Lay Abstract Autism spectrum disorders are reported to affect nearly one out of every one hundred children, with over 90% of these children showing behavioral disturbances related to the processing of basic sensory information. Behavioral sensitivity to light touch, such as profound discomfort with clothing tags and physical contact, is a ubiquitous finding in children on the autism spectrum. In this study, we investigate the strength and timing of brain activity in response to simple, light taps to the fingertip. Our results suggest that children with autism show a diminished early response in the primary somatosensory cortex (S1). This finding is most evident in the left hemisphere. In exploratory analysis, we also show that tactile sensory behavior, as measured by the Sensory Profile, may be a better predictor of the intensity and timing of brain activity related to touch than a clinical autism diagnosis. We report that children with atypical tactile behavior have significantly lower amplitude somatosensory cortical responses in both hemispheres. Thus sensory behavioral phenotype appears to be a more powerful strategy for investigating neural activity in this cohort. This study provides evidence for atypical brain activity during sensory processing in autistic children and suggests that our sensory behavior based methodology may be an important approach to investigating brain activity in people with autism and neurodevelopmental disorders. Scientific Abstract The neural underpinnings of sensory processing differences in autism remain poorly understood. This prospective magnetoencephalography (MEG) study investigates whether children with autism show atypical cortical activity in the primary somatosensory cortex (S1) in comparison to matched controls. Tactile stimuli were clearly detectable, painless taps applied to the distal phalanx of the second (D2) and third (D3) fingers of the right and left hands. Three tactile paradigms were administered: an oddball paradigm (standard taps to D3 at an inter-stimulus interval (ISI) of 0.33 and deviant taps to D2 with ISI ranging from 1.32–1.64s); a slow-rate paradigm (D2) with an ISI matching the deviant taps in the oddball paradigm; and a fast-rate paradigm (D2) with an ISI matching the standard taps in the oddball. Study subjects were boys (age 7–11 years) with and without autism disorder. Sensory behavior was quantified using the Sensory Profile questionnaire. Boys with autism exhibited smaller amplitude left hemisphere S1 response to slow and deviant stimuli during the right hand paradigms. In post-hoc analysis, tactile behavior directly correlated with the amplitude of cortical response. Consequently, the children were re-categorized by degree of parent-report tactile sensitivity. This regrouping created a more robust distinction between the groups with amplitude diminution in the left and right hemispheres and latency prolongation in the right hemisphere in the deviant and slow-rate paradigms for the affected children. This study suggests that children with aut...

Background and Purpose: More than half of patients with acute ischemic stroke have minor neurological deficits; however, the frequency and outcomes of reperfusion therapy in regular practice has not been well-delineated. Methods: Analysis of US National Inpatient Sample of hospitalizations with acute ischemic stroke and mild deficits (National Institute of Health Stroke Scale [NIHSS] score0–5) from October 1, 2016, to December 31, 2017. Patient-and hospital-level characteristics associated with use and outcome of reperfusion therapies were analyzed. Primary outcomes included excellent discharge disposition (discharge to home without assistance); poor discharge disposition (discharge to facility or death); in-hospital mortality; and radiological intracranial hemorrhage. Results: Among 179 710 acute ischemic stroke admissions with recorded NIHSS during the 15-month study period, 103 765 (57.7%) had mild strokes (47.3% women; median age, 69 [interquartile range, 59–79] years; median NIHSS score of 2 [interquartile range, 1–4]). Considering reperfusion therapies among strokes with documented NIHSS, mild deficit hospitalizations accounted for 40.0% of IVT and 10.7% of mechanical thrombectomy procedures. Characteristics associated with IVT and with mechanical thrombectomy utilization were younger age, absence of diabetes, higher NIHSS score, larger/teaching hospital status, and Western US region. Excellent discharge outcome occurred in 48.2% of all mild strokes, and in multivariable analysis, was associated with younger age, male sex, White race, lower NIHSS score, absence of diabetes, heart failure, and kidney disease, and IVT use. IVT was associated with increased likelihood of excellent outcome (odds ratio, 1.90 [95% CI, 1.71–2.13], P <0.001) despite an increased risk of intracranial hemorrhage (odds ratio, 1.41 [95% CI, 1.09–1.83], P <0.001). Conclusions: In national US practice, more than one-half of acute ischemic stroke hospitalizations had mild deficits, accounting for 4 of every 10 IVT and 1 of every 10 mechanical thrombectomy treatments, and IVT use was associated with increased discharge to home despite increased intracranial hemorrhage.

Cerebral acidosis is a consequence of secondary injury mechanisms following traumatic brain injury (TBI), including excitotoxicity and ischemia, with potentially significant clinical implications. However, there remains an unmet clinical need for technology for non-invasive, high resolution pH imaging of human TBI for studying metabolic changes following injury. The current study examined 17 patients with TBI and 20 healthy controls using amine chemical exchange saturation transfer echoplanar imaging (CEST EPI), a novel pH-weighted molecular MR imaging technique, on a clinical 3T MR scanner. Results showed significantly elevated pH-weighted image contrast (MTR asym at 3 ppm) in areas of T2 hyperintensity or edema (P < 0.0001), and a strong negative correlation with Glasgow Coma Scale (GCS) at the time of the MRI exam ( R 2 = 0.4777, P = 0.0021 ), Glasgow Outcome Scale - Extended (GOSE) at 6 months from injury ( R 2 = 0.5334, P = 0.0107 ), and a non-linear correlation with the time from injury to MRI exam ( R 2 = 0.6317, P = 0.0004 ). This evidence suggests clinical feasibility and potential value of pH-weighted amine CEST EPI as a high-resolution imaging tool for identifying tissue most at risk for long-term damage due to cerebral acidosis.

Cerebrovascular events have emerged as a central feature of the clinical syndrome associated with Sars-CoV-2 infection. This increase in infection-related strokes is marked by atypical presentations including stroke in younger patients and a high rate of hemorrhagic transformation after ischemia. A variety of pathogenic mechanisms may underlie this connection. Efforts to identify synergism in the pathophysiology underlying stroke and Sars-CoV-2 infection can inform the understanding of both conditions in novel ways. In this review, the molecular cascades connected to Sars-CoV-2 infection are placed in the context of the cerebral vasculature and in relationship to pathways known to be associated with stroke. Cytokine-mediated promotion of systemic hypercoagulability is suggested while direct Sars-CoV-2 infection of cerebral endothelial cells may also contribute. Endotheliopathy resulting from direct Sars-CoV-2 infection of the cerebral vasculature can modulate ACE2/AT1R/MasR signaling pathways, trigger direct viral activation of the complement cascade, and activate feed-forward cytokine cascades that impact the blood-brain barrier. All of these pathways are already implicated as independent mechanisms driving stroke and cerebrovascular injury irrespective of Sars-CoV-2. Recognizing the overlap of molecular pathways triggered by Sars-CoV-2 infection with those implicated in the pathogenesis of stroke provides an opportunity to identify future therapeutics targeting both Sars-CoV-2 and stroke thereby reducing the impact of the global pandemic.

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