Differential effects of speech and Language therapy and rTMS in chronic versus subacute post-stroke aphasia: Results of the NORTHSTAR-CA trial

Background & objective: Contralesional 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis combined with speech-language therapy (SLT) has shown positive results on the recovery of naming in subacute (5–45 days) post-stroke aphasia. NORTHSTAR-CA is an extension of the previously reported NORTHSTAR trial to chronic aphasia (\u3e6 months post-stroke) designed to compare the effectiveness of the same rTMS protocol in both phases. Methods: Sixty-seven patients with left middle cerebral artery infarcts (28 chronic, 39 subacute) were recruited (01-2014 to 07-2019) and randomized to receive rTMS (N = 34) or sham stimulation (N = 33) with SLT for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment. Chronic and subacute results were compared. Results: Adverse events were rare, mild, and did not differ between groups. Language outcomes improved significantly in all groups irrespective of treatment and recovery phase. At 30-day follow-up, there was a significant interaction of stimulation and recovery phase on naming recovery (P \u3c.001). Naming recovery with rTMS was larger in subacute (Mdn = 1.91/IQR =.77) than chronic patients (Mdn =.15/IQR = 1.68/P =.015). There was no significant rTMS effect in the chronic aphasia group. Conclusions: The addition of rTMS to SLT led to significant supplemental gains in naming recovery in the subacute phase only. While this needs confirmation in larger studies, our results clarify neuromodulatory vs training-induced effects and indicate a possible window of opportunity for contralesional inhibitory stimulation interventions in post-stroke aphasia. NORTHSTAR trial registration: https://clinicaltrials.gov/ct2/show/NCT02020421

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient– control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019

Understanding factors that limit the productivity of suspension-based perfusion cultures operated at high medium renewal rates

NRC publication: Ye

Understanding factors that limit the productivity of suspension-based perfusion cultures operated at high medium renewal rates

NRC publication: Ye

Isolated angiitis of the CNS frequently recurs in children

info:eu-repo/semantics/nonPublishe

Computed tomography derived liver volume: a prognostic factor in decompensated alcoholic cirrhosis?

Introduction: Decompensated alcoholic liver disease (ALD) causes high morbidity and mortality. Factors associated with a poor clinical evolution, as well as the impact of liver atrophy linked with cirrhosis are poorly determined. The goal of this study is to explore the link between the liver volumetry calculated by computed tomography (CT) and the evolution of liver insufficiency in patients admitted for decompensated ALD. Materials and methods: Non-abstinent patients with acute decompensation of ALD (increase in serum bilirubin and deterioration of liver function) from a prospective study were included. This trial did not evidence any benefice of cellular therapy during the 3 months of follow up (Spahr L et al. Autologous bone marrow stem cell transplantation versus standard of care in patients with decompensated alcoholic liver disease: interim analysis of a RCT. Hepatology 2011;54:A62). Liver volumes evaluated by CT performed rapidly after patient admission were compared to further evolution of hepatic insufficiency, irrespective of treatment allocation. We defined patients with a ≥ 3 points decrease in MELD compared to baseline value as “improvers”, and those with less than 3 points decrease in MELD as “non-improvers”. Results: Fifty-eight patients were included. At admission, mean MELD score was 20.6 points. All patients had cirrhosis. Biopsy proven alcoholic steatohepatitis was diagnosed in 81% of cases. Patients with severe steatohepatitis (Maddrey score ≥ 32) were treated by steroids (66 %). 34 patients (59%) with a good evolution at 3 months (decrease in MELD score of 3 points or more) were classified as improvers meanwhile 24 patients (41%) were classified as non-improvers. Patients’ characteristics at admission depending on the 3 month evolution are reported in this table. Parameter Improvers n=34 Non-improvers n=24 P Age (years) 54 [35-63] 55 [44-67] 0.11 Hepatovenous pressure gradient (mmHg) 19.2 ± 2.7 19.2 ± 4.1 0.25 MELD score 20.7 ± 5.9 20.6 ± 3.3 0.96 Albumin (g/l) 22.2 ± 4.4 22.4 ± 6.7 0.41 Steroid treatment (%) 67.6 62.5 0.68 Cellular therapy (%) 52.9 41.7 0.39 Liver volume (cm3) 2389 ± 998 1646 ± 489 0.0005 Ratio liver volume-body weight (%) 3.2 ± 1.5 2.2 ± 1.0 0.002 Conclusion: This study highlights the link between the severity of hepatic atrophy associated with cirrhosis and the prognosis in case of liver decompensation. Indeed, in patients with decompensated ALD, a low liver volume evaluated by CT is associated with a bad evolution of hepatic function evaluated by MELD score

Primary angiitis of the central nervous system: neurologic deterioration despite treatment.

Primary angiitis of the central nervous system (PACNS) is an idiopathic vasculitis confined to the central nervous system. In children with PACNS, small-vessel (SV) involvement is characterized clinically by progressive neurologic symptoms, multifocal lesions on brain imaging, occasional pseudo-tumor presentation, and normal angiogram results in most patients. Small case series of patients with SV PACNS with short follow-up usually reveal favorable outcomes in children treated with immunosuppressive therapy. We report here the cases of 3 children with biopsy-confirmed SV PACNS and long-term follow-up who developed different patterns of neurologic deterioration despite immunosuppressive therapy. One patient had transient ischemic attacks shortly after initiation of corticosteroid treatment. Early ischemic events probably result from residual thrombogenicity or residual inflammation of recently affected vessels, which supports the use of antiplatelet agents and suggests potential benefits of stronger immunosuppressive therapy. In contrast, the other 2 patients had later neurologic deterioration after corticosteroid withdrawal, which suggests failure of initial immunosuppressant treatment and the need for stronger agents, longer treatment duration, or both. All patients responded to long-term treatment with corticosteroids combined with cytotoxic agents. This particular combination is probably indicated in many cases of SV PACNS, including those with neurologic deterioration that occurs during maintenance corticotherapy or after corticosteroid withdrawal. In 1 case, SV PACNS recurred several years after discontinuation of combination therapy. Long-term relapses may reflect intrinsic predispositions to SV PACNS rather than treatment failure. These cases highlight different chronological patterns of neurologic deterioration despite immunosuppressive therapy, which supports the relevance of monitoring clinical, laboratory, and radiologic responses to treatment and of long-term follow-up of patients with SV PACNS.Case ReportsJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe