Probabilistic Refinement of Focused Ultrasound Thalamotomy Targeting for Parkinson's Disease Tremor.

BACKGROUND: There remains high variability in clinical outcomes when the same magnetic resonance image-guided focused ultrasound (MRgFUS) thalamotomy target is used for both essential tremor (ET) and tremor-dominant Parkinson's disease (TDPD). OBJECTIVE: Our goal is to refine the MRgFUS thalamotomy target for TDPD versus ET. METHODS: We retrospectively performed voxel-wise efficacy and structural connectivity mapping using 3-12-month post-procedure hand tremor scores for a multicenter cohort of 32 TDPD patients and a previously published cohort of 79 ET patients, and 24-hour T1-weighted post-MRgFUS brain images. We validated our findings using Unified Parkinson's Disease Rating Scale part III scores for an independent cohort of nine TDPD patients. RESULTS: The post-MRgFUS clinical improvements were 45.9% ± 35.9%, 55.5% ± 36%, and 46.1% ± 18.6% for ET, multicenter TDPD and validation TDPD cohorts, respectively. The TDPD and ET efficacy maps differed significantly (ppermute < 0.05), with peak TDPD improvement (87%) at x = -13.5; y = -15.0; z = 1.5, ~3.5 mm anterior and 3 mm dorsal to the ET target. Discriminative connectivity projections were to the motor and premotor regions in TDPD, and to the motor and somatosensory regions in ET. The disorder-specific voxel-wise efficacy map could be used to estimate outcome in TDPD patients with high accuracy (R = 0.8; R2 = 0.64; P < 0.0001). The model was validated using the independent cohort of nine TDPD patients (R = 0.73; R2 = 0.53; P = 0.025-voxel analysis). CONCLUSION: We demonstrated that the most effective MRgFUS thalamotomy target in TDPD is in the ventral intermediate nucleus/ventralis oralis posterior border region. This finding offers new insights into the thalamic regions instrumental in tremor control, with pivotal implications for improving treatment outcomes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Statistical learning in epilepsy: Behavioral and anatomical mechanisms in the human brain.

OBJECTIVE: Statistical learning, the fundamental cognitive ability of humans to extract regularities across experiences over time, engages the medial temporal lobe (MTL) in the healthy brain. This leads to the hypothesis that statistical learning (SL) may be impaired in patients with epilepsy (PWE) involving the temporal lobe, and that this impairment could contribute to their varied memory deficits. In turn, studies done in collaboration with PWE, that evaluate the necessity of MTL circuitry through disease and causal perturbations, provide an opportunity to advance basic understanding of SL. METHODS: We implemented behavioral testing, volumetric analysis of the MTL substructures, and direct electrical brain stimulation to examine SL across a cohort of 61 PWE and 28 healthy controls. RESULTS: We found that behavioral performance in an SL task was negatively associated with seizure frequency irrespective of seizure origin. The volume of hippocampal subfields CA1 and CA2/3 correlated with SL performance, suggesting a more specific role of the hippocampus. Transient direct electrical stimulation of the hippocampus disrupted SL. Furthermore, the relationship between SL and seizure frequency was selective, as behavioral performance in an episodic memory task was not impacted by seizure frequency. SIGNIFICANCE: Overall, these results suggest that SL may be hippocampally dependent and that the SL task could serve as a clinically useful behavioral assay of seizure frequency that may complement existing approaches such as seizure diaries. Simple and short SL tasks may thus provide patient-centered endpoints for evaluating the efficacy of novel treatments in epilepsy.

Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound.

The blood-brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer's disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We report initial clinical trial results evaluating the safety, feasibility, and reversibility of BBB opening with FUS treatment of the hippocampus and entorhinal cortex (EC) in patients with early AD. Six subjects tolerated a total of 17 FUS treatments with no adverse events and neither cognitive nor neurological worsening. Post-FUS contrast MRI revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 h. The average opening was 95% of the targeted FUS volume, which corresponds to 29% of the overall hippocampus volume. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions.

Targeting the vim by direct visualization of the cerebello-thalamo-cortical pathway in 3 T proton density MRI: correlation with focused ultrasound lesioning.

Surgical targeting of the ventral intermediate nucleus of the thalamus (VIM) has been historically done using indirect strategies. Here we depict the cerebello-thalamo-cortical tract (CTCT) through 3 T proton density (PD) in a cohort of patients who underwent high-intensity focus ultrasound (HIFUS) thalamotomy. Forty-seven patients treated in our institution with MR-guided HIFUS VIM thalamotomy were included in this study. PD weighted 3 T MRI used for presurgical planning was compared with postoperative MRI obtained 1 month after surgery. Images were processed with ISTX software (Brain lab, Munich, Germany). The coordinates of the VIM lesion concerning the inter-commissural line (ICL) were annotated. Deterministic tractographies using three ROIs were used to verify the different tracts. The triangle seen in the 3 T PD sequence at the level of the mesencephalic-diencephalic junction was systematically recognized. The posterior angle of this triangle at the junction of the CTCT and the ZI was denominated as "point P." The area of this triangle corresponds to the posterior subthalamic area (PSA) harboring the Raprl fibers. The CTCT was visible from 1 to 2.5 mm below the ICL. The average center of the final HIFUS lesion (point F) was 11 mm from the medial thalamic border of the thalamus (14.9 mm from the midline), 6.4 mm anterior to PC, and 0.6 mm above the ICL. The FUS point was consistently 1-2 mm directly above point P. The anterior border of the external angle of this triangle (point P) can be used as an intraparenchymal point for targeting the ventral border of the VIM. Three ROIs placed in a single slice around this triangle are a fast way to originate tractography of the CTCT, lemniscus medialis, and pyramidal tract.

Utility of the Polestar N30 low-field MRI system for resecting non-enhancing intra-axial brain lesions.

BACKGROUND: To determine the utility of an intraoperative magnetic resonance imaging (iMRI) system, the Polestar N30, for enhancing the resection control of non-enhancing intra-axial brain lesions. MATERIALS AND METHODS: Seventy-three patients (60 males [83.3%], mean age 37 years) with intra-axial brain lesions underwent resection at Sheba Medical Centre using the Polestar between February 2012 and the end of August 2018. Demographic and imaging data were retrospectively analysed. Thirty-five patients had a non-enhancing lesion (48%). RESULTS: Complete resection was planned for 60/73 cases after preoperative imaging. Complete resection was achieved in 59/60 (98.3%) cases. After iMRI, additional resection was performed in 24/73 (32.8%) cases, and complete resection was performed in 17/60 (28.8%) cases in which a complete resection was intended. In 6/13 (46%) patients for whom incomplete resection was intended, further resection was performed. The extent of resection was extended mainly for non-enhancing lesions: 16/35 (46%) as opposed to only 8/38 (21%) for enhancing lesions. Further resection was not significantly associated with sex, age, intended resection, recurrence, or affected side. Univariate analysis revealed non-eloquent area, intended complete resection, and enhancing lesions to be predictive factors for complete resection, and non-enhancing lesions and scan time to be predictive factors for an extended resection. Non-enhancement was the only independent factor for extended resection. CONCLUSIONS: The Polestar N30 is useful for evaluating residual non-enhancing intra-axial brain lesions and achieving maximal resection.

A novel swine model of subarachnoid hemorrhage-induced cerebral vasospasm.

OBJECTIVE: One of the most serious complications following subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI) secondary to symptomatic vasospasm. An animal model mimicking post SAH vasospasm is essential for enabling the translation of newer technologies from the conceptual phase to animal studies, and eventually to clinical trials. Various animal models of DCI following SAH have been reported, with canine models being the most common. Due to the similarity of the swine cardiovascular system and its dimensions to the human's system, the main objective of this study was to establish a consistent and quantitatively representative model of SAH-induced vasospasm in swine. MATERIALS AND METHODS: Twelve female swines (57 ± 3 kg) were injected twice (with a 2-day interval between injections) with autologous blood into the subarachnoid space at the level of C2-3 vertebrae. Different volumes were injected to identify clinical and radiological changes. The effect of volume variations on hematoma size and vasospasm intensity in the circle of Willis arteries were studied 7-14 days after the first injection using ascending pharyngeal angiographic measurements of vessel diameter. Neurological outcome using a modified scoring table based on clinical parameters (e.g., appetite, behavior, walking, posture, and eye movement) was recorded. RESULTS: Our results demonstrate that between volume combinations, intrathecal injection of 12 ml followed by 15 ml, with a 2-day interval in between, resulted in the most extensive angiographically-assessed vasospasm 12 ± 2 days following the first injection. The degree of vasospasm in the intracranial internal carotid artery was 22% and 16% for the left and right sides, respectively. Vasoconstriction of the anterior cerebral artery was 34% and 27% for the left and right sides, respectively. The vasoconstriction was not associated with either overt clinical signs or clinical outcome, which is indicative of an ischemic event. CONCLUSIONS: The relative scarcity of swine models for SAH-induced vasospasm motivated us to develop and quantify a straightforward protocol for producing consistent mild-to-moderate vasospasm following SAH. As swine is commonly used in translational cardiovascular research, we believe that this study constitutes an important phase in the study of SAH and in developing pharmacological agents and medical devices for interventions.

Sandwich technique, peripheral nerve stimulation, peripheral field stimulation and hybrid stimulation for inguinal region and genital pain.

OBJECTIVE: Ilioinguinal neuralgia (IG) and genitofemoral (GF) neuralgia following inguinal hernia repair is a chronic and debilitating neuropathic condition. Recently, peripheral nerve stimulation has become an effective and minimally invasive option for the treatment of refractory pain. Here we present a retrospective case series of six patients who underwent placement of peripheral nerve stimulation electrodes using various techniques for treatment of refractory post-intervention inguinal region pain. METHODS: Six patients with post-intervention inguinal, femoral or GF neuropathic pain were evaluated for surgery. Either octopolar percutaneous electrodes or combination of paddle and percutaneous electrodes were implanted in the area of their pain. Pain visual analog scores (VAS), surgical complication rate, preoperative symptom duration, degree of pain relief, preoperative and postoperative work status, postoperative changes in medication usage, and overall degree of satisfaction with this therapy was assessed. RESULTS: All six patients had an average improvement of 62% in the immediate post-operative follow-up. Four patients underwent stimulation for IG, one for femoral neuralgia, and another for GF neuralgia. Peripheral nerve stimulation provided at least 50% pain relief in all the six patients with post-intervention inguinal region pain. 85% of patients indicated they were completely satisfied with the therapy overall. There was one treatment failure with an acceptable complication rate. CONCLUSION: Peripheral nerve or field stimulation for post-intervention inguinal region pain is a safe and effective treatment for this refractory and complex problem for patients who have exhausted other management options.

Novel tunneling system for implantation of percutaneous nerve field stimulator electrodes: a technical note.

INTRODUCTION: The field of neuromodulation continues to grow, especially in the area of pain management. Percutaneous nerve field stimulation continues to gain significant popularity for chronic, focal, and intractable neuropathic pain. MATERIALS AND METHODS: Tuohy needles have been traditionally used as the instrument of choice for subcutaneous implantation of peripheral field stimulators. The ON-Q® Tunneling System (Braun Melsungen AG, Melsungen, Germany) provides an adaptable option for subcutaneous implantation of electrodes, with a variety of lengths and gauges available. This system uses a disposable blunt needle and a peel-away sheath and is firm but malleable. Gentle curves can be applied to the stylet prior to implantation. The blunt, malleable nature of the needle and the soft Silastic sheath allow for applications in areas with greater curvature, such as the face, and ensure a subcutaneous placement. CONCLUSIONS: The great adaptability of this system allows for implantation of electrodes subcutaneously with efficacy and ease. Here we present a technical note on the use of this system for subcutaneous implantation of peripheral nerve field stimulators.

Brain biopsy in AIDS patients: diagnostic yield and treatment applications.

OBJECTIVE: Central nervous system involvement in AIDS patients can present at any stage of the disease. Brain lesions detected in imaging studies are usually treated empirically. A brain biopsy is indicated in the absence of clinical and radiologic improvement. In the present study, 16 AIDS patients underwent brain biopsy. We evaluated the diagnostic yield of the brain biopsy and the changes in the disease course. MATERIALS AND METHODS: Sixteen consecutive AIDS patients (12 men, 4 women; mean age 40.8 years) underwent a brain biopsy at Sheba Medical Center between 1997 and 2009. A retrospective analysis was performed and the clinical outcome was recorded. RESULTS: Median CD4 count before biopsy was 62.6. Magnetic resonance images revealed multiple lesions in 12 patients and enhancing lesions in 12 patients. A total of 19 biopsies were performed in 16 patients. In the present series, the initial procedures provided a diagnostic yield of 81.25% (13 diagnostic cases from 16 procedures in 16 patients). Two of these patients underwent repeated biopsies that were eventually diagnostic . If repeated biopsies were taken into consideration, the diagnostic yield was 93.75% (15 diagnostic cases in 16 patients). The rate of hemorrhagic complications was 10.5% (2 hemorrhages in 19 procedures).Pathologic examination revealed parasitic and fungal infections in 6 patients (6/16; 38%), progressive multifocal leukoencephalopathy in 4 patients (4/16; 25%), AIDS encephalopathy in 4 patients (4/16; 25%), and lymphoma in 1 patient (1/16; 6%). One patient had a nonspecific inflammatory process (6%). The treatment modality was modified in 12 patients and led to clinical and radiologic improvement in 8 patients. CONCLUSIONS: Brain biopsy should be considered when empiric treatment of central nervous system lesions in AIDS patients fails. Biopsy is diagnostic in the majority of patients. The diagnosis allows for treatment modifications, which lead to clinical and radiologic improvement in some patients.

Potential of magnetic resonance-guided focused ultrasound for intracranial hemorrhage: an in vivo feasibility study.

BACKGROUND: Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an alternative noninvasive treatment through the precise delivery of FUS under real-time MR imaging (MRI) guidance. The purpose of the present study was to optimize the parameters for rapid, effective, and safe trans-skull large clot liquefaction using in vivo porcine and ex vivo human skull models to provide a clinically relevant proof of concept. METHODS: The transcranial effectiveness of MRgFUS was tested ex vivo by introducing a porcine blood clot into a human skull, without introducing tissue plasminogen activator (tPA). We used an experimental human head device to deliver pulsed FUS sonications at an acoustic power of 600-900 W for 5-10 seconds. A 3-mL clot was also introduced in a porcine brain and sonicated in vivo with one 5-second pulse of 700 W through a bone window or with 3000 W when treated through an ex vivo human skull. Treatment targeting was guided by MRI, and the tissue temperature was monitored online. Liquefied volumes were measured as hyperintense regions on T2-weighted MR images. RESULTS: In both in vivo porcine blood clot through a craniectomy model and the porcine clot in an ex vivo human skull model targeted clot liquefaction was achieved, with only marginal increase in temperature in the surrounding tissue. CONCLUSIONS: Our results demonstrate the feasibility of fast, efficient, and safe thrombolysis in an in vivo porcine model of ICH and in 2 ex vivo models using a human skull, without introducing tPA. Future studies will further optimize parameters and assess the nature of sonication-mediated versus natural clot lysis, the risk of rebleeding, the potential effect on the adjacent parenchyma, and the chemical and toxicity profiles of resulting lysate particles.

Minimally Invasive Anterolateral Cervical Cordotomy for Intractable Cancer Pain Using Microtubular Retractors: A Single Institution Case Series.

BACKGROUND AND OBJECTIVES: As advancements in cancer treatments have allowed patients with a high burden of disease to live longer, the number of patients who present with debilitating refractory pain has increased. Anterolateral cordotomy has long been used for the treatment of intractable unilateral cancer pain using either an imaging-guided percutaneous approach or an open surgical approach. In this report, we describe a novel minimally invasive modification to the open surgical approach. It combines the benefits of both approaches by providing direct visualization for lesioning without the collateral tissue damage of an open approach. METHODS: This retrospective study evaluated medical records, operative reports, and imaging studies of patients who underwent a minimally invasive cordotomy at a single institute between 2018 and 2022. The surgical technique involved a microscope-assisted C2 hemilaminectomy using microtubular retractors followed by dural opening and anterolateral cordotomy under direct visualization and with intraoperative neurophysiological monitoring. RESULTS: Eleven patients were included in the study. None were converted to an open approach, and no wound-related postoperative complications were observed. A clinically significant decrease in pain was observed after the procedure, and 10 of the 11 patients (91%) were ambulatory by the time of analysis. CONCLUSION: Compared with image-guided percutaneous cordotomy, anterolateral cervical cordotomy with microtubular retractors potentially improves the safety of the procedure through direct visualization while being less invasive than a conventional open approach. Our preliminary experience with this technique demonstrates the feasibility of the approach, as it was both safe and effective.

Are LRRK2 p.G2019S or GBA1 variants associated with long-term outcomes of deep brain stimulation for Parkinson's disease?

BACKGROUND: Deep brain stimulation (DBS) is a well-established treatment option for individuals with advanced Parkinson's disease (PD). The potential influence of the LRRK2 p.G2019S or GBA1 variants on its lasting efficacy and adverse effects should be better characterized. METHODS: We conducted a retrospective single-center case-control study involving PD patients who were carriers of a GBA1 variant (GBA1-PD), the LRRK2 p.G2019S variant (LRRK2-PD), and non-carriers (Nc-PD). All participants underwent DBS and were followed up for at least a year. Assessments before surgery and at 1, 2, 3, 5, and 10 years post-DBS included the following: the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) Part III, Hoehn and Yahr scale, Levodopa Equivalent Daily Dose (LEDD) and non-motor symptoms (psychotic episodes, depressive symptoms, and cognitive decline). RESULTS: The sample was composed of 103 patients (72 males, mean age at DBS surgery 61.5 ± 8.7 years, mean postoperative follow-up 7.0 ± 4.1 years). Of these, 19 were LRRK2-PD, 20 GBA1-PD, and 64 were Nc-PD. No significant differences in motor outcomes were observed between the groups. Compared to the Nc-PD patients, the GBA1-PD patients were at increased risk of both psychotic episodes [hazard ratio (HR) 2.76 (95 % CI: 1.12-6.80), p = 0.027], and cognitive decline [HR 2.28 (95 % CI: 1.04-5.00), p = 0.04]. CONCLUSION: LRRK2 and GBA1 variant status did not affect the motor outcomes of DBS in PD patients. However, GBA1-PD patients were at increased risk for psychosis and cognitive decline. Further studies are required to determine the role of genetic stratification in referral to DBS.

Indocyanine green video angiography-assisted surgical management of coil migration resulting from the endovascular treatment of anterior communicating artery aneurysm: technical case report and instrumentation assessment.

We describe surgical management of herniated coil using indocyanine green video angiography (ICGA) following failure of endovascular retrieval methods in a patient who had endovascular treatment for anterior communicating artery aneurysm. The interdisciplinary cooperation between the endovascular and neurosurgical teams proved to be crucial for obtainment of a desirable outcome in this case. ICGA technology applied in such difficult cases may improve the surgical outcome.

Focused ultrasound-mediated blood-brain barrier opening in Alzheimer's disease: long-term safety, imaging, and cognitive outcomes.

OBJECTIVE: MRI-guided low-intensity focused ultrasound (FUS) has been shown to reversibly open the blood-brain barrier (BBB), with the potential to deliver therapeutic agents noninvasively to target brain regions in patients with Alzheimer's disease (AD) and other neurodegenerative conditions. Previously, the authors reported the short-term safety and feasibility of FUS BBB opening of the hippocampus and entorhinal cortex (EC) in patients with AD. Given the need to treat larger brain regions beyond the hippocampus and EC, brain volumes and locations treated with FUS have now expanded. To evaluate any potential adverse consequences of BBB opening on disease progression, the authors report safety, imaging, and clinical outcomes among participants with mild AD at 6-12 months after FUS treatment targeted to the hippocampus, frontal lobe, and parietal lobe. METHODS: In this open-label trial, participants with mild AD underwent MRI-guided FUS sonication to open the BBB in ß-amyloid positive regions of the hippocampus, EC, frontal lobe, and parietal lobe. Participants underwent 3 separate FUS treatment sessions performed 2 weeks apart. Outcome assessments included safety, imaging, neurological, cognitive, and florbetaben ß-amyloid PET. RESULTS: Ten participants (range 55-76 years old) completed 30 separate FUS treatments at 2 participating institutions, with 6-12 months of follow-up. All participants had immediate BBB opening after FUS and BBB closure within 24-48 hours. All FUS treatments were well tolerated, with no serious adverse events related to the procedure. All 10 participants had a minimum of 6 months of follow-up, and 7 participants had a follow-up out to 1 year. Changes in the Alzheimer's Disease Assessment Scale-cognitive and Mini-Mental State Examination scores were comparable to those in controls from the Alzheimer's Disease Neuroimaging Initiative. PET scans demonstrated an average ß-amyloid plaque of 14% in the Centiloid scale in the FUS-treated regions. CONCLUSIONS: This study is the largest cohort of participants with mild AD who received FUS treatment, and has the longest follow-up to date. Safety was demonstrated in conjunction with reversible and repeated BBB opening in multiple cortical and deep brain locations, with a concomitant reduction of ß-amyloid. There was no apparent cognitive worsening beyond expectations up to 1 year after FUS treatment, suggesting that the BBB opening treatment in multiple brain regions did not adversely influence AD progression. Further studies are needed to determine the clinical significance of these findings. FUS offers a unique opportunity to decrease amyloid plaque burden as well as the potential to deliver targeted therapeutics to multiple brain regions in patients with neurodegenerative disorders.

A novel rodent model of spinal metastasis and spinal cord compression.

BACKGROUND: Spinal cord metastatic lesions affect a high number of cancer patients usually resulting in spinal cord compression syndrome. A major obstacle in the research of spinal metastatic disease is the lack of a simple reproducible animal model that mimics the natural course of the disease. In this study, we present a highly reproducible rodent model that can be used for different types of cancers while mimicking the natural course of human metastatic spinal cord compression syndrome. RESULTS: All sixteen Fisher 344 rats survived the dorsal approach intraosseous implantation of CRL-1666 adenocarcinoma cells and both rats survived the sham control surgery. By Day 13 functional analysis via the modified Basso-Beattie-Bresnahan (BBB) locomotor rating scale showed significant decrease in motor function; median functional score was 3 for the tumor group (p = 0.0011). Median time to paresis was 8.7 days post-operatively. MR imaging illustrated repeated and consistent tumor formation, furthermore, onset of neurological sequale was the result of tumor formation and cord compression as confirmed by histological examination. CONCLUSIONS: Analysis of these findings demonstrates a repeatable and consistent tumor growth model for cancer spinal metastases in rats. This novel rat model requires a less intricate surgical procedure, and as a result minimizes procedure time while subsequently increasing consistency. Therefore, this model allows for the preclinical evaluation of therapeutics for spinal metastases that more closely replicates physiological findings.

The rat rotenone model reproduces the abnormal pattern of central catecholamine metabolism found in Parkinson's disease.

Recent reports indicate that Parkinson's disease (PD) involves specific functional abnormalities in residual neurons - decreased vesicular sequestration of cytoplasmic catecholamines via the vesicular monoamine transporter (VMAT) and decreased aldehyde dehydrogenase (ALDH) activity. This double hit builds up the autotoxic metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), the focus of the catecholaldehyde hypothesis for the pathogenesis of PD. An animal model is needed that reproduces this abnormal catecholamine neurochemical pattern. Adult rats received subcutaneous vehicle or the mitochondrial complex 1 inhibitor rotenone (2 mg/kg/day via a minipump) for 10 days. Locomotor activity was recorded, and striatal tissue sampled for catechol contents and catechol ratios that indicate the above abnormalities. Compared to vehicle, rotenone reduced locomotor activity (P=0.002), decreased tissue dopamine concentrations (P=0.00001), reduced indices of vesicular sequestration (3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine) and ALDH activity (DOPAC/DOPAL) (P=0.0025, P=0.036), and increased DOPAL levels (P=0.04). The rat rotenone model involves functional abnormalities in catecholaminergic neurons that replicate the pattern found in PD putamen. These include a vesicular storage defect, decreased ALDH activity and DOPAL build-up. The rat rotenone model provides a suitable in vivo platform for studying the catecholaldehyde hypothesis.

Comparison of Frame-Based Versus Frameless Image-Guided Intracranial Stereotactic Brain Biopsy: A Retrospective Analysis of Safety and Efficacy.

BACKGROUND: A definitive diagnosis of brain lesions not amenable to surgery is mainly made by stereotactic needle biopsy. The diagnostic yield and safety of the frameless versus frame-based image-guided stereotactic techniques is unclear. Our objective was to evaluate the safety and accuracy of frameless versus frame-based stereotactic brain biopsy techniques. METHODS: A total of 278 patients (153 men; mean age: 65.5 years) with intra-axial brain lesions underwent frame-based (n = 148) or frameless image-guided stereotactic brain biopsy (n = 130) using a minimally invasive twist drill technique during 2010-2016 at Sheba Medical Center. Demographic, imaging, and clinical data were retrospectively analyzed. RESULTS: The diagnostic yield (>90%) did not differ significantly between groups. Overall morbidity (6.8% vs. 8.5%), incidence of permanent neurologic deficits (2.1% vs. 1.6%), mortality rate (0.7% vs. 0.8%), and postoperative computed tomography-detected asymptomatic (14.2% vs. 16.1%) and symptomatic (2.0% vs. 1.6%) bleeding also did not differ significantly between the frame-based and frameless cohorts, respectively. The diagnostic yield and complication rates related to the biopsy technique were not significantly associated with sex, age, entry angle to the skull and skull thickness, lesion location or depth, or radiologic characteristics. Diagnostic yield was significantly associated with the mean lesion volume. Smaller lesions were less diagnostic than larger lesions in both techniques (P = 0.043 frame-based and P = 0.048 frameless). CONCLUSIONS: The frameless biopsy technique is as efficient as the frame-based brain biopsy technique with a low complication rate. Lesion volume was the only predictive factor of diagnostic yield. The minimally invasive twist drill technique is safe and efficient.

Magnetic resonance imaging analysis predicts nanoparticle concentration delivered to the brain parenchyma.

Ultrasound in combination with the introduction of microbubbles into the vasculature effectively opens the blood brain barrier (BBB) to allow the passage of therapeutic agents. Increased permeability of the BBB is typically demonstrated with small-molecule agents (e.g., 1-nm gadolinium salts). Permeability to small-molecule agents, however, cannot reliably predict the transfer of remarkably larger molecules (e.g., monoclonal antibodies) required by numerous therapies. To overcome this issue, we developed a magnetic resonance imaging analysis based on the ΔR2* physical parameter that can be measured intraoperatively for efficient real-time treatment management. We demonstrate successful correlations between ΔR2* values and parenchymal concentrations of 3 differently sized (18 nm-44 nm) populations of liposomes in a rat model. Reaching an appropriate ΔR2* value during treatment can reflect the effective delivery of large therapeutic agents. This prediction power enables the achievement of desirable parenchymal drug concentrations, which is paramount to obtaining effective therapeutic outcomes.

Neuro-ophthalmologic outcomes of standard versus hypo-fractionated stereotactic radiotherapy of AVPM.

BACKGROUND: Most anterior visual pathway meningiomas (AVPM) are benign and slow-growing, but these tumors may affect visual functions, including visual acuity (VA) and visual field (VF). Due to location, most are treated non-surgically by fractionated stereotactic radiotherapy (FSRT), aiming to prevent tumor progression and visual functions deterioration. Unfortunately, FSRT in itself may affect visual functions. The current preferred treatment regimen (in terms of safety and effectiveness) is undetermined. While most cases are treated with conventional fractionation (cFSRT)-50.4-54 Gy in 28-30 fractions of 1.8-2 Gy, advances in technology have allowed shortening of total treatment length to hypofractionation (hSRT)-25-27 Gy in 3-5 fractions of 5-9 Gy. Our aim was to evaluate the association of radiotherapy regimen for treating AVPM (cFSRT vs. hSRT) with visual function outcomes (VA, VF) at the last neuro-ophthalmologic evaluation. METHODS: We conducted a retrospective cohort study of AVPM cases treated at Sheba Medical Center during 2004-2015. We compared cFSRT and hSRT regimens regarding visual function (VA, VF) outcomes at the last neuro-ophthalmologic evaluation. VA was determined by the logarithm of the minimum angle of resolution (LogMAR). VF was determined by the mean deviation (MD). A clinically relevant change in VA was defined as 0.2 LogMAR. RESULTS: 48 patients (13 receiving hSRT, 35 receiving cFSRT) were included, with a median follow-up of 55 months. No significant difference was evident regarding LogMAR or MD of involved eyes at the last evaluation. Six (17%) patients in the cFSRT group experienced clinically relevant VA deterioration in the involved eye, compared with six (46%) in hSRT (p = 0.06). CONCLUSION: Our findings, using comprehensive and meticulous investigation of visual outcomes, suggest that hSRT may be associated with higher risk for VA and VF deterioration in AVPM especially in ONSM. We recommend the use of cFSRT for ONSM.