Sagi Harnof

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by delayed cerebral vasospasm (DCV), a major cause of morbidity and mortality. Balloon angioplasty is standard for refractory cases but carries a high risk in distal vessels. This study reports preliminary single-center experience with the Comaneci device for DCV, emphasizing distal segments beyond the circle of Willis, where evidence remains limited. Methods: We retrospectively analyzed patients with aSAH and symptomatic DCV refractory to medical therapy treated with Comaneci-assisted angioplasty (CAA). Demographic, procedural, clinical, and angiographic data were collected from electronic records. Angiographic response was graded using a vasospasm severity scale. Results: CAA was performed in 94 vessels across 14 patients (median age 63 years; 85.7% female). Severe-to-critical vasospasm was present in 88.6%. Most interventions involved the anterior circulation (79.1%), with distal segments (M2 and A2–A4) comprising 54.1%. The M2 segment was most frequently treated (36.4%). Patients underwent a median of three interventions (range 2–6). Angioplasty resulted in significant resolution of vasospasm in 92.7% of vessels, with retreatment required in 8.3%. At 6 months, a favorable outcome (mRS 0–2) was observed in 51.5% of patients, while 90-day mortality was 21.4%. No vessel perforations or long-term complications occurred; one transient occlusion was successfully managed with aspiration. Conclusions: CAA appears feasible and safe for DCV, particularly in the distal vasculature where balloon angioplasty is rarely used. These findings suggest the device may provide a valuable alternative to conventional therapy. Larger prospective studies are required to confirm safety, efficacy, and long-term clinical impact.

Traumatic brain injury (TBI) is known to have a substantial, though highly variable, impact on cognitive abilities. Due to the wide range of cognitive abilities among healthy individuals, an objective assessment of TBI-related cognitive loss requires an accurate measurement of premorbid cognitive performance. To address this problem, we recruited 50 adults who sustained a TBI and had performed a cognitive baseline assessment in adolescence as part of the aptitude tests mandated by the Israeli Defense Forces. This group was matched with non-injured controls (N=35). Pre and Post-injury cognitive assessments consisted of three domains, namely verbal abstraction, mathematical reasoning and non-verbal abstract reasoning (from the Wechsler adult intelligence scale-WAIS-III). The difference between post and pre-injury scores was calculated as a measure of domain-specific cognitive decline. Voxel-based regression was used to correlate cognitive decline with modulated gray matter probability maps controlling for age, Glasgow Coma Scale, and total intracranial volume. Using objectively assessed cognitive scores, we found that abstract reasoning declined in both moderate-severe and mild TBI patients, whereas verbal abstraction declined only in the moderate-severe group. Mathematical reasoning was not affected by TBI. In the TBI patients, non-verbal abstract reasoning post-pre injury change scores were negatively correlated with the volume of the insula. We conclude that access to premorbid neuropsychological data may have facilitated the discovery of the effects of mild TBI on abstract reasoning as well as a significant correlation between TBI-related decline in this cognitive domain and the volume of the bilateral insula, both of which had not been appreciated in the past.

Minimal traumatic brain injury (mTBI) is partially defined by the existence of retrograde amnesia and is associated with microscopic bleeds containing activated coagulation factors. In a previous study, we have found that mTBI immediately releases thrombin like activity in the brain, which induces amnesia by activating Protease Activated Receptor 1 (PAR-1) and blocking Long Term Potentiation (LTP). In the present study we assessed the effects of mTBI on thrombin and PAR-1 levels in the brain using the same model. Following the immediate elevation, thrombin activity returned to baseline 1 hour following the trauma and increased again 72 hours later (42% relative to control, p<0.005). These changes were associated with a significant increase in PAR-1 levels 24 hours (17%, p<0.05) and 72 hours (20%, p<0.05) following the trauma. Interestingly, the late elevation in thrombin-like activity was also associated with elevation of the major CNS thrombin inhibitor protease nexin-1, (PN-1) 72 hours following mTBI (10%, p<0.005). When thrombin was injected into the brain ventricles, an increased sensitivity to seizure like activity was detected at 72 hours post mTBI. The results are compatible with astrocyte activation following mTBI resulting in increased thrombin secretion, PAR-1 expression and seizure sensitivity.

BACKGROUND AND PURPOSE: The interpretation of the radiologic response of bevacizumab-treated patients with recurrent high-grade gliomas represents a unique challenge. Delayed-contrast MR imaging was recently introduced for calculating treatment-response-assessment maps in patients with brain tumors, providing clear separation between active tumor and treatment effects. We studied the application of standard and delayed-contrast MR imaging for assessing and predicting the response to bevacizumab. MATERIALS AND METHODS: Twenty-four patients with recurrent high-grade gliomas were scanned before and during bevacizumab treatment by standard and delayed-contrast MR imaging. The mean change in lesion volumes of responders (overall survival, ≥1 year) and nonresponders (overall survival, RESULTS: Response and progression patterns were identified from the mean change in lesion volumes, depicted from conventional T1WI, delayed contrast-enhanced MR imaging, and DSC MR imaging. Thresholds for early prediction of response were calculated by using these sequences. For each predictor, sensitivity, specificity, positive predictive values, and negative predictive values were calculated, reaching 85.7%, 87.5%, 75%, and 93.3% for conventional T1WI; 100%, 87.5%, 77.8%, and 100% for delayed-contrast MR imaging; and 75%, 78.6%, 50%, and 91.7% for DSC MR imaging. The benefit of delayed-contrast MR imaging in separating responders and nonresponders was further confirmed by using log-rank tests (conventional T1WI, P = .0022; delayed-contrast MR imaging, P < .0001; DSC MR imaging, P = .0232) and receiver operating characteristic analyses. At progression, the increase in lesion volumes in delayed-contrast MR imaging was 37.5% higher than the increase in conventional T1WI (P < .01); these findings suggest that progression may be depicted more effectively in treatment-response-assessment maps. CONCLUSIONS: The benefit of contrast-enhanced MR imaging for assessing and predicting the response to bevacizumab was demonstrated. The increased sensitivity of the treatment-response-assessment maps reflects their potential contribution to the management of bevacizumab-treated patients with recurrent high-grade glioma.

A phantom experiment, two thermocouple experiments, three in vivo pig experiments, and a simulated treatment on a healthy human volunteer were conducted to test the feasibility, safety, and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for treating facet joint pain. The goal of the current study was to develop a novel method for accurate and safe noninvasive facet joint ablation using MRgFUS. Facet joints are a common source of chronic back pain. Direct facet joint interventions include medial branch nerve ablation and intra-articular injections, which are widely used, but limited in the short and long term. MRgFUS is a breakthrough technology that enables accurate delivery of high-intensity focused ultrasound energy to create a localized temperature rise for tissue ablation, using MR guidance for treatment planning and real-time feedback. We validated the feasibility, safety, and efficacy of MRgFUS for facet joint ablation using the ExAblate 2000® System (InSightec Ltd., Tirat Carmel, Israel) and confirmed the system's ability to ablate the edge of the facet joint and all terminal nerves innervating the joint. A phantom experiment, two thermocouple experiments, three in vivo pig experiments, and a simulated treatment on a healthy human volunteer were conducted. The experiments showed that targeting the facet joint with energies of 150-450 J provides controlled and accurate heating at the facet joint edge without penetration to the vertebral body, spinal canal, or root foramina. Treating with reduced diameter of the acoustic beam is recommended since a narrower beam improves access to the targeted areas. MRgFUS can safely and effectively target and ablate the facet joint. These results are highly significant, given that this is the first study to demonstrate the potential of MRgFUS to treat facet joint pain.

Background. Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PM-NASAH) is characterized by a benign course compared with aneurysmal SAH. While vasospasm (VS) after aneurysmal SAH is considered responsible for serious complications, VS post-PM-NASAH is not well documented. Our purpose was to characterize the incidence and course of VS among 63 patientsone of the largest databases of PM-NASAH patients with documented blood flow velocities in the literature. Methods. Data from 63 patients that were admitted with PM-NASAH from 2000 to 2012 and underwent transcranial Doppler tests to assess cranial vessel flow velocity was analyzed. Results. On average, the maximal flow velocity was measured on the 7th day after hemorrhage. Higher risk for VS was associated with younger age, female sex, and higher Hunt and Hess scores, a lower risk for patients treated with statins (). Using velocity thresholds for diagnosis of VS, 49.2% showed evidence of VS. This is the first description of blood flow velocities in PM-NASAH. VS average onset was on the 4th day, average cessation on day 15 after hemorrhage. No patients showed clinical manifestation of VS. Conclusions. VS post-PM-NASAH is not as rare as previously believed. However, its lack of clinical significance raises questions regarding the need for diagnosis and may suggest a less intensive treatment protocol.