Physical activity protects brain function in healthy individuals and those with Alzheimer's disease (AD). Evidence for beneficial effects of parental exercise on the health status of their progeny is sparse and limited to nondiseased individuals. Here, we questioned whether maternal running interferes with offspring's AD-like pathology and sought to decipher the underlying mechanisms in TgCRND8 mice. Maternal stimulation was provided by voluntary wheel running vs. standard housing during pregnancy. Following 5 mo of standard housing of transgenic and wild-type offspring, their brains were examined for AD-related pathology and/or plasticity changes. Running during pregnancy reduced β-amyloid (Aβ) plaque burden (-35%, P=0.017) and amyloidogenic APP processing in transgenic offspring and further improved the neurovascular function by orchestrating different Aβ transporters and increasing angiogenesis (+29%, P=0.022). This effect was accompanied by diminished inflammation, as indicated by reduced microgliosis (-20%, P=0.002) and down-regulation of other proinflammatory mediators, and resulted in less oxidative stress, as nitrotyrosine levels declined (-28%, P=0.029). Moreover, plasticity changes (in terms of up-regulation of reelin, synaptophysin, and ARC) were found not only in transgenic but also in wild-type offspring. We conclude that exercise during pregnancy provides long-lasting protection from neurodegeneration and improves brain plasticity in the otherwise unstimulated progeny.

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Background: The implementation of rescue efforts for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage remains largely empirical for a lack of supporting evidence, while the associated risk profile is also unclear. Objective: The present study evaluates the safety and efficacy of endovascular rescue treatment (ERT, continuous intraarterial nimodipine; IAN, transcutaneous balloon angioplasty, TBA). Methods: In this prospective observational study, we assessed periprocedural complications and side effects in context of ERT. We evaluated neurological status, multimodal neuromonitoring (p ti O 2 , lactate/pyruvate ratio, transcranial doppler), and cranial imaging (CTP, DSA). All parameters were included into multivariate analysis to determine predictors for the need of retreatment. Results: We included 33 consecutive patients with 54 ERT (IAN n = 35; TBA n = 13; TBA + IAN n = 6). We recorded no serious complications and initial improvement in all parameters (neurostatus 72.3% of patients; p ti O 2 15.0 ± 11.7 to 25.8 ± 15.5 mmHg, p < 0.0001; lactate/pyruvate ratio 46.3 ± 27.5 to 31.0 ± 9.7, p <0.05; transcranial doppler 139.0 ± 46.3 to 98.9 ± 29.6 cm/s, p < 0.05; CTP 81.6% of patients; DSA 93.1% of patients). Retreatment ( n = 16, 48.5%) was independently associated with preinterventional p ti O 2 < 5 mmHg ( p <0.01) and early (<72 h) discontinuation of IAN treatment ( p = 0.08). DCI related cerebral infarction was noted in n = 8 patients (24.2%). At 3 months after discharge, favorable outcome was noted for n = 11 (35.5%) patients. Conclusion: Provided a detailed decision tree, timely ERT can provide a relatively safe and effective treatment option in those highly-selected patients undergoing multimodality monitoring where conservative treatment options are exhausted. Continuous treatment in particular may be suitable to surpass sustained DCI and was associated with a low rate of DCI related infarction and comparably high percentage of good outcome.

OBJECTIVEThe current definition of delayed cerebral ischemia (DCI) is based on clinical characteristics precluding its use in patients with poor-grade subarachnoid hemorrhage (SAH). Additional concepts to evaluate the unconscious patient are required. Invasive neuromonitoring (INM) may allow timely detection of metabolic and oxygenation crises before irreversible damage has occurred.METHODSThe authors present a cohort analysis of all consecutive SAH patients referred to a single tertiary care center between 2010 and 2018. The cohort (n = 190) was split into two groups: one before (n = 96) and one after (n = 94) the introduction of INM in 2014. A total of 55 poor-grade SAH patients were prospectively monitored using parenchymal oxygen saturation measurement and cerebral microdialysis. The primary outcome was the Glasgow Outcome Scale–Extended (GOSE) score after 12 months.RESULTSWith neuromonitoring, the first DCI event was detected earlier (mean 2.2 days, p = 0.002). The overall rate of DCI-related infarctions decreased significantly (from 44.8% to 22.3%; p = 0.001) after the introduction of invasive monitoring. After 12 months, a higher rate of favorable outcome was observed in the post-INM group, compared to the pre-INM group (53.8% vs 39.8%), with a significant difference in the GOSE score distribution (OR 4.86, 95% CI −1.17 to −0.07, p = 0.028).CONCLUSIONSIn this cohort analysis of poor-grade SAH patients, the introduction of INM and the extension of the classic DCI definition toward a functional dimension resulted in an earlier detection and treatment of DCI events. This led to an overall decrease in DCI-related infarctions and an improvement in outcome.

Multimodal event neuromonitoring is able to quantify treatment efficacy in subarachnoid hemorrhage-related vasospasm. In our small cohort of highly selected cases, ERT was associated with improvement in cerebral oxygenation and metabolism with reasonable outcome. Event neuromonitoring may facilitate individual and timely optimization of treatment modality according to the individual clinical course.

Background Good-grade aneurysmal subarachnoid hemorrhage (Hunt and Hess 1–2) is generally associated with a favorable prognosis. Nonetheless, patients may still experience secondary deterioration due to delayed cerebral ischemia (DCI), contributing to poor outcome. In those patients, neurological assessment is challenging and invasive neuromonitoring (INM) may help guide DCI treatment. Methods An observational analysis of 135 good-grade SAH patients referred to a single tertiary care center between 2010 and 2018 was performed. In total, 54 good-grade SAH patients with secondary deterioration evading further neurological assessment, were prospectively enrolled for this analysis. The cohort was separated into two groups: before and after introduction of INM in 2014 (pre-INMSecD: n = 28; post-INMSecD: n = 26). INM included either parenchymal oxygen saturation measurement (ptiO2), cerebral microdialysis or both. Episodes of DCI (ptiO2 < 10 mmHg or lactate/pyruvate > 40) were treated via induced hypertension or in refractory cases by endovascular means. The primary outcome was defined as the extended Glasgow outcome scale after 12 months. In addition, we recorded the amount of imaging studies performed and the occurrence of silent and overall DCI-related infarction. Results Secondary deterioration, impeding neurological assessment, occurred in 54 (40.0%) of all good-grade SAH patients. In those patients, a comparable rate of favorable outcome at 12 months was observed before and after the introduction of INM (pre-INMSecD 14 (50.0%) vs. post-INMSecD 16, (61.6%); p = 0.253). A significant increase in good recovery (pre-INMSecD 6 (50.0%) vs. post-INMSecD 14, (61.6%); p = 0.014) was observed alongside a reduction in the incidence of silent infarctions (pre-INMSecD 8 (28.6%) vs. post-INMSecD 2 (7.7%); p = 0.048) and of overall DCI-related infarction (pre-INMSecD 12 (42.8%) vs. post-INMSecD 4 (23.1%); p = 0.027). The number of CT investigations performed during the DCI time frame decreased from 9.8 ± 5.2 scans in the pre-INMSecD group to 6.1 ± 4.0 (p = 0.003) in the post-INMSecD group. Conclusions A considerable number of patients with good-grade SAH experiences secondary deterioration rendering them neurologically not assessable. In our cohort, the introduction of INM to guide DCI treatment in patients with secondary deterioration increased the rate of good recovery after 12 months. Additionally, a significant reduction of CT scans and infarction load was recorded, which may have an underestimated impact on quality of life and more subtle neuropsychological deficits common after SAH.

BackgroundCarpal tunnel syndrome (CTS) causes a substantial burden of disease in society. While CTS can be resolved by surgical carpal tunnel release, it still remains unclear as to what degree outcomes depend on patients’ characteristics. This study assesses patient-centered outcomes after surgical carpal tunnel release in a large outpatient clinic in Germany.MethodsPatients with CTS were recruited prospectively between August 1st and December 31st, 2013. We assessed socio-demographic and psychological factors as well as nerve conduction velocities at baseline (before the surgery) and at three and six months after surgery. We analyzed the improvement of patient-centered outcomes (symptoms and function of the affected hand as well as measures of well-being and subjective quality of life) at the two follow-up time points and investigated if socio-demographic characteristics and CTS-related variables predict the success of the surgery with respect to nerve conduction velocities and patient-centered outcomes by means of analysis of covariance (ANCOVA). Factors influencing the duration of sick leave were investigated by means of Cox regression.ResultsThe study sample consisted of 71 CTS cases. Surgical carpal tunnel release generally improved nerve conduction velocity and patient-centered outcomes. Regarding the former, the improvement was proportional to the severity score at baseline. The presence of muscular atrophy in the thenar area at baseline displayed medium size effects for the patient-centered outcomes. Other socio-demographic characteristics and CTS-related variables did not have a strong predictive effect on the improvement of nerve conduction velocity and patient-centered outcomes.ConclusionsThere is a significant improvement of clinical and subjective outcomes after CTS surgery in the outpatient sector. The improvement is largely independent of socio-demographic and clinical characteristics of the patients.

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