Brain Connectivity Measures Improve Modeling of Functional Outcome After Acute Ischemic Stroke.

Background and Purpose- The ability to model long-term functional outcomes after acute ischemic stroke represents a major clinical challenge. One approach to potentially improve prediction modeling involves the analysis of connectomics. The field of connectomics represents the brain's connectivity as a graph, whose topological properties have helped uncover underlying mechanisms of brain function in health and disease. Specifically, we assessed the impact of stroke lesions on rich club organization, a high capacity backbone system of brain function. Methods- In a hospital-based cohort of 41 acute ischemic stroke patients, we investigated the effect of acute infarcts on the brain's prestroke rich club backbone and poststroke functional connectomes with respect to poststroke outcome. Functional connectomes were created using 3 anatomic atlases, and characteristic path-length (L) was calculated for each connectome. The number of rich club regions affected were manually determined using each patient's diffusion weighted image. We investigated differences in L with respect to outcome (modified Rankin Scale score; 90 days) and the National Institutes of Health Stroke Scale (NIHSS; early: 2-5 days; late: 90-day follow-up). Furthermore, we assessed the effect of including number of rich club regions and L in outcome models, using linear regression and assessing the explained variance (R2). Results- Of 41 patients (mean age [range]: 70 [45-89] years), 61% were male. Lower L was generally associated with better outcome. Including number of rich club regions in the backward selection models of outcome, R2 increased between 1.3- and 2.6-fold beyond that of traditional markers (age and acute lesion volume) for NIHSS and modified Rankin Scale score. Conclusions- In this proof-of-concept study, we showed that information on network topology can be leveraged to improve modeling of poststroke functional outcome. Future studies are warranted to validate this approach in larger prospective studies of outcome prediction in stroke.

Isolated Upper Limb Weakness From Ischemic Stroke: Mechanisms and Outcome.

OBJECTIVE: To characterize isolated upper extremity (UE) weakness from stroke. METHODS: In our Get with the Guidelines-Stroke dataset (n = 7643), 87 patients (1.14%) had isolated UE weakness and underwent thorough stroke evaluation with diffusion-weighted magnetic resonance imaging and good-quality arterial imaging. We analyzed clinical-imaging features, etiology, management, and outcome. Since isolated UE weakness is typically associated with contralateral hand-knob area infarcts, patients were classified into Group-A (motor strip infarct) or Group-B (non-motor strip infarct). RESULTS: The mean age was 68 years; 66% were male, 72% had hypertension, 22% diabetes, 53% hyperlipidemia, and 16% were smokers. In Group-A (n = 71), 18 patients had single and 53 had multiple infarcts involving the contralateral motor strip. In Group-B (n = 16), 6 patients had contralateral subcortical white matter infarcts, 9 had bihemispheric infarcts and 1 had a brainstem infarct. Compared to Group-B, patients in Group-A more often had carotid artery stenosis or irregular plaque (84.5% versus 50%, P = .006) and large-artery atherosclerosis mechanism (46% versus 19%, P = .05), and less often cardioembolic mechanism (13% versus 44%, P = .008). Among 36 patients with large-artery mechanism, 27 had less than 70% stenosis including 19 with plaque ulceration/thrombus. Recurrent strokes occurred in 10 patients (11.5%), including 5 with mild-moderate carotid stenosis and plaque ulceration/thrombosis, over 1515 days follow-up. CONCLUSION: Stroke mechanism in acute isolated UE weakness is variable. Contralateral motor-strip infarcts are associated with carotid stenosis, often with plaque ulceration ("vulnerable carotid plaque"), and infarcts in other locations with cardioembolism. Recurrent stroke risk is high especially with mild-moderate carotid artery stenosis and plaque ulceration/thrombus.

High-flow oxygen therapy for treatment of acute migraine: A randomized crossover trial.

Background Impaired oxygen utilization and cerebrovascular dysfunction are implicated in migraine. High-flow oxygen is effective in cluster headache and has shown promise in animal models of migraine, but has not been adequately studied in patients with migraine. Methods In this randomized, crossover-design, placebo-controlled trial, adult migraineurs self-administered high-flow oxygen or medical air at 10-15 l/min via face mask in blinded fashion starting soon after symptom onset for 30 minutes, for a total of four migraine attacks. Participants recorded the severity of headache, nausea, and visual symptoms on visual analog scales periodically up to 60 minutes. Results We enrolled 22 individuals (mean age 36 years, 20 women) who self-treated 64 migraine attacks (33 oxygen, 31 air). The pre-specified primary endpoint (mean decrease in pain score from baseline to 30 minutes) was 1.38 ± 1.42 in oxygen-treated and 1.22 ± 1.61 in air-treated attacks ( p = 0.674). Oxygen therapy resulted in relief (severity score 0-1) of pain (24% versus 6%, p = 0.05), nausea (42% versus 23%, p = 0.08) and visual symptoms (36% versus 7%, p = 0.004) at 60 minutes. Exploratory analysis showed that in moderately severe attacks (baseline pain score <6), pain relief was achieved in six of 13 (46%) oxygen versus one of 15 (7%) air ( p = 0.02). Gas therapy was used per protocol in 91% of attacks. There were no significant adverse events. Conclusion High-flow oxygen may be a feasible and safe strategy to treat acute migraine. Further studies are required to determine if this relatively inexpensive, widely available treatment can be used as an adjunct or alternative migraine therapy.