Surgical and endovascular cerebral revascularization for cerebral vasculitis with inflammatory vessel stenosis: a case series.

Autoimmune vasculitides affect the cerebral vasculature significantly in a considerable number of cases. When immunosuppressive treatments fail to prevent stenosis in cerebral vessels, treatment options for affected patients become limited. In this case series, we present four cases of pharmacoresistant vasculitis with recurrent transient ischemic attacks (TIAs) or stroke successfully treated with either extracranial-intracranial (EC-IC) bypass surgery or endovascular stenting. Both rescue treatments were effective and safe in the selected cases. Our experience suggests that cases of pharmacoresistant cerebral vasculitis with recurrent stroke may benefit from rescue revascularization in combination with maximum medical management.

Novel Insights into Pathophysiology of Delayed Cerebral Ischemia: Effects of Current Rescue Therapy on Microvascular Perfusion Heterogeneity.

General microvascular perfusion and its heterogeneity are pathophysiological features of delayed cerebral ischemia (DCI) that are gaining increasing attention. Recently, CT perfusion (CTP) imaging has made it possible to evaluate them radiologically using mean transit time (MTT) and its heterogeneity (measured by cvMTT). This study evaluates the effect of multimodal rescue therapy (intra-arterial nimodipine administration and elevation of blood pressure) on MTT and cvMTT during DCI in aneurysmal subarachnoid haemorrhage (aSAH) patients. A total of seventy-nine aSAH patients who underwent multimodal rescue therapy between May 2012 and December 2019 were retrospectively included in this study. CTP-based perfusion impairment (MTT and cvMTT) on the day of DCI diagnosis was compared with follow-up CTP after initiation of combined multimodal therapy. The mean MTT was significantly reduced in the follow-up CTP compared to the first CTP (3.7 ± 0.7 s vs. 3.3 ± 0.6 s; p < 0.0001). However, no significant reduction of cvMTT was observed (0.16 ± 0.06 vs. 0.15 ± 0.06; p = 0.44). Mean arterial pressure was significantly increased between follow-up and first CTP (98 ± 17 mmHg vs. 104 ± 15 mmHg; p < 0.0001). The combined multimodal rescue therapy was effective in addressing the general microvascular perfusion impairment but did not affect the mechanisms underlying microvascular perfusion heterogeneity. This highlights the need for research into new therapeutic approaches that also target these pathophysiological mechanisms of DCI.

Effect of Previous Disease-Modifying Therapy on Treatment Effectiveness for Patients Treated With Ocrelizumab.

BACKGROUND AND OBJECTIVES: B cell-depleting antibodies were proven as effective strategy for the treatment of relapsing multiple sclerosis (RMS). The monoclonal antibody ocrelizumab was approved in 2017 in the United States and in 2018 in the European Union, but despite proven efficacy in randomized, controlled clinical trials, its effectiveness in the real-world setting remains to be fully elucidated. In particular, most study patients were treatment naive or switched from injectable therapies, whereas oral substances or monoclonal antibodies made up >1% of previous treatments. METHODS: We evaluated ocrelizumab-treated patients with RMS enrolled in the prospective cohorts at the University Hospitals Duesseldorf and Essen, Germany. Epidemiologic data at baseline were compared, and Cox proportional hazard models were applied to evaluate outcomes. RESULTS: Two hundred eighty patients were included (median age: 37 years, 35% male patients). Compared with using ocrelizumab as a first-line treatment, its use as a third-line therapy increased hazard ratios (HRs) for relapse and disability progression, whereas differences between first- vs second-line and second- vs third-line remained smaller. We stratified patients according to their last previous disease-modifying treatment and here identified fingolimod (FTY) (45 patients, median age 40 years, 33% male patients) as a relevant risk factor for ongoing relapse activity despite 2nd-line (HR: 3.417 [1.007-11.600]) or 3rd-line (HR: 5.903 [2.489-13.999]) ocrelizumab treatment, disability worsening (2nd line: HR: 3.571 [1.013-12.589]; 3rd line: HR: 4.502 [1.728-11.729]), and occurrence of new/enlarging MRI lesions (2nd line: HR: 1.939 [0.604-6.228]; 3rd line: HR: 4.627 [1.982-10.802]). Effects were persistent throughout the whole follow-up. Neither peripheral B-cell repopulation nor immunoglobulin G levels were associated with rekindling disease activity. DISCUSSION: Our prospectively collected observational data suggest suboptimal effectiveness of ocrelizumab in patients switching from FTY compared with those switching from other substances or having been treatment naive. These findings support previous studies indicating abated effectiveness of immune cell-depleting therapies following FTY treatment in patients with RMS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RMS, previous treatment with FTY compared with previous treatment with other immunomodulating therapies decreases the effectiveness of ocrelizumab.

Meta-review on Perforation Model of Subarachnoid Hemorrhage in Mice: Filament Material as a Possible Moderator of Mortality.

Robust preclinical models are inevitable for researchers to unravel pathomechanisms of subarachnoidal hemorrhage (SAH). For the mouse perforation model of SAH, the goal of this meta-review was the determination of variances in mortality, SAH severity grade, and vasospasm, and their experimental moderators, as many researchers are facing with incomparable results. We searched on the databases PubMed, Embase, and Web of Science for articles describing in vivo experiments using the SAH perforation mouse model and measuring mortality, SAH grade, and/or vasospasm. After screening, 42 articles (total of 1964 mice) were included into systematic review and meta-analysis. Certain model characteristics were insufficiently reported, e.g., perforation location (not reported in six articles), filament (material (n = 15) and tip texture (n = 25)), mouse age (n = 14), and weight (n = 10). Used injective anesthetics and location of perforation showed large variation. In a random-effects meta-analysis, the overall animal mortality following SAH was 21.3% [95% CI: 17.5%, 25.7%] and increased with longer observational periods. Filament material significantly correlated with animal mortality (p = 0.024) after exclusion of hyperacute studies (time after SAH induction < 24 h). Reported mean SAH grade was 10.7 [9.6, 11.7] on the scale of Sugawara (J Neurosci Methods 167:327-34, 2008). Furthermore, mean diameter of large cerebral arteries after SAH was reduced by 27.6% compared to sham-operated non-SAH mice. Uniforming standards of experimental procedures and their reporting are indispensable to increase overall comparability.

Synthetic vascular grafts as a new treatment option for space-occupying tumor bed cysts.

INTRODUCTION: Several authors have reported the formation of slit valves as the underlying pathomechanism of space-occupying tumor bed cysts. Iatrogenic slit valves following the resection of high-grade gliomas have been linked to certain risk factors such as intraoperative opening of the ventricles and attempts to seal these. The best therapeutic management of such cystic lesions remains elusive. Several treatment options such as cyst fenestration or cystoperitoneal shunting have been employed but remain associated with high rates of recurrence. With the given complications of the above-described treatment options, the objective was to devise a new therapy option that is safe and effective and treats the slit valve itself rather than its symptoms. METHODS: Between the years of 2010 and 2020, we successfully treated four patients with high-pressure tumor bed cysts following glioma resection by implantation of synthetic ringed vascular grafts into the slit valve. RESULTS: Postoperatively, the tumor bed cysts were regressive in all patients. Moreover, none of the treatment patients developed any complications associated with the implanted vascular grafts. Revision-free survival was 10, 12, 53, and 126 months, respectively. CONCLUSION: The use of synthetic vascular grafts as a means of stenting slit valves is a safe and effective novel treatment option for high-pressure tumor bed cysts.

Robot-Assisted Stereotactic Shunting as a Novel Treatment for Pontine Glioependymal Cysts.

In this case report, the authors describe the first case of a glioependymal cyst of the brainstem managed by robot-assisted, stereotactic, cysto-ventricular shunting. Glioependymal cysts are rare congenital cystic lesions that are thought to form by displacement of ependymal cells during the embryonal period. Glioependymal cysts have been reported in a variety of different locations within the central nervous system. However, glioependymal cysts of the brainstem have only been described once before. Here, we report the case of a 53-year-old man who was referred to our department due to hemiparesis, hemihypesthesia, and hemidysesthesia, as well as facial and abducens nerve palsy. A large pontine glioependymal cyst was confirmed via magnetic resonance imaging (MRI) scans. The cyst was subsequently decompressed by connecting the cyst with the fourth ventricle via robot-assisted stereotactic shunt placement. In the postoperative course, the patient made a quick recovery and did not report any permanent neurologic deficits.

10 kHz cervical SCS for chronic neck and upper limb pain: 12 months' results.

OBJECTIVE: Spinal Cord Stimulation (SCS) overlaps painful areas with paresthesia to alleviate pain. Ten kHz High-Frequency SCS (HF10 cSCS) constitutes a treatment option that can provide pain relief without inducing paresthesia. In this retrospective, open-label study, we evaluated the efficacy of HF10 cSCS in chronic neck and/or upper limb pain. METHODS: Between May 2015 and August 2017, 24 consecutive patients with neck and/or upper limb pain were treated with HF10 cSCS. The patients' mean age was 61.4 years (range: 40.1-82.6 years). The mean neck and upper limb pain at baseline was 8.8 (range: 7.0-10) and 7.5 (range: 6.0-9.0) according to the visual analog scale (VAS). Functionality was evaluated using the Oswestry Disability Index (ODI). To assess health-related psychological impairment, we used the Global Assessment of Functioning questionnaire. RESULTS: Twenty-three patients responded to treatment. Pain intensity reduced significantly to a mean score of VAS 2.5 (range: 2.0-4.0) for neck and 2.0 (range: 1.0-3.0) for upper limb pain after 6 months. At 12 months, VAS scores for neck and upper limb pain reduced to 2.2 (range: 1.0-3.0) and 1.7 (range: 1.0-3.0), respectively. Mean ODI scores decreased from 31 (range: 21-42) at baseline to 19.9 (range: 8-26) after 12 months. In three patients, infection of the IPG pocket occurred r and 8.7 months after surgery. One patient has had lead migration resulting in a surgical revision. INTERPRETATION: HF10 cSCS therapy has proven to be effective in reducing neck and upper limb pain significantly and increasing functional capacity. These results warrant further studies with larger patient series and longer follow-ups.

A Retrospective Case Series of High-Frequency Spinal Cord Stimulation (HF10-SCS) in Neurogenic Bladder Incontinence.

BACKGROUND: Current treatment options for bladder disorders of neurogenic etiology often leave unsatisfactory results. Therefore, new and effective treatments must be investigated. High-frequency spinal cord stimulation (HF-SCS) at 10 kHz has proven to be effective in the treatment of refractory chronic back and leg pain. OBJECTIVE: To evaluate the efficacy of HF-SCS at 10 kHz in alleviating lower urinary tract dysfunction and bladder incontinence in 5 patients with underlying neurological disease or spinal cord injury, through retrospective study. METHODS: Urodynamic parameters such as voiding frequency, residual volume, episodes of incontinence, and the patients' subjective impression impairment of life were assessed and compared pre- and postoperatively. Reduction in pain intensity was assessed as change on the Numeric Rating Scale (NRS). RESULTS: All 5 patients had significantly positive outcomes. Episodes of leakage per day improved by 83% on average. Quality of life questionnaires and subjective bother scale revealed an improvement of 36% and 57%, respectively. Individual symptoms among the patient group such as residual volume also responded to the treatment as well. Mean pain NRS of 8.6 cm was reduced to 3.9 cm (55%) at 6 mo follow-up. CONCLUSION: HF-SCS at 10 kHz significantly alleviated symptoms of neurogenic bladder incontinence in patients suffering from neurological disease or spinal cord injury. However, larger and prospective, randomized studies are necessary to make a clear statement regarding the efficacy of this therapy in lower urinary tract dysfunction and bladder incontinence.