Background: Light chain (AL) amyloidosis is a plasma cell disorder characterized by abnormal fibrillary light chain deposition causing cardiac, renal, hepatic, gastrointestinal and peripheral nervous system dysfunction. Muscle disease occurs in 1.5% of individuals causing progressive proximal weakness thus far considered untreatable. Methods: We reviewed two cases of AL amyloidosis associated myopathy at our institution who had robust response to plasmapheresis. Both were at stringent clinical response following CyBorME therapy during peak severity of their myopathy. Results: In case 1, a 70-year-old male with recently diagnosed kappa light chain multiple myeloma and cardiac/renal amyloidosis developed severe subacute proximal weakness preventing ambulation. CK was normal and electromyography was consistent with irritable myopathy. Deltoid biopsy showed perimysial and endomysial amyloidosis. A trial of plasmapheresis in a tapering schedule resulted in robust recovery of strength. In case 2, a 67-year-old female with recently diagnosed kappa light chain multiple myeloma with amyloidosis on fat pad aspirate developed severe subacute proximal weakness requiring prolonged hospital admission. CK was normal and electromyography demonstrated non-irritable myopathy. Bicep biopsy showed perivascular amyloidosis. A trial of plasmapheresis in a tapering schedule resulted in robust recovery of strength. Conclusions: Plasmapheresis is a novel and potentially effective treatment for patients with AL amyloidosis associated myopathy.

Background: Mutations in GDP-Mannose Pyrophosphorylase B (GMPPB) cause a spectrum of disease ranging from muscular dystrophy to congenital myasthenic syndrome (CMS). Recognition of neuromuscular junction dysfunction has important treatment implications. Methods: We describe a person with GMPPB mutation causing an overlapping limb girdle muscular dystrophy - myasthenic syndrome with robust response to acetylcholinesterase inhibitors. We review the literature on the muscular dystrophy - CMS and explore the phenotypic features that aid in recognizing neuromuscular junction dysfunction. Results: A 35-year-old woman presented with a 10-year history of debilitating myalgias, symmetrical limb girdle and neck weakness, and chronic CK elevation. Electromyography showed a non-irritable myopathy. Biopsies were consistent with muscular dystrophy. Whole genome sequencing revealed two heterozygous pathogenic mutations in the GMPPB gene, giving a diagnosis of genetically confirmed limb girdle muscular dystrophy. Subsequently, repetitive nerve stimulation revealed decrement in the trapezius muscle suggestive of an overlap myasthenic syndrome. She was started on pyridostigmine resulting in recovery of full motor power with significant functional improvement. Conclusions: Identification and treatment of neuromuscular junction dysfunction caused by GMPPB mutations can significantly improve motor power and function. Early onset of progressive fatigable proximal weakness, spared ocular and facial muscles, and pyridostigmine responsiveness are important features of GMPPB-related CMS.

Background: Transthyretin Amyloidosis (ATTR) is a common cause of both cardiomyopathy and carpal tunnel syndrome, with many patients needing carpal tunnel release (CTR). Although tafamidis is now an approved treatment of ATTR cardiomyopathy, insurers in most provinces require biopsy confirmation of amyloidosis. Endomyocardial biopsy is often the chosen approach due to optimal sensitivity, albeit with risk of serious adverse events such as stroke, cardiac tamponade, and arrhythmias. CTR may present an ideal opportunity for obtaining amyloidosis biopsy confirmation. Methods: ATTR patients undergoing CTR had biopsy of their transverse carpal ligament (TCL) and/or flexor tenosynovium to assess the sensitivity of both sites for biopsy confirmation of amyloidosis. Results: Twelve patients consecutively underwent biopsies during CTR, with 4 (33%) having bilateral CTR and biopsy. Among 16 TCL biopsies and 14 tenosynovium biopsies, 100% demonstrated amyloid deposition. Another patient had isolated tenosynovium biopsy without CTR and also demonstrated amyloidosis. There were no serious adverse events, and 1/13 (8%) had wound dehiscence requiring repeat suturing. Conclusions: Biopsy of the TCL and/or tenosynovium during CTR is safe, cost-effective, and sensitive, and may represent an alternative to endomyocardial biopsy in patients requiring tissue confirmation for tafamidis approval. ATTR patients eligible for tafamidis may benefit from early neurology assessment.

Background: Weakness is frequently a reason to attend neurology consultation which entails a challenge due to its wide range of diagnostic possibilities. We present the case of an elderly woman with long-standing right upper limb weakness. Methods: Patient data was obtained from medical records and an extensive neuropathological evaluation was performed. Results: Weakness started off in her right hand, which progressed insidiously to her right hemibody. with hyperreflexia, atrophy, fasciculations and foot drop. Subsequently, bulbar and left hemibody deterioration began. She died due to ventilatory failure four years after the first symptom appeared. A tigroid pattern in the neuroimaging studies suggest white matter involvement, while the neuropathological studies showed loss of motor neurons in the spinal cord. Conclusions: The available evidence does not allow us to dismiss the hypothesis of a motor neuron disease or a leukodystrophy. Cases like this one establish a diagnostic challenge due to their complexity and unusual etiology.

Background: Criteria to formalize the diagnosis of amyotrophic lateral sclerosis (ALS) and refine clinical trial populations have evolved. The recently proposed Gold Coast criteria (GCC) are intended to simplify use and increase sensitivity. We evaluated sensitivity of GCC and potential impacts on therapeutic trial enrollment. Methods: We performed a single center retrospective study including patients diagnosed with ALS between 2016 – 2021. We determined criteria met at diagnosis according to revised El Escorial (rEEC), Awaji (AC) and GCC. We compared sensitivity and examined impacts GCC would have on enrollment in landmark ALS trials. Results: We included 203 people with ALS. Sensitivity of GCC (96.1%, 95% confidence interval [CI] = 92.2-98.2%) was significantly higher than rEEC (89.8%, 95% CI 84.6-93.4%, χ2 = 5.3, p = 0.01) and AC (89.3%, 95% CI 84.1-93.0%, χ2 = 6.1, p = 0.006). GCC was more sensitive than clinically definite or probable rEEC (47.6%, 95% CI 40.6-54.6%, χ2 = 117.6, p = < 0.001) and use would result in increased eligibility in landmark therapeutic trials. Conclusions: GCC are more sensitive than rEEC and AC at time of diagnosis in ALS. Use of GCC in our population would expand clinical trial participation and make results more widely generalizable.

Background: Sensory ganglionopathy (SG) is a rare form of neuropathy affecting the dorsal root ganglia and leading to non-length-dependent sensory abnormalities. Although balance problems are frequently reported by patients, a comprehensive balance assessment in SG has not been conducted. This study quantifies balance deficits in SG and examines their relation to patient-reported outcome measures (PROMs). Methods: Prospective data was collected from five participants with SG. Balance assessments included Fullerton Advanced Balance scale, Berg Balance scale, and 360 degree turn. Participants completed PROMs assessing balance confidence (ABC scale), pain, fatigue, quality of life (QoL), and daily activity and participation. Assessment also included neurological exam, nerve conduction studies (NCS) and posturography. Results: All participants had severe SG on NCS with normal strength and significant sensory abnormalities. Balance scores indicated severe balance deficits in all participants and aligned with posturography and truncal sway measures. PROMs revealed low confidence in balance, high levels of pain and fatigue, difficulties with daily activities, and reduced QoL. Conclusions: Although balance testing is not part of routine clinical practice, PROMs and targeted assessment may help monitor patients with SG and their response to treatment. Larger sample sizes are needed to understand the impact of balance on PROMs and optimize bedside balance testing.

Background: In ALS, determining whether individuals have a substantial response to therapy is a challenge for the field. ALS naturally progresses at variable rates and a personalized approach is required to determine if individuals have a substantial response. A new method to evaluate individual response is proposed and applied to data from the CENTAUR trial of sodium phenylbutyrate/ursodoxicoltaurine (PB/TURSO). Methods: In a post hoc analysis, CENTAUR participants whose actual rate of change from baseline in the ALSFRS-R at week 18 was ≤ their own trial baseline progression rate (ΔFS) were defined as having a substantial individual response in slowing ALS progression. Results: Substantial individual response was observed in a greater proportion of participants receiving PB/TURSO (41%, n=87) vs placebo (19%, n=48; P=0.0076). Conclusions: Response versus ΔFS provides a personalized metric to determine substantial individual response in ALS. ΔFS has been shown to be highly correlated with, but to proportionally underestimate, ALSFRS-R decline in clinical trials. Consequently, those who outperform the ΔFS may be considered to have a substantial individual response. Application to CENTAUR data demonstrates a greater proportion of participants with a substantial individual response in the PB/TURSO arm. These methods may enable greater personalization and analysis of individual response in ALS.

Background: Patients with neurological conditions account for 15% of patients admitted to the Intensive Care Unit (ICU). Neurocritical care (NCC) has been proven to reduce mortality, improve functional outcomes and increase patient/family satisfaction. Trainees often lack the knowledge, skills, and experience needed to provide quality NCC. Consequently, timely effective care is compromised, team dynamics suffer, and trainees may experience distress. Methods: To fully understand educational needs, we surveyed University of Calgary residents from various programs who rotate through the Neuro-ICU. Results: Trainees indicated a lack of confidence in their knowledge and skills of most NCC disorders/scenarios in the ICU. While the majority expressed interest in learning NCC, 58% were not aware of the NCC-related competencies outlined for their specialties by the Royal College of Physicians and Surgeons, and 30% had no objectives of their own. Teaching modalities most preferred included patient-centred bedside teaching (96%) and easily accessible resources such as pocket-sized cards (90%) and/or a phone app (96%). Conclusions: Trainees rotating through Neuro-ICU need more accessible and improved learning resources and tools. An NCC curriculum may help improve patient outcomes, team dynamics, and relieve trainee distress.

Background: Resident physicians often observe stroke alerts before managing them alone, which exposes patients to potential harm from trainees’ lack of experience. Simulation training offers a low-risk environment for skill acquisition. This project assessed learners’ confidence in leading stroke codes before and after completing a stroke simulation training program during neurology rotations at the University of Saskatchewan. Methods: High-fidelity simulation cases were developed encompassing several diagnostic and therapeutic goals of acute stroke care. Standardized patients were trained for increased fidelity. Standardized debriefing was given after each session. Pre- and post-simulation surveys captured learner confidence and cognitive load. Results: Pilot data reveal learners’ confidence and comfort in providing acute stroke care, including thrombolysis treatment decisions, significantly increases after simulation training (n=8; p=0.0006-0.01). They also felt more prepared to conduct future acute stroke care (p=0.009). Skills not directly addressed in simulation did not show significant improvement (p=0.09-1.89). Learners consistently rated the session as requiring high mental effort. Conclusions: Implementation of high-fidelity simulation training leads to significant improvement in learner confidence. Future cases will capture additional objectives and ensure acceptable cognitive load. Ongoing data collection to explore residents’ experiences and knowledge improvement in stroke care and assess local reductions in treatment delays is underway.

Background: Neurology Residency training in Canada is transitioned to competence based medical education (CBME) in July 2020 and the Royal College Neurology Specialty Committee has identified “providing consultation for and managing patients at outlying centres,” to be an entrustable professional activity (EPA). At Western University, neurology telephone consultations from outlying centres are attended by both the resident and the staff Neurologist. This scenario provides the ideal situation for direct observation and immediate formative feedback. The resident’s performance was assessed using an entrustment scale along with a short narrative portion. Methods: This mixed methods study aims to determine the reliability and validity of the entrustment scale with narrative feedback in assessing the performance on the telephone consultation by senior neurology residents. Informed consent was obtained from residents (9) and staff (7) involved. Scores on the entrustment scale and narrative comments were analyzed. Results: Information on 37 encounters (involving 9 residents) was collected. Assessment results demonstrated higher entrustment scores in PGY4 and PGY5 levels. Overall, ratings were consistent across the 7 consultant assessors. Conclusions: The use of an entrustment scale appears to be reliable and valid in assessing competence in the telephone consultation and provide coaching feedback to help learners improve their performance.

Background: Canadian neurology residency programs recently transitioned to Competence Based Medical Education (CBME), designed to provide residents with stage-appropriate learning to develop and demonstrate competence. The successful implementation of CBME requires iterative evaluation as the adoption process may differ from the intended design due to systemic or program-specific factors. This study aims to (1) examine the variability in CBME implementation across Canadian neurology residency programs; (2) determine the barriers toward uptake of CBME; and (3) identify the benefits and pitfalls of CBME in neurology residency programs. Methods: A separate national survey was developed for residents and staff neurologists who participated in CBME for at least six months. Surveys were distributed through email, and responses were anonymized. Quantitative data were analyzed by response frequency and mean, where applicable. Free-form responses were analyzed qualitatively. Results: Staff neurologists felt prepared for CBME, but were divided on its fairness and impact on education quality. Residents experienced frequent but not necessarily timely or high-quality feedback. Barriers to implementation included increased paperwork, dissatisfaction with online platforms used to facilitate CBME, and bidirectional burden of initiating evaluations. Conclusions: Staff and residents have expressed unique perspectives on the first iteration of CBME. There remain opportunities for improvement in subsequent iterations.

Background: Recent evidence suggests that the cerebellum is involved in cognitive functions. Theta burst stimulation (TBS), a modality of transcranial magnetic stimulation (TMS), on the cerebellum can change its contribution to working memory. Therefore, we hypothesize that excitatory intermittent TBS (iTBS) on the cerebellum would improve performance on working memory tasks, whereas inhibitory continuous TBS (cTBS) would disrupt it. Methods: As this is an ongoing study, nine participants (6 women) took part in this study so far. TBS was applied on the cerebellum bilaterally. All subjects received iTBS, cTBS, and sham iTBS in three sessions in random order. After TBS in each session, participants performed three types of working memory tasks: letter 2-back, digit span forward (DSF), and digit span backward (DSB). Results: The preliminary results suggest that participants performed better in the sham condition in the letter 2-back and the DSB tasks compared to the iTBS and cTBS conditions, but the results did not reach statistical significance due to the small sample size. Conclusions: The preliminary results show that the cerebellar contribution to working memory may be disrupted by TBS. As we gain more statistical power by recruiting more participants, we hope to further demonstrate the effects of cerebellar TBS on working memory.

Background: Carotid artery stenosis causes up to 20% of ischemic strokes. Stenting is used as an alternative to endarterectomy in symptomatic patients. Most centers customize each individual stenosis to a specific stent size. However, this process can be time consuming and costly while the relative benefit has not been well evaluated yet. We hypothesized that a ‘one-size-fits-all’ approach to carotid stenting results in non-inferior results to a customized approach. Methods: We conducted a descriptive retrospective cohort study on patients who underwent carotid artery stenting looking for peri- and post-procedural complications. The primary outcomes were periprocedural (within 24 hours) or post procedural (within 30 day) TIA, stroke, or death. The secondary outcome was the estimated degree of stenosis on follow up ultrasound performed within 6 months of the procedure. Results: The complication rate was 4.5%, 6.5% for 24 hours and 30 day post-procedure, respictively. Age and degree of stenosis on post procedural cerebral angiogram were associated with increased risk of complication. Severe restenosis or occlusion was reported in 16.8% of patients within 6 months post-procedure. Conclusions: Our study suggests that using a simplified, one-size-fits-all, approach to carotid stenting results in safe and effective outcomes, suggesting a route to possibly simplify a complex medical procedure.

Background: Basilar artery stenting is a rescue therapy in the management of hyperacute stroke Published data on efficacy and safety are limited. Methods: A systematic review of published studies was performed in accordance with PRISMA guidelines. Inclusion criteria were adult patients with ischemic stroke with permanent basilar artery stent placement within 48 hours of onset. Data were extracted by two independent reviewers. Additional cases from our institution were identified via a local stroke registry. Results: Of 212 screened articles, patient-level data was reported in 35 studies (93 individuals) and six additional patients were included from our registry. Patients (n=99, 63% male; median age 64) most often presented with mid-basilar occlusion (52%) and 76% received treatment within 12 hours of onset. Favorable angiographic results occurred in 67%. The final modified Rankin Scale score (mRS) was 0-3 for 56% of patients; mortality was 29%. Those with complete flow post-procedure were more likely to have a final mRS of 0-3 (p=0.05). Conclusions: In 99 cases of basilar stenting in hyperacute stroke, favourable angiographic and functional outcomes were reported in 67% and 56% of patients, respectively. International multicenter registries are required to establish benefit and identify patient and technical factors that predict favorable outcomes.

Background: HIV-associated CD8 encephalitis (CDE) is a severe inflammatory disorder characterized by infiltration of the brain by CD8+ T-lymphocytes in HIV positive patients, often when the virus is well-controlled by anti-retroviral therapy (ART). Hallmark clinical features include headache, confusion and progressive cognitive decline. Most patients who receive prompt corticosteroid therapy evolve favorably, though if left untreated, CDE can lead to coma and even death. The therapeutic impact of altering the ART regimen while giving corticosteroids remains unclear. Methods: Patient chart, functional measures, and laboratory findings were reviewed for the length of the patient’s two hospitalisations for CDE in 2019 and 2021. Results: Here we present a case of an HIV positive 43-year-old male who presented with headache, confusion and memory issues both in 2019 and 2021. Imaging and lumbar puncture guided the diagnosis of CDE in 2019, while careful patient history on the patient’s second hospitalisation confirmed the diagnosis of HIV encephalitis due to medication non-compliance in 2021. Conclusions: This case adds to the current state of knowledge regarding the clinical presentation of CD8 encephalitis, while highlighting both similarities and differences with other CNS pathology seen in the context of HIV.

Background: Spinal arachnoiditis is a rare condition involving progressive fibrosis of the spinal arachnoid membrane and can be secondary to multiple spinal surgeries, intrathecal chemotherapy, or infection. This condition can manifest as lumbosacral radiculopathy, cauda equina syndrome, myelopathy, or syringomyelia. Methods: We present a case of a 38-year-old female with recent cryptococcal meningitis treated with amphotericin B and flucytosine, who re-presented to hospital several weeks after discharge with decreased mobility requiring a wheelchair, falls, and urinary and fecal incontinence. Results: Examination revealed lower extremity pyramidal weakness, hyperreflexia, and upgoing plantar responses. CSF analysis showed white blood cells of 147x106 cells/L, protein of 4.07 g/L, and glucose of 0.4 mmol/L. Cryptococcal antigen was positive, but fungal culture was negative x 5 days, suggesting adequate initial treatment of cryptococcal meningitis. MRI spine revealed tethering of the cervical cord posteriorly at C4-5 and tethering of the midthoracic cord anteriorly. The patient was treated with IV methylprednisolone 1 g/kg daily for 5 days without significant improvement. Conclusions: Spinal arachnoiditis secondary to infection is thought to be caused by post-infectious inflammatory response syndrome (PIRIS) and is treated with IV methylprednisolone. In spinal arachnoiditis secondary to cryptococcus, the clinical findings may be confounded by the presence of hydrocephalus or myelopathy.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Oral medications for control of motor symptoms are the mainstay of treatment however, as the disease progresses, patients with PD may develop dysphagia or other medical illnesses that prohibit them from safely taking oral medications. Currently there are no clinical guidelines for managing distressing motor symptoms in patients with PD and severe dysphagia, which can therefore be quite challenging. Methods: A scoping review using MEDLINE, EMBASE, CENTRAL, CINAHL, AgeLine and Psyc INFO databases (1946-2021) was conducted. Articles examining PD with dysphagia in palliative care or at end-of-life were included. Studies that included patients who were also on oral PD medications or received device-aided therapy were excluded. Results: Of 3836 articles screened for title and abstract, 274 were selected for full text review, and 20 articles were finally selected for data extraction. These included five case reports, one retrospective cohort study, one book chapter and 13 narrative reviews. Conclusions: There are very few articles addressing the issue of treatment of patients with advanced PD who are unable to take oral medications. Although rotigotine patch and apormorphine injections are most frequently recommended, there are no clinical trials in this patient population to support those recommendations.

Background: Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA) are neurodegenerative disorders with disabling morbidities and premature death. Variable illness trajectories make the timing for initiating neuropalliative care unclear. This scoping review aims to identify milestones relevant to survival and neuropalliative care in PSP and MSA. Methods: A systematic literature search was performed in Medline and EMBASE databases to identify publications investigating predictors of survival in PSP and MSA. Titles and abstracts of 2091 articles were independently screened by two reviewers and 22 research studies published after 2010 were included. Results were qualitatively combined to suggest triggers for targeted palliative care throughout the disease trajectory. Results: ‘Milestones’ are well documented, clinically relevant disease points prompting further care. Important milestones include frequent falls, cognitive impairment, severe dysarthria, severe dysphagia, wheelchair dependence, urinary catheterisation, and institutionalization. Early disease milestones include falls and cognitive impairment in PSP, and urinary catherization and falls in MSA. Time from milestone to death is variable. Conclusions: Milestones can be used to follow disease progression and help predict survival. We propose a framework in which milestones are used as triggers for targeted neuropalliative care interventions including the early initiation of a primary palliative care or referral to specialised palliative care services.

Background: People with acute ischemic stroke (IS) have a higher prevalence of occult malignancy. Consensus is lacking, however, on the extent of cancer screening tests that should be offered in this population. We performed a single-center study to review curent cancer screening practices in acute IS. Methods: We reviewed consecutive admissions for acute IS at our institution between January and December 2020. We defined extensive cancer screening as i) a cancer investigation test falling outside Canadian guidelines, or ii) any chest, abdomen or pelvis imaging by CT, TEP/CT or ultrasound. We compared clinical features of people with and without extensive screening with Fisher and Mann-Whitney U tests. Results: Among 171 patients with acute IS, 11 (6.4%) underwent extensive cancer screening. A lower BMI was the only clinical feature associated with extensive cancer screening (p=0.013). Markers that were not associated with extensive screening included age (p=0.479), male sex (p=0.758), cryptogenic etiology (p=1.000), infarctions in multiple vascular territories (p=0.748), hemoglobin (p=0.505), fibrinogen (p=0.162) and C-reactive protein (p=0.442). Conclusions: Common predictors of occult cancer were not associated with more extensive cancer screening in this small sample of IS. Validated clinical prediction models may help clinicians guide cancer investigations in IS.

Background: There are uncertainties regarding the optimal management of acutely symptomatic carotid stenosis (“hot carotids”). We sought to explore the approaches of stroke physicians to anti-thrombotic management, imaging, and revascularization in patients with “hot carotids”. Methods: We used a qualitative descriptive methodology to examine decision-making approaches of physicians regarding the management of hot carotids. We conducted semi-structured interviews with 22 stroke physicians from various specialties in 16 centers across 4 continents. Results: Important themes regarding anti-thrombotic included limitations of existing clinical trial evidence, competing physician preferences, antiplatelet therapy while awaiting revascularization and various regional differences. Timely imaging availability, breadth of information gained, and surgeon/interventionalist preferences were important themes influencing the choice of imaging modality. The choice of revascularization intervention was influenced by healthcare system factors such as use of multidisciplinary review and operating room/angiography suite availability, and patient factors like age and infarct size. Many themes related to uncertainties in the management of hot carotids were also discussed. Conclusions: Our study revealed themes that are important to international stroke experts. We highlight common and divergent practices while underscoring important areas of clinical equipoise and uncertainty. Teams designing international carotid trials may wish to accommodate identified variations in practice patterns and areas of uncertainty.