Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces IgG autoantibody levels through FcRn blockade. This study reports safety of efgartigimod across IgG-mediated disorders. Methods: The safety of intravenous efgartigimod was evaluated in 204 efgartigimod-treated subjects with generalized myasthenia gravis (phase 3 ADAPT and 3-year open-label extension ADAPT+ trials), primary immune thrombocytopenia (phase 3 ADVANCE trial), or pemphigus (open-label phase 2 trial). These studies examined different efgartigimod doses (10–25 mg/kg), including cyclical dosing in generalized myasthenia gravis and continuous weekly dosing in primary immune thrombocytopenia and pemphigus. Results: Across all indications and doses studied, efgartigimod demonstrated a consistent safety profile, with treatment-emergent adverse event (TEAE) rates comparable to placebo (ADAPT, 77.4% efgartigimod/84.3% placebo; ADVANCE, 93.0% efgartigimod/95.6% placebo; and 85% in the pemphigus study). Most TEAEs were mild to moderate in severity. Discontinuation rates due to adverse events were consistently low (ADAPT, 3.6% efgartigimod/3.6% placebo; ADVANCE, 3.5% efgartigimod/2.2% placebo; and 3% of pemphigus study participants). In ADAPT+, no increases in TEAEs or infections occurred with additional efgartigimod dosing (19 cycles). Conclusions: Efgartigimod was well tolerated across indications and doses studied. Most TEAEs, including infections, were mild or moderate in severity and did not increase in frequency with recurrent dosing.

Background: ALS is a progressive neurodegenerative disease without a cure and limited treatment options. Edaravone, a free radical scavenger, was shown to slow disease progression in a select group of patients with ALS over 6 months; however, the effect on survival was not investigated in randomized trials. The objective of this study is to describe real-world survival effectiveness over a longer timeframe. Methods: This retrospective cohort study included patients with ALS across Canada with symptom onset up to three years. Those with a minimum 6-month edaravone exposure between 2017 and 2022 were enrolled in the interventional arm, and those without formed the control arm. The primary outcome of tracheostomy-free survival was compared between the two groups, accounting for age, sex, ALS-disease progression rate, disease duration, pulmonary vital capacity, bulbar ALS-onset, and presence of frontotemporal dementia or C9ORF72 mutation using inverse propensity treatment weights. Results: 182 patients with mean ± SD age 60±11 years were enrolled in the edaravone arm and 860 in the control arm (mean ± SD age 63±12 years). Mean ± SD time from onset to edaravone initiation was 18±10 months. Tracheostomy-free survival will be calculated. Conclusions: This study will provide evidence for edaravone effectiveness on tracheostomy-free survival in patients with ALS.

Background: Lemborexant (LEM), a dual-orexin-receptor-antagonist approved to treat adults with insomnia, increases total sleep time (TST) and rapid eye movement (REM) sleep. Patients with obstructive sleep apnea (OSA) or co-morbid insomnia and OSA (COMISA) report sleeping difficulties and reduced REM, therefore sleep architecture was analyzed during LEM treatment. Methods: Study E2006-G000-304 (NCT02783729) was a 1-month, randomized, double-blind, placebo (PBO)- and active-comparator zolpidem-ER 6.25mg (ZOL)-controlled study in adults ≥55y with insomnia disorder. Subjects received PBO, LEM 5mg (LEM5), 10mg (LEM10), or ZOL. Least-square-mean duration of each sleep stage (minutes) was compared from pooled data on Nights (NT)1/2 and NT29/30 for mild OSA subjects (apnea hypopnea index ≥5 to <15 events/h). Treatment-emergent adverse events (TEAEs) were recorded. Results: Of 409 subjects with mild OSA (LEM5=114/LEM10=105/ZOL=112/PBO=78) change from baseline (CFB) in TST and REM sleep was significantly larger with both LEM doses versus ZOL/PBO on both nights. CFB for total nonREM sleep was significantly higher (P<0.0001) with both LEM doses versus PBO on both nights. LEM5 showed significantly higher (P<0.05) nonREM sleep versus ZOL at NT29/30. Most TEAEs were mild/moderate. Conclusions: LEM significantly increased TST, REM, and nonREM sleep versus PBO in subjects with insomnia and mild OSA. Data support LEM treatment in the COMISA population.

Background: Sodium phenylbutyrate and ursodoxicoltaurine/taurursodiol (PB&TURSO) is indicated for the treatment of amyotrophic lateral sclerosis (ALS) in Canada and the U.S. In the CENTAUR trial, a phase 2 U.S. multicenter trial in ALS, PB&TURSO was generally well-tolerated. The most common adverse reactions were gastrointestinal (GI) and occurred most often during the first three weeks of therapy. Although the occurrence of GI events in people living with ALS (PLWALS) and treated with PB&TURSO are recognisable and generally manageable, many of the symptoms are often not managed proactively. We sought to develop an evidence-based tool to help guide clinicians on managing diarrhea and abdominal pain in PLWALS and treated with PB&TURSO. Methods: Three ALS specialized neurologists and one gastroenterologist combined their clinical experience, research, and each Medications respective product monograph, to develop a patient-centric GI tool. Results: A guide to monitoring and managing potential GI events with PB&TURSO was developed. The tool provides clinicians a proactive, step-by-step guide to help manage diarrhea and abdominal pain in PLWALS treated with PB&TURSO. Conclusions: The GI tool has the potential to improve monitoring, recognition, and treatment of GI events in PLWALS treated with PB&TURSO. Proactively managing GI events may aid medication adherence and improve patient quality of life.

Background: Despite significant advances in the treatment of neurological disorders, many conditions remain palliative. Neurologists are in a unique position as they are integral in providing patient centered care, understanding neurologic disease and illness trajectory, and how disease can affect patients’ sense of self and values. Currently, little is known about neurologists’ perceptions and challenges in care planning and palliative care for their patients. Methods: A qualitative approach was utilized with semi-structured interviews of ten neurologists. Data was analyzed using a constant comparative method (constructivist grounded theory). Results: Participants represented a broad spectrum of neurologist experience and subspecialties. Four theories were identified: (1) care planning and palliative care are high priorities, (2) neurologic diseases uniquely affect patients and require a dynamic, patient-centered care plan, (3) a care gap exists in providing palliative care for neurologic patients with multifactorial barriers, and (4) opportunities to improve care exist with continuing education, collaboration, and health system support. Conclusions: Neurologists have a key role in care planning and palliative care for patients with chronic neurological diseases. Our findings show that there is a gap in the provision of palliative care. Future directions may include exploring educational opportunities and dedicated health systems to improve care management.

Background: Obstructive sleep apnea (OSA) may be associated with sleep difficulties and decreased rapid eye movement (REM) sleep. Lemborexant (LEM), a dual-orexin-receptor-antagonist approved to treat adults with insomnia, increases total sleep time (TST) and REM sleep, and demonstrated respiratory safety in subjects with mild through severe OSA. Sleep architecture was thus analyzed after LEM treatment in those subjects. Methods: Studies E2006-A001-102 and E2006-A001-113 enrolled adults with mild (apnea-hypopnea index [AHI] ≥5 – <15) or moderate (AHI ≥15 – <30)/severe (AHI ≥30) OSA without insomnia. Subjects received LEM 10mg (LEM10) or placebo (PBO) in 2 treatment periods, Days 1 (D1) and 8 (D8), separated by ≥14 days. Least-squares-mean (minutes) for each sleep stage was compared. Treatment-emergent adverse events (TEAEs) were recorded. Results: Thirty-nine subjects with mild and 33 with moderate/severe OSA were randomized. On both days, TST was significantly higher in the LEM period for these subjects. Total non-REM on D1 in subjects with mild OSA and on both days in subjects with moderate/severe OSA were higher with LEM than PBO; REM also significantly increased in subjects with mild and moderate/severe OSA. Most TEAEs were mild. Conclusions: In OSA subjects without insomnia, LEM was associated with higher TST, non-REM, and REM versus PBO.

Background: Some sleep-promoting medications are associated with cognitive impairment, making treatment of comorbid obstructive-sleep-apnea (OSA) and insomnia (COMISA) challenging. Lemborexant is a dual-orexin-receptor-antagonist approved for insomnia treatment. This post-hoc analysis evaluated cognition in the subgroup of subjects with mild-OSA (apnea-hypopnea-index ≥5–<15 events/h-of-sleep). Methods: Study E2006-G000-304 was a 1-month, randomized, double-blind, placebo (PBO)- and active-comparator (zolpidem-ER 6.25mg [ZOL])-controlled study of lemborexant 5/10mg (LEM5/LEM10). Subjects ≥55y with insomnia disorder/sleep maintenance problems were enrolled (N=1006). A cognitive-performance assessment battery (CPAB) was performed at morning waketime of Days(D)2/3 and D30/31. Change-from-baseline (CFB) for mean power-of-attention (PoA), continuity-of-attention (CoA), quality-of-memory (QoM), and speed-of-memory-retrieval (SoMR) for CPAB tasks was analyzed. Results: The mild-OSA subgroup comprised 410 (40.8%) subjects. On D2/3 and D30/31, CFB for PoA, CoA, QoM, and SoMR for LEM5/LEM10 were not significantly different than PBO. On D2/3, PoA and QoM were significantly worse with ZOL vs PBO; QoM was significantly better with LEM5/LEM10 vs ZOL. On D30/31, SoMR was significantly worse with ZOL vs PBO and significantly better with LEM5/LEM10 vs ZOL. LEM safety in the subgroup was consistent with the overall study population. Conclusions: Memory and attention domains in subjects with COMISA characterized by mild-OSA were not impacted by LEM, unlike ZOL.

Support: Eisai Inc.

Background: Although unapproved by the FDA for treating insomnia, trazodone is commonly prescribed in the US partly due to lack of scheduling, hence it’s perceived as safer than z-drugs and benzodiazepines. This study investigated trazodone abuse/dependence potential and safety risks. Methods: Cases involving trazodone or benzodiazepines (temazepam, triazolam, estazolam) frequently prescribed for insomnia were identified from the FDA Adverse Events Reporting System (FAERS), National Forensic Laboratory Information System (NFLIS) for confiscation data, and the American Association of Poison Control Centers’-National Poison Data System (AAPCC-NPDS). Drug-related falls risk was assessed from claims databases. Results: FAERS included 11,228 trazodone and 5120 benzodiazepine reports. Of these, drug-abuse and drug-dependence cases with trazodone were lower than benzodiazepines (drug-abuse: 6.4%/12.6%; drug-dependence: 1.1%/3.6%). Serious cases (81.8%/83.9%) and deaths (35.4%/36.0%), were similar between trazodone and benzodiazepines. NFLIS reported 612/1,575,874 (0.04%) drug-seizure cases that included trazodone. AAPCC-NPDS reported 22,225/1,446,011 (1.54%) total case mentions of trazodone/all pharmaceuticals and 8445 trazodone-related single-exposure cases. Falls risk (1year-period) in Medicare beneficiaries ≥65y and commercially-insured enrollees ≥18y was reported for trazodone and benzodiazepines: Medicare, 9.5%/11.3%; Commercially-insured: 4.6%/3.7%. Conclusions: Trazodone has abuse/dependence potential and important safety risks. Given limited data from well-controlled studies and off-label use, re-evaluation of trazodone prescribing rates in patients with insomnia is warranted.

Background: Improvements in sleep-onset, maintenance, and daytime functioning, are all important outcomes for the treatment of insomnia. These improvements are usually assessed by objective or patient-reported (subjective) measures or both. Some sleep-promoting drugs do not report consistently aligned subjective and objective outcomes. Therefore, we examined concordance in change from baseline (CFB) in sleep parameters (objective/subjective measures) and daytime functioning (subjective measures) in the clinical program of lemborexant (LEM), a dual-orexin receptor antagonist. Methods: Study E2006-G000-304 (NCT02783729), a 1-month, placebo (PBO)- and active-controlled (zolpidem; not discussed here) study, and Study E2006-G000-303 (NCT02952820), a 12-month, randomized, PBO-controlled study (first 6-months), evaluated the efficacy/safety of LEM 5mg (LEM5) and LEM 10mg (LEM10) in subjects with insomnia disorder. The primary/secondary endpoints in both studies included multiple objective/subjective sleep parameters and patient-reported measures, which were assessed for concordance. Results: In both studies, statistically significant improvements with LEM5/LEM10 were reported in multiple objective and patient-reported measures versus PBO, showing a concordance of results, with observed improvements continuing through 12 months. LEM was well tolerated; most treatment-emergent adverse events were mild/moderate. Conclusions: When deciding which sleep agent to prescribe, it is important that improvement can be demonstrated in both objective and patient-reported measures. LEM treatment showed concordance among observed measures.

Background: There is a well-established reciprocal relationship between pain and poor sleep. Therefore, we evaluated whether an approved sleep-promoting drug, lemborexant (LEM), could improve sleep in older adults who reported both insomnia and pain. Methods: Study E2006-G000-304 (NCT02783729) was a 1-month, placebo (PBO)- and active-controlled study in subjects (age ≥55y) with insomnia disorder. Those reporting some/severe pain on the pain/discomfort dimension of the EQ-5D-3L at baseline were included. Subjects were randomized to placebo (PBO), LEM 5mg (LEM5), 10mg (LEM10) or zolpidem (not reported here). Changes from baseline (CFB) in objective sleep parameters latency-to-persistent sleep (LPS) and total-sleep-time (TST) were analyzed in paired polysomnograms. Results: 183/743 (24.6%) subjects in the PBO (n=55/208[26.4%]), LEM5 (n=78/266[29.3%]) and LEM10 (n=50/269[18.6%]) treatment groups reported some/extreme pain at baseline, with median LPS (minutes): 31.0, 29.4, 42.1, respectively. Respective median CFB for LPS at the beginning (Nights[NT]1/2: +2.5, –8.4, –15.8; P<0.005) was significantly larger/decreased for LEM5/LEM10 versus PBO and LEM5 at treatment end (NT29/30: –7.1, –9.9, –9.0; P=0.031). Mean baseline TST (minutes) was 335.3 (PBO), 336.3 (LEM5), 324.3 (LEM10), and mean CFB was significantly larger/increased (P<0.001) for LEM5/LEM10 versus PBO at NT1/2 and NT29/30. Conclusions: Results suggest LEM may effectively treat insomnia in older adults with comorbid pain.

Support: Eisai Inc.

Background: The Canadian Resident Matching Services (CaRMS) collects comprehensive data on residency applicants. However, match outcomes by age were not reported. It was unclear whether older applicants found it more difficult to match to the specialties of their choice, i.e. does age influence match? We ask in particular, does age affect the neurology match? Methods: In response to written request, CaRMS provided pre-pandemic age data for 2015-2019 inclusive, divided into group 1 (30 or younger) and group 2 (31-40 inclusive). Results: In 2019, 39 of the 69 group 1 and 6 of the 23 group 2 neurology applicants were matched into neurology (odds ratio (OR)=2.2|p=0.01). In contrast, urology (OR=6|p=0.001) had the worst odds and family medicine (OR=1.2|p=0.002) had the best odds for older applicants in 2019. Average OR (2015-2019) was 1.6 for neurology, 3.1 for urology, 1.3 for family medicine, and between 1.3 and 3.1 for nearly all other specialties. Conclusions: Older neurology applicants were less likely to match than younger peers while match probability was statistically significantly lower in nearly all specialties for older applicants.

Background: Thrombolysis (tPA) and endovascular thrombectomy (EVT) are interventions for acute ischemic stroke (AIS) that can be accompanied by intracerebral hemorrhage (ICH), which can alter the patient’s management, or contrast extravasation (CE), which is relatively benign. Previous retrospective studies have shown that dual-energy CT (DECT) is significantly more accurate for differentiating ICH from CE compared to conventional, single-energy CT (SECT). We are performing a prospective study to investigate this question. Methods: Our primary outcome is the sensitivity and specificity of DECT in differentiating ICH from CE. In AIS patients who receive intervention, we will be performing a DECT scan at the same time as the standard-of-care SECT scan at 24 hours post-intervention. In patients who have a hyperdensity on CT, a repeat scan will be done at 72-hours, which will be used as the gold-standard to determine if the hyperdensity was ICH or CE. Results: We expect that DECT will be significantly more sensitive and specific for differentiating ICH from CE compared to SECT. Conclusions: This study will determine if DECT is superior to SECT in differentiating ICH from CE, validate the use of DECT in AIS patients who receive intervention, and potentially change the imaging paradigm for acute stroke in the future.

Background: A 64-year-old man underwent an elective right total hip arthroplasty. Post-operatively, his GCS was 6, despite reversal of anesthetic agents. His toes were upgoing bilaterally. He did not have other focal neurologic deficits. He was intubated for airway protection. His only vascular risk factor was hypertension. Methods: [Case Report]Results: A CT/CTA/CTP head was unremarkable. A 1.5T MRI showed a few tiny, bihemispheric, embolic infarcts. These were not significant enough to account for his decreased level of consciousness. His blood work did not show evidence of coagulopathy. A subsequent 3T MRI demonstrated widespread, tiny embolic infarcts in a starfield pattern, consistent with cerebral fat embolism. A transesophageal echocardiogram with bubble study failed to demonstrate a right-to-left shunt. By post-operative day 11, he returned to his neurological baseline. Conclusions: A high degree of suspicion is required to diagnose cerebral fat embolism. There are reports of cerebral fat embolism in the absence of right-to-left shunt. The proposed mechanism is physiologic stress leading to systemic release of free fatty acids and inflammatory mediators, which damage capillary beds and disrupt the blood-brain barrier. This diagnosis has important prognostic implications as fat vacuoles deform easily and deficits are typically more reversible than those occurring with other embolic events.

Background: Stroke is a leading cause of death and disability worldwide, including Canada. Treatments for stroke are time dependent and IV tPA for acute ischemic stroke decreases the chance of disability at 90 days if given within 4.5 hours of symptom onset. The onset of the Covid-19 pandemic was initially associated with a decrease in acute stroke treatment with thrombolysis across North America. These decreases seemed transient, with a rebound in numbers seen in other provinces across Canada as widespread lockdown orders were lifted. However, a rebound in thrombolysis was not seen at Royal University Hospital (RUH) in Saskatoon, Saskatchewan during the same period. We will analyze documented reasons why thrombolysis was withheld. Methods: We conducted a retrospective chart review of adult patients with ischemic strokes presenting within 4.5 hours of symptom onset to the RUH from March 2019 –January 2021. We received a waiver of consent from the Research Ethics Board. Results: 128 patients met the inclusion criteria. Statistical analysis is currently ongoing. Conclusions: Initial results suggest that there are similar reasons for withholding tPA before and after the Covid-19 pandemic. The main reasons include rapidly resolving/resolved symptoms and a documented tPA exclusion criterion.

Background: Cerebral small vessel disease (CSVD) is associated with stroke, cognitive decline, and dementia. In this study, we examined how SVD is longitudinally related to cognitive performance in transient ischemic attack (TIA) patients compared to controls. Methods: We rated CSVD at baseline on MRI in TIA patients (n=197) and controls (n=113) for microbleeds (CMB), lacunes, white matter hyperintensities (WMH), and perivascular spaces (EPVS). Neuropsychological testing was administered across 5 years using the following assessments: BVMT, RAVLT, TMTA, TMTB, WAIS-R. Results: Periventricular WMH≥2 yielded slower performance on TMTB across all timepoints (adjusted difference 20.3 seconds, 95%CI [8.4,32.2]), as did deep WMH≥2 (20.1 sec, 95%CI [7.6,32.6]). Basal ganglia EPVS>20 performed slower on TMTA (10.1 sec, 95%CI [4.7,15.5]) and TMTB (21.2 sec, 95%CI [3.4,39.1]). Centrum semiovale EPVS>20 performed slower on TMTB (27.2 sec, 95%CI [10.6,43.8]) and worse on WAIS-R at 5-years (-18.6, 95%CI [-35.0,-2.2]). Lacunes≥3 performed slower on TMTA across all timepoints (4.0 sec, 95%CI [0.1,7.9]). Total CSVD≥2 performed slower on TMTA (3.7 sec, 95%CI [0.4,7.0]) and TMTB (13.9 sec, 95%CI [2.9,24.9]) across 5 years. When stratifying results, associations were generally found in TIA, not controls. Conclusions: Findings demonstrate that CSVD is associated with poorer cognitive performance longitudinally, and is more pronounced in TIA compared to control.

Background: Interprofessional collaboration is at the center of much of our work as Neurologists, yet often Medical Education inadequately prepares students for the complexities of interdisciplinary practice. Authentic, meaningful Interprofessional Education (IPE) requires consideration in involement of all individuals involved in interprofessional health care (IPHC) (Holbrook, 2013). Methods: We have collected authentic stories of acute stroke care through interviews with patients and other health care professionals on the acute stroke care team. Drawing on these narratives, we have crafted a multimedia story combining film, photography, and art. Results: This case will be integrated into Western University’s Undergraduate Medical Education curriculum but is intended to be a valuable tool for teaching IPE competencies in all IPE contexts. All media will be available thorugh Western Libaries open access Health Education Media Library. Main learning outcomes include improved recognition of HCP roles and the vital and diverse contributions of each team member. Conclusions: Drawing on the experiences of real stroke patients, families, and all other HCPs, we have crafted a rich educational case portraying the complexity of IPHC that will allow learners to reflect on the complex roles of health professoinals in a successful interprofessional team.

Background: Cervical and lumber spine manipulation therapy is widely used treatment of spinal degenerative disc disease. Serous side affects can be associated with this treatment especially in cervical spine. Stroke represents an infrequent adverse reaction associated with cervical spine manipulation therapy. Methods: 34 year old lady presented to Emergency Department (ED) referring Hospital 20 minutes after having neck manipulation by a chiropractor, she complained of neck pain after the manipulation with syncope, half hour later developed visual field loss, with few episodes of emesis, and increasing headache. Results: The patient was started on Aspirin and admitted locally for observation. Computers tomography (CT) head , CT-Angiography showed left Vertebral artery (V3 segment) , MRI showed acute infarction within the both cerebellar hemisphere, after 3 days patient transferred to our unit, patient had posterior fossa decompressive craniotomy with external ventricular drainage (EVD), discharged to rehabilitation 2 weeks, 2 months follow-up patient improving. Conclusions: There is inceased evidence that shows increased association between spinal manipulation and adverse effects and dissection of vertebral arteries in younger population. Younger patients (< 45 years) are particulary high risk, they should be informed of the risk of stroke or vascular injury from this procedure. No aggresive manipulation in younger population.

Background: Around 10% of ischemic stroke patients have pre-existing dementia and are excluded from stroke trials and routine care. Little is known about physician practices in the stroke care of people living with dementia (PLWD) leading to limited understanding of their experiences, priorities, and outcomes. This study aims to better understand PLWD through in-depth interviews. Methods: This study employs a qualitative descriptive methodology with two sets of 20 semi-structured interviews with PLWD and their primary caregivers (dyads), and with stroke physicians. Interviews with dyads investigate their experiences, priorities, and attitudes towards stroke care. Participants will be recruited through snowball sampling and interviews will be analyzed through qualitative data analysis software. Results: Initial analyses of the PLWD-caregiver dyad interviews have been completed, revealing themes of independence, uncertainty about the future, and fears of another stroke. Conclusions: As the population ages, stroke teams will likely encounter more PLWD. Engaging PLWD and their caregivers is crucial to better understand their experiences and priorities, which will inform future studies and improve their care. The findings from the dyad and physician interviews will be relevant to a broad audience, including patients, caregivers, physicians, researchers, and policymakers.

Background: The presence of intraluminal thrombi (ILT) in acutely symptomatic carotid stenosis (“hot carotid”) represents a therapeutic dilemma for physicians. With little evidence to guide treatment, current ILT management approaches rely on individual or institutional preferences. Methods: This mixed methods study analyzed themes from semi-structured interviews with 22 stroke physicians from 16 centers, paired with a worldwide case-based survey of 628 stroke physicians conducted through the “Practice Current” section of Neurology: Clinical Practice. Results: In the thematic analysis of the interviews and quantitative analysis of the survey, participants favoured using anticoagulation with or without antiplatelet agents in patients with ILT (463/628, 74%). Despite a preference for anticoagulation, uncertainty regarding optimal antithrombotic management was noted in the thematic analysis. Additional themes identified included a preference for re-imaging patients in 3-5 days after initiating treatment to look for complete or partial clot resolution, at which point most experts would then be comfortable proceeding with revascularization if indicated, though uncertainty regarding the optimal timing of revascularization was noted. Conclusions: In cases of ILT in the “hot carotid” practice patterns of global experts show a preference for using anticoagulation and reimaging patients in 3-5 days, though there is considerable equipoise regarding the most appropriate management of these patients.

Background: Edaravone (EDV) is an antioxidant that scavengs ROS, which is known to associate with pathophysiology of ischemic stroke. Low stability and bioavailability are major EDV drawbacks. Decorating nanogel surface with glutathione to target brain tissue was performed to optimize drug delivery. Methods: Nano vehicle characterization was assessed with FT-IR and HNMR. Images from the surface of nano vehicle was captured by AFM and TEM instruments. After development of mPEG-b-PLGA EDV nano particles, their effect on biochemical factors including malondialdehyde and protein carbonyl level was measured on Wistar rats under global ischemia. The level of GSH and FRAP were also measured. Results: The Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation was assessed and the calibration curve in deionized water was created at 244 nm. In-vitro drug release profile depicted a sustained release process. EDV and glutathione presence in one vehicle simultaneously, resulted in elevated spatial memory and learning along with cognitive function. In addition, significantly lower MDA and PCO, and higher level of neural GSH and FRAP were observed. Conclusions: The developed mPEG-b-PLGA EDV nanogel can be a suited vehicle for brain drug delivery of EDV, while managing to minimize the biochemical and pathophysiological alterations in ischemic-like disorder.