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BACKGROUND: Artificial intelligence (AI)-based algorithms have been developed to facilitate rapid and accurate computed tomography angiography (CTA) assessment in proximal large vessel occlusion (LVO) acute ischemic stroke, including internal carotid artery and M1 occlusions. In clinical practice, however, the detection of medium vessel occlusion (MeVO) represents an ongoing diagnostic challenge in which the added value of AI remains unclear.PURPOSE: To assess the diagnostic performance of AI platforms for detecting M2 occlusions.METHODS: Studies that report the diagnostic performance of AI-based detection of M2 occlusions were screened, and sensitivity and specificity data were extracted using the semi-automated AutoLit software (Nested Knowledge, MN) platform. STATA (version 16 IC; Stata Corporation, College Station, Texas, USA) was used to conduct all analyses.RESULTS: Eight studies with a low risk of bias and significant heterogeneity were included in the quantitative and qualitative synthesis. The pooled estimates of sensitivity and specificity of AI platforms for M2 occlusion detection were 64% (95% CI, 53 to 74%) and 97% (95% CI, 84 to 100%), respectively. The area under the curve (AUC) in the SROC curve was 0.79 (95% CI, 0.74 to 0.83).CONCLUSION: The current performance of the AI-based algorithm makes it more suitable as an adjunctive confirmatory tool rather than as an independent one for M2 occlusions. With the rapid development of such algorithms, it is anticipated that newer generations will likely perform much better.

To investigate whether unfavorable cerebral venous outflow (VO) predicts reperfusion hemorrhage after endovascular treatment (EVT), we conducted a retrospective multicenter cohort study of patients with acute ischemic stroke and large vessel occlusion (AIS-LVO). 629 AIS-LVO patients met inclusion criteria. VO profiles were assessed on admission CT angiography using the Cortical Vein Opacification Score (COVES). Unfavorable VO was defined as COVES ≤ 2. Reperfusion hemorrhages on follow-up imaging were subdivided into no hemorrhage (noRH), hemorrhagic infarction (HI) and parenchymal hematoma (PH). Patients with PH and HI less frequently achieved good clinical outcomes defined as 90-day modified Rankin Scale scores of ≤ 2 (PH: 13.6% vs. HI: 24.6% vs. noRH: 44.1%; p

BackgroundPrevious studies comparing a direct aspiration first pass technique (ADAPT) and stent retrievers have inconsistent methodologies and data reporting, limiting the ability to accurately assimilate data from different studies that would inform treatment of acute ischemic stroke (AIS) treatment.ObjectiveTo conduct a systematic review to discuss and compare the findings of all relevant meta-analysis studies comparing the efficacy of the ADAPT and stent retriever techniques.MethodsThe study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), where meta-analyses comparing the efficacy of the ADAPT technique and stent retrievers in the treatment of AIS were included. We extracted all relevant data from the included studies and assessed the quality of the included meta-analyses using the Assessment of Multiple Systematic Review (AMSTAR-2).ResultsSeven relevant studies met our inclusion criteria and were suitable for the qualitative synthesis. All included studies obtained data from randomized controlled trials (RCTs) and observational investigations (including levels II, III, and IV). At the same time, none of them used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for quality assessment. In accordance with AMSTAR-2, two studies were rated ‘high’, while the other five were rated ‘moderate’.ConclusionsPresent evidence is insufficient to clarify the superiority of one modality over the other. Further RCTs on this comparison must be conducted prior to designing further meta-analyses or making conclusive interpretations. Procedure duration and cost should be taken into consideration for any future studies.

Cross study heterogeneity has limited the evidence based evaluation of middle meningeal artery embolization (MMAE) as a treatment for chronic subdural hematoma (CSDH). Ongoing trials and prospective studies suggest that heterogeneity in upcoming publications may detract from subsequent meta-analyses and systemic reviews. This study aims to describe this data heterogeneity to promote harmonization with common data elements (CDEs) in publications. ClinicalTrials.gov and PubMed were searched for published or ongoing prospective trials of MMAE. The Nested Knowledge AutoLit living review platform was utilized to classify endpoints from randomized control trials (RCTs) and prospective cohort studies comparing MMAE with other treatments. The qualitative synthesis feature was used to determine cross study overlap of outcome related data elements. Eighteen studies were included: 12 RCTs, two non-randomized controlled studies, two prospective single arm trials, one combined prospective and retrospective controlled study, and one prospective cohort study. The most commonly reported data element was recurrence (15/18), but seven heterogenous (non-comparable) definitions were used for ‘recurrence’. Mortality was reported in 10/18 studies, but no common timepoint was reported in more than four studies. Re-intervention and CSDH volume were reported in eight studies, CSDH width in seven, and no other outcome was common across more than five studies. There was significant heterogeneity in data element collection even among prospective registered trials of MMAE. Even among CDEs, variation in definition and timepoints prevented harmonization. A standardized approach based on CDEs may be necessary to facilitate future meta-analyses and evidence driven evaluation of MMAE treatment of CSDH.

Background: Parenchymal hematoma (PH) is a major complication after endovascular treatment (EVT) for ischemic stroke. The hypoperfusion intensity ratio (HIR) represents a perfusion parameter reflecting arterial collateralization and cerebral microperfusion in ischemic brain tissue. We hypothesized that HIR correlates with the risk of PH after EVT. Methods: Retrospective multicenter cohort study of patients with large vessel occlusion who underwent EVT between 2013 and 2021 at one of the 2 comprehensive stroke centers (University Medical Center Hamburg-Eppendorf, Germany and Stanford University School of Medicine, CA). HIR was automatically calculated on computed tomography perfusion studies as the ratio of brain volume with time-to-max (Tmax) delay >10 s over volume with Tmax >6 s. Reperfusion hemorrhages were assessed according to the Heidelberg Bleeding Classification. Primary outcome was PH occurrence (PH+) or absence (PH−) on follow-up imaging. Secondary outcome was good clinical outcome defined as a 90-day modified Rankin Scale score of 0 to 2. Results: A total of 624 patients met the inclusion criteria. We observed PH in 91 (14.6%) patients after EVT. PH+ patients had higher HIR on admission compared with PH− patients (median, 0.6 versus 0.4; P P P =0.002), and higher HIR (aOR, 1.22 [1.09–1.38]; P P P =0.013) were independently associated with lower odds of achieving good clinical outcome. Conclusions: Poorer (higher) HIR on admission perfusion imaging was strongly associated with PH occurrence after EVT. HIR as a surrogate for cerebral microperfusion might reflect tissue vulnerability for reperfusion hemorrhages. This automated and quickly available perfusion parameter might help to assess the need for intensive medical care after EVT.

BackgroundPrevious randomized controlled trials (RCTs) and meta-analyses were underpowered to demonstrate the superiority of endovascular thrombectomy (EVT) over medical therapy (MEDT) in the treatment of acute ischemic stroke due to large vessel occlusion of the posterior circulation (PC-LVO). We performed an updated systematic review and meta-analysis after the publication of the BAOCHE and ATTENTION trials to determine whether EVT can benefit patients presenting with PC-LVO.MethodsUsing Nested Knowledge, we screened literature for RCTs on EVT in PC-LVO. The primary outcome was 90-day modified Rankin Scale (mRS) score 0–3, and secondary outcomes included 90-day mRS score 0–2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A random-effects model was used to compute rate ratios (RRs) and their corresponding 95% confidence intervals (CIs).ResultsFour RCTs with 988 patients, 556 patients in the EVT arm and 432 patients in the MEDT arm, were included in the meta-analysis. EVT resulted in significantly higher rates of mRS score 0–3 (RR=1.54; 95% CI 1.16 to 2.04; P=0.002) and functional independence (RR=1.83; 95% CI 1.08 to 3.08; P=0.024), and lower rates of mortality (RR=0.76; 95% CI 0.65 to 0.90; P=0.002) at 90-day follow-up compared with MEDT alone. However, EVT patients had higher rates of sICH (RR=7.48; 95% CI 2.27 to 24.61; PConclusionsEVT conferred significant patient benefit over MEDT alone in the treatment of PC-LVO. Future studies should better define patients for whom EVT is futile and determine factors that contribute to higher rates of sICH.

Mechanical thrombectomy for acute ischemic stroke (AIS) is traditionally performed via transfemoral access. While the majority of AISs are due to anterior circulation large vessel occlusions (AC-LVO), we performed a systematic review and meta-analysis to examine the feasibility of and outcomes following a transradial artery access for posterior circulation large vessel occlusion (PC-LVO) strokes. A systematic literature review of the English language literature was conducted using PubMed, MEDLINE, and Embase as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes of interest included 90-day modified Rankin scale (mRS) 0-2, puncture to recanalization time, and thrombolysis in cerebral infarction (TICI) scores 2b/3 and 3. We calculated pooled event rates and their corresponding 95% confidence intervals (CI) for all outcomes. We included seven studies with 68 patients in our analysis. All patients underwent mechanical thrombectomy via transradial artery access for AIS due to PC-LVO. The pooled meantime of puncture to recanalization was 29.19 (95% CI=24.05 to 35.42) minutes. Successful recanalization (TICI2b/3) was achieved in 98.69% (95% CI=93.50 to 100) of patients and complete recanalization (TICI 3) in 52.16% (95% CI=34.18 to 79.60) of the patients. Overall, 56.84% (95% CI=41.26 to 78.30) of patients achieved mRS 0-2. Transradial artery access for mechanical thrombectomy for PC-LVO stroke displays early promise and feasibility, particularly regarding very high rates of successful recanalization and low puncture to recanalization time.

ImportancePrevious randomized clinical trials (RCTs) have supported the use of endovascular therapy (EVT) in late-window acute ischemic stroke (AIS; 6-24 hours). However, little is known about the use of EVT in very late-window AIS (>24 hours).ObjectiveTo examine outcomes following EVT for very late-window AIS.Data SourcesA systematic review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed to search for articles published from database inception until December 13, 2022.Study SelectionThis systematic review and meta-analysis included published studies regarding very late-window AIS treated with EVT. Multiple reviewers screened studies, and an extensive manual search of the references of included articles was performed to identify any missed articles. Of the 1754 initially retrieved studies, 7 published between 2018 and 2023 were ultimately included.Data Extraction and SynthesisData were extracted independently by multiple authors and evaluated for consensus. Data were pooled using a random-effects model. This study is reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guideline, and the protocol was prospectively registered with PROSPERO.Main Outcomes and MeasuresThe primary outcome of interest was functional independence, as assessed with 90-day modified Rankin Scale (mRS) scores (0-2). Secondary outcomes included thrombolysis in cerebral infarction (TICI) scores (2b-3 or 3), symptomatic intracranial hemorrhage (sICH), 90-day mortality, early neurological improvement (ENI), and early neurological deterioration (END). Frequencies and means were pooled with the corresponding 95% CIs.ResultsThis review included 7 studies involving a total of 569 patients. The mean baseline National Institutes of Health Stroke Scale score was 13.6 (95% CI, 11.9-15.5), and the mean Alberta Stroke Program Early CT Score was 7.9 (95% CI, 7.2-8.7). The mean time from last known well and/or onset to puncture was 46.2 hours (95% CI, 32.4-65.9 hours). Frequencies for the primary and secondary outcomes were 32.0% (95% CI, 24.7%-40.2%) for functional independence (90-day mRS scores of 0-2) and 81.9% (95% CI, 78.5%-84.9%) for TICI scores of 2b to 3, 45.3% (95% CI, 36.6%-54.4%) for TICI scores of 3, 6.8% (95% CI, 4.3%-10.7%) for sICH, and 27.2% (95% CI, 22.9%-31.9%) for 90-day mortality. In addition, frequencies were 36.9% (95% CI, 26.4%-48.9%) for ENI and 14.3% (95% CI, 7.1%-26.7%) for END.Conclusions and RelevanceIn this review, EVT for very late-window AIS was associated with favorable frequencies of 90-day mRS scores of 0 to 2 and TICI scores of 2b to 3 and with low frequencies of 90-day mortality and sICH. These results suggest that EVT may be safe and associated with improved outcomes for very late-window AIS, although RCTs and prospective, comparative studies are needed to determine which patients may benefit from very late intervention.

Objective Multiple sclerosis (MS) lesions are heterogeneous with regard to inflammation, demyelination, axonal injury, and neuronal loss. We previously developed a diffusion basis spectrum imaging (DBSI) technique to better address MS lesion heterogeneity. We hypothesized that the profiles of multiple DBSI metrics can identify lesion‐defining patterns. Here we test this hypothesis by combining a deep learning algorithm using deep neural network (DNN) with DBSI and other imaging methods. Methods Thirty‐eight MS patients were scanned with diffusion‐weighted imaging, magnetization transfer imaging, and standard conventional MRI sequences (cMRI). A total of 499 regions of interest were identified on standard MRI and labeled as persistent black holes (PBH), persistent gray holes (PGH), acute black holes (ABH), acute gray holes (AGH), nonblack or gray holes (NBH), and normal appearing white matter (NAWM). DBSI, diffusion tensor imaging (DTI), and magnetization transfer ratio (MTR) were applied to the 43,261 imaging voxels extracted from these ROIs. The optimized DNN with 10 fully connected hidden layers was trained using the imaging metrics of the lesion subtypes and NAWM. Results Concordance, sensitivity, specificity, and accuracy were determined for the different imaging methods. DBSI‐DNN derived lesion classification achieved 93.4% overall concordance with predetermined lesion types, compared with 80.2% for DTI‐DNN model, 78.3% for MTR‐DNN model, and 74.2% for cMRI‐DNN model. DBSI‐DNN also produced the highest specificity, sensitivity, and accuracy. Conclusions DBSI‐DNN improves the classification of different MS lesion subtypes, which could aid clinical decision making. The efficacy and efficiency of DBSI‐DNN shows great promise for clinical applications in automatic MS lesion detection and classification.

Background and Purpose: Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke (AIS) due to large vessel occlusion of the anterior circulation (AC-LVO). Randomized trials of posterior circulation large vessel occlusion (PC-LVO) patients have failed to show a benefit of EVT over medical therapy (MEDT). We performed a systematic review and meta-analysis to understand better whether EVT is beneficial for PC-LVO. Methods: Using the Nested Knowledge AutoLit living review platform, we identified randomized control trials and prospective studies that reported functional outcomes in patients with PC-LVO treated with EVT versus MEDT. The primary outcome variable was 90-day modified Rankin Scale (mRS) 0-3, and secondary outcome variables included 90-day mRS 0-2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure to calculate pooled odds ratios. Results: Three studies with 1,248 patients, 860 in the EVT arm and 388 in the MEDT arm, were included in the meta-analysis. The favorable outcome rate (mRS 0-3) in EVT patients was 39.9% (95% CI: 30.6-50.1%) versus 24.5% in MEDT patients (95% CI: 9.6-49.8%). EVT patients had higher mRS 0-2 rates (31.8% [95% CI: 25.7-38.5%] versus 19.7% [95% CI: 7.4-42.7%]) and lower mortality (42.1% [95% CI: 35.9-48.6%] versus 52.8% [95% CI: 33.3-71.5%]) compared to MEDT patients, but neither result was statistically significant. EVT patients were more likely to develop sICH (OR=10.36; 95% CI: 3.92-27.40). Conclusions: EVT treatment of PC-LVO trended toward superior functional outcomes and reduced mortality compared to MEDT despite a trend toward increased sICH in EVT patients. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MEDT in PC-LVO patients.

Introduction Mechanical thrombectomy (MT) is the standard of care in eligible patients presenting with acute ischemic stroke (AIS). The question of whether intravenous thrombolysis (IVT) improves outcomes in conjunction with MT remains unanswered. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) to explore outcomes of MT with and without IVT. Methods Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Embase, Web of science, and Scopus. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0–2, thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), distal embolization, and mortality. We calculated pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CI). Results Six RCTs with 2334 patients compared outcomes of patients treated with MT alone and MT with IVT. Both treatments resulted in comparable rates of mRS 0–2 (RR = 0.96, 95% CI = 0.88–1.04; p-value = 0.282), sICH (RR = 0.80, 95% CI = 0.55–1.17; p-value = 0.253), mortality at 90-days (RR = 1.06, 95% CI = 0.88–1.28; p-value = 0.529), and distal embolization (RR = 1.10, 95% CI = 0.79–1.52; p-value = 0.572). MT alone was associated with a lower rate of TICI 2b-3 compared to MT with IVT (RR = 0.96, 95% CI = 0.93–0.99; p-value = 0.006). Conclusions In this meta-analysis of six RCTs, MT alone was comparable to MT plus IVT for mRS 0–2, sICH, mortality, and distal embolization; however, MT alone resulted in lower rates of TICI 2b-3. Further trials are needed to determine which patient populations benefit from MT plus IVT and to increase the power of future meta-analyses.

Background There is limited evidence on the optimal endovascular strategy for treatment of distal medium-vessel occlusions (DMVO). The low-profile Tigertriever 13 stent-triever shows early promise as an adaptable device that can navigate the distal vasculature without increasing complication risk in DMVO. Methods Using Nested Knowledge, we screened literature for RCTs and cohort studies on the endovascular treatment of DMVO. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction (TICI) ≥ 2b and secondary outcomes included rate of symptomatic intracranial hemorrhage (sICH), mortality at 90 days, and modified Rankin scale (mRS) scores 0–2 at 90 days. A random-effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI). Results Eleven studies with 1402 patients, 167 patients treated by Tigertriever 13 and 1235 patients treated by other devices, were included in the meta-analysis. The rate of reperfusion success was similar in patients treated by Tigertriever 13 (83.2% [95% CI: 71.5–96.7%]) versus other devices (81.6% [95% CI: 75.3–88.4%], p > 0.05). The rate of sICH was also similar in patients treated by Tigertriever 13 (7.2% [95% CI: 4.1–12.5%]) versus other devices (6.9% [95% CI: 5.5–8.8%]). There was significant heterogeneity in the reporting of mortality and mRS. Conclusions Tigertriever 13 had similar rates of reperfusion success and sICH as other devices used for the treatment of DMVO. Heterogeneity in data element reporting prevented further analyses. Further studies evaluating Tigertriever 13 and other potential devices in DMVO should attempt to harmonize data element reporting.

Most studies define the technical success of endovascular thrombectomy (EVT) as a Thrombolysis in Cerebral Infarction (TICI) revascularization grade of 2b or higher. However, growing evidence suggests that TICI 3 is the best angiographic predictor of improved functional outcomes. To assess the association between successful TICI revascularization grades and functional independence at 90 days, we performed a systematic review and network meta-analysis of thrombectomy studies that reported TICI scores and functional outcomes, measured by the modified Rankin Scale, using the semi-automated AutoLit software platform. Forty studies with 8691 patients were included in the quantitative synthesis. Across TICI, modified TICI (mTICI), and expanded TICI (eTICI), the highest rate of good functional outcomes was observed in patients with TICI 3 recanalization, followed by those with TICI 2c and TICI 2b recanalization, respectively. Rates of good functional outcomes were similar among patients with either TICI 2c or TICI 3 grades. On further sensitivity analysis of the eTICI scale, the rates of good functional outcomes were equivalent between eTICI 2b50 and eTICI 2b67 (OR 0.81, 95% CI 0.52 to 1.25). We conclude that near complete or complete revascularization (TICI 2c/3) is associated with higher rates of functional outcomes after EVT.

Background We aimed to determine the rate of herbal medicine usage and the treatment-seeking patterns of children aged ≤5 y with presumed or confirmed malaria in an endemic area of Uganda. Methods We interviewed guardians of 722 children aged 6 months to 5 y, who had experienced an episode of presumed malaria in the previous 3 months, about the illness history. Results Overall, 36.1% of patients took herbal medicines but most also sought modern medical care; 79.2% received Artemether-Lumefantrine (AL), but only 42.7% received the correct AL dose. Of the 36.6% of patients treated in drug shops, 9.8% had a diagnostic test and 30.2% received the correct dose of AL. Antibiotics were frequently provided with AL at drug shops (62%) and formal health centers (45%). There were no significant differences in the self-reported outcomes associated with different treatments. Conclusion Almost all of the patients who took herbal medicine also took modern antimalarials, so further research is needed to explore potential interactions between them. Although formal health facilities provided the correct diagnosis and dose of AL to a majority of children with malaria, many children still received inappropriate antibiotics. Quality of care was worse in drug shops than in formal health facilities.

The Erlenmeyer flask deformity is a common skeletal modeling deformity, but current classification systems are binary and may restrict its utility as a predictor of associated skeletal conditions. A quantifiable 3-point system of severity classification could improve its predictive potential in disease. Ratios were derived from volumes of regions of interests drawn in 50 Gaucher’s disease patients. ROIs were drawn from the distal physis to 2 cm proximal, 2 cm to 4 cm, and 4 cm to 6 cm. Width was also measured at each of these boundaries. Two readers rated these 100 femurs using a 3-point scale of severity classification. Weighted kappa indicated reliability and one-way analysis of variance characterized ratio differences across the severity scale. Accuracy analyses allowed determination of clinical cutoffs for each ratio. Pearson’s correlations assessed the associations of volume and width with a shape-based concavity metric of the femur. The volume ratio incorporating the metaphyseal region from 0 to 2 cm and the diametaphyseal region at 4–6 cm was most accurate at distinguishing femurs on the 3-point scale. Receiver operating characteristic curves for this ratio indicated areas of 0.95 to distinguish normal and mild femurs and 0.93 to distinguish mild and severe femurs. Volume was moderately associated with the degree of femur concavity. The proposed volume ratio method is an objective, proficient method at distinguishing severities of the Erlenmeyer flask deformity with the potential for automation. This may have application across diseases associated with the deformity and deficient osteoclast-mediated modeling of growing bone. Electronic supplementary material The online version of this article (10.1007/s00256-020-03561-2) contains supplementary material, which is available to authorized users.

Background High-quality evidence exists for mechanical thrombectomy (MT) treatment of acute ischemic stroke (AIS) due to large vessel occlusion of the anterior circulation (AC-LVO). The evidence for MT treatment of posterior circulation large vessel occlusion (PC-LVO) is weaker, largely drawn from lower quality studies specific to PC-LVO and extrapolated from findings in AC-LVO, and ambiguous with regards to technical success. We performed a systematic review and meta-analysis to compare the technical success and functional outcomes of MT in PC-LVO versus AC-LVO patients. Methods We identified comparative studies reporting on patients treated with MT in AC-LVO versus PC-LVO. The primary outcome of interest was thrombolysis in cerebral infarction (TICI) ≥ 2b. Secondary outcomes included rates of TICI 3, 90-day functional independence, first-pass-effect, average number of passes, and 90-day mortality. A separate random effects model was fit for each outcome measure. Results Twenty studies with 12,911 patients, 11,299 (87.5%) in the AC-LVO arm and 1612 (12.5%) in the PC-LVO arm, were included. AC-LVO and PC-LVO patients had comparable rates of successful recanalization [OR = 1.02 [95% CI: 0.79–1.33], p = 0.848). However, the AC-LVO group had greater odds of 90-day functional independence (OR = 1.26 [95% CI: 1.00; 1.59], p = 0.050) and lower odds of 90-day mortality (OR = 0.58 [95% CI: 0.43; 0.79], p = 0.002). Conclusions MT achieves similar rates of recanalization with a similar safety profile in PC-LVO and AC-LVO patients. Patients with PC-LVO are less likely to achieve functional independence after MT. Future studies should identify PC-LVO patients who are likely to achieve favourable functional outcomes.

Gait impairments in persons with multiple sclerosis (pwMS) leading to decreased ambulation and reduced walking endurance remain poorly understood. Our objective was to assess gait asymmetry (GA) and bilateral coordination of gait (BCG), among pwMS during the six-minute walk test (6MWT), and determine their association with disease severity. We recruited 92 pwMS (age: 46.6 ± 7.9; 83% females) with a range of clinical disability, who completed the 6MWT wearing gait analysis system. GA was assessed by comparing left and right swing times, and BCG was assessed by the phase coordination index (PCI). Several functional and subjective gait assessments were performed. Results show that gait is more asymmetric and less coordinated as the disease progresses (p

Gait impairments in persons with multiple sclerosis (pwMS) underlying reduced walking endurance are still poorly understood. Thus, our objective was to assessed gait asymmetry (GA) and bilateral coordination of gait (BCG), among pwMS during the six-minute walk test (6MWT) and their association with disease severity. For this aim, we recruited ninety-two pwMS (age: 46.6 ± 7.9; 83% females) with a broad range of clinical disability who completed the 6MWT wearing gait analysis system. GA was assessed by comparing left and right swing times, and BCG by using the phase coordination index (PCI). Several functional and subjective gait assessments were performed. Results show that gait is more asymmetric and less coordinated as the disease progresses (p

Background Improved imaging methods are critical to assess neurodegeneration and remyelination in multiple sclerosis. Chronic hypointensities observed on T1-weighted brain MRI, "persistent black holes," reflect severe focal tissue damage. Present measures consist of determining persistent black holes numbers and volumes, but do not quantitate severity of individual lesions. Objective Develop a method to differentiate black and gray holes and estimate the severity of individual multiple sclerosis lesions using standard magnetic resonance imaging. Methods 38 multiple sclerosis patients contributed images. Intensities of lesions on T1-weighted scans were assessed relative to cerebrospinal fluid intensity using commercial software. Magnetization transfer imaging, diffusion tensor imaging and clinical testing were performed to assess associations with T1w intensity-based measures. Results Intensity-based assessments of T1w hypointensities were reproducible and achieved > 90% concordance with expert rater determinations of "black" and "gray" holes. Intensity ratio values correlated with magnetization transfer ratios (R = 0.473) and diffusion tensor imaging metrics (R values ranging from 0.283 to −0.531) that have been associated with demyelination and axon loss. Intensity ratio values incorporated into T1w hypointensity volumes correlated with clinical measures of cognition. Conclusions This method of determining the degree of hypointensity within multiple sclerosis lesions can add information to conventional imaging.

BackgroundDiagnosing MS through magnetic resonance imaging (MRI) requires extensive clinical experience and tedious work. Furthermore, MRI-indicated MS lesion locations rarely align with the patients’ symptoms and often contradict with pathology studies. Our lab has developed and modified a novel diffusion basis spectrum imaging (DBSI) technique to address the shortcomings of MRI-based MS diagnoses. Although primary DBSI metrics have been demonstrated to be associated with axonal injury/loss, demyelination and inflammation, a more detailed analysis using multiple DBSI-structural metrics to improve the accuracy of MS lesion detection and differentiation is still needed. Here we report that Diffusion Histology Imaging (DHI), an improved approach that combines a deep neural network (DNN) algorithm with improved DBSI analyses, accurately detected and classified various MS lesion types.MethodsThirty-eight multiple sclerosis patients were scanned with T2-weighted imaging (T2WI) using fluid attenuated inversion recovery (FLAIR), T1-weighted imaging (T1WI) using magnetization-prepared rapid acquisition with gradient echo (MPRAGE), magnetization transfer contrast (MTR) imaging and diffusion-weighted imaging. The imaging results identified 43,261 voxels from 91 persistent black hole (PBH) lesions, 89 persistent gray hole (PGH) lesions, 16 acute gray hole (AGH) lesions, 189 non-black hole (NBH) lesions and 113 normal-appearing white matter (NAWM) areas. Data extracted from these lesions were randomly split into training, validation, and testing groups with an 8:1:1 ratio. The DNN was constructed with 10 fully-connected hidden layers using TensorFlow 2.0 in Python. Batch normalization and dropout regularization were used for model optimization.ResultsEach MS lesion type had unique DBSI derived diffusion metric profiles. Based on these DBSI diffusion metric profiles, DHI achieved a 93.6% overall concordance with neurologist determinations of all five MS lesions, compared with 74.3% from conventional MRI (cMRI)-DNN model, 78.2% from MTR-DNN model, and 80% from DTI-DNN model. DHI also achieved greater performances on detecting individual MS lesion types compared to other models. Specifically, DHI showed great performances on prediction of PBH (AUC: 0.991; F1-score: 0.923), PGH (AUC: 0.977; F1-score: 0.823) and AGH (AUC: 0.987; F1-score: 0.887), which significantly outperformed other models.ConclusionsDHI significantly improves the detection and classification accuracy for various MS lesion types, which could greatly aid the clinical decisions of neurologists and neuroradiologists. The efficacy and efficiency of this DNN model shows great promise for clinical application.

Aim To investigate the current prevalence and management of dyspepsia in rural Eastern Uganda. Methods Residents older than 18 years of age across 95 study sites in Namutumba District, Eastern Uganda were surveyed. Each respondent was administered a questionnaire about dyspepsia and pertinent health-seeking behaviors. Health workers at 12 different clinics were also assessed on their competence in managing dyspepsia. Proportion-based analysis was used to determine self-reported outcome variables reported in this study, including: prevalence of dyspepsia; breakdown of symptoms; initial diagnosis location; management strategies; and appropriate medication usage. Results 397 residents (average age of 41.2 years) participated in this study (54.4% males, 45.6% females). 57.9% self-reported currently having dyspepsia, of average duration 4.5 years. Of this subset, 87% reported experiencing epigastric pain, and 42.2% believed that ulcers were "wounds in the stomach." Only 3% of respondents had heard of Helicobacter pylori (Hp). Respondents varied in their management of dyspepsia, with frequent eating (39.1%), doing nothing (23.9%), and taking Western medicine (20%) being the most common strategies. The diagnosis of "peptic ulcer disease" was made by a health worker in 64.3% of cases, and 27% of cases were self-diagnosed. Notably, 70.3% of diagnoses at formal health centers were based on clinical symptoms alone and only 22.7% of respondents received treatment according to Ugandan Ministry of Health guidelines. Among the 12 health care workers surveyed, 10 cited epigastric pain as a common symptom of "ulcer," although only two reported having heard of Hp. Only two out of 12 clinics had the capability to prescribe the triple therapy as treatment for presumed Hp. Conclusion There is a high incidence of dyspepsia in Eastern Uganda, and current management strategies are poor and inconsistent, and may contribute to antibiotic resistance. Further studies are needed to investigate the causes of dyspepsia to guide appropriate management.

BackgroundPerformance tests are important to characterize patient disabilities and functional changes. The Osteoarthritis Research Society International and others recommend the 30-second Chair Stand Test and Stair Climb Test, among others, as core tests that capture two distinct types of disability during activities of daily living. However, these two tests are limited by current protocols of testing in clinics. There is a need for an alternative that allows remote testing of functional capabilities during these tests in the osteoarthritis patient population. ObjectiveObjectives are to (1) develop an app for testing the functionality of an iPhone’s accelerometer and gravity sensor and (2) conduct a pilot study objectively evaluating the criterion validity and test-retest reliability of outcome variables obtained from these sensors during the 30-second Chair Stand Test and Stair Climb Test. MethodsAn iOS app was developed with data collection capabilities from the built-in iPhone accelerometer and gravity sensor tools and linked to Google Firebase. A total of 24 subjects performed the 30-second Chair Stand Test with an iPhone accelerometer collecting data and an external rater manually counting sit-to-stand repetitions. A total of 21 subjects performed the Stair Climb Test with an iPhone gravity sensor turned on and an external rater timing the duration of the test on a stopwatch. App data from Firebase were converted into graphical data and exported into MATLAB for data filtering. Multiple iterations of a data processing algorithm were used to increase robustness and accuracy. MATLAB-generated outcome variables were compared to the manually determined outcome variables of each test. Pearson’s correlation coefficients (PCCs), Bland-Altman plots, intraclass correlation coefficients (ICCs), standard errors of measurement, and repeatability coefficients were generated to evaluate criterion validity, agreement, and test-retest reliability of iPhone sensor data against gold-standard manual measurements. ResultsApp accelerometer data during the 30-second Chair Stand Test (PCC=.890) and gravity sensor data during the Stair Climb Test (PCC=.865) were highly correlated to gold-standard manual measurements. Greater than 95% of values on Bland-Altman plots comparing the manual data to the app data fell within the 95% limits of agreement. Strong intraclass correlation was found for trials of the 30-second Chair Stand Test (ICC=.968) and Stair Climb Test (ICC=.902). Standard errors of measurement for both tests were found to be within acceptable thresholds for MATLAB. Repeatability coefficients for the 30-second Chair Stand Test and Stair Climb Test were 0.629 and 1.20, respectively. ConclusionsApp-based performance testing of the 30-second Chair Stand Test and Stair Climb Test is valid and reliable, suggesting its applicability to future, larger-scale studies in the osteoarthritis patient population.

BACKGROUND Performance tests are important to characterize patient disabilities and functional changes. The Osteoarthritis Research Society International and others recommend the 30-second Chair Stand Test and Stair Climb Test, among others, as core tests that capture two distinct types of disability during activities of daily living. However, these two tests are limited by current protocols of testing in clinics. There is a need for an alternative that allows remote testing of functional capabilities during these tests in the osteoarthritis patient population. OBJECTIVE Objectives are to (1) develop an app for testing the functionality of an iPhone’s accelerometer and gravity sensor and (2) conduct a pilot study objectively evaluating the criterion validity and test-retest reliability of outcome variables obtained from these sensors during the 30-second Chair Stand Test and Stair Climb Test. METHODS An iOS app was developed with data collection capabilities from the built-in iPhone accelerometer and gravity sensor tools and linked to Google Firebase. A total of 24 subjects performed the 30-second Chair Stand Test with an iPhone accelerometer collecting data and an external rater manually counting sit-to-stand repetitions. A total of 21 subjects performed the Stair Climb Test with an iPhone gravity sensor turned on and an external rater timing the duration of the test on a stopwatch. App data from Firebase were converted into graphical data and exported into MATLAB for data filtering. Multiple iterations of a data processing algorithm were used to increase robustness and accuracy. MATLAB-generated outcome variables were compared to the manually determined outcome variables of each test. Pearson’s correlation coefficients (PCCs), Bland-Altman plots, intraclass correlation coefficients (ICCs), standard errors of measurement, and repeatability coefficients were generated to evaluate criterion validity, agreement, and test-retest reliability of iPhone sensor data against gold-standard manual measurements. RESULTS App accelerometer data during the 30-second Chair Stand Test (PCC=.890) and gravity sensor data during the Stair Climb Test (PCC=.865) were highly correlated to gold-standard manual measurements. Greater than 95% of values on Bland-Altman plots comparing the manual data to the app data fell within the 95% limits of agreement. Strong intraclass correlation was found for trials of the 30-second Chair Stand Test (ICC=.968) and Stair Climb Test (ICC=.902). Standard errors of measurement for both tests were found to be within acceptable thresholds for MATLAB. Repeatability coefficients for the 30-second Chair Stand Test and Stair Climb Test were 0.629 and 1.20, respectively. CONCLUSIONS App-based performance testing of the 30-second Chair Stand Test and Stair Climb Test is valid and reliable, suggesting its applicability to future, larger-scale studies in the osteoarthritis patient population.

The standard functional tool for gait assessment in multiple sclerosis (MS) clinical trials has been the 25-Foot Timed Walk Test, a measure of gait speed. Straight-line gait assessment may not reflect adequately upon balance and coordination. Walking tests with turns may add additional information towards understanding gait and balance status, and be more reflective of ambulation in the community. Understanding the impact of turn parameters on patient-reported outcomes of balance and walking would help MS clinicians better formulate treatment plans for persons with gait limitations. In this study, ninety-one persons with MS (Expanded Disability Status Score; EDSS, range: 0-6.5) were enrolled in an initial cross-sectional study. Twenty-four subjects (EDSS, range:1.0-6.0) completed a follow-up visit an average of 12 months later. Spatiotemporal gait analysis was collected at both visits using APDM Opal wireless body-worn sensors while performing the Timed-Up-and-Go (TUG) and 6-Minute Walk Test (6MWT). For both cross-sectional and longitudinal data, regression analyses determined the impact on the addition of turning parameters to stride velocity (SV), in the prediction of self-reported balance confidence (Activities-Specific Balance Confidence Scale (ABC)) and walking limitation (12-item Multiple Sclerosis Walking Scale (MSWS-12)). The addition of 6MWT peak turn velocity (PTV) to 6MWT SV increased the predictive power of the 6MWT for the ABC from 20% to 33%, and increased the predictive power from 28% to 41% for the MSWS-12. TUG PTV added to TUG SV also strengthened the relationship of the TUG for the ABC from 19% to 28%, and 27% to 36% for the MSWS-12. For those with 1 year follow-up, percent change in turn number of steps (TNS%Δ) during the 6MWT added to 6MWT SV%Δ improved the modeling of ABC%Δ from 24% to 33%. 6MWT PTV%Δ added to 6MWT SV%Δ increased the predictive power of MSWS-12%Δ from 8% to 27%. Conclusively, turn parameters improved modeling of self-perceived balance confidence and walking limitations when added to the commonly utilized measure of gait speed. Tests of longer durations with multiple turns, as opposed to shorter durations with a single turn, modeled longitudinal change more accurately. Turn speed and stability should be qualitatively assessed during the clinic visit, and use of multi-faceted tests such as the TUG or 6MWT may be required to fully understand gait deterioration in persons with MS.