In migraine with previous treatment failures, eptinezumab safely reduced migraine days at 1 to 12 wk.

SOURCE CITATION: Ashina M, Lanteri-Minet M, Pozo-Rosich P, et al. Safety and efficacy of eptinezumab for migraine prevention in patients with two-to-four previous preventive treatment failures (DELIVER): a multi-arm, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2022;21:597-607. 35716692.

Spontaneous spinal epidural hemorrhage and sentinel headache-A case report.

OBJECTIVES/BACKGROUND: Expand the differential diagnosis of sentinel headache to include spontaneous spinal epidural hematoma (SSEH) and reinforce the need for lumbar puncture in the evaluation of thunderclap headache. SSEH is a rare clinical presentation especially in the absence of bleeding tendencies. Clinicians recognize SSEH with typical presenting signs and symptoms including regional paraspinal muscular contraction and pain along with myelopathy. Although thunderclap headache usually does not connote vascular rupture in the spinal epidural compartment, SSEH may rarely present with sentinel headache and later evolve into a myelopathy. RESULTS AND CONCLUSION: Sentinel headache may be the sole symptom following spontaneous spinal epidural hemorrhage preceding both myelopathic and meningeal signs and symptoms. SSEH can best be diagnosed by lumbar puncture at this early moment potentially averting spinal cord injury.

Stable multivariate lesion symptom mapping.

Multivariate lesion-symptom mapping (MLSM) considers lesion information across the entire brain to predict impairments. The strength of this approach is also its weakness-considering many brain features together synergistically can uncover complex brain-behavior relationships but exposes a high-dimensional feature space that a model is expected to learn. Successfully distinguishing between features in this landscape can be difficult for models, particularly in the presence of irrelevant or redundant features. Here, we propose stable multivariate lesion-symptom mapping (sMLSM), which integrates the identification of reliable features with stability selection into conventional MLSM and describe our open-source MATLAB implementation. Usage is showcased with our publicly available dataset of chronic stroke survivors (N=167) and further validated in our independent public acute stroke dataset (N = 1106). We demonstrate that sMLSM eliminates inconsistent features highlighted by MLSM, reduces variation in feature weights, enables the model to learn more complex patterns of brain damage, and improves model accuracy for predicting aphasia severity in a way that tends to be robust regarding the choice of parameters for identifying reliable features. Critically, sMLSM more consistently outperforms predictions based on lesion size alone. This advantage is evident starting at modest sample sizes (N>75). Spatial distribution of feature importance is different in sMLSM, which highlights the features identified by univariate lesion symptom mapping while also implicating select regions emphasized by MLSM. Beyond improved prediction accuracy, sMLSM can offer deeper insight into reliable biomarkers of impairment, informing our understanding of neurobiology.

Longevity in the South Carolina Alzheimer's disease registry.

Background: South Carolina has arguably the most robust Alzheimer's Registry in the United States. For enhanced planning in both clinical practice and research and better utilization of the Registry data, it is important to understand survival after Registry entry. To this end, we conducted exploratory analyses to examine the patterns of longevity/survival in the South Carolina Alzheimer's Disease Registry. Methods: The sample included 42,028 individuals in the South Carolina Alzheimer's Disease Registry (SCADR). Participants were grouped into four cohorts based on their year of diagnosis. Longevity in the Registry (LIR), or the length of survival in the registry, was calculated based on the years of reported diagnosis and death. Results: The median LIR varied between 24 to 36 months depending on the cohort, with 75% of individuals in the three recent cohorts surviving for at least 12 months. Across all cohorts, 25% of the participants survived at least 60 months. The median LIR of females was longer than that of males. Individuals whose race was classified as Asian, American Indian, and other than listed had longer LIR compared to White, African American, and Hispanic individuals. Median LIR was shorter for Registry cases diagnosed at an earlier age (less than 65 years). Conclusion: Our data indicate that significant longevity is to be expected in the SCADR but that there is interesting variability which needs to be explored in subsequent studies. The SCADR is a rich data source prime for use in research studies and analyses.

The stroke outcome optimization project: Acute ischemic strokes from a comprehensive stroke center.

Stroke is a leading cause of disability, and Magnetic Resonance Imaging (MRI) is routinely acquired for acute stroke management. Publicly sharing these datasets can aid in the development of machine learning algorithms, particularly for lesion identification, brain health quantification, and prognosis. These algorithms thrive on large amounts of information, but require diverse datasets to avoid overfitting to specific populations or acquisitions. While there are many large public MRI datasets, few of these include acute stroke. We describe clinical MRI using diffusion-weighted, fluid-attenuated and T1-weighted modalities for 1715 individuals admitted in the upstate of South Carolina, of whom 1461 have acute ischemic stroke. Demographic and impairment data are provided for 1106 of the stroke survivors from this cohort. Our validation demonstrates that machine learning can leverage the imaging data to predict stroke severity as measured by the NIH Stroke Scale/Score (NIHSS). We share not only the raw data, but also the scripts for replicating our findings. These tools can aid in education, and provide a benchmark for validating improved methods.

Ascertaining dementia-related outcomes for deceased or proxy-dependent participants: an overview of the Women's Health Initiative Memory Study supplemental case ascertainment protocol.

OBJECTIVE: The aim of the study was to compare a two-staged clinic-based standardized protocol with a supplemental proxy-based protocol. METHODS: The Women's Health Initiative Memory Study enrolled 7479 women, aged 65-79 years and free of dementia, in a clinical trial of postmenopausal hormone therapy who were followed for up to 13 years with annual two-staged clinic-based standardized protocols to identify incidence of probable dementia. A supplemental proxy-based protocol, involving telephone administration of the dementia questionnaire, was designed to assess the cognitive status of women who could no longer attend clinic visits because they died (n = 1058) or became dependent (n = 228). Chi-squared tests were used to compare characteristics of women eligible for proxy-based versus clinic-based assessment. Risk factor relationships were described using proportional hazards regression. RESULTS: Women who were eligible for proxy-based assessments tended to have worse cognitive impairment risk factor profiles and had higher rates of probable dementia (15.2% vs 3.5%) than clinic-assessed participants. Augmenting the clinic-based cases with those identified from proxy interviews reduced undercounting and materially altered observed relationships that years since menopause, smoking status, diabetes, and prior use of hormone therapy had with incidence of probable dementia. CONCLUSIONS: Although proxy interviews were successful in reducing biases in estimated incidence rates and risk factor relationships, it is unlikely that they will fully eliminate many biases. Proxy-based assessments are necessary in longer term studies to reduce undercounting of dementia cases and to characterize risk factor relationships.

Opsoclonus-Myoclonus-Ataxia Syndrome (OMAS) Associated with SARS-CoV-2 Infection: Post-Infectious Neurological Complication with Benign Prognosis.

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is the cause of the COVID-19 pandemic [5]. SARS-Cov-2 demonstrates partial resemblance to SARS-CoV and MERS-CoV in phylogenetic analysis, clinical manifestations, and pathological findings [6, 7]. Reports emerging from China have described ataxia as a neurological symptom of the SARS-CoV-2 infection [5]. Opsoclonus consists of back-to-back multidirectional conjugate saccades without an inter-saccadic interval [8]. Myoclonus is defined as a sudden, brief, "shock-like", nonepileptic involuntary movement [9], which has been described as a symptom of SARS-CoV-2 infection [10]. Opsoclonus-Myoclonus-Ataxia syndrome (OMAS) associated COVID-19 infection has been reported recently [1112].

Subtypes of mild cognitive impairment in older postmenopausal women: the Women's Health Initiative Memory Study.

Mild cognitive impairment (MCI) is a transitional state between normal cognitive functioning and dementia. A proposed MCI typology classifies individuals by the type and extent of cognitive impairment, yet few studies have characterized or compared these subtypes. Four hundred forty-seven women 65 years of age and older from the Women's Health Initiative Memory Study were classified into the 4 MCI subgroups and a "no impairment" group and compared on clinical, sociodemographic, and health variables. A cognitive deficit in at least 1 domain was present in 82.1% of participants, with most (74.3%) having deficits in multiple cognitive domains. Only 4.3% had an isolated memory deficit, whereas 21.3% had an isolated nonmemory deficit. Of the 112 women who met all MCI criteria examined, the most common subtype was amnestic multidomain MCI (42.8%), followed by nonamnestic multiple domain MCI (26.7%), nonamnestic single domain (24.1%), and amnestic single domain MCI (6.3%). Subtypes were similar with respect to education, health status, smoking, depression, and prestudy and onstudy use of hormone therapy. Despite the attention it receives in the literature, amnestic MCI is the least common type highlighting the importance of identifying and characterizing other nonamnestic and multidomain subtypes. Further research is needed on the epidemiology of MCI subtypes, clinical and biologic differences between them, and rates for conversion to dementia.

A pianist's recovery from stroke.

OBJECTIVE: To determine alternative neural pathways for restitution of piano playing after right hemispheric infarction causing left arm and hand paralysis. DESIGN: Case report testing coordinated bimanual skills using structured motor skills tests and neuroimaging. SETTING: A professional pianist sustained a lacunar infarction in the posterior limb of his right internal capsule, which resulted in left hemiparesis with immobilized left-hand and -finger movements persisting for 13 weeks. After 6 months, he had recovered bimanual coordinated piano skills by "ignoring" his left hand while concentrating or discussing subjects other than music while playing. PATIENT: A 63-year-old, male professional pianist. INTERVENTION: Detailed neurological examination including computed cranial tomography, functional magnetic resonance imaging, and positron emission tomography. RESULTS: Functional magnetic resonance imaging activation patterns correlated with rapid movements of fingers in each hand separately and together demonstrating that subcortical and cerebellar pathways were activated during skilled motor function of his left hand. Contralateral cerebral and cerebellar activation occurred with both left- and right-hand movements. During tapping of the left fingers, there was bilateral cerebellar, parietal, and left premotor strip and left thalamic activation. CONCLUSION: Patterns of activation relate to task performance and they are not similar to subjects engaged in simpler tasks such as finger opposition.

Quality improvement in neurology: dementia management quality measures.

Professional and advocacy organizations have long urged that dementia should be recognized and properly diagnosed. With the passage of the National Alzheimer's Project Act in 2011, an Advisory Council for Alzheimer's Research, Care, and Services was convened to advise the Department of Health and Human Services. In May 2012, the Council produced the first National Plan to address Alzheimer's disease, and prominent in its recommendations is a call for quality measures suitable for evaluating and tracking dementia care in clinical settings. Although other efforts have been made to set dementia care quality standards, such as those pioneered by RAND in its series Assessing Care of Vulnerable Elders (ACOVE), practitioners, healthcare systems, and insurers have not widely embraced implementation. This executive summary (full manuscript available at www.neurology.org) reports on a new measurement set for dementia management developed by an interdisciplinary Dementia Measures Work Group (DWG) representing the major national organizations and advocacy organizations concerned with the care of individuals with dementia. The American Academy of Neurology (AAN), the American Geriatrics Society, the American Medical Directors Association, the American Psychiatric Association, and the American Medical Association-convened Physician Consortium for Performance Improvement led this effort. The ACOVE measures and the measurement set described here apply to individuals whose dementia has already been identified and properly diagnosed. Although similar in concept to ACOVE, the DWG measurement set differs in several important ways; it includes all stages of dementia in a single measure set, calls for the use of functional staging in planning care, prompts the use of validated instruments in patient and caregiver assessment and intervention, highlights the relevance of using palliative care concepts to guide care before the advanced stages of illness, and provides evidence-based support for its recommendations and guidance on the selection of instruments useful in tracking patient-centered outcomes. It also specifies annual reassessment and updating of interventions and care plans for dementia-related problems that affect families and other caregivers as well as individuals with dementia. Here, a brief synopsis of why major reforms in healthcare design and delivery are needed to achieve substantive improvements in the quality of care is first provided, and then the final measures approved for publication, dissemination, and implementation are listed.

Quality improvement in neurology: dementia management quality measures (executive summary).

This article represents the efforts of an interdisciplinary work group, the Dementia Measures Work Group (DWG), composed of representatives of diverse national organizations who convened specifically to define optimal standards of dementia care for individual practitioners as well as multidisciplinary teams. The DWG measurement set includes all stages of dementia in a single measure set, calls for the use of functional staging in planning care, prompts the use of validated instruments in patient and caregiver assessment and intervention, highlights the relevance of using palliative care concepts to guide care prior to the advanced stages of illness, and provides evidence-based support for its recommendations and guidance on the selection of instruments for tracking patient-centered outcomes. In addition, it specifies annual reassessment and updating of interventions and care plans for dementia-related problems that affect families and other caregivers as well as patients.

The relationship between cognitive function and physical performance in older women: results from the women's health initiative memory study.

BACKGROUND: Cognitive function and physical performance are associated, but the common sequence of cognitive and physical decline remains unclear. METHODS: In the Women's Health Initiative Memory Study (WHIMS) clinical trial, we examined associations at baseline and over a 6-year follow-up period between the Modified Mini-Mental State (3MS) Examination and three physical performance measures (PPMs): gait speed (meters/second), chair stands (number of stands in 15 seconds), and grip strength (kilograms). Using mixed models, we examined the baseline 3MS as predictor of change in PPM, change in the 3MS as predictor of change in PPM, and baseline PPM as predictors of 3MS change. RESULTS: Among 1,793 women (mean age = 70.3 years, 89% white, and mean 3MS score = 95.1), PPM were weakly correlated with 3MS-gait speed: r = .06, p = .02; chair stands: r = .09, p < .001; and grip strength: r = .10, p < .001. Baseline 3MS score was associated with subsequent PPM decline after adjustment for demographics, comorbid conditions, medications, and lifestyle factors. For every SD (4.2 points) higher 3MS score, 0.04 SD (0.04 m/s) less gait speed and 0.05 SD (0.29 kg) less grip strength decline is expected over 6 years (p

Patterns of impaired verbal, spatial, and object working memory after thalamic lesions.

Working memory processes in six individuals with isolated thalamic lesions were assessed. Participants were given a verbal, spatial, and object n-back task, each at three levels of task load (1-back, 2-back, and 3-back). Relative to a control group, the patients were impaired on the verbal and spatial n-back tasks, and possibly on the object n-back task as well. None of the patients showed impaired short-term memory as measured by digit span. Group differences on trials measuring matching, sequencing, and inhibitory abilities were consistent with other reports suggesting that thalamic lesions may impair the operation of executive processes.