Three Pillars of Recovery After Aneurysmal Subarachnoid Hemorrhage: A Narrative Review.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurologic disease with high mortality and disability. There have been global improvements in survival, which has contributed to the prevalence of patients living with long-term sequelae related to this disease. The focus of active research has traditionally centered on acute treatment to reduce mortality, but now there is a great need to study the course of short- and long-term recovery in these patients. In this narrative review, we aim to describe the core pillars in the preservation of cerebral function, prevention of complications, the recent literature studying neuroplasticity, and future directions for research to enhance recovery outcomes following aSAH.

Artery of Percheron Infarction: Clinical Presentation and Outcomes.

Background and Objectives: Occlusion of the artery of Percheron (AOP) produces bilateral thalamic infarction classically leading to deficits of arousal. This nonspecific presentation complicates the diagnosis of acute ischemic stroke. We sought to describe the spectrum of clinical presentation, diagnostic neuroimaging findings, and outcomes in AOP infarction (AOPi). Methods: We conducted a keyword search of our health system's neuroimaging database from 2014 to 2022 to identify patients with AOPi. We abstracted patient demographics, clinical presentation, neuroimaging findings, acute treatment, and modified Rankin Scale (mRS) scores (at baseline, 3 months, and 12 months). We used descriptive statistics to report our findings. Results: Our initial keyword search identified 192 potential AOPi cases. Fifteen cases of AOPi were confirmed and included in our study (8 female [53%], median age 65 years [interquartile range (IQR): 59.5-79.5], median presenting NIHSS 6 [IQR: 2-22]). Common clinical findings on presentation were systolic blood pressure (SBP) > 140: 12 patients (80%); decreased level of consciousness (LOC): 11 patients (73%); diplopia: 8 patients (57%); disorientation: 6 patients (42%); dysarthria: 4 patients (28%); and acute memory/cognitive disturbance: 3 patients (21%). Twelve cases (80%) presented to the emergency department (ED). Median time from symptom onset to ED arrival was 774.5 minutes (IQR: 202.25-3789.0), 4 cases (27%) arrived within 4.5 hours, and one patient (7%) received intravenous thrombolysis. The median time from ED arrival to stroke diagnosis was 519.0 minutes (IQR: 227.5-1307). Head CT was only diagnostic when obtained >570 minutes from time last known well; MRI was diagnostic at all time points. Rates of functional independence (mRS ≤2) at baseline, 3 months, and 12 months were 64%, 21%, and 18%, respectively. Discussion: The diagnosis of stroke was considerably delayed in patients with AOPi, and only one patient received IV thrombolysis. SBP >140, impaired consciousness, and diplopia were the most common findings at presentation. CT was often nondiagnostic, but MRI demonstrated bilateral thalamic infarct in all cases. AOPi caused considerable long-term morbidity. Clinicians should maintain a high degree of suspicion for AOP stroke and consider thrombolysis in appropriately selected patients.

Neuromodulation for Post-Stroke Motor Recovery: a Narrative Review of Invasive and Non­Invasive Tools.

PURPOSE OF REVIEW: Stroke remains a leading disabling condition, and many survivors have permanent disability despite acute stroke treatment and subsequent standard-of-care rehabilitation therapies. Adjunctive neuromodulation is an emerging frontier in the field of stroke recovery. In this narrative review, we aim to highlight and summarize various neuromodulation techniques currently being investigated to enhance recovery and reduce impairment in patients with stroke. RECENT FINDINGS: For motor recovery, repetitive transcranial magnetic simulation (rTMS) and direct current stimulation (tDCS) have shown promising results in many smaller-scale trials. Still, their efficacy has yet to be proven in large-scale pivotal trials. A promising large-scale study investigating higher dose tDCS combined with constraint movement therapy to enhance motor recovery is currently underway. MRI-guided tDCS studies in subacute and chronic post-stroke aphasia showed promising benefits for picture-naming recovery. rTMS, particularly inhibitory stimulation over the contralesional homolog, could represent a pathway forward in post-stroke motor recovery in the setting of a well-designed and adequately powered clinical trial. Recently evidenced-based guideline actually supported Level A (definite efficacy) for the use of low-frequency rTMS of the primary motor cortex for hand motor recovery in the post-acute stage of stroke based on the meta-analysis result. Adjunctive vagal nerve stimulation has recently received FDA approval to enhance upper limb motor recovery in chronic ischemic stroke with moderate impairment, and progress has been made to implement it in real-world practice. Despite a few small and large-scale studies in epidural stimulation (EDS), further research on the utilization of EDS in post-stroke recovery is needed. Deep brain stimulation or stent-based neuromodulation has yet to be further tested regarding safety and efficacy. Adjunctive neuromodulation to rehabilitation therapy is a promising avenue for promoting post-stroke recovery and decreasing the overall burden of disability. The pipeline for neuromodulation technology remains strong as they span from the preclinical stage to the post-market stage. We are optimistic to see that more neuromodulation tools will be available to stroke survivors in the not-to-distant future.

Active contact proximity to the cerebellothalamic tract predicts initial therapeutic current requirement with DBS for ET: an application of 7T MRI.

Objective: To characterize how the proximity of deep brain stimulation (DBS) active contact locations relative to the cerebellothalamic tract (CTT) affect clinical outcomes in patients with essential tremor (ET). Background: DBS is an effective treatment for refractory ET. However, the role of the CTT in mediating the effect of DBS for ET is not well characterized. 7-Tesla (T) MRI-derived tractography provides a means to measure the distance between the active contact and the CTT more precisely. Methods: A retrospective review was conducted of 12 brain hemispheres in 7 patients at a single center who underwent 7T MRI prior to ventral intermediate nucleus (VIM) DBS lead placement for ET following failed medical management. 7T-derived diffusion tractography imaging was used to identify the CTT and was merged with the post-operative CT to calculate the Euclidean distance from the active contact to the CTT. We collected optimized stimulation parameters at initial programing, 1- and 2-year follow up, as well as a baseline and postoperative Fahn-Tolosa-Marin (FTM) scores. Results: The therapeutic DBS current mean (SD) across implants was 1.8 mA (1.8) at initial programming, 2.5 mA (0.6) at 1 year, and 2.9 mA (1.1) at 2-year follow up. Proximity of the clinically-optimized active contact to the CTT was 3.1 mm (1.2), which correlated with lower current requirements at the time of initial programming (R2 = 0.458, p = 0.009), but not at the 1- and 2-year follow up visits. Subjects achieved mean (SD) improvement in tremor control of 77.9% (14.5) at mean follow-up time of 22.2 (18.9) months. Active contact distance to the CTT did not predict post-operative tremor control at the time of the longer term clinical follow up (R2 = -0.073, p = 0.58). Conclusion: Active DBS contact proximity to the CTT was associated with lower therapeutic current requirement following DBS surgery for ET, but therapeutic current was increased over time. Distance to CTT did not predict the need for increased current over time, or longer term post-operative tremor control in this cohort. Further study is needed to characterize the role of the CTT in long-term DBS outcomes.

Propranolol or Beta-Blockers for Cerebral Cavernous Malformation: a Systematic Review and Meta-analysis of Literature in Both Preclinical and Clinical Studies.

Cerebral cavernous malformation (CCM), either sporadic or familial, is a devastating vascular malformation affecting the central nervous system that can present with intracerebral hemorrhage, seizure, and new focal neurologic deficits resulting in substantial morbidity and mortality. To date, there is no effective evidence-based preventive regimen. There have been several preclinical and clinical studies investigating the potential mechanisms and benefits of beta-blockers, especially on propranolol. We aimed to conduct a systematic review on the published literature investigating the use of beta-blockers in the treatment of CCM, including both preclinical and clinical studies between 2008 and 2023 using public databases. A total of 2 preclinical studies and 6 clinical studies met the inclusion/exclusion criteria and were included. Data was extracted and synthesized from 5 clinical studies for meta-analysis. The meta-analysis failed to demonstrate a statistically significant protective effect of beta-blockers in preventing intracerebral hemorrhage or developing focal neurologic deficits in subjects with CCM (overall effect = 0.78 (0.20, 3.11), p = 0.73). Overall, there was a paucity of high quality clinical trials, partially due to limited cases of CCM. Addressing this gap may require collaborative efforts at a national or international level. In this review, we summarized all barriers and opportunities on this topic. Additionally, we proposed establishing an evidence-based approach on the use of beta-blockers in preventing recurrent hemorrhage and focal neurological deficits in patients with CCM.

Frequency settings of subthalamic nucleus DBS for Parkinson's disease: A systematic review and network meta-analysis.

INTRODUCTION: Deep Brain Stimulation (DBS) is an effective treatment for the motor symptoms of Parkinson's Disease. The targeted physiological structure for lead location is commonly the subthalamic nucleus (STN). The efficacy of DBS for improving motor symptoms is assessed via the Unified Parkinson's Disease Rating III Scale (UPDRS-III). In this study, we sought to compare the efficacy of frequency settings utilized for STN-DBS. METHODS: Following PRISMA Guidelines, a search on PUBMED and MEDLINE was performed to include full-length randomized controlled trials evaluating STN-DBS. The frequency stimulation parameters and Unified Parkinson's Disease Rating Scale (UPDRS-III) outcomes were extracted in the search. High-frequency stimulation (HFS) was defined as ≥100 Hz and low-frequency stimulation (LFS) was defined as <100 Hz. A frequentist network meta-analysis was performed with odds ratios (OR) and pooling performed using the Mantel-Haenszel method. Statistics are presented as OR [95% CI]. RESULTS: 15 studies consisting of 298 patients were included for analysis. Bilateral HFS -0.68 [-0.89; -0.46] was associated with better UPDRS-III scores compared to bilateral LFS. On the other hand, bilateral LFS with medications (MEDS) was favored over HFS with MEDS (-0.28 [-0.63; 0.07]). Bilateral LFS and MEDS, HFS and MEDS, stimulation (STIM) OFF MEDS ON, HFS, LFS, STIM OFF MEDS OFF UPDRS outcomes were ranked from best to worst outcomes. DISCUSSION: The outcomes of this study suggest that bilateral HFS has better utility for those with no response to medication, while LFS has additive benefits to medication by improving unique symptoms via different neurophysiological mechanisms.

WITHDRAWN: Laterality and frequency settings of subthalamic nucleus DBS for Parkinson's disease: A systematic review and network meta-analysis.

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Lateral cerebellothalamic tract activation underlies DBS therapy for Essential Tremor.

BACKGROUND: While deep brain stimulation (DBS) therapy can be effective at suppressing tremor in individuals with medication-refractory Essential Tremor, patient outcome variability remains a significant challenge across centers. Proximity of active electrodes to the cerebellothalamic tract (CTT) is likely important in suppressing tremor, but how tremor control and side effects relate to targeting parcellations within the CTT and other pathways in and around the ventral intermediate (VIM) nucleus of thalamus remain unclear. METHODS: Using ultra-high field (7T) MRI, we developed high-dimensional, subject-specific pathway activation models for 23 directional DBS leads. Modeled pathway activations were compared with post-hoc analysis of clinician-optimized DBS settings, paresthesia thresholds, and dysarthria thresholds. Mixed-effect models were utilized to determine how the six parcellated regions of the CTT and how six other pathways in and around the VIM contributed to tremor suppression and induction of side effects. RESULTS: The lateral portion of the CTT had the highest activation at clinical settings (p < 0.05) and a significant effect on tremor suppression (p < 0.001). Activation of the medial lemniscus and posterior-medial CTT was significantly associated with severity of paresthesias (p < 0.001). Activation of the anterior-medial CTT had a significant association with dysarthria (p < 0.05). CONCLUSIONS: This study provides a detailed understanding of the fiber pathways responsible for therapy and side effects of DBS for Essential Tremor, and suggests a model-based programming approach will enable more selective activation of lateral fibers within the CTT.

Castleman disease: A single-center case series.

BACKGROUND: Castleman disease (CD) is a rare lymphocytic disorder. Unicentric CD (UCD) has an excellent long-term prognosis after surgical excision; however, multicentric CD (MCD) has a severe clinical course with poor outcomes. STUDY DESIGN: We analyzed the clinical presentation of 28 patients treated at a single institution from 1995 to 2017. Demographics, clinical variables, anatomical site, centricity, histopathology, immunochemistry, and surgical approach were reviewed. We evaluated the 5-year recurrence and survival for patients with UCD and MCD. RESULTS: Of the 28 patients, 57 % (n = 16) were female, with a mean age of 41.6 ± 15.6 years. CD was asymptomatic in 57 % (n = 16) of patients, 21 % (n = 6) presented with local symptoms such as pain, and 21 % (n = 6) of patients also had systemic symptoms, including weight loss and fever. CD was unicentric in 64 % (n = 18) and multicentric in 36 % (n = 10). The hyaline vascular variant was noted in 57 % (n = 16) of the tumors, plasmacytoid variant in 36 % (n = 10), and mixed variants in 7% (n = 2) of tumors. Anatomical distributions included: head and neck (20 %), thorax and axilla (24 %), retroperitoneal (13 %), abdominopelvic (30 %) regions, and other (13 %). Complete surgical resection was performed in 95 % of patients with UCD. Surgical biopsy and medical therapy were provided to all patients with MCD. The recurrence rate for UCD and MCD was 6 % (n = 1) and 14 % (n = 1), respectively. The five-year disease-free survival rate for UCD was 95 % (n = 19) and MCD was 33 % (n = 2). We found 100 % survival in patients with UCD and histology demonstrating the HV variant. CONCLUSION: CD is rare and often misdiagnosed due to the absence of specific clinical symptoms. Surgeons should include CD in their differential diagnoses when evaluating patients with lymph node hyperplasia. Surgery can be curative in nearly all patients with UCD. Patients with MCD require a combination of surgical therapy, chemotherapy, and immunotherapy; however, cytoreductive surgery benefits for patients with MCD have not been established.

Health Care Provider Adherence to Surgical Guidelines for Risk-Reducing Salpingo-Oophorectomy.

OBJECTIVE: To evaluate health care provider adherence to the surgical protocol endorsed by the National Comprehensive Cancer Network and the American College of Obstetricians and Gynecologists at the time of risk-reducing salpingo-oophorectomy and compare adherence between gynecologic oncologists and obstetrician-gynecologists (ob-gyns). METHODS: In this multicenter retrospective cohort study, women were included if they had a pathogenic BRCA mutation and underwent risk-reducing salpingo-oophorectomy between 2011 and 2017. Adherence was defined as completing all of the following: collection of washings, complete resection of the fallopian tube, and performing the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) pathologic protocol. RESULTS: Of 290 patients who met inclusion criteria, 160 patients were treated by 18 gynecologic oncologists and 130 patients by 75 ob-gyns. Surgery was performed at 10 different hospitals throughout a single metropolitan area. Demographic and clinical characteristics were similar between groups. Overall, 199 cases (69%) were adherent to the surgical protocol. Gynecologic oncologists were more than twice as likely to fully adhere to the full surgical protocol as ob-gyns (91% vs 41%, P<.01). Specifically, gynecologic oncologists were more likely to resect the entire tube (99% vs 95%, P=.03), to have followed the SEE-FIM protocol (98% vs 82%, P<.01), and collect washings (94% vs 49%, P<.01). Complication rates did not differ between groups. Occult neoplasia was diagnosed in 11 patients (3.8%). The incidence of occult neoplasia was 6.3% in gynecologic oncology patients and 0.8% in obstetrics and gynecology patients (P=.03). CONCLUSION: Despite clear surgical guidelines, only two thirds of all health care providers were fully adherent to guidelines. Gynecologic oncologists were more likely to follow surgical guidelines compared with general ob-gyns and more likely to diagnose occult neoplasia despite similar patient populations. Rates of risk-reducing surgery will likely continue to increase as genetic testing becomes more widespread, highlighting the importance of health care provider education for this procedure. Centralized care or referral to subspecialists for risk-reducing salpingo-oophorectomy may be warranted.