Motor Band Sign in Motor Neuron Disease: A Marker for Upper Motor Neuron Involvement.

BACKGROUND AND OBJECTIVE: The prevalence and role of the motor band sign (MBS) remain unclear in motor neuron disease. We report the frequency of MBS in amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), its correlation with clinical upper motor neuron (UMN) signs, and prognostic value in ALS. METHODS: We conducted a retrospective study of ALS, PLS, and controls with retrievable MRI between 2010 and 2018. We compared the frequencies of MBS across the three groups, and studied correlation between susceptibility-weighted MRI measurements in primary motor cortices and contralateral UMN features. Clinical outcomes were compared between ALS with and without MBS. RESULTS: Thirteen ALS, 5 PLS, and 10 controls were included (median age 60 years, IQR 54-66 years; 14/28 males). MBS was present in 9/13 (69.2%, 95% CI 38.9-89.6%) and 4/5 (80.0%, 95% CI 29.9-99.0%) of ALS and PLS, respectively, and none in controls. 2/13 (15.4%, 95% CI 2.7-46.3%) ALS and 3/5 (60.0%, 95% CI 17.0-92.7%) PLS had MBS in the absence of corticospinal T2/FLAIR hyperintensity sign. Susceptibility measurements in left motor cortices had a significantly positive correlation with contralateral UMN signs in ALS (τb = 0.628, p = 0.03). Similar but nonsignificant trends was observed for right motor cortices in ALS (τb = 0.516, p = 0.07). There were no significant differences in mRS at last follow-up, mortality, or time from symptom onset to last follow-up between ALS patients with and without MBS. CONCLUSIONS: We provide limited evidence that MBS and susceptibility quantification measurements in motor cortices may serve as surrogate markers of UMN involvement in motor neuron disease.

How outcomes are measured after spontaneous intracerebral hemorrhage: A systematic scoping review.

BACKGROUND AND PURPOSE: Recovery after intracerebral haemorrhage (ICH) is often slower than ischemic stroke. Despite this, ICH research often quantifies recovery using the same outcome measures obtained at the same timepoints as ischemic stroke. The primary objective of this scoping review is to map the existing literature to determine when and how outcomes are being measured in prospective studies of recovery after ICH. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Web of Science from inception to November 2019, for prospective studies that included patients with ICH. Two investigators independently screened the studies and extracted data around timing and type of outcome assessment. RESULTS: Among the 9761 manuscripts reviewed, 395 met inclusion criteria, of which 276 were observational studies and 129 were interventional studies that enrolled 66274 patients. Mortality was assessed in 93% of studies. Functional outcomes were assessed in 85% of studies. The most frequently used functional assessment tool was the modified Rankin Scale (mRS) (60%), followed by the National Institute of Health Stroke Severity Scale (22%) and Barthel Index (21%). The most frequent timepoint at which mortality was assessed was 90 days (41%), followed by 180 days (18%) and 365 days (12%), with 2% beyond 1 year. The most frequent timepoint used for assessing mRS was 90 days (62%), followed by 180 days (21%) and 365 days (17%). CONCLUSION: While most prospective ICH studies report mortality and functional outcomes only at 90 days, a significant proportion do so at 1 year and beyond. Our results support the feasibility of collecting long-term outcome data to optimally assess recovery in ICH.

Prevalence and the predictive performance of the dynamic CT-angiography spot sign in an observational cohort with intracerebral hemorrhage.

The CT-angiography (CTA) spot sign is a predictor of hematoma expansion (HE). We have previously reported on the use of dynamic CTA (dCTA) to detect spot sign, and to study its formation over the acquisition period. In this study, we report the frequency of dCTA spot sign in acute intracerebral hemorrhage, its sensitivity and specificity to predict HE, and explore the rate of contrast extravasation in relation to hematoma growth.We enrolled consecutive patients presenting with primary intracerebral hemorrhage within 4.5 hours. All patients underwent a dCTA protocol acquired over 60 seconds following contrast injection. We calculated frequency of the dCTA spot sign, predictive performance, and rate of contrast extravasation. We compared extravasation rates to the dichotomous definition of significant HE (defined as 6 mL or 33% growth).In 78 eligible patients, dCTA spot sign frequency was 44.9%. In 61 patients available for expansion analysis, sensitivity and specificity of dCTA spot sign was 65.4% and 62.9%, respectively. Contrast extravasation rate did not significantly predict HE (Odds Ratio 15.6 for each mL/min [95% confidence interval 0.30-820.25], P = .17). Correlation between extravasation rate and HE was low (r = 0.297, P= .11). Patients with significant HE had a higher rate of extravasation as compared to those without (0.12 mL/min vs 0.04 mL/min, P = .03).Dynamic CTA results in a higher frequency of spot sign positivity, but with modest sensitivity and specificity to predict expansion. Extravasation rate is likely related to HE, but a single measurement may be insufficient to predict the magnitude of expansion.

Distribution and predictive performance of the temporal phase of dynamic spot sign appearance in acute intracerebral hemorrhage.

BACKGROUND: Dynamic CT angiography (dCTA) contrast extravasation, known as the "dynamic spot sign", can predict hematoma expansion (HE) in intracerebral hemorrhage (ICH). Recent reports suggest the phase of spot sign appearance is related to the magnitude of HE. We used dCTA to explore the association between the phase of spot sign appearance and HE, clinical outcome, and contrast extravasation rates. METHODS: We assessed consecutive patients who presented with primary ICH within 4.5 hours from symptom onset who underwent a standardized dCTA protocol and were spot sign positive. The independent variable was the phase of spot sign appearance. The primary outcome was significant HE (either 6 mL or 33% growth). Secondary outcomes included total absolute HE, mortality, and discharge mRS. Mann-Whitney U, Fisher's exact test, and logistic regression were used, as appropriate. RESULTS: Of the 35 patients with spot signs, 27/35 (77%) appeared in the arterial phase and 8/35 (23%) appeared in the venous phase. Thirty patients had follow-up CT scans. Significant HE was seen in 14/23 (60.87%) and 3/7 (42.86%) of arterial and venous cohorts, respectively (p = 0.67). The sensitivity and specificity in predicting significant HE were 82% and 31% for the arterial phase and 18% and 69% for the venous phase, respectively. There was a non-significant trend towards greater total HE, in-hospital mortality, and discharge mRS of 4-6 in the arterial spot sign cohort. Arterial spot signs demonstrated a higher median contrast extravasation rate (0.137 mL/min) compared to venous spot signs (0.109 mL/min). CONCLUSION: Our exploratory analyses suggest that spot sign appearance in the arterial phase may be more likely associated with HE and poorer prognosis in ICH. This may be related to higher extravasation rates of arterial phase spot signs. However, further studies with larger sample sizes are warranted to confirm the findings.

Identifying stroke therapeutics from preclinical models: A protocol for a novel application of network meta-analysis.

Introduction: Globally, stroke is the second leading cause of death. Despite the burden of illness and death, few acute interventions are available to patients with ischemic stroke. Over 1,000 potential neuroprotective therapeutics have been evaluated in preclinical models. It is important to use robust evidence synthesis methods to appropriately assess which therapies should be translated to the clinical setting for evaluation in human studies. This protocol details planned methods to conduct a systematic review to identify and appraise eligible studies and to use a network meta-analysis to synthesize available evidence to answer the following questions: in preclinical in vivo models of focal ischemic stroke, what are the relative benefits of competing therapies tested in combination with the gold standard treatment alteplase in (i) reducing cerebral infarction size, and (ii) improving neurobehavioural outcomes? Methods: We will search Ovid Medline and Embase for articles on the effects of combination therapies with alteplase. Controlled comparison studies of preclinical in vivo models of experimentally induced focal ischemia testing the efficacy of therapies with alteplase versus alteplase alone will be identified. Outcomes to be extracted include infarct size (primary outcome) and neurobehavioural measures. Risk of bias and construct validity will be assessed using tools appropriate for preclinical studies. Here we describe steps undertaken to perform preclinical network meta-analysis to synthesise all evidence for each outcome and obtain a comprehensive ranking of all treatments. This will be a novel use of this evidence synthesis approach in stroke medicine to assess pre-clinical therapeutics. Combining all evidence to simultaneously compare mutliple therapuetics tested preclinically may provide a rationale for the clinical translation of therapeutics for patients with ischemic stroke.  Dissemination: Review findings will be submitted to a peer-reviewed journal and presented at relevant scientific meetings to promote knowledge transfer. Registration: PROSPERO number to be submitted following peer review.