Degenerative cervical myelopathy (DCM) is a recently coined term encompassing a variety of age-related and genetically associated pathologies, including cervical spondylotic myelopathy, degenerative disc disease, and ligamentous aberrations such as ossification of the posterior longitudinal ligament. All of these pathologies produce chronic compression of the spinal cord causing a clinical syndrome characterized by decreased hand dexterity, gait imbalance, and potential genitourinary or sensorimotor disturbances. Substantial variability in the underlying etiology of DCM and its natural history has generated heterogeneity in practice patterns. Ongoing debates in DCM management most commonly center around clinical decision-making, timing of intervention, and the ideal surgical approach. Pivotal basic science studies during the past two decades have deepened our understanding of the pathophysiologic mechanisms surrounding DCM. Growing knowledge of the key pathophysiologic processes will help us tailor personalized approaches in an increasingly heterogeneous patient population. This article focuses on summarizing the most exciting approaches in personalizing DCM patient treatments including biomarkers, factors affecting clinical decision-making, and choice of the optimal surgical approach. Throughout we provide a concise review on the conditions encompassing DCM and discuss the underlying pathophysiology of chronic spinal cord compression. We also provide an overview on clinical-radiologic diagnostic modalities as well as operative and nonoperative treatment strategies, thereby addressing knowledge gaps and controversies in the field of DCM.

Recent evidence shows that subcutaneous immunoglobulin (SCIG) is as efficacious as intravenous immunoglobulin (IVIG) and has a better safety profile and acceptance rate among patients with neuromuscular disorders who require maintenance IVIG treatment. Awareness of the practical aspects of patient selection, enrollment, dose calculation, administration, and follow-up would help physicians coordinate a smooth and seamless transition from IVIG to SCIG. SCIG is ideally offered to patients having intolerable side effects during IVIG or wearing-off effect and in those keen for treatment autonomy. The weekly dose of SCIG is calculated by multiplying the maintenance dose of IVIG by the dose adjustment factor and dividing by the interval between IVIG in weeks and is initiated 1 week after the last dose of IVIG. The physician places the order for the SCIG and the clinic nurse or the physician refers the patient to the home care nursing program for further education and training. The necessary supplies are dispatched to the patient who would also collect the SCIG from the transfusion center of the nearest hospital. The patient is educated on assembling and administering the infusion, and home visits are continued until the patient or caregiver is confident. Regular follow-up with the patient is maintained to assess treatment response and side effects if any. With a smooth transition, most patients have excellent tolerance to SCIG and in our experience seldom request switching back to IVIG. Transitioning patients from IVIG to SCIG offers several advantages and thus, in general, is preferable for multiple stakeholders.

The 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Stroke includes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

Background: The mechanisms underlying the severity and wide heterogeneity of multiple sclerosis (MS) remain poorly understood. A persistent challenge has been determining whether genetic variation influences these traits. Methods: In 12,584 people with MS (pwMS), we estimated the proportion of age-related MS severity score variance attributable to additive genetic variation (SNP-heritability). Then, we interrogated for enrichment in hundreds of tissues and cell types using gene expression annotations. We performed a genome-wide association study (GWAS) using 7.8 million variants and attempted replication in an independent cohort of 9,805 pwMS. A subset of 8,325 pwMS was examined longitudinally over 54,113 visits. Results: We observed a 10% SNP-heritability for MS severity. In contrast to MS susceptibility, robust tissue-level enrichment was apparent in the brain and cervical spinal cord, but not in immune cells. We identified a novel MS severity locus (p<5×10−8) and confirmed this in the replicate population. The lead variant was associated with higher hazards of 6-month confirmed disability worsening (p=0.008) and faster EDSS worsening (p=0.002). Time to walking aid (EDSS 6.0) was 3.2 years earlier in homozygous risk carriers. Conclusions: This study identifies the first genetic modifier of MS progression, establishes the genetic contributions to its heterogeneity and describes a distinct genetic architecture from susceptibility.

The brain has the innate ability to undergo neuronal plasticity, which refers to changes in its structure and functions in response to continued changes in the environment. Although these concepts are well established in animal slice preparation models, their application to a large number of human subjects could only be achieved using noninvasive brain stimulation (NIBS) techniques. In this review, we discuss the mechanisms of plasticity induction using NIBS techniques including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), random noise stimulation (RNS), transcranial ultrasound stimulation (TUS), vagus nerve stimulation (VNS), and galvanic vestibular stimulation (GVS). We briefly introduce these techniques, explain the stimulation parameters and potential clinical implications. Although their mechanisms are different, all these NIBS techniques can be used to induce plasticity at the systems level, to examine the neurophysiology of brain circuits and have potential therapeutic use in psychiatric and neurological disorders. TMS is the most established technique for the treatment of brain disorders, and repetitive TMS is an approved treatment for medication-resistant depression. Although the data on the clinical utility of the other modes of stimulation are more limited, the electrical stimulation techniques (tDCS, tACS, RNS, VNS, GVS) have the advantage of lower cost, portability, applicability at home, and can readily be combined with training or rehabilitation. Further research is needed to expand the clinical utility of NIBS and test the combination of different modes of NIBS to optimize neuromodulation induced clinical benefits.

Neurodegeneration with brain iron accumulation (NBIA) is a term used for a group of hereditary neurological disorders with abnormal accumulation of iron in basal ganglia. It is clinically and genetically heterogeneous with symptoms such as dystonia, dysarthria, Parkinsonism, intellectual disability, and spasticity. The age at onset and rate of progression are variable among individuals. Current therapies are exclusively symptomatic and unable to hinder the disease progression. Approximately 16 genes have been identified and affiliated to such condition with different functions such as iron metabolism (only two genes: Ferritin Light Chain (FTL) Ceruloplasmin (CP)), lipid metabolism, lysosomal functions, and autophagy process, but some functions have remained unknown so far. Subgroups of NBIA are categorized based on the mutant genes. Although in the last 10 years, the development of whole-exome sequencing (WES) technology has promoted the identification of disease-causing genes, there seem to be some unknown genes and our knowledge about the molecular aspects and pathogenesis of NBIA is not complete yet. There is currently no comprehensive study about the NBIA in Iran; however, one of the latest discovered NBIA genes, GTP-binding protein 2 (GTPBP2), has been identified in an Iranian family, and there are some patients who have genetically remained unknown.

The goal of effective neuroprotection in acute ischemic stroke remains elusive. Despite decades of experimental preclinical and clinical experience with innumerable agents, no strategy has proven to be beneficial in humans. As endovascular therapies mature and approach the limits of speed and efficacy, neuroprotection will become the next frontier of acute stroke care. This review will briefly summarize the history, preclinical and clinical triumphs and failures, and future directions of cerebral neuroprotection.

Background: Only one disease modifying therapy (DMT), ocrelizumab, was found to slow disability progression in primary progressive multiple sclerosis (PPMS). Modeling the conditional average treatment effect (CATE) using deep learning could identify individuals more responsive to DMTs, allowing for predictive enrichment to increase the power of future clinical trials. Methods: Baseline clinical and MRI data were acquired as part of three placebo-controlled randomized clinical trials: ORATORIO (ocrelizumab), OLYMPUS (rituximab) and ARPEGGIO (laquinimod). Data from ORATORIO and OLYMPUS was separated into a training (70%) and testing (30%) set, while ARPEGGIO served as additional validation. An ensemble of multitask multilayer perceptrons was trained to predict the rate of disability progression on both treatment and placebo to estimate CATE. Results: The model could separate individuals based on their predicted treatment effect. The top 25% of individuals predicted to respond most have a larger effect size (HR 0.442, p=0.0497) than the entire group (HR 0.787, p=0.292). The model could also identify responders to laquinimod. A simulated study where the 50% most responsive individuals are randomized would require 6-times less participants to detect a significant effect. Conclusions: Individuals with PPMS who respond favourably to DMTs can be identified using deep learning based on their baseline clinical and imaging characteristics.

Mercury (Hg) exists in the environment as inorganic (metallic Hg vapor, mercurous and mercuric salts) or organic (bonded to a structure containing carbon atoms) forms. Neurotoxic effect of Hg is known for years. While the organic form (methylmercury (meHg)) led to the Minamata incidence in Japan and “wonder-wheat” disaster in Iraq, the “mad hatters” and “Danbury shakes” were related to the inorganic elemental form (Hg vapor). Human exposure to toxic Hg continues in the modern world to a large extent by artisanal gold mining, biomass combustion, chloralkali production, and indigenous medicine use to name a few. Heavy industrial use of Hg contaminates air and landfills, affecting the aquatic ecosystem and marine food chain. A detailed social and occupational history with a high index of clinical suspicion is required to not miss this toxic etiology for movement disorders like ataxia, tremor, or myoclonus. In this review, we have discussed the past and present global health impact of Hg from a movement disorder perspective. The connection of Hg with neurodegeneration and autoimmunity has been highlighted. We have also discussed the role of chelating agents and the preventive strategies to combat the neurotoxic effects of Hg in the modern world.

Endovascular thrombectomy (EVT) has significantly improved outcomes for patients with acute ischemic stroke due to large vessel occlusion. However, despite advances, more than half of patients remain functionally dependent 3 months after their initial stroke. Anesthetic strategy may influence both the technical success of the procedure and overall outcomes. Conventionally, general anesthesia (GA) has been widely used for neuroendovascular procedures, particularly for the distal intracranial circulation, because the complete absence of movement has been considered imperative for procedural success and to minimize complications. In contrast, in patients with acute stroke undergoing EVT, the optimal anesthetic strategy is controversial. Nonrandomized studies suggest GA negatively affects outcomes while the more recent anesthesia-specific RCTs report improved or unchanged outcomes in patients managed with versus without GA, although these findings cannot be generalized to other EVT capable centers due to a number of limitations. Potential explanations for these contrasting results will be addressed in this review including the effect of different anesthetic strategies on cerebral and systemic hemodynamics, revascularization times, and periprocedural complications.