[CHANGING CONCEPTS IN THE CLINICAL APPROACH FOR EPILEPSY SURGERY].

INTRODUCTION: Epilepsy is a common disease state, occurring in approximately 1% of the population worldwide, including both pediatric and adult populations. It is characterized by recurrent episodes of unpredictable pathologic cortical brain activity. One-third of patients develop drug intractability and experience recurrent seizures, despite optimal treatment. These result in cognitive decline, behavioral changes, decreased quality of life, and increased risk for trauma and death (SUDEP- sudden unprovoked death from epilepsy). Therefore, the international league against epilepsy (ILAE) recommends referral of intractable patients to highly specialized epilepsy centers, for further evaluation for epilepsy surgery.

Deep, spontaneous intracerebral hemorrhages: Clinical differences and risk factors associated with anterior versus posterior circulation.

BACKGROUND: spontaneous intracerebral hemorrhages (ICH) in different anatomical locations are considered different clinical entities, associated with different vascular etiologies. However, such a distinction between deep ICH in the posterior vs. the anterior circulation is not well documented. OBJECTIVE: to look for different demographic, clinical, laboratory and radiological variables in order to clarify any distinction between deep ICH of the posterior versus the anterior circulations. MATERIAL AND METHODS: Retrospective study on patients diagnosed with deep, spontaneous ICH at a single tertiary center. Patients were divided into two groups: posterior circulation (group 1) and anterior circulation (group 2). Computerized medical records were extracted for multiple variables. RESULTS: A total of 142 patients with deep ICH were included in the study; 54.9 % (n = 78) with posterior (group 1) and 45.1 % (n = 64) with anterior circulation hemorrhages (group 2). In group 1, 67.9 % (n = 53) of hemorrhages were in the cerebellum and 28.2 % (n = 22) in the thalamus. Patients in group 1 were older at time of hemorrhage (68.69 ± 11.66 vs. 64.95 ± 13.34, p = 0.073) and had nearly threefold increased rate of BMI≥ 35 (22.0 % vs. 8.6 %, p = 0.071). In multivariate analysis, use of anti-aggregates (OR=2.391; 95 % CI 1.082-5.285, p = 0.031) and past medical history of HTN (OR=2.904; 95 % CI 1.102-7.654, p = 0.031) were significantly associated with ICH of the posterior circulation. When excluding patients with thalamic hemorrhages, BMI ≥ 35 was also associated with significant risk of having a deep hemorrhage in the posterior circulation vs. the anterior circulation (OR=3.420; 95 % CI 1.011-11.574, p = 0.048). No significant differences were found between the two groups in terms of functional and survival outcomes. CONCLUSION: HTN, use of anti-aggregates and morbid obesity are associated with deep ICHs of the posterior circulation and should be considered significant risk factors for this major clinical event. The growing data on pathophysiology of distinct subgroups of ICH will provide useful tools that will aid in preventing and treating these neurological emergencies. Future epidemiological and clinical studies should use the distinction between ICH subgroups based on their anatomical location and vascular territories as accurately as possible in order to reach solid conclusions.

Cranioplasty With Customized Craniofacial Implants and Intraoperative Resizing for Single-Stage Reconstruction Following Oncologic Resection of Skull Neoplasms.

BACKGROUND: Craniectomies requiring skull reconstruction are indicated following oncological resection of masses involving the underlying brain and/or skull. Immediate cranioplasties have previously been performed using suboptimal hand-bending or molding techniques using "off - the - shelf" products. Today with computer - aided design, customized craniofacial implants have become widely available for personalized reconstruction of resected bone and soft tissue. We present here the largest series to date of single stage reconstruction using alloplastic biomaterials in consecutive patient series with oversized customized implants. METHODS: A single-surgeon, retrospective, 8-year study was conducted on all consecutive patients undergoing single stage cranioplasty with prefabricated implants using a myriad of biomaterials. All outcomes were analyzed in detail and compared with previous studies utilizing similar alloplastic implants. RESULTS: In total, 56 patients underwent resection of skull neoplasms and subsequent cranioplasty reconstruction using customized implants. The most common neoplasms were meningiomas (39%). The most common complications seen among patients were dehiscence - (7%), and extrusion of implant - (3.5%). There was no significant difference in the incidence of postoperative complications between patients who had postoperative chemotherapy/radiotherapy versus those that did not (22.2% versus 13.1%, P = 0.39). One-year follow-up revealed acceptable cranial contour and symmetry in all 56 cases. CONCLUSIONS: This is a consecutive case series of prefabricated single-stage cranioplasty, following resection of brain tumors with bone extension or skull bone neoplasm, demonstrating excellent results with regards to safety and patient satisfaction. There are several advantages such as comprehensive resection and reconstruction plan using 3D models, shorter operative time, and better restoration of complex anatomy.

Quick cell-free DNA testing for the prediction of postconcussion syndrome: a single-center prospective pilot trial.

OBJECTIVE: Mild traumatic brain injury (mTBI) is a major cause of emergency room (ER) admission. Thirty percent of mTBI patients have postconcussion syndrome (PCS), and 15% have symptoms for over a year. This population is underdiagnosed and does not receive appropriate care. The authors proposed a fast and inexpensive fluorometric measurement of circulating cell-free DNA (cfDNA) as a biomarker for PCS. cfDNA is a proven, useful marker of a variety of acute pathological conditions such as trauma and acute illness. METHODS: Thirty mTBI patients were recruited for this prospective single-center trial. At admission, patients completed questionnaires and blood was drawn to obtain cfDNA. At 3-4 months after injury, 18 patients returned for cognitive assessments with questionnaires and the Color Trails Test (CTT). The fast SYBR Gold assay was used to measure cfDNA. RESULTS: Seventeen men and 13 women participated in this trial. The mean ± SD age was 50.9 ± 13.9 years. Of the 18 patients who returned for cognitive assessment, one-third reported working fewer hours, 4 (22.2%) changed their driving patterns, and 5 (27.7%) reduced or stopped performing physical activity. The median cfDNA level of the mTBI group was greater than that of the matched healthy control group (730.5 vs 521.5 ng/ml, p = 0.0395). Admission cfDNA concentration was negatively correlated with performance on the CTT1 and CTT2 standardized tests (r = -0.559 and -0.599), meaning that greater cfDNA level was correlated with decreased cognitive performance status. The performance of the patients with normal cfDNA level included in the mTBI group was similar to that of the healthy participants. In contrast, the increased cfDNA group (> 800 ng/ml) had lower scores on the CTT tests than the normal cfDNA group (p < 0.001). Furthermore, patients with moderate/severe cognitive impairment according to CTT1 results had a greater median cfDNA level than the patients with scores indicating mild impairment or normal function (1186 vs 473.5 ng/ml, p = 0.0441, area under the receiver operating characteristic curve = 0.8393). CONCLUSIONS: The data from this pilot study show the potential to use cfDNA, as measured with a fast test, as a biomarker to screen for PCS in the ER. A large-scale study is required to establish the value of cfDNA as an early predictor of PCS.

Neurological event prediction for patients with symptomatic cerebral cavernous malformation: the BLED2 score.

OBJECTIVE: Retrospective patient cohort studies have identified risk factors associated with recurrent focal neurological events in patients with symptomatic cerebral cavernous malformations (CCMs). Using a prospectively maintained database of patients with CCMs, this study identified key risk factors for recurrent neurological events in patients with symptomatic CCM. A simple scoring system and risk stratification calculator was then created to predict future neurological events in patients with symptomatic CCMs. METHODS: This was a dual-center, prospectively acquired, retrospectively analyzed cohort study. Adult patients who presented with symptomatic CCMs causing focal neurological deficits or seizures were uniformly treated and clinically followed from the time of diagnosis onward. Baseline variables included age, sex, history of intracerebral hemorrhage, lesion multiplicity, location, eloquence, size, number of past neurological events, and duration since last event. Stepwise multivariable Cox regression was used to derive independent predictors of recurrent neurological events, and predictive accuracy was assessed. A scoring system based on the relative magnitude of each risk factor was devised, and Kaplan-Meier curve analysis was used to compare event-free survival among patients with different score values. Subsequently, 1-, 2-, and 5-year neurological event rates were calculated for every score value on the basis of the final model. RESULTS: In total, 126 (47%) of 270 patients met the inclusion criteria. During the mean (interquartile range) follow-up of 54.4 (12-66) months, 55 patients (44%) experienced recurrent neurological events. Multivariable analysis yielded 4 risk factors: bleeding at presentation (HR 1.92, p = 0.048), large size ≥ 12 mm (HR 2.06, p = 0.016), eloquent location (HR 3.01, p = 0.013), and duration ≤ 1 year since last event (HR 9.28, p = 0.002). The model achieved an optimism-corrected c-statistic of 0.7209. All factors were assigned 1 point, except duration from last event which was assigned 2 points. The acronym BLED2 summarizes the scoring system. The 1-, 2-, and 5-year risks of a recurrent neurological event ranged from 0.6%, 1.2%, and 2.3%, respectively, for patients with a BLED2 score of 0, to 48%, 74%, and 93%, respectively, for patients with a BLED2 score of 5. CONCLUSIONS: The BLED2 risk score predicts prospective neurological events in symptomatic CCM patients.

Role of Thrombin in Central Nervous System Injury and Disease.

Thrombin is a Na+-activated allosteric serine protease of the chymotrypsin family involved in coagulation, inflammation, cell protection, and apoptosis. Increasingly, the role of thrombin in the brain has been explored. Low concentrations of thrombin are neuroprotective, while high concentrations exert pathological effects. However, greater attention regarding the involvement of thrombin in normal and pathological processes in the central nervous system is warranted. In this review, we explore the mechanisms of thrombin action, localization, and functions in the central nervous system and describe the involvement of thrombin in stroke and intracerebral hemorrhage, neurodegenerative diseases, epilepsy, traumatic brain injury, and primary central nervous system tumors. We aim to comprehensively characterize the role of thrombin in neurological disease and injury.

Minimally Invasive Intracerebral Hematoma Evacuation Using a Novel Cost-Effective Tubular Retractor: Single-Center Experience.

BACKGROUND: Spontaneous intracerebral hematoma (ICH) is a common disease with a dismal overall prognosis. Recent development of minimally invasive ICH evacuation techniques has shown promising results. Commercially available tubular retractors are commonly used for minimally invasive ICH evacuation yet are globally unavailable. METHODS: A novel U.S. $7 cost-effective, off-the-shelf, atraumatic tubular retractor for minimally invasive intracranial surgery is described. Patients with acute spontaneous ICH underwent microsurgical tubular retractor-assisted minimally invasive ICH evacuation using the novel retractor. Patient outcome was retrospectively analyzed and compared with open surgery and with commercial tubular retractors. RESULTS: Ten adult patients with spontaneous supratentorial ICH and median preoperative Glasgow Coma Scale score of 10 were included. ICH involved the frontal lobe, parietal lobe, occipitotemporal region, and solely basal ganglia in 3, 3, 2, and 2 patients, respectively. Mean preoperative ICH volume was 80 mL. Mean residual hematoma volume was 8.7 mL and mean volumetric hematoma reduction was 91% (median, 94%). Seven patients (70%) underwent >90% volumetric hematoma reduction. The total median length of hospitalization was 26 days. On discharge, the median Glasgow Coma Scale score was 12.5 (mean, 11.7). Thirty to 90 days' follow-up data were available for 9 patients (90%). The mean follow-up modified Rankin Scale score was 3.7 and 5 patients (56%) had a modified Rankin Scale score of 3. CONCLUSIONS: The novel cost-effective tubular retractor and microsurgical technique offer a safe and effective method for minimally invasive ICH evacuation. Cost-effective tubular retractors may continue to present a valid alternative to commercial tubular retractors.

Treatment of Diabetic Neuropathy with A Novel PAR1-Targeting Molecule.

Diabetic peripheral neuropathy (DPN) is a disabling common complication of diabetes mellitus (DM). Thrombin, a coagulation factor, is increased in DM and affects nerve function via its G-protein coupled protease activated receptor 1 (PAR1). METHODS: A novel PAR1 modulator (PARIN5) was designed based on the thrombin PAR1 recognition site. Coagulation, motor and sensory function and small fiber loss were evaluated by employing the murine streptozotocin diabetes model. RESULTS: PARIN5 showed a safe coagulation profile and showed no significant effect on weight or glucose levels. Diabetic mice spent shorter time on the rotarod (p <0.001), and had hypoalgesia (p <0.05), slow conduction velocity (p <0.0001) and reduced skin innervation (p <0.0001). Treatment with PARIN5 significantly improved rotarod performance (p <0.05), normalized hypoalgesia (p <0.05), attenuated slowing of nerve conduction velocity (p <0.05) and improved skin innervation (p <0.0001). CONCLUSION: PARIN5 is a novel pharmacological approach for prevention of DPN development, via PAR1 pathway modulation.

Local Tolerance and Biodegradability of a Novel Artificial Dura Mater Graft Following Implantation Onto a Dural Defect in Rabbits.

Dura mater defects are a common problem following neurosurgery. Dural grafts are used to repair these defects; among them are biodegradable polymeric synthetic grafts. ArtiFascia is a novel synthetic and fibrous Dural graft, composed of poly(l-lactic-co-caprolactone acid) (PLCL) and poly(d-lactic-co-caprolactone acid). In this study, the biodegradability and local tolerance of ArtiFascia was evaluated in rabbits and compared with a bovine collagen matrix as a reference control. ArtiFascia implantation resulted in the formation of neo-dura at the site of implantation and recovery of the dural damage and the calvaria bone above. The implanted graft was completely absorbed after 12 months and the remaining macrophages were morphologically consistent with the anti-inflammatory M2-like phenotype, which contributes to tissue healing and are not pro-inflammatory. The site of the drilled skull bone had a continuous smooth surface, without exuberant tissue or inflammation and a newly formed trabecular bone formation indicated the healing process of the bone. These results support the local tolerability and biodegradability of ArtiFascia when used as a dural graft in rabbits. This study suggests that PLCL-based grafts including ArtiFascia are safe and effective to repair Rabbit Dura.

Traumatic Brain Injury Severity in a Network Perspective: A Diffusion MRI Based Connectome Study.

Traumatic brain injury (TBI) is often characterized by alterations in brain connectivity. We explored connectivity alterations from a network perspective, using graph theory, and examined whether injury severity affected structural connectivity and modulated the association between brain connectivity and cognitive deficits post-TBI. We performed diffusion imaging network analysis on chronic TBI patients, with different injury severities and healthy subjects. From both global and local perspectives, we found an effect of injury severity on network strength. In addition, regions which were considered as hubs differed between groups. Further exploration of graph measures in the determined hub regions showed that efficiency of six regions differed between groups. An association between reduced efficiency in the precuneus and nonverbal abstract reasoning deficits (calculated using actual pre-injury scores) was found in the controls but was lost in TBI patients. Our results suggest that disconnection of network hubs led to a less efficient network, which in turn may have contributed to the cognitive impairments manifested in TBI patients. We conclude that injury severity modulates the disruption of network organization, reflecting a "dose response" relationship and emphasize the role of efficiency as an important diagnostic tool to detect subtle brain injury specifically in mild TBI patients.

The human tumor microbiome is composed of tumor type-specific intracellular bacteria.

Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients' smoking status, and the response to immunotherapy.

[IS ROUTINE CT SCAN NECESSARY AFTER THE REMOVAL OF BENIGN BRAIN TUMORS?]

AIMS: Determine if early CT evaluation is justified in patients operated on for benign brain tumors. BACKGROUND: Researchers have recently questioned the common practice of referring all patients after cranial surgery for CT scans to rule out silent complications. METHODS: The cohort included 257 consecutive patients who underwent surgical removal of a benign brain tumor in the years 2011-2016. The neuroradiology scans performed before and after surgery were reviewed. The postoperative findings considered significant were hemorrhage in ≥50% of the tumor bed, ischemic changes, worsening brain edema, and mass effect. The relationship of the CT findings with the neurological outcome and their effect on the clinical management were evaluated. RESULTS: No significant complications were found by CT in 247 patients (96%). In the remaining 10 patients (4%), CT showed increased brain edema in 5 and hemorrhage in 5. The clinical management was influenced by the CT findings in 6/10 patients. One had a temporary neurological deficit. None died or required a second operation. CONCLUSIONS: Elective patients operated on uneventfully for benign brain tumors rarely benefit from routine CT after surgery. In most cases, CT follow-up can be replaced by careful neurological monitoring. Exceptions to this rule may be based on clinical judgment and local resources.

The Utility of Early Postoperative Neuroimaging in Elective/Semielective Craniotomy Patients: A Single-Arm Prospective Trial.

BACKGROUND: The necessity and timing of early postoperative imaging (POI) are debated in many studies. Despite the consensus that early POI does not change patient management, these examinations are routinely performed. This is the first prospective study related to POI. Our aims were to assess the necessity of early POI in asymptomatic patients and to verify accuracy of the presented algorithm. METHODS: This was an algorithm-based prospective single-center study. The algorithm addressed preoperative, perioperative, and postoperative considerations, including estimated pathology type, device placement, and postoperative neurologic change. Early computed tomography scans were obtained in all patients, but if postoperative algorithm indications did not recommend a scan, the treating team was blinded to them, and patient management was conducted based on clinical examinations alone. A neuroradiologist and study-independent neurosurgeon reviewed all the scans. RESULTS: Of 103 enrolled patients, 88 remained asymptomatic, and 15 experienced symptoms postoperatively. Pathology was present on POI in 1% of the asymptomatic patients and 53% of the symptomatic patients (P < 0.001). In the asymptomatic group, no treatment modifications were made postoperatively. Blinding of the surgical team was not removed, and 20% of the symptomatic patients returned to the operating room because of imaging and neurologic findings. The goal of <5% algorithm failure was reached with statistical significance. CONCLUSIONS: In asymptomatic postoperative patients in whom early imaging is not performed for oncologic indications, device placement verification, or similar reasons, POI is unnecessary and does not change the management of these patients.

Natural History of Untreated Transverse/Sigmoid Sinus Thrombosis Following Posterior Fossa Surgery: Case Series and Literature Review.

BACKGROUND: Transverse or sigmoid sinus thrombosis occurs in 4% to 11% of patients following posterior fossa surgery. Anticoagulation has been the mainstay treatment, mostly based on extrapolation from the literature on spontaneous sinus thrombosis. OBJECTIVE: To analyze the rate and associated complications of postoperative transverse/sigmoid sinus thrombosis for patients undergoing posterior fossa tumor resection. In this series, no antithrombotic therapy was initiated, and no postoperative treatment alterations were made following thrombosis diagnosis. METHODS: Prospectively accrued cases from a single surgeon operating at a single academic center were retrospectively reviewed to determine the natural history of untreated transverse/sigmoid sinus thrombosis following posterior fossa surgery. Inclusion criteria were patients 18 yr or older undergoing resection of a posterior fossa tumor. A total of 538 patients were analyzed. RESULTS: In all 26 out of 538 (4.8%) patients were diagnosed with transverse/sigmoid sinus thrombosis on routine postoperative imaging. Early postoperative complication rate was 38% in the sinus thrombosis group, as compared to 15% in the no-thrombosis group (P = .02). A significantly higher rate of pseudomeningocele, dysphagia requiring gastrostomy, and cerebellar stroke signs were noted in patients with postoperative sinus thrombosis. However, only 3 of the 26 patients (12%) with postoperative sinus occlusion suffered prolonged central nervous system complications. CONCLUSION: Transverse/sigmoid sinus thrombosis following suboccipital craniectomy results in a higher rate of early complications; however, most of these complications resolve without anticoagulation. It may be reasonable, therefore, to manage these patients conservatively in order to avoid the risks associated with anticoagulation in the perioperative period.

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial.

BACKGROUND: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. METHODS: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. FINDINGS: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). INTERPRETATION: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. FUNDING: National Institute of Neurological Disorders and Stroke and Genentech.

Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model.

BACKGROUND: Essential tremor (ET) is one of the most common movement disorders of adults, characterized by postural and kinetic tremor. With drug treatment only partially efficient, new treatments are being developed. OBJECTIVES: The goal of this study was to demonstrate the feasibility of non-thermal focused-ultrasound (FUS) to induce tremor-suppression in an ET rat model. METHODS: Harmaline-induced tremor rats were treated with FUS along the inferior olivary (IO) system. EMG was recorded continuously during treatment in order to quantify FUS-induced tremor suppression. T2-weighted MRI was performed immediately following treatment and periodically thereafter. RESULTS: FUS treatment at an intensity of 27.2 W/cm2 (Isppa) induced significant reduction of tremor in 12 out of 13 ET rats. Tremor frequency was reduced from 6.2 ±â€¯2.8 to 2 ±â€¯1 Hz, p < 0.0003. In 6 of the 12 responding rats, tremor was completely suppressed. Response duration was 70 ±â€¯61s, on average. FUS induced motor response, depicted as movement of the tail and/or the limbs synchronized with the FUS sonication, was also demonstrated both in ET rats and in naïve rats when treated in the medulla oblongata region. CONCLUSIONS: These results demonstrate the feasibly for obtaining significant tremor reduction or tremor suppression induced by non-thermal, non-invasive, reversible focused-ultrasound.

Radiation-induced vascular malformations in the brain, mimicking tumor in MRI-based treatment response assessment maps (TRAMs).

•Of 310 brain tumors patients recruited, histology of 99 lesions was available.•Of those, 5 were histologically confirmed as radiation-induced malformations.•TRAMs cannot differentiate active tumor from vascular malformation.

Antithrombotic Treatment Prior to Intracerebral Hemorrhage: Analysis in the National Acute Stroke Israeli Registry.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is the most disastrous stroke subtype. Prognosis is considered worse with prior antithrombotic treatment. Our aim was to evaluate the association of prior antithrombotic treatment on the radiological and clinical outcome after ICH in a subgroup of patients included in a national registry. METHODS: Based on the National Acute Stroke Israeli (NASIS) registry during 2004, 2007, 2010, and 2013 (2-month periods), characteristics, volumetric parameters, and prognosis of a subgroup of patients with ICH were analyzed. RESULTS: Among the 634 patients with ICH in the NASIS registry, 310 (49%) were not treated previously with antithrombotic medications, 232 (37%) were treated with an antiplatelet agent, and 92 (14.5%) patients were on oral anticoagulant therapy, of them 30 patients (33%) with an international normalised ratio (INR) value below 2, 33 (36%) patients with an INR value of 2-3, and 29 patients (31%) with an INR value above 3 upon admission. Patients with deep hemorrhage on prior anticoagulants treatment had the highest probability for poor outcome at hospital discharge. Patients with low bleeding volume (0-30 cm3), were likely to have admission National Institute of Health Stroke Scale < 10 (62%), while those with higher volumes (30-59 cm3 and > 60 cm3), had only 16.7% and 14.3% chance, respectively. We did not observe a significant difference between prior antithrombotic treatment and functional outcome at discharge, yet prior anticoagulant treatment was associated with higher long-term mortality rates. CONCLUSIONS: Our findings, based on a national registry, support the high mortality and poor outcome of anticoagulant related ICH.

Declining Rate and Severity of Hospitalized Stroke From 2004 to 2013: The National Acute Stroke Israeli Registry.

BACKGROUND AND PURPOSE: Stroke is a leading cause of morbidity and disability. We assessed trends in rates of hospitalized stroke and stroke severity on admission in a prospective national registry of stroke from 2004 to 2013. METHODS: All 6693 acute ischemic strokes and intracerebral hemorrhage in the National Acute Stroke Israeli participants ≥20 years old were included. Data were prospectively collected in 2004 (February-March), 2007 (March-April), 2010 (April-May), and 2013 (March-April). Rates of hospitalized stroke from 2004 to 2013 were studied using generalized linear models assuming a quasi-Poisson error distribution with a log link. Stroke severity on admission was determined using the National Institutes of Health Stroke Scale score and trends were studied. Analysis was performed for stroke overall and by sex and age-group as well as by stroke type. RESULTS: Estimated average annual rates of hospitalized stroke decreased from 24.9/10 000 in 2004 to 19.5/10 000 in 2013. The age and sex-adjusted rates ratio (95% confidence interval) for hospitalized stroke overall was 0.82 (0.76-0.89) for 2007, 0.71 (0.65-0.77) for 2010, and 0.72 (0.66-0.78) for 2013 compared with 2004. Severity on admission decreased over time: rates (95% confidence interval) of severe stroke (National Institutes of Health Stroke Scale score of ≥11) decreased from 27% (25%-29%) in 2004 to 19% (17%-21%) in 2013, whereas rates (95% confidence interval) of minor stroke (National Institutes of Health Stroke Scale score of ≤5) increased from 46% (44%-49%) in 2004 to 60% (57%-62%) in 2013 (P<0.0001). Findings were consistent by sex, age-group, and stroke type. CONCLUSIONS: Based on our national data, rates of hospitalized stroke and severity of stroke on admission have decreased from 2004 to 2013 overall and by stroke type, in men and women. Despite the observed declines in rates and severity, stroke continues to place a considerable burden to the Israeli health system.

Focused Ultrasound-Induced Suppression of Auditory Evoked Potentials in Vivo.

The goal of this study was to determine the feasibility of focused ultrasound-based neuromodulation affecting auditory evoked potentials (AEPs) in animals. Focused ultrasound-induced suppression of AEPs was performed in 22 rats and 5 pigs: Repetitive sounds were produced, and the induced AEPs were recorded before and repeatedly after FUS treatment of the auditory pathway. All treated animals exhibited a decrease in AEP amplitude post-treatment in contrast to animals undergoing the sham treatment. Suppression was weaker for rats treated at 2.3 W/cm2 (amplitudes decreased to 59.8 ± 3.3% of baseline) than rats treated at 4.6 W/cm2 (36.9 ± 7.5%, p <0.001). Amplitudes of the treated pigs decreased to 27.7 ± 5.9% of baseline. This effect lasted between 30 min and 1 mo in most treated animals. No evidence of heating during treatment or later brain damage/edema was observed. These results demonstrate the feasibility of inducing significant neuromodulation with non-thermal, non-invasive, reversible focused ultrasound. The long recovery times may have clinical implications.