores were used for reasons other than self-study. The vast majority (86%) of residents will enter fellowship training following residency and were satisfied with the fellowship offers they received.ConclusionsGraduating residents had largely favorable neurology training experiences. Several common deficiencies include education in basic neuroscience and clinical practice management. Importantly, prior changes to duty hours did not negatively affect the resident perception of neurology residency training.