Sleep Pathophysiology

Sleep is a natural, reversible, and periodic behavioral state characterized by perceptual inattention and decreased responsiveness to external stimuli. The processes governing sleep, sleep-wake transitions, and maintenance of wakefulness are mediated by complex physiologic mechanisms, the primary neurobiological substrates of which include the neocortex, basal forebrain, thalamus, hypothalamus, pontine tegmentum, and brainstem monoaminergic nuclei. Moreover, the integrity of brainstem autonomic respiratory control networks becomes critical in the maintenance of ventilation during sleep. Pathologic insults to these systems may result in a broad constellation of clinical deficits.

Acute Stroke With Large Vessel Occlusion and Minor Clinical Deficits: Prognostic Factors and Therapeutic Implications

Background and Purpose: The optimal acute management of patients with large vessel occlusion (LVO) and minor clinical deficits on admission [National Institutes of Health Stroke Scale (NIHSS) ≤ 4] remains to be elucidated. The aim of the present study was to investigate the prognostic factors and therapeutic management of those patients.Methods: In this retrospective cohort study, we investigated (1) all patients with acute ischemic stroke due to an LVO who underwent mechanical thrombectomy (MT) and (2) all patients with minor clinical deficits (NIHSS ≤ 4) on admission due to an LVO between January 2013 and December 2016 at the University Medical Center Erlangen. We dichotomized management of patients with minor deficits treated with MT for analysis according to immediate mechanical thrombectomy (IT) and initial medical management with rescue intervention (MM) in case of secondary deterioration. Primary endpoints were secondary deterioration, in-hospital mortality, and functional outcome on day 90 (dichotomized modified Rankin Scale 0–2: favorable, 3–6: poor).Results: Two hundred twenty-three patients (83% with anterior circulation stroke, 13 (6%) with minor deficits) treated with MT and 88 patients with minor deficits due to LVO [13 (15%) treated with MT] were included. Secondary deterioration (n = 19) was independently associated with poor outcome in patients with minor deficits and LVO [odds ratio (OR), 0.060; 95% confidence interval (CI), 0.013–0.280], which in turn was associated with the occlusion site [especially M1 occlusion: 11 (58%) vs. 3 (4%) in patients without secondary deterioration, p < 0.0001]. IT (n = 8) was associated with a lower intrahospital mortality compared to MM (n = 5; 13 vs. 80%; OR, 0.036; 95% CI, 0.002–0.741). Seven of eight patients with IT survived until discharge, with 29% showing a favorable functional outcome on day 90.Conclusions: Secondary deterioration is associated with poor outcome in patients with LVO and minor deficits, which in turn was associated with occlusion site. Future randomized controlled trials should assess whether selected patients, depending on occlusion site and associated characteristics, may benefit from MT.

Iatrogenic Diffusion-Weighted Imaging Lesions

Infarct volume in acute ischemic stroke is closely linked with clinical outcome, with larger infarct volumes being associated with a worse prognosis. Small iatrogenic infarcts, which can occur as a result of surgical or endovascular procedures, are often only seen on diffusion-weighted MR imaging. They often do not lead to any overtly appreciable clinical deficits, hence the term covert or silent infarcts. There is relative paucity of data on the clinical impact of periprocedural hyperintense diffusion-weighted MR imaging lesions, partly because they commonly remain undiagnosed. Clearly, a better understanding of iatrogenic periprocedural diffusion-weighted MR imaging lesions and their clinical significance is needed. In this article, we describe the current limitations of our understanding of the significance of iatrogenic diffusion-weighted MR imaging lesions using exemplary data from the ENACT trial (Safety and Efficacy of NA-1 in Patients With Iatrogenic Stroke After Endovascular Aneurysm Repair) and outline a framework for how to investigate their clinical impact.

One nerve suffices: A clinically guided nerve ultrasound protocol for the differentiation of multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS)

Objective To investigate diagnostic accuracy of a nerve ultrasound (US) protocol that is individualized to a patient’s clinical deficits for the differentiation of amyotrophic lateral sclerosis with predominant lower motoneuron disease (ALS/LMND) and multifocal motor neuropathy (MMN). Methods Single-center, prospective, examiner-blinded, diagnostic study in two cohorts. Cohort I (model development): Convenience sample of subjects with ALS/LMND or MMN according to revised El-Escorial or EFNS guidelines. Cohort II (model validation): Consecutively recruited treatment-naïve subjects with suspected diagnosis of ALS/LMND or MMN. Cutoffs for 28 different US values were determined by Receiver Operating Curve (ROC) in cohort I. Area Under The Curve (AUC) of US was compared to nerve conduction studies (NCS). Diagnostic accuracy of US protocols, individualized according to clinical deficits, was compared to former rigid non-individualized protocols and to random examination site selection in cohort II. Results 48 patients were recruited. In cohort I (28 patients), US had higher ROC AUCs than NCS, US 0.82 (0.12) (mean (standard deviation)), NCS (compound muscle action potential (CMAP) 0.60 (0.09), p < .001; two-sided t-test). US models based on the nerve innervating the clinically most affected muscles had higher correct classification rates (CCRs, 93%) in cohort II than former rigid protocols (85% and 80%), or models with random measurement site selection (66% and 80%). Conclusions Clinically guided US protocols for differentiation of ALS/LMND from MMN increase diagnostic accuracy when compared to clinically unguided protocols. They also require less measurements sites to achieve this accuracy.

Outcome Measures in Clinical Trials of Patients With Myasthenia Gravis

Myasthenia gravis (MG) is a heterogeneous disorder whose clinical presentation ranges from mild ocular deficits to severe widespread weakness. This variance poses a challenge when quantifying clinical deficits. Deficits and symptoms are quantified using standardized clinical scales and questionnaires which are often used as outcome measures. The past decades have seen the development of several validated outcome measures in MG, which are used in clinical trials to obtain regulatory approval. In recent years, emphasis has moved from objective assessments to patient-reported outcomes. Despite a growing body of literature on the validity of the MG-specific outcome measures, several unresolved factors remain. As several novel therapeutics are currently in clinical development, knowledge about capabilities and limitations of outcome measures is needed. In the present paper, we describe the most widely used clinical classifications and scales in MG. We highlight the choice of outcome measures in published and ongoing trials, and we denote whether trial efficacy was reached on these outcomes. We discuss advantages and limitations of the individual scales, and discuss some of the unresolved factors relating to outcome assessments in MG.

First in Man Pilot Feasibility Study in Extracranial Carotid Robotic-Assisted Endovascular Intervention

BACKGROUND Robotic-assistance in endovascular intervention represents a nascent yet promising innovation. OBJECTIVE To present the first human experience utilizing robotic-assisted angiography in the extracranial carotid circulation. METHODS Between March 2019 and September 2019, patients with extracranial carotid circulation pathology presenting to Houston Methodist Hospital were enrolled. RESULTS A total of 6 patients met inclusion criteria: 5 underwent diagnostic angiography only with robotic-assisted catheter manipulation, while 1 underwent both diagnostic followed by delayed therapeutic intervention. Mean age was 51 +/− 17.5 yr. Mean anesthesia time was 158.7 +/− 37.9 min, mean fluoroscopic time was 22.0 +/− 7.3 min, and mean radiation dose was 815.0 +/− 517.0 mGy. There were no technical complications and no clinical deficits postprocedure. None of the cases required conversion to manual neurovascular intervention (NVI). CONCLUSION Incorporating robotic technology in NVI can enhance procedural technique and diminish occupational hazards. Its application in the coronary and peripheral vascular settings has established safety and efficacy, but in the neurovascular setting, this has yet to be demonstrated. This study presents the first in human feasibility experience of robotic-assisted NVI in the extracranial carotid circulation.

These legs were made for propulsion: advancing the diagnosis and treatment of post-stroke propulsion deficits

Advances in medical diagnosis and treatment have facilitated the emergence of precision medicine. In contrast, locomotor rehabilitation for individuals with acquired neuromotor injuries remains limited by the dearth of (i) diagnostic approaches that can identify the specific neuromuscular, biomechanical, and clinical deficits underlying impaired locomotion and (ii) evidence-based, targeted treatments. In particular, impaired propulsion by the paretic limb is a major contributor to walking-related disability after stroke; however, few interventions have been able to target deficits in propulsion effectively and in a manner that reduces walking disability. Indeed, the weakness and impaired control that is characteristic of post-stroke hemiparesis leads to heterogeneous deficits that impair paretic propulsion and contribute to a slow, metabolically-expensive, and unstable gait. Current rehabilitation paradigms emphasize the rapid attainment of walking independence, not the restoration of normal propulsion function. Although walking independence is an important goal for stroke survivors, independence achieved via compensatory strategies may prevent the recovery of propulsion needed for the fast, economical, and stable gait that is characteristic of healthy bipedal locomotion. We posit that post-stroke rehabilitation should aim to promote independent walking, in part, through the acquisition of enhanced propulsion. In this expert review, we present the biomechanical and functional consequences of post-stroke propulsion deficits, review advances in our understanding of the nature of post-stroke propulsion impairment, and discuss emerging diagnostic and treatment approaches that have the potential to facilitate new rehabilitation paradigms targeting propulsion restoration.

Task-Based Functional Connectomes Predict Cognitive Phenotypes Across Psychiatric Disease

ImportanceWe show that three common approaches to clinical deficits (cognitive phenotype, disease group, disease severity) each offer useful and perhaps complimentary explanations for the brain’s underlying functional architecture as affected by psychiatric disease.ObjectiveTo understand how different clinical frameworks are represented in the brain’s functional connectome.DesignWe use an openly available dataset to create predictive models based on multiple connectomes built from task-based functional MRI data. We use these models to predict individual traits corresponding to multiple cognitive constructs across disease category. We also show that these same connectomes statistically differ depending on disease category and symptom burden.SettingThis was a population-based study with data collected in UCLA.ParticipantsHealthy adults were recruited by community advertisements from the Los Angeles area. Participants with adult ADHD, bipolar disorder, and schizophrenia were recruited using a patient-oriented strategy involving outreach to local clinics and online portals (separate from the methods used to recruit healthy volunteers)