Clinical and radiological characteristics and outcomes of patients with recurrent or relapsing tumefactive demyelination.

BACKGROUND: Relapsing or recurrent tumefactive demyelination is rare and has not been studied beyond individual case reports. OBJECTIVE: We examined the clinical course, neuroimaging, cerebrospinal fluid (CSF), treatment and outcomes of patients with recurrent tumefactive demyelinating lesions (TDLs). METHODS: We used PubMed to identify reports of recurrent TDLs and included the details of an additional, unpublished patient. RESULTS: We identified 18 cases (11F, 7 M). The median age at onset of the index TDL was 37 years (range 12-72) and most were solitary lesions 72 % (13/18). CSF-restricted oligoclonal bands (OCBs) were detected in 25 % (4/16). Only one of those tested (n = 13) was positive for AQP4-IgG. A moderate-to-marked treatment response (high dose corticosteroid with or without additional plasmapheresis, IVIg or disease modifying therapies) was evident in 89 % of treated patients. Median EDSS at the median follow-up of 36 months (range 6-144) was 2 (range 1-10). Most remained ambulatory (EDSS < 4 in 13/18), but 1 patient died. CONCLUSION: The median age of patients with relapsing TDLs is similar to that of typical MS, but differences include a lower female:male sex ratio, larger lesions, and a comparative lack of CSF-restricted OCBs. Outcomes vary among this group of patients ranging from minimal disability through to death.

Prior anticoagulation and bridging thrombolysis improve outcomes in patients with atrial fibrillation undergoing endovascular thrombectomy for anterior circulation stroke.

BACKGROUND: Where stroke occurs with pre-existing atrial fibrillation (AF)studies validating the safety and efficacy of bridging thrombolysis, and the use of endovascular thrombectomy (EVT) in the setting of prior anticoagulation, are limited to single-center reports. METHODS: In a retrospective analysis, AF patients undergoing EVT for anterior circulation large vessel occlusion stroke enrolled in a prospectively-maintained, international multicenter database (International Stroke Perfusion Imaging Registry (INSPIRE)) between 2016 and 2019 were studied. Patients were categorized by anticoagulation status: anticoagulated (warfarin/non-vitamin K oral anticoagulants) versus not anticoagulated. Patients not anticoagulated were further divided into intravenous thrombolysis versus no thrombolysis. Outcomes compared between groups included 90-day modified Rankin Scale, 90-day mortality, rates of symptomatic intracerebral hemorrhage (sICH), and good reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3). RESULTS: Of 563 AF patients, 118 (21%) were on anticoagulation. AF patients on anticoagulation showed improved 90-day functional outcomes (adjusted odds ratio (aOR) 1.68, 95% confidence interval (95% CI) 1.00 to 2.82). Mortality (26.3% vs 23.8%), sICH (4.5% vs 3.9%), and rates of good reperfusion (91.3% vs 88.0%) were similar between those anticoagulated and those not anticoagulated. Thrombolysis before EVT in AF patients was independently associated with improved 90-day functional outcomes (aOR 1.81, 95% CI 1.18 to 2.79) and reduced mortality (aOR 0.51, 95% CI 0.31 to 0.84), with similar sICH rates (3.4% vs 4.5%). CONCLUSIONS: Anticoagulated patients with AF who underwent EVT had improved 90-day functional outcomes and similar sICH rates. Thrombolysis before EVT in AF patients was associated with improved 90-day functional outcomes and reduced mortality.

Cerebrovascular Disease Profiles of Culturally and Linguistically Diverse Communities in South Western Sydney and New South Wales.

INTRODUCTION: Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in CALD communities may improve health outcomes through culturally specific interventions. We compared rates of transient ischaemic attack (TIA)/stroke (ischaemic stroke, intracerebral haemorrhage) and stroke risk factor prevalence in overseas and Australian-born people in South Western Sydney (SWS) and New South Wales (NSW). METHODS: This was a 10-year retrospective analysis (2011-2020) of SWS and NSW age-standardized rates per 100,000 person-years of TIA/stroke. Data were extracted from Health Information Exchange and Secure Analytics for Population Health Research and Intelligence systems. Rates of hypertension, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), smoking, and obesity were also calculated. RESULTS: The SWS and NSW age-standardized rate of TIA/stroke for people born in Australia was 100 per 100,000 person-years (100/100,000/year). In SWS, 56.6% of people were overseas-born compared to 29.8% for NSW. The age-standardized rate of TIA/stroke for Polynesian-born people was more than double that of Australian-born people (p < 0.001). Hypertension (33 [SWS] vs. 27/100,000/year [NSW]) and T2DM (36 [SWS] vs. 26/100,000/year [NSW]) were the most common risk factors with rates >50/100,000/year (hypertension) and >80/100,000/year (T2DM) for people born in Polynesia, Melanesia, and Central America. Rates of T2DM, AF, and obesity for Polynesian-born people were over threefold greater than people born in Australia. DISCUSSION/CONCLUSION: Greater rates of TIA/stroke were observed in specific CALD communities, with increased rates of cerebrovascular risk factors. Culturally specific, targeted interventions may bridge health inequalities in cerebrovascular disease.

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort.

OBJECTIVE: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. METHODS: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri ) were compared to those who received primary MM (MMpri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). RESULTS: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MMpri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MMpri : 3 [2-4], p < 0.001). Functional independence was similar (EVTpri : 77.4% vs MMpri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri : 16.3% vs MMpri : 1.3%, p < 0.001) and neurological worsening (EVTpri : 19.6% vs MMpri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri : 77.4% vs MMpri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri : 77.4% vs MMpri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (pinteraction  = 0.06). Similar findings were observed in a propensity score-matched subpopulation. INTERPRETATION: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378.

Neuro-Ophthalmic Complications in Patients Treated With CTLA-4 and PD-1/PD-L1 Checkpoint Blockade.

BACKGROUND: In recent years, CTLA-4 and PD-1/PD-L1 checkpoint inhibitors have proven to be effective and have become increasingly popular treatment options for metastatic melanoma and other cancers. These agents work by enhancing autologous antitumor immune responses. Immune-related ophthalmologic complications have been reported in association with checkpoint inhibitor use but remain incompletely characterized. This study seeks to investigate and further characterize the neuro-ophthalmic and ocular complications of immune checkpoint blockade treatment. METHODS: A survey was distributed through the secure electronic data collection tool REDCap to neuro-ophthalmology specialists in the North American Neuro-Ophthalmology Society listserv. The study received human subjects approval through the University of California at Los Angeles Institutional Review Board. The survey identified patients sent for neuro-ophthalmic consultation while receiving one or more of a PD-1 inhibitor (pembrolizumab, nivolumab, or cemiplimab); PD-L1 inhibitor (atezolizumab, avelumab, or durvalumab); or the CTLA-4 inhibitor ipilimumab. Thirty-one patients from 14 institutions were identified. Patient demographics, neuro-ophthalmic diagnosis, diagnostic testing, severity, treatment, clinical response, checkpoint inhibitor drug used, and cancer diagnosis was obtained. RESULTS: The checkpoint inhibitors used in these patients included pembrolizumab (12/31), nivolumab (6/31), combined ipilimumab with nivolumab (7/31, one of whom also received pembrolizumab during their course of treatment), durvalumab (3/31), ipilimumab (2/31), and cemiplimab (1/31). Malignant melanoma (16/31) or nonsmall cell lung carcinoma (6/31) were the most common malignancies. The median time between first drug administration and the time of ophthalmological symptom onset was 14.5 weeks. Eleven patients had involvement of the optic nerve, 7 patients had inflammatory orbital or extraocular muscle involvement, 6 patients had ocular involvement from neuromuscular junction dysfunction, 4 patients had cranial nerve palsy, and 4 patients had non neuro-ophthalmic complications. Use of systemic corticosteroids with or without stopping the checkpoint inhibitor resulted in improvement of most patients with optic neuropathy, and variable improvement for the other ophthalmic conditions. CONCLUSION: This study describes the variable neuro-ophthalmic adverse events associated with use of immune checkpoint inhibitors and contributes a more thorough understanding of their clinical presentations and treatment outcomes. We expect this will increase awareness of these drug complications and guide specialists in the care of these patients.

Myasthenia gravis and concurrent myositis following PD-L1 checkpoint inhibitor for non-small cell lung cancer.

BACKGROUND: There are increasing reports of myasthenia gravis (MG) following oncological treatment with immune checkpoint inhibitors (ICIs). METHODS AND RESULTS: A 66-year-old man with stage 3A lung adenocarcinoma was treated with second weekly infusions of durvalumab, a programmed cell death ligand-1 inhibitor, at a dose of 10 mg/kg. After the fourth infusion, he developed diplopia, dyspnoea and constitutional symptoms including headache, weakness and anorexia. 1 month later, he developed dysphagia and dysphonia. Examination showed proximal limb weakness with fatigability. An ice pack test was positive. Blood tests revealed a raised creatine kinase and positive PM-Scl75 antibody. Antititin antibody was strongly positive in the serum and cerebrospinal fluid. Antibodies for acetylcholinesterase receptor and antimuscle-specific kinase were negative. Electromyography showed myopathic changes. The patient was treated with steroids, pyridostigmine, mycophenolate mofetil and intravenous immunoglobulin. Eight weeks after treatment initiation ptosis, eye movements and limb strength were markedly improved and repeat creatine kinase was normal. CONCLUSION: Clinicians using ICIs should have a high index of suspicion for ICI-induced MG and concurrent myositis as disease can be severe and is associated with high mortality rates.

Chronic inflammatory demyelinating polyradiculoneuropathy presenting as predominantly sciatic monomelic neuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a common yet underdiagnosed cause of potentially treatable chronic sensorimotor neuropathy. The classical form of the disease is characterised by symmetrical weakness in both distal and proximal muscle groups accompanied by sensory dysfunction and diminished tendon reflexes lasting more than 2 months. METHOD: The diagnosis of CIDP is supplemented by electrodiagnostic studies and biopsy findings confirming demyelination, in accordance with well-established diagnostic criteria. Atypical presentations of CIDP often pose a diagnostic challenge. RESULTS: In this paper, we present a case of isolated lower limb involvement due to CIDP to raise awareness of this focal lower limb variant. Of particular, significance is the use of lumbosacral plexus MRI to assist in the diagnosis. CONCLUSION: Focal CIDP is an atypical presentation that should be considered in patients presenting with chronic monomelic neuropathy and should be investigated with electrodiagnostic studies, lumbar puncture, nerve biopsy and MRI of the nerve roots and plexuses.

Clinical and laboratory factors related to acute isolated vertigo or dizziness and cerebral infarction.

OBJECTIVE: To clarify the relationship of clinical factors with isolated vertigo or dizziness of cerebrovascular origin. METHODS: Clinical data of patients admitted in East Hospital from Jan. 2015 to Apr. 2016, whose complaint were acute vertigo or dizziness were retrospectively collected. All patients arrived at the emergency department within 24 hr of symptom onset, had no acute ischemic lesion first CT and NIHSS score of 0. Patients were divided into cerebral infarction group and noncerebral infarction group according to subsequent cerebral imaging results and clinical and laboratory factors related to cerebral infarction were analyzed. RESULT: 51.6% of patients were female (n = 141). 46 patients (16.8%) were diagnosed with acute cerebral infarction. Baseline demographic data of the two groups was not significantly different. Univariate analysis found that history of smoking (p = 0.009), headache (p = 0.028), unsteadiness (p = 0.009), neuron specific enolase (p = 0.001), and vertebral artery abnormalities found on imaging (p = 0.009) were the significant difference between two groups. Increased neuron specific enolase (p = 0.005) and an abnormal vertebral artery (p = 0.044) were significant on multivariate analysis. CONCLUSIONS: 16.8% of acute isolated vertigo or dizziness presentations were diagnosed with acute cerebral infarction. Increased serum neuron specific enolase and vertebral artery abnormalities were the strongest indicators of acute cerebral infarction.

Reflection on stroke deaths and end-of-life stroke care.

BACKGROUND: The benefit of palliative care referral for severe stroke patients on end-of-life care pathway (EOLCP) is increasingly recognised. Palliative care provides assistance with symptom management and transition to end-of-life care. Advance care planning (ACP) may help accommodate patient/family expectations and guide management. METHODS: This is a retrospective study of all stroke deaths (2014-2015) at Liverpool Hospital, Sydney, Australia. Data examined included age, comorbidities, living arrangements, pre-existing ACP, palliative care referral rates and 'survival time'. RESULTS: In total, 123 patient (mean age ± SD = 76 ± 13 years) deaths were identified from 1067 stroke admissions (11.5% mortality); 64 (52%) patients had ischaemic stroke and 59 (48%) intracerebral haemorrhage (ICH), and 40% suffered a prior stroke, and 43% required a carer at home or were in an aged care facility. Survival time from admission was significantly longer in patients with ischaemic stroke compared to intracerebral haemorrhage (median, interquartile range [IQR]: 9.5 [18] vs 2 [4] days, P < 0.001). Only two patients had pre-existing ACP; 44% of patients were referred to palliative care and 41% were commenced on dedicated EOLCP. Palliative care referral was less likely in patients who died under neurosurgery. EOLCP were significantly less likely to be commenced in patients who underwent acute intervention or were not referred to palliative care. CONCLUSION: In this cohort, palliative care referral and EOLCP were commenced in less than 50% of patients, highlighting significant variations in clinical care. These data support the need to promote awareness of ACP, particularly in patients with prior stroke or significant comorbidities. This may help reduce potentially futile invasive investigations and treatment.

Nontraumatic spinal cord ischaemic syndrome.

This study presents the clinical features and functional outcomes of eight consecutive patients who were admitted to our institution between 2012 and 2014 with nontraumatic spinal cord infarction (SCI), a rare and devastating condition. We also present a literature review of aetiologies and prognostic factors relevant to our case series. The mean age of our cohort was 64 years and five patients were female. Aortic disease was causative in three, including one patient with biopsy confirmed giant cell arteritis. Fibrocartilaginous embolism was a possible aetiology in two others, anterior spinal artery aneurysm in one, and the cause was undetermined in two patients. American Spinal Injury Association impairment scale (ASIA) scores at nadir (time of maximum severity of signs) were B in three, C in three and D in two patients (all were wheelchair dependent). At last follow-up, ASIA scores were C in one, D in five and E in one patient. One patient died, two remained wheelchair dependent, four required a walking aid or frame and one was mobilising independently. A literature review of 11 patient series of nontraumatic SCI found that prognosis is primarily determined by the severity of motor or sensory involvement, in particular, initial and nadir ASIA A/B scores which strongly correlate with poor outcome. In the majority of series, 40-60% of patients had initial ASIA A/B scores with a similar proportion remaining wheelchair dependent on follow-up. Most patients in our cohort had nadir ASIA C/D scores, which may explain their better outcomes.

Delayed angiographic changes in postpartum cerebral angiopathy.

Postpartum cerebral angiopathy is a well-recognised subgroup of the reversible vasoconstriction syndromes. Increasingly described is a delay between clinical onset and angiographic changes. We report a patient who presented 19 days postpartum with severe thunderclap headaches, vertigo and a seizure. The clinical syndrome preceded evidence of extensive vasoconstriction on MRA imaging by 15 days; the changes were reversible at 3 months.

Responses of human sensory and motor axons to the release of ischaemia and to hyperpolarizing currents.

This study compared directly the post-ischaemic behaviour of sensory and motor axons in the human median nerve, focusing on the excitability changes produced by ischaemia and its release and by continuous polarizing DC. The decrease in threshold during ischaemia for 13 min was greater, the post-ischaemic increase in threshold was more rapid, and the return to the pre-ischaemic excitability took longer in sensory axons. However, a transient depolarizing threshold shift developed in sensory axons a few minutes after release of ischaemia. This pattern could not be reproduced by polarizing currents designed to mimic the probable pump-induced changes in membrane potential, even though the applied currents produced greater changes in threshold. Hyperpolarizing currents of equivalent intensity produced a greater increase in threshold for motor axons than sensory axons and, in studies of threshold electrotonus using graded hyperpolarizing DC, accommodation was greater in sensory than motor axons. The post-ischaemic changes in threshold were not uniform for axons of different threshold, whether sensory or motor, the threshold increase was usually less prominent for low-threshold axons. A transient post-ischaemic depolarization could be produced in motor axons with ischaemia of 20 min duration. Greater ischaemic and post-ischaemic changes in threshold for sensory axons could reflect greater dependence on the electrogenic Na+-K+ pump to maintain resting membrane potential and/or greater extracellular K+ accumulation in ischaemic sensory axons. Inward K+ currents due to extracellular K+ accumulation would then be more likely to trigger a depolarizing shift in membrane potential, the degree of K+ accumulation and pump activity being dependent on the duration of ischaemia. In sensory axons the greater tendency to accommodate to hyperpolarizing stimuli presumably contributes to shaping their post-ischaemic behaviour but is probably insufficient to explain why their behaviour differs from that of motor axons.