Adjuvant proton beam therapy in patients with grade 2 meningiomas.

Background: The World Health Organization (WHO) grade 2 meningiomas behave aggressively with a high proclivity toward recurrence despite maximal surgical resection. Our institution, a pioneer of proton therapy, uses exclusively proton beam radiation, and thus, we present a retrospective cohort analysis of patients with WHO grade 2 meningiomas treated with adjuvant proton beam therapy (PBT) at our institution between 2007 and 2019. The effects of adjuvant PBT were evaluated. Methods: Data collected include diagnosis, gender, histological subtype, WHO grade, the extent of surgical resection, adjuvant PBT radiation, details of the PBT radiation, recurrence, any additional PBT radiation, systemic medical therapy, and disease-specific survival. Results: Among the WHO grade 2 meningiomas (n = 50) recommended PBT, 80% and 78% of patients with gross-total resection (GTR) and subtotal resection (STR), respectively, followed through with PBT. The median radiation dose of PBT was 59.5 Gy and 59.92 Gy for patients with GTR and STR, respectively, with a median of 33 fractions delivered in 1.8 Gy doses for both groups. Combined 3-year progression-free survival (PFS) was 96%, and 5-year PFS was 92%. Combined overall survival was 95% at five years. Minimal radiation side effects were reported with no grade 3 or higher toxicities. Conclusion: Our results suggest that adjuvant PBT is well tolerated with minimal radiation toxicity. Alternative to photon radiation, PBT may be considered at least as safe and effective for adjuvant treatment of WHO grade 2 meningiomas when it is available.

Delayed revascularization in acute ischemic stroke patients.

Stroke shares a significant burden of global mortality and disability. A significant decline in the quality of life is attributed to the so-called post-stroke cognitive impairment including mild to severe cognitive alterations, dementia, and functional disability. Currently, only two clinical interventions including pharmacological and mechanical thrombolysis are advised for successful revascularization of the occluded vessel. However, their therapeutic effect is limited to the acute phase of stroke onset only. This often results in the exclusion of a significant number of patients who are unable to reach within the therapeutic window. Advances in neuroimaging technologies have allowed better assessment of salvageable penumbra and occluded vessel status. Improvement in diagnostic tools and the advent of intravascular interventional devices such as stent retrievers have expanded the potential revascularization window. Clinical studies have demonstrated positive outcomes of delayed revascularization beyond the recommended therapeutic window. This review will discuss the current understanding of ischemic stroke, the latest revascularization doctrine, and evidence from clinical studies regarding effective delayed revascularization in ischemic stroke.

Stem Cell Therapy in Brain Ischemia: The Role of Mitochondrial Transfer.

Mitochondrial dysfunction is an important pathological process in the setting of ischemic brain injury. Stem cell-mediated mitochondrial transfer provides an efficient intercellular process to supply additional mitochondria in the ischemic brain tissues. In this review, we summarize the mitochondrial pathology associated with brain ischemia, mechanisms of stem cell-mediated mitochondrial transfer, and in vitro/in vivo experimental findings of mitochondrial transfer from stem cells to ischemic vascular endothelial cells/neurons as potential therapeutic strategy in the management of ischemic brain injury.

SCING-Spinal Cord Injury Neuroprotection with Glyburide: a pilot, open-label, multicentre, prospective evaluation of oral glyburide in patients with acute traumatic spinal cord injury in the USA.

INTRODUCTION: Acute traumatic spinal cord injury (tSCI) is a devastating neurological disorder with no pharmacological neuroprotective strategy proven effective to date. Progressive haemorrhagic necrosis (PHN) represents an increasingly well-characterised mechanism of secondary injury after tSCI that negatively impacts neurological outcomes following acute tSCI. Preclinical studies evaluating the use of the Food and Drug Administration-approved sulfonylurea receptor 1-transient receptor potential melastatin 4 channel blocker glyburide in rodent models have shown reduced secondary microhaemorrhage formation and the absence of capillary fragmentation, the pathological hallmark of PHN. METHODS AND ANALYSIS: In this initial phase multicentre open-label pilot study, we propose to enrol 10 patients with acute cervical tSCI to primarily assess the feasibility, and safety of receiving oral glyburide within 8 hours of injury. Secondary objectives include pharmacokinetics and preliminary evaluations on neurological recovery as well as blood and MRI-based injury biomarkers. Analysis will be performed using the descriptive and non-parametric statistics. ETHICS AND DISSEMINATION: Glyburide has been shown as an effective neuroprotective agent in preclinical tSCI models and in the treatment of ischaemic stroke with the additional risk of a hypoglycaemic response. Given the ongoing secondary injury and the traumatic hyperglycaemic stress response seen in patients with tSCI, glyburide; thus, offers an appealing neuroprotective strategy to supplement standard of care treatment. The study protocol was approved by the Ohio State University Biomedical Institutional Review Board. The protocol was amended in February 2017 with changes related to study feasibility and patient recruitment. Specifically, the route of administration was changed to the oral form to allow for streamlined and rapid drug administration, and the injury-to-drug time window was extended to 8 hours in an effort to further enhance enrolment. Participants or legally authorised representatives are informed about the trial and its anticipated risks orally and in written form using an approved informed consent form prior to inclusion. The findings of this study will be disseminated to the participants and to academic peers through scientific conferences and peer-reviewed journal publications. TRIAL REGISTRATION NUMBERS: NCT02524379 and 2014H0335.

Surgical Considerations of Intractable Mesial Temporal Lobe Epilepsy.

Surgery of temporal lobe epilepsy is the best opportunity for seizure freedom in medically intractable patients. The surgical approach has evolved to recognize the paramount importance of the mesial temporal structures in the majority of patients with temporal lobe epilepsy who have a seizure origin in the mesial temporal structures. For those individuals with medically intractable mesial temporal lobe epilepsy, a selective amygdalohippocampectomy surgery can be done that provides an excellent opportunity for seizure freedom and limits the resection to temporal lobe structures primarily involved in seizure genesis.

Establishment of a comprehensive epilepsy center in pakistan: initial experiences, results, and reflections.

Background. Developing countries, home to 80% of epilepsy patients, do not have comprehensive epilepsy surgery programs. Considering these needs we set up first epilepsy surgery center in Pakistan. Methods. Seventeen teleconferences focused on setting up an epilepsy center at the Aga Khan University (AKU), Karachi, Pakistan were arranged with experts from the University of Alberta Hospital, Alberta, Canada and the University of West Virginia, USA over a two-year period. Subsequently, the experts visited the proposed center to provide hands on training. During this period several interactive teaching sessions, a nationwide workshop, and various public awareness events were organized. Results. Sixteen patients underwent surgery, functional hemispherectomy (HS) was done in six, anterior temporal lobectomy (ATL) in six, and neuronavigation-guided selective amygdalohippocampectomy (SAH) using keyhole technique in four patients. Minimal morbidity was observed in ATL and, SAH groups. All patients in SAH group (100%) had Grade 1 control, while only 5 patients (83%) in ATL group, and 4 patients (66%) in HS group had Grade 1 control according to Engel's classification, in average followups of 12 months, 24 months and 48 months for SAH, ATL, and HS, respectively. Conclusion. As we share our experience we hope to set a practical example for economically constrained countries that successful epilepsy surgery centers can be managed with limited resources.

Delineation of the safe zone in surgery of sylvian insular triangle: morphometric analysis and magnetic resonance imaging study.

BACKGROUND: Surgery within the insula carries significant risk of morbidity, particularly hemiparesis, because of the difficulty in detecting the internal capsule boundaries. OBJECTIVE: We analyzed the anatomy of the insula and identified landmarks anticipated to facilitate surgery for intrinsic insular lesions. METHODS: Insular region anatomy was studied in 11 cadaveric brains harvested within 72 hours postmortem. MRI of the specimens was acquired using 3.0 T with T2-weighting and 25 directions of diffusion tensor imaging. Landmarks easily recognizable during surgery were identified on the surface of the insula. The interrelationships between surface landmarks and critical structures were analyzed. RESULTS: The posterior inferior insular point (PIIP) and the upper central insular point (UCIP) were newly established as landmarks on the insula. The PIIP corresponded to the obvious bend in the posterior long insular gyrus. The UCIP is the meeting point between the central insular sulcus and superior peri-insular sulcus. The corticospinal tract was identified as a high-intensity area in the posterior limb of the internal capsule on T2-weighted imaging and its course confirmed with diffusion tensor imaging tractography. The corticospinal tract took a course deep to the posterosuperior insula on T2-weighted imaging, 4.8 mm from the UCIP and 6.2 mm from the PIIP. CONCLUSION: The posterosuperior part of the insula forms the region at greatest risk to corticospinal tract injury. The PIIP and UCIP are crucial to understanding the relationship of the insula with the posterior limb of the internal capsule including the corticospinal tract.

Professor Uchimura, Ammon's horn sclerosis, and the German influence on Japanese neuroscience.

In the early twentieth century, the German laboratories of Spielmeyer and the Vogts proposed competing pathogenetic theories for Ammon's horn sclerosis. Spielmeyer's vascular pathogenesis theory was initially preferred, but the Vogts' Pathoklise theory was later favored. From 1925 to 1927, Uchimura worked in the Spielmeyer's laboratory. There, Uchimura first described the detailed vascular anatomy of the hippocampus. His work formed the basis for the vascular theory of Ammon's horn sclerosis. Because of Germany's prominence in medical science and Japan's preference for the German medical system, Uchimura among many young Japanese medical scientists, travelled to the institutes of German-speaking Europe for training.

Fluorodeoxyglucose-positron emission tomographic imaging for the diagnosis of mesial temporal lobe epilepsy.

OBJECTIVE: Fluorodeoxyglucose (FDG)-positron emission tomographic (PET) imaging plays an important role in the evaluation of intractable epilepsy. The metabolic defect has proven utility in the lateralization of temporal lobe epilepsy. However, the role of FDG-PET imaging in the localization of a seizure focus within the temporal lobe is uncertain. We evaluated FDG-PET imaging for the capability to localize a temporal seizure focus within the mesial structures. METHODS: Twenty-eight patients who underwent selective amygdalohippocampectomy for intractable temporal lobe epilepsy were studied. Patients were divided into 2 groups: those who were free of seizures (FS) and those with persisting seizures postoperatively. FS patients were defined by having mesial temporal lobe epilepsy (MTLE). Preoperative FDG-PET activity was evaluated in temporal lobe structures and contrasted with magnetic resonance imaging (MRI) for usefulness in identifying MTLE in an individual. RESULTS: Pathology of the hippocampus revealed mesial temporal sclerosis in all but 1 patient. Qualitative visual inspection of the MRI scan was not reliable in the identification of MTLE (P = 0.15). MRI volumetry found smaller mesial temporal structures (P = 0.04) in FS patients. Mesial temporal metabolic activity was reduced in the FS group (hippocampus, P = 0.001). However, a combination of imaging modalities was found to be the best predictor of MTLE. PET imaging plus MRI qualitative inspection identified all patients with and without MTLE correctly and was superior to MRI alone (P = 0.01 and P = 0.02, respectively). CONCLUSION: MRI volumetry and PET imaging were comparable (P = 0.73) and able to identify MTLE in most patients, but a combination of PET imaging and MRI visual inspection was superior in the recognition of MTLE.

Localization of hand sensory function to the pli de passage moyen of Broca.

OBJECT: The goal of this study was to identify a reliable landmark for hand sensory function in the central area. METHODS: Hand sensory activation on positron emission tomography (PET) scans was analyzed in 27 patients. Each PET study was coregistered with the patient's magnetic resonance image and analyzed in two-dimensional and three-dimensional cortical surface reconstructions to define anatomicofunctional relationships. CONCLUSIONS: The substratum of hand sensory function is a prominent fold of cortex elevating the floor of the central sulcus and connecting the pre- and postcentral gyri. Broca named this cortical fold the pli de passage moyen, and hand motor function has been localized to the precentral component of this structure. In this study the authors demonstrate that hand sensory function is highly correlated with the postcentral component of the pli de passage moyen, and that this structure is a reliable cortical landmark for identifying the aforementioned function.