Chronic glucocorticoid management in neuromuscular disease: A survey of neuromuscular neurologists.

INTRODUCTION/AIMS: Glucocorticoids (GC) are first-line therapy for many neuromuscular diseases. There is a lack of guidelines regarding the prevention and management of GC complications in the context of neuromuscular disease, introducing the potential for practice variation, that may compromise quality of care. Our aim was to evaluate the practice patterns among Canadian adult neuromuscular neurologists on the screening, management, and treatment of GC-related complications and to identify variances in practice. METHODS: A web-based anonymous questionnaire was disseminated to 99 Canadian adult neuromuscular neurologists. Questions addressed patterns of screening, prevention, monitoring, and treatment of GC-induced adverse events, including infection prophylaxis, vaccination, bone health, hyperglycemia, and other complications. RESULTS: Seventy-one percent completed the survey. Of those, 52% perform screening blood work prior to initiating GC, 56% screen for infections, and 18% for osteoporosis. The majority monitor glycemic control and blood pressure (>85%). Thirty-two (46%) reported that they do not primarily monitor GC complications, but rather provide recommendations to the primary care physician. Pneumocystis jiroveci pneumonia prophylaxis was never used by 29%, and 29% recommend vaccinations prior to GC initiation. Calcium supplementation was recommended by 80% to prevent osteoporosis. Only 36% were aware of any existing guidelines for preventing GC complications, and 91% endorsed a need for neurology-specific guidelines. DISCUSSION: There is substantial variability in the management of GC adverse effects among neuromuscular neurologists, often not corresponding to limited published literature. Our results support the need for improved education and neurology-specific guidelines to help standardize practice and improve and prevent complications.

Pregnancy planning may impact maternal and neonatal outcomes in people with myasthenia gravis.

INTRODUCTION: Myasthenia Gravis (MG) is an acquired autoimmune condition commonly diagnosed in young people of reproductive age resulting in neuromuscular junction dysfunction. The course of MG during pregnancy and its impact on maternal and neonatal outcomes is vary in the literature. Pregnancy planning is a known strategy and modifiable risk factor in obstetric practice to decrease maternal and neonatal morbidity. We aim to assess if planning a pregnancy impacts maternal and neonatal outcomes, MG exacerbation, and pregnancy-related complications. METHODS: This study utilized data from an online, North American survey entitled "A Patient Centered study on Pregnancy in People with Myasthenia Gravis", distributed with the assistance of MG advocacy groups in the United States and Canada. It included individuals with MG who had at least one pregnancy in the last 10-years. Key maternal and neonatal outcomes were compared between planned and unplanned pregnancies. RESULTS: Out of 156 survey participants, 58 had a pregnancy following MG diagnosis, totaling 90 reported pregnancies. Of these, 56 (62.2%) were planned and 34 (37.8%) were unplanned pregnancies. The unplanned pregnancies were associated with more MG exacerbations, hospitalizations, and intensive care unit admission (37.7% vs. 13.7%, 26.5% vs. 11%, and 17.6% vs. 8.9%, respectively, p ≤ .05). The neonatal outcomes did not significantly differ between the groups. DISCUSSION: Planned pregnancies in people with MG may be associated with a reduced gestational and post-partum risk of MG exacerbation, hospitalizations, and ICU admissions. Larger studies are required to confirm this association and account for potential contributing variables.

Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases.

OBJECTIVE: This article reviews the clinical spectrum of amyotrophic lateral sclerosis (ALS), its variant presentations, and the approach to diagnosis and management. This review includes a detailed discussion of current and emerging disease-modifying therapies and the management of respiratory and bulbar manifestations of disease. An updated review of ALS genetics and pathophysiology is also provided. This article also touches on several other important motor neuron diseases. LATEST DEVELOPMENTS: A new set of simplified diagnostic criteria may help identify patients at earlier stages of the disease. A coformulation of sodium phenylbutyrate and tauroursodeoxycholic acid has been shown to have a significant benefit on disease progression and survival, leading to approval by regulatory authorities in the United States and Canada. An oral formulation of edaravone and an antisense oligonucleotide to a SOD1 gene variation (tofersen) have also recently been approved by the US Food and Drug Administration (FDA). Phase 3 trials of intrathecal mesenchymal stem cells failed to meet primary end points for efficacy. Updated American Academy of Neurology quality measures for the care of patients with ALS were published in 2023. ESSENTIAL POINTS: There has been continued progress in ALS genetics, diagnosis, and disease-modifying therapies. However, we still lack a definitive biomarker or a treatment that can halt the progression or reverse the course of disease. The evolving understanding of the genetic and pathophysiologic underpinnings of disease offers promise for more effective and clinically meaningful treatments in the future.

Genetic testing for amyotrophic lateral sclerosis in Canada - an assessment of current practices.

Objective: To understand current genetic testing practices at Canadian ALS clinics. Methods: An online survey and phone interviews, with clinicians practicing in 27 ALS clinics in Canada, were employed to collect data. Quantitative and qualitative analyses were conducted. Results: Ninety-three percent (25/27) of ALS clinics in Canada are routinely ordering genetic testing for familial ALS, while 33% (9/27) of clinics are routinely ordering genetic testing for sporadic ALS. Barriers to genetic testing include a perceived lack of an impact on treatment plan, difficulty in obtaining approvals, primarily from provincial Ministries of Health, and limited access to genetic counseling. Predictive testing practices were found to be the most variable across the country. The average wait time for a symptomatic patient living with ALS to see a genetic counselor in Canada is 10 months (range 0-36 months). Conclusions: Access to genetic testing, and testing practices, vary greatly across Canadian ALS clinics. There may be patients with a monogenetic etiology to their ALS who are not being identified given that genetic testing for patients diagnosed with ALS is not routinely performed at all clinics. This study highlights potential inequities for patients with ALS that can arise from variability in health care delivery across jurisdictions, in a federally-funded, but provincially-regulated, health care system. Clinical trials for both symptomatic ALS patients and pre-symptomatic ALS gene carriers are ongoing, and ALS clinicians in Canada are motivated to improve access to genetic testing for ALS.

Modification to Neurology Residency Training: The Toronto Neurology COVID-19 Pandemic Experience.

We describe the University of Toronto Adult Neurology Residency Program's early experiences with and response to the coronavirus disease 2019 pandemic, including modifications to the provision of neurologic care while upholding neurology education and safety. All academic and many patient-related activities were virtualized. This maintained physical distancing while creating a city-wide videoconference-based teaching curriculum, expanding the learning opportunities to trainees at all academic sites. Furthermore, we propose a novel split-team model to promote resident safety through physical distancing of teams and to establish a capacity to rapidly adapt to redeployment, service needs, and trainee illness. Finally, we developed a unique protected code stroke framework to safeguard staff and trainees during hyperacute stroke assessments in this pandemic. Our shared experiences highlight considerations for contingency planning, maintenance of education, sustainability of team members, and promotion of safe neurologic care. These interventions serve to promote trainee safety, wellness, and resiliency.

A Canadian Adult Spinal Muscular Atrophy Outcome Measures Toolkit: Results of a National Consensus using a Modified Delphi Method.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a rare disease that affects 1 in 11 000 live births. Recent developments in SMA treatments have included new disease-modifying therapies that require high quality data to inform decisions around initiation and continuation of therapy. In Canada, there are no nationally agreed upon outcome measures (OM) used in adult SMA. Standardization of OM is essential to obtain high quality data that is comparable among neuromuscular clinics. OBJECTIVE: To develop a recommended toolkit and timing of OM for assessment of adults with SMA. METHODS: A modified delphi method consisting of 2 virtual voting rounds followed by a virtual conference was utilized with a panel of expert clinicians treating adult SMA across Canada. RESULTS: A consensus-derived toolkit of 8 OM was developed across three domains of function, with an additional 3 optional measures. Optimal assessment frequency is 12 months for most patients regardless of therapeutic access, while patients in their first year of receiving disease-modifying therapy should be assessed more frequently. CONCLUSIONS: The implementation of the consensus-derived OM toolkit will improve monitoring and assessment of adult SMA patients, and enrich the quality of real-world evidence. Regular updates to the toolkit must be considered as new evidence becomes available.

A National Spinal Muscular Atrophy Registry for Real-World Evidence.

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population. METHODS: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials. RESULTS: The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner. CONCLUSION: Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.

The Virtual Neurologic Exam: Instructional Videos and Guidance for the COVID-19 Era.

OBJECTIVE: To outline features of the neurologic examination that can be performed virtually through telemedicine platforms (the virtual neurological examination [VNE]), and provide guidance for rapidly pivoting in-person clinical assessments to virtual visits during the COVID-19 pandemic and beyond. METHODS: The full neurologic examination is described with attention to components that can be performed virtually. RESULTS: A screening VNE is outlined that can be performed on a wide variety of patients, along with detailed descriptions of virtual examination maneuvers for specific scenarios (cognitive testing, neuromuscular and movement disorder examinations). CONCLUSIONS: During the COVID-19 pandemic, rapid adoption of virtual medicine will be critical to provide ongoing and timely neurological care. Familiarity and mastery of a VNE will be critical for neurologists, and this article outlines a practical approach to implementation.

Peripheral Nerve Ultrasound Imaging Shows Enlargement of Peripheral Nerves Outside the Brachial Plexus in Neuralgic Amyotrophy.

PURPOSE: Neuralgic amyotrophy is characterized by acute or subacute onset of shoulder and arm pain, followed by muscle atrophy and weakness, and variable sensory abnormalities. Historically, the site of inflammation has been localized to the brachial plexus, although the involvement of individual nerve branches has been well recognized. METHODS: We describe ultrasound findings in two cases with a clinical presentation suggestive of neuralgic amyotrophy, involving individual peripheral nerves, correlating with clinical and electrophysiological findings. RESULTS: In the first case, selective fusiform enlargement of the left radial nerve in the proximal forearm is shown, whereas in the second case, fusiform enlargement of the left median nerve in the antecubital fossa is shown. DISCUSSION: These cases confirm that the site of nerve inflammation may lie outside the brachial plexus, keeping with previous reports, and suggests that peripheral nerve ultrasound imaging might aid in the diagnosis of neuralgic amyotrophy and exclude mimicking conditions.

Physician-assisted death: A Canada-wide survey of ALS health care providers.

OBJECTIVE: To survey amyotrophic lateral sclerosis (ALS) health care providers to determine attitudes regarding physician-assisted death (PAD) after the Supreme Court of Canada (SCC) invalidated the Criminal Code provisions that prohibit PAD in February 2015. METHODS: We conducted a Canada-wide survey of physicians and allied health professionals (AHP) involved in the care of patients with ALS on their opinions regarding (1) the SCC ruling, (2) their willingness to participate in PAD, and (3) the PAD implementation process for patients with ALS. RESULTS: We received 231 responses from ALS health care providers representing all 15 academic ALS centers in Canada, with an overall response rate for invited participants of 74%. The majority of physicians and AHP agreed with the SCC ruling and believed that patients with moderate and severe stage ALS should have access to PAD; however, most physicians would not provide a lethal prescription or injection to an eligible patient. They preferred the patient obtain a second opinion to confirm eligibility, have a psychiatric assessment, and then be referred to a third party to administer PAD. The majority of respondents felt unprepared for the initiation of this program and favored the development of PAD training modules and guidelines. CONCLUSIONS: ALS health care providers support the SCC decision and the majority believe PAD should be available to patients with moderate to severe ALS with physical or emotional suffering. However, few clinicians are willing to directly provide PAD and additional training and guidelines are required before implementation in Canada.

Diabetic Neuropathies.

Diabetes mellitus is a common condition and diabetics are prone to develop a spectrum of neuropathic complications ranging from symmetric and diffuse to asymmetric and focal neuropathies that may be associated with significant morbidity. Diabetic sensorimotor polyneuropathy is the most common of these complications, occurring in patients with type 1 and 2 diabetes mellitus, as well as in those with prediabetes and glucose intolerance. In this review, the authors discuss the wide variety of neuropathies that can present in the context of diabetes, including the clinical manifestations, diagnostic features, and approach to management.

Crescendo transient Aura attacks: a transient ischemic attack mimic caused by focal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Diagnosis of transient ischemic attack can be difficult because many mimics exist. We report the clinical and neuroimaging features of a distinct hemorrhagic transient ischemic attack mimic. METHODS: Case series. RESULTS: We describe 4 elderly patients presenting with a cluster of stereotyped somatosensory migraine auras, initially referred for "crescendo transient ischemic attacks". Neuroimaging in each patient revealed an unexpected finding of spontaneous focal subarachnoid hemorrhage conforming to a cortical sulcus in the contralateral hemisphere. We postulate that the episodic aura symptoms corresponded to recurrent cortical spreading depression triggered by the presence of subarachnoid blood, and speculate that such episodes could be a presenting feature of cerebral amyloid angiopathy in the absence of typical cerebral microbleeds or history of cognitive impairment. CONCLUSIONS: Focal subarachnoid hemorrhage can present clinically with transient repetitive migraine auras. Awareness of this entity is important because misdiagnosis as cerebral ischemic events could lead to incorrect treatment. We recommend that elderly patients presenting with a cluster of new unexplained migraine auras should be investigated ideally with MRI to detect focal subarachnoid hemorrhage.

Magnetic resonance imaging in frontotemporal dementia shows subcortical atrophy.

BACKGROUND/AIMS: The clinical syndrome of the frontotemporal dementias (FTD) overlaps with frontal-subcortical circuit syndromes. We explored the extent to which subcortical atrophy on structural magnetic resonance imaging may indicate a subcortical contribution to the progression of FTD. METHODS: This cross-sectional case-control study compared striatal and thalamic gray matter volumes and functional levels from 30 FTD cases and 30 age- and gender-matched controls. RESULTS: The FTD group had significantly more atrophy in all gray matter subcortical regions, correlating with ipsilateral frontocortical atrophy. Subcortical atrophy was also associated with functional disability. Subcortical asymmetry was most marked in subjects with primary progressive aphasia. CONCLUSION: Subcortical gray matter atrophy may contribute as significantly to symptoms of FTD as cortical atrophy.

Alcohol consumption impairs stimulus- and error-related processing during a Go/No-Go Task.

Alcohol consumption has been shown to increase the number of errors in tasks that require a high degree of cognitive control, such as a go/no-go task. The alcohol-related decline in performance may be related to difficulties in maintaining attention on the task at hand and/or deficits in inhibiting a prepotent response. To test these two accounts, we investigated the effects of alcohol on stimulus- and response-locked evoked potentials recorded during a go/no-go task that involved the withholding of key presses to rare targets. All participants performed the task prior to drinking and were then assigned randomly to either a control, low-dose, or moderate-dose treatment. Both doses of alcohol increased the number of errors relative to alcohol-free performance. Success in withholding a prepotent response was associated with an early-enhanced stimulus-locked negativity at inferior parietal sites, which was delayed when participants failed to inhibit the motor command. Moreover, low and moderate doses of alcohol reduced N170 and P3 amplitudes during go, no-go, and error trials. In comparison with the correct responses, errors generated large response-locked negative (Ne) and positive (Pe) waves at central sites. Both doses of alcohol reduced the Ne amplitude whereas the Pe amplitude decreased only after moderate doses of alcohol. These results are consistent with the interpretation that behavioral disinhibition following alcohol consumption involved alcohol-induced deficits in maintaining and allocating attention thereby affecting the processing of incoming stimuli and the recognition that an errant response has been made.