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Background: For cardiac arrest survivors who are initially comatose after restoration of spontaneous circulation, the extent of brain injury and expected recovery are crucial for management decisions. Advanced diffusion imaging approaches may provide additional insight into microstructural integrity and potential for arousal recovery (AR). Methods: Multi-shell diffusion imaging was acquired in a prospective study. Neurite orientation dispersion (OD), intracellular volume fraction (ICVF), free water fraction (ISO), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA) were calculated (see Figure). Median whole-brain values in patients with AR by discharge were compared with those with no AR and to controls (ANOVA, post-hoc 2-tailed Wilcoxon test). Multivariable backward stepwise logistic regression was performed to predict AR. Results: 19 patients (mean ±SD 48±23 y, 42% men) and 5 controls (37±19 y, 40% men) were analyzed (10 patients with AR, 9 without). Median [IQR] time-to-MRI was 5 [4-8] days. Patients with no AR had higher AK (P=0.037), and RK (P=.045) than those with AR. Controls exhibited higher FA than either AR (P=.009) or no AR (P=.02), lower MK than no AR (P=.02), lower AK than no AR (P=.02), lower RK than no AR (P=0.02), lower OD than no AR (P=.008), and lower ICVF than no AR (P=.046). AK (P=.049) and ICVF (P=.01) were found in multivariable regression to be significant predictors of AR with 81% area under the receiver operating curve (AUC). Discussion: Advanced diffusion imaging metrics, AK and ICVF, were able to predict which patients were likely to regain consciousness, with 81% AUC. Despite the small sample size, we note statistically significant differences using more sensitive measures of microstructural injury compared to more commonly used diffusivity metrics. Further investigation of advanced diffusion imaging methods is warranted.

Chronic white matter structural injury is a risk factor for poor long-term outcomes after acute ischemic stroke (AIS). However, it is unclear how white matter structural injury predisposes to poor outcomes after AIS. To explore this question, in 42 AIS patients with moderate to severe white matter hyperintensity (WMH) burden, we characterized WMH and normal-appearing white matter (NAWM) diffusivity anisotropy metrics in the hemisphere contralateral to acute ischemia in relation to ischemic tissue and early functional outcomes. All patients underwent brain MRI with dynamic susceptibility contrast perfusion and diffusion tensor imaging within 12 h and at day 3–5 post stroke. Early neurological outcomes were measured as the change in NIH Stroke Scale score from admission to day 3–5 post stroke. Target mismatch profile, percent mismatch lost, infarct growth, and rates of good perfusion were measured to assess ischemic tissue outcomes. NAWM mean diffusivity was significantly lower in the group with early neurological improvement (ENI, 0.79 vs. 0.82 × 10−3, mm2/s; P = 0.02). In multivariable logistic regression, NAWM mean diffusivity was an independent radiographic predictor of ENI (β = − 17.6, P = 0.037). Median infarct growth was 118% (IQR 26.8–221.9%) despite good reperfusion being observed in 65.6% of the cohort. NAWM and WMH diffusivity metrics were not associated with target mismatch profile, percent mismatch lost, or infarct growth. Our results suggest that, in AIS patients, white matter structural integrity is associated with poor early neurological outcomes independent of ischemic tissue outcomes.

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.

Background: Alterations to microstructural integrity in white matter hyperintensities (WMH) in patients with severe leukoaraiosis are poorly understood. Neurite density and orientation dispersion imaging (NODDI) produce better estimates of myelin density than diffusion tensor MRI (DTI) and therefore may provide additional in vivo insight into WMH pathophysiology. Methods: NODDI was acquired in a prospective study of acute ischemic stroke patients with advanced white matter disease (N=36). Neurite density (ND), and orientation dispersion (OD) were calculated along with model-free diffusion parameters: mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA). Median values were measured in in the hemisphere contralateral to the incident stroke in regions of WMH and in normal appearing white matter (NAWM) and compared (paired Wilcoxon-exact test). Linear regression was performed to evaluate univariate predictors of log-transformed WMH volumes (log WMHv). Results: Patient characteristics were: mean±SD age 69±10 y, time-to-MRI 2.8±1.2 days, median [IQ] normalized WMHv 4.7 [2.3-9.3] and 61% men. MD, AD and RD were greater, while FA, MK, AK, RK, OD and ND were lower in WMH compared to NAWM (P Discussion: Diffusivity, kurtosis and ND and OD in acute stroke patients with moderate to severe leuokoaraiosis differed significantly between NAWM and WMH in the contralateral hemisphere. Reduced neurite density is suggestive of microstructural injury. Reduced OD is typically associated with greater organization, but might also reflect restricted extracellular space diffusivity. The association of MD, AD, AK and OD in NAWM with WMH burden suggests there is ongoing risk for developing future WMH.

Background: For cardiac arrest survivors initially comatose after restoration of spontaneous circulation (ROSC), the extent of brain injury and expected neurologic outcome are crucial for patient management decisions. Advanced diffusion imaging approaches such as neurite orientation dispersion and density imaging (NODDI) or diffusion kurtosis imaging may provide additional insight into tissue integrity and potential for recovery of consciousness complementary to standard diffusion tensor imaging (DTI). Methods: Multi-shell diffusion imaging was acquired in a prospective study of comatose cardiac arrest patients and in 5 controls. Neurite orientation dispersion (OD), intracellular volume fraction (ICVF), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA) were calculated. Median whole-brain values in patients with poor outcomes (no arousal recovery [AR] by discharge) were compared with those with AR and to controls (1-way ANOVA, post-hoc 1-sided Wilcoxon exact test). Results: 18 patients (mean ±SD 48±23 y, 39% men) and 5 controls (37±19 y, 40% men) were analyzed. Median (range) Glasgow Coma Scale was 3 [3-5]. 10 patients exhibited AR, 8 did not. Median [IQR] time-to-MRI was 5 [4-8] days. FA (P=0.009), MK (P=0.017), AK (P=0.026), RK (P=0.014), OD (P=0.018) and ICVF (P=0.0038) were significantly different (see Figure). FA control values were greater than AR and no AR (P Discussion: This is the first report investigating early NODDI and diffusional heterogeneity changes in post-cardiac arrest comatose patients. Patients who failed to recover arousal demonstrated greater values for all kurtosis and NODDI metrics compared to controls. Potential bias from early withdrawal of life sustaining treatment and small cohorts are limitations.

Background: Advanced diffusion imaging approaches that model intracellular and extracellular diffusion components such as neurite orientation dispersion and density imaging (NODDI) may provide additional insight into evolution of acute ischemic stroke (AIS) injury over standard diffusion tensor imaging approaches (DTI). Methods: NODDI was acquired at discharge in a prospective study of acute ischemic stroke patients with advanced white matter disease (N=36). Neurite density (ND), and orientation dispersion (OD) were calculated along with model-free diffusion parameters: mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA). Follow-up (FU) infarct volumes were drawn on discharge FLAIR. MD, AD, RD, FA, MK, AK, RK, OD and ND values were compared (1-way ANOVA) in infarct core (abnormal acute DWI), Growth (normal acute DWI, abnormal FU) and normal contralateral gray matter (nGM) and white matter (nWM). Results: Patient characteristics were: mean±SD age 69±10 y, median [IQR] initial NIH SS score 6 [3-11], time-to-acute MRI 7.3±5.3 h, time-to-FU MRI 2.8±1.2 days, acute DWI lesion 3.1 [0.5-18.8] cm 3 , FU lesion 8.1 [1.2-45.4] cm 3 and 61% men. Figure A shows examples of maps from a single subject. Core and growth values differed significantly (P Discussion: Increased OD is expected with tissue infarction due to loss of structural integrity. In contrast, increased ND in the subacute time-frame is paradoxical. One possible mechanism could be that hyperacute ischemia-induced cellular swelling increases tortuosity of water diffusion paths, imposing direction-dependent restrictions upon diffusion, increasing intracellular and extracellular diffusion.

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 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.

Background Long-term outcomes of reversible cerebral vasoconstriction syndrome (RCVS) have not been systematically investigated. Methods The following validated questionnaires were mailed to patients recruited from the RCVS registries of two academic hospitals: headache screening form, Headache Impact Test, Migraine Disability Assessment Test, Barthel Index (BI), EuroQoL (EQ-5D-5L) and Patient Health Questionnaire (PHQ-9). Results Of the 191 patients in the registries, 109 could be contacted and 45 responded. Median follow-up time after symptom onset was 78 months. After RCVS resolution, 24 (53%) patients continued to have headache, but the majority (88%) reported improvement in its severity. Thirteen of the 24 patients with persistent headache had a history of migraine prior to RCVS diagnosis. The majority (97.5%) of respondents were functionally independent based on BI scores. EQ-5D-5L showed better scores in the domains of mobility, self-care and usual activities, as compared to pain and anxiety/depression. Patients with persistent headache had significantly higher levels of EQ-5D-5L pain scores. PHQ-9 scores revealed only one patient (3%) with severe depression. Conclusion More than half of RCVS patients will continue to have chronic headaches of mild to moderate intensity that are distinct from the “thunderclap” headaches at RCVS onset. The vast majority regain complete functional ability. However, pain and anxiety/depression are frequent, often aggravated by concomitant chronic headaches, and may be associated with lower quality of life.