Whole-body magnetic resonance neurography in patients with chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION/AIMS: Whole-body magnetic resonance neurography (MRN) is an imaging modality that shows peripheral nerve signal change in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We aimed to explore the diagnostic potential of whole-body MRN and its potential as a monitoring tool after immunotherapy in treatment-naïve CIDP patients. METHODS: Whole-body MRN using coronal 3-dimensional short tau inversion recovery (STIR) sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) techniques was performed in patients being investigated for CIDP and in healthy controls. Baseline clinical neuropathy scales and electrophysiologic parameters were collected, and MRN findings were compared before and after CIDP treatment. RESULTS: We found highly concordant symmetrical thickening and increased T2 signal intensities in the brachial/lumbosacral plexus, femoral, or sciatic nerves in five of the eight patients with a final diagnosis of CIDP and none of the healthy controls. There were no treatment-related imaging changes in five patients with CIDP who completed a follow-up study. Diffuse, symmetrical thickening, and increased T2 signal in root, plexus, and peripheral nerves were found in two patients ultimately excluded due to a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome in addition to signal changes in the muscles, bony lesions, organomegaly, and lymphadenopathy. DISCUSSION: Whole-body MRN imaging shows promise in detecting abnormalities in proximal nerve segments in patients with CIDP. Future studies evaluating the role of MRN in assessing treatment response should consider follow-up scans after treatment durations of more than 4 months.

Qualitative Analysis of Initial Palliative Care Consultations in Amyotrophic Lateral Sclerosis.

BACKGROUND: Palliative care (PC) benefits patients with amyotrophic lateral sclerosis (ALS), however the needs of patients and caregivers and the optimal timing of PC discussions remains unclear. This study reports the analysis of PC consult notes from a larger feasibility trial. The specific aims of this analysis were to i) identify the PC needs of patients with ALS via qualitative analysis and ii) identify characteristics of patients and caregivers that could predict specific PC needs. METHODS: This study was nested within a nonrandomized, prospective study of patients with ALS (and their caregivers) being treated at a multidisciplinary ALS clinic. Exclusion criteria of the main study were age <18 years, inability to complete questionnaires, and prior receipt of PC. All patients were offered a PC consultation (PCC); those who accepted were included in this nested study. Consultation notes were reviewed and thematic and content analyses were conducted. The occurrence of themes across patient and caregiver contextual variables were examined. RESULTS: Thirty-two PCCs were completed between October 2020 and April 2022. Six major themes were identified: PC roles (with subthemes encompassing the spectrum of specialist PC practice including symptom management and advance care planning), engagement with PC, patients' concerns for their caregivers, caregiver-specific concerns, finances, and COVID-19. An average of 12 topics were discussed per PCC (range = 3-22). Discussion of advance care planning, care coordination, and symptom management was common, and these topics were not discussed more frequently in PCCs with patients with lower functional status, more bulbar symptoms, or lower quality of life. Time from diagnosis did not impact topics of discussion. Patients reporting more symptoms of depression more frequently required psychological support, particularly regarding loss of independence, employment, and leisure activities. DISCUSSION: Patients with ALS and their caregivers have a wide range of PC needs. These needs vary irrespective of time from diagnosis, functional status, or quality of life, therefore PCC is recommended for all patients with ALS. PCC should be individualized based on patient and caregiver preferences. TRIAL REGISTRATION INFORMATION: The study was registered with ClinicalTrials.gov (NCT04257760; https://clinicaltrials.gov/ct2/show/NCT04257760) on February 6, 2020. The first enrollment occurred on October 20, 2020.

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.

Subcutaneous batoclimab in generalized myasthenia gravis: Results from a Phase 2a trial with an open-label extension.

OBJECTIVES: To assess the safety, tolerability, and key pharmacodynamic effects of subcutaneous batoclimab, a fully human anti-neonatal Fc receptor monoclonal antibody, in patients with generalized myasthenia gravis and anti-acetylcholine receptor antibodies. METHODS: A Phase 2a, proof-of-concept, randomized, double-blind, placebo-controlled trial is described. Eligible patients were randomized (1:1:1) to receive once-weekly subcutaneous injections of batoclimab 340 mg, batoclimab 680 mg, or matching placebo for 6 weeks. Subsequently, all patients could enter an open-label extension study where they received batoclimab 340 mg once every 2 weeks for 6 weeks. Primary endpoints were safety, tolerability, and change from baseline in total immunoglobulin G, immunoglobulin G subclasses, and anti-acetylcholine receptor antibodies at 6 weeks post-baseline. Secondary endpoints included changes from baseline to 6 weeks post-baseline for Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, Myasthenia Gravis Composite, and revised 15-item Myasthenia Gravis Quality of Life scores. RESULTS: Seventeen patients were randomized to batoclimab 680 mg (n = 6), batoclimab 340 mg (n = 5), or placebo (n = 6). Batoclimab was associated with significantly greater reductions in total immunoglobulin G and anti-acetylcholine receptor antibodies from baseline to 6 weeks post-baseline than placebo. Reductions in immunoglobulin G subclasses were generally consistent with total immunoglobulin G. While clinical measures showed directionally favorable improvements over time, the study was not powered to draw conclusions about therapeutic efficacy. No safety issues were identified. INTERPRETATION: The safety profile, pharmacodynamics, and preliminary clinical benefits observed in this study support further investigation of subcutaneous batoclimab injections as a potential patient-administered therapy for seropositive generalized myasthenia gravis.

Palliative care at any stage of amyotrophic lateral sclerosis: a prospective feasibility study.

Introduction: Many patients with amyotrophic lateral sclerosis (ALS) receive palliative care (PC) very late or not at all. The impact of PC on patients with ALS and caregivers has not been quantified. Study goals included (1) measuring the impact of early PC on quality of life and mood of patients/caregivers and (2) describing patient/caregiver satisfaction with PC. Methods: The study was a non-randomized, prospective feasibility study of patients with ALS being treated at The Ottawa Hospital ALS Clinic and their caregivers. Exclusion criteria were age < 18 years, inability to complete questionnaires, and prior receipt of PC. The ALS Specific Quality of Life-Revised (ALSSQOL-R) questionnaire (patients only) and Hospital Anxiety and Depression Scale (HADS) were completed at regular intervals for up to 2 years. Patients accepting a PC consultation completed a post-PC satisfaction survey. Primary outcome measures included ALSSQOL-R and HADS scores compared before and after PC consultation, and between groups receiving and not receiving a PC consultation. Secondary outcome measures included responses on the post-PC satisfaction survey (1 = strongly disagree, 5 = strongly agree). Results: 39 patients with ALS (age 66 ± 10 years, median time from diagnosis = 6 months) and 22 caregivers were enrolled. 32 patients had a PC consultation (30 were virtual). Patients and caregivers agreed with statements that the PC consult was helpful (mean ± SD = 4.54 ± 0.60, range = 3-5) and they would recommend PC to others with ALS (4.59 ± 0.59, range = 3-5). Participants disagreed with statements that the consult would have been better later in disease course (1.87 ± 0.80, range = 1-4) and that it took too much time/energy (1.44 ± 0.85, range = 1-4). Average ALSSQOL-R scores worsened significantly over time. HADS and ALSSQOL-R scores did not significantly differ between groups receiving and not receiving PC. Conclusion: Patients with ALS and their caregivers found virtual PC consultations beneficial irrespective of disease duration or severity. Offering routine PC to all patients with ALS is feasible and should be considered as part of standard care. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04257760, identifier NCT04257760.

Novel Homozygous Variant in COQ7 in Siblings With Hereditary Motor Neuropathy.

Background and Objectives: Coenzyme Q10 (CoQ10) is an important electron carrier and antioxidant. The COQ7 enzyme catalyzes the hydroxylation of 5-demethoxyubiquinone-10 (DMQ10), the second-to-last step in the CoQ10 biosynthesis pathway. We report a consanguineous family presenting with a hereditary motor neuropathy associated with a homozygous c.1A > G p.? variant of COQ7 with abnormal CoQ10 biosynthesis. Methods: Affected family members underwent clinical assessments that included nerve conduction testing, histologic analysis, and MRI. Pathogenicity of the COQ7 variant was assessed in cultured fibroblasts and skeletal muscle using a combination of immunoblots, respirometry, and quinone analysis. Results: Three affected siblings, ranging from 12 to 24 years of age, presented with a severe length-dependent motor neuropathy with marked symmetric distal weakness and atrophy with normal sensation. Muscle biopsy of the quadriceps revealed chronic denervation pattern. An MRI examination identified moderate to severe fat infiltration in distal muscles. Exome sequencing demonstrated the homozygous COQ7 c.1A > G p.? variant that is expected to bypass the first 38 amino acid residues at the n-terminus, initiating instead with methionine at position 39. This is predicted to cause the loss of the cleavable mitochondrial targeting sequence and 2 additional amino acids, thereby preventing the incorporation and subsequent folding of COQ7 into the inner mitochondrial membrane. Pathogenicity of the COQ7 variant was demonstrated by diminished COQ7 and CoQ10 levels in muscle and fibroblast samples of affected siblings but not in the father, unaffected sibling, or unrelated controls. In addition, fibroblasts from affected siblings had substantial accumulation of DMQ10, and maximal mitochondrial respiration was impaired in both fibroblasts and muscle. Discussion: This report describes a new neurologic phenotype of COQ7-related primary CoQ10 deficiency. Novel aspects of the phenotype presented by this family include pure distal motor neuropathy involvement, as well as the lack of upper motor neuron features, cognitive delay, or sensory involvement in comparison with cases of COQ7-related CoQ10 deficiency previously reported in the literature.

Quantitative vs qualitative muscle MRI: Imaging biomarker in patients with Oculopharyngeal Muscular Dystrophy (OPMD).

Oculopharyngeal muscular dystrophy (OPMD) is a genetic muscle disease causing ptosis, severe swallowing difficulties and progressive limb weakness, although atypical presentations may be difficult to diagnose. Sensitive biomarkers of disease progression in OPMD are needed to enable more effective clinical trials. This study was designed to test the feasibility of using MRI to aid OPMD diagnosis and monitor OPMD progression. Twenty-five subjects with Dixon whole-body muscle MRI were enrolled: 10 patients with genetically confirmed OPMD, 10 patients with non-OPMD muscular dystrophies, and 5 controls. Using the MRI Dixon technique, muscle fat replacement was evaluated in the tongue, serratus anterior, lumbar paraspinal, adductor magnus, and soleus muscles using quantitative and semi-quantitative rating methods. Changes were compared with muscle strength testing, dysphagia severity, use of gait aids, and presence of dysarthria. Quantitative MRI scores of muscle fat replacement in the tongue could differentiate OPMD from other muscular dystrophies and from controls. Moreover, fat fraction in the tongue correlated with clinical severity of dysphagia. This study provides preliminary support for the use of Dixon-based quantitative MRI images as outcome measures for monitoring disease progression in clinical trials and provides rationale for future prospective studies aimed at methodological refinement and covariate identification.

Biallelic SOX8 Variants Associated With Novel Syndrome With Myopathy, Skeletal Deformities, Intellectual Disability, and Ovarian Dysfunction.

Background and Objectives: The human genome contains ∼20,000 genes, each of which has its own set of complex regulatory systems to govern precise expression in each developmental stage and cell type. Here, we report a female patient with congenital weakness, respiratory failure, skeletal dysplasia, contractures, short stature, intellectual delay, respiratory failure, and amenorrhea who presented to Medical Genetics service with no known cause for her condition. Methods: Whole-exome and whole-genome sequencing were conducted, as well as investigational functional studies to assess the effect of SOX8 variant. Results: The patient was found to have biallelic SOX8 variants (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)). SOX8 is a transcriptional regulator, which is predicted to be imprinted (expressed from only one parental allele), but this has not yet been confirmed. We provide evidence that while SOX8 was maternally expressed in adult-derived fibroblasts and lymphoblasts, it was biallelically expressed in other cell types and therefore suggest that biallelic variants are associated with this recessive condition. Functionally, we showed that the paternal variant had the capacity to affect mRNA splicing while the maternal variant resulted in low levels of a truncated protein, which showed decreased binding at and altered expression of SOX8 targets. Discussion: Our findings associate SOX8 variants with this novel condition, highlight how complex genome regulation can complicate novel disease-gene identification, and provide insight into the molecular pathogenesis of this disease.

Does Diabetes Alter CSF Total Protein Levels? A Retrospective Cohort Study.

Background and Purpose: Elevation of total protein level in cerebrospinal fluid (CSF-TP) in diabetic patients is often disregarded by clinicians. However, existing studies on the topic have significant limitations, and therefore we aimed to explore the relationship between diabetes and CSF-TP in a large database of CSF samples. Methods: Retrospective review of all diagnostic lumbar punctures at the Ottawa Hospital between 1996-2016. Patients were excluded if they had elevated CSF cell counts, or a condition known to elevate CSF-TP. Multivariate linear regression modeling considered the effects of age, sex, and diabetes. Results: Among 6124 patients (746 with diabetes, 5378 without), mean CSF-TP did not differ significantly between groups (0.39 and 0.35 mmol/L, p = 0.2). When controlled for age and sex, there was no significant effect of diabetes on CSF-TP and no significant correlation between mean serum glucose and CSF-TP (R2 = 0.12). Conclusions: CSF-TP did not differ significantly between diabetic and non-diabetic groups, once the influence of age and sex was controlled. Elevated CSF-TP should be regarded as pathologic, even in the setting of diabetes.

Case Report: Severe Peripartum Cardiac Disease in Myotonic Dystrophy Type 1.

Background: Myotonic dystrophy type 1 (DM1) is a hereditary muscular dystrophy affecting ∼2.1-14.3/100,000 adults. Cardiac manifestations of DM1 include conduction disorders and rarely cardiomyopathies. DM1 increases the risk of obstetric complications, however, little is known about the relationship between pregnancy and cardiomyopathy in DM1 due to disease rarity. Case: A 23-year-old with DM1 developed cardiomyopathy during pregnancy. Despite initial medical stabilization, she subsequently developed multiple spontaneous coronary artery dissections postpartum, worsening cardiomyopathy and multiorgan failure. She died 5 months postpartum. Conclusion: Though cardiomyopathy and arterial dissection are both known complications of pregnancy, this case suggests individuals with myotonic dystrophy type 1 may be at heightened risk for cardiac disease during the peripartum period. Physicians caring for women with suspected or proven DM1 should offer counseling and be alerted to the risk of cardiac complications with pregnancy and in the peripartum period. Pregnant and peripartum women with DM1 are likely to benefit from more frequent assessments of cardiac function including echocardiograms and early institution of heart failure management protocols when symptoms of cardiomyopathy present.

Canadian Guidelines for Hereditary Transthyretin Amyloidosis Polyneuropathy Management.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.

Lignes directrices sur la prise en charge de l'amylose héréditaire à transthyrétine, accompagnée de polyneuropathie, au Canada.L'amylose héréditaire à transthyrétine (ATTRh) est une maladie évolutive, causée par des mutations du gène de la transthyrétine (TTR), qui entraînent un dysfonctionnement plurisystémique. L'agrégation, le mauvais repliement et la fibrillisation pathogènes de la TTR aboutissent au dépôt de protéines amyloïdes dans plusieurs organes, et affectent souvent le système nerveux périphérique et le cœur. Les troubles neurologiques fréquents comprennent une polyneuropathie sensorimotrice (PN), une neuropathie autonome, une polyneuropathie des petites fibres et le syndrome du canal carpien. Chez bon nombre de patients, la maladie a connu une évolution importante en raison de la pose tardive du diagnostic, la PN-ATTRh ne faisant pas l'objet d'un diagnostic différentiel. Santé Canada a approuvé, depuis peu, deux nouveaux médicaments modificateurs de la PN-ATTRh et efficaces contre l'affection, soit l'inotersen et le patisiran. La pose précoce du diagnostic revêt une importance cruciale dans l'instauration, en temps opportun, de ces tout nouveaux traitements qui atténuent les troubles, améliorent la qualité de vie et prolongent la survie. Les auteurs, par l'élaboration de la nouvelle ligne directrice, espèrent sensibiliser la communauté médicale à la PN-ATTRh, et améliorer les résultats cliniques qui y sont associés, en formulant des recommandations sur le diagnostic et le traitement de la maladie au Canada ainsi que sur la surveillance de son évolution.

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.

Laryngospasm in amyotrophic lateral sclerosis.

INTRODUCTION: Laryngospasm is an involuntary, sustained closure of sphincter musculature that leads to an unpleasant subjective experience of dyspnea and choking. It is an underreported symptom in amyotrophic lateral sclerosis (ALS). In this study we aimed to better characterize the prevalence and clinical characteristics of laryngospasm in ALS patients. METHODS: The medical records of 571 patients with ALS followed between 2008 and 2018 were searched for evidence of laryngospasm. A total of 23 patients with laryngospasm were identified and the data related to patient and laryngospasm characteristics were extracted. RESULTS: Laryngospasm was reported in 4% of ALS patients. Females comprised 57% of patients and their mean age was 63.4 years. Laryngospasm frequently manifested in patients with moderate bulbar dysfunction and seemed independent of respiratory function. Among laryngospasm patients, 26% were cigarette smokers and 13% had a history of gastroesophageal reflux. The most common reported trigger was excessive saliva irritating the vocal cords (35%) followed by eating a meal (17%). There was significant variation in laryngospasm frequency (up to 5 per hour) and duration (seconds to minutes). Most patients could not identify an effective coping mechanism, although 13% reported that drinking water was effective. DISCUSSION: Despite its low prevalence in ALS, laryngospasm should be included in the symptom inquiry. The present findings may improve patient care through increased recognition of the clinical features of laryngospasm in ALS patients, identifying a link between laryngospasm and moderate bulbar dysfunction, and highlighting trigger avoidance as a management strategy. Additional research is required to understand the pathophysiology and optimal treatment.

MuSK not MNGIE: Atypical MuSK-antibody myasthenia presenting as a genetic disorder.

Myasthenia gravis is a treatable autoimmune disease caused by autoantibodies directed against membrane proteins at the neuromuscular junction. While acetylcholine receptor antibodies are most common, a minority of patients have antibodies directed against muscle-specific kinase (MuSK-antibody). Differentiating features often include subacute onset and rapid progression of bulbar, respiratory and neck extensor muscles, with sparing of distal appendicular muscles, most commonly in middle-aged females. Here we present an atypical presentation of MuSK-antibody myasthenic syndrome in a young male consisting of a gradual-onset, insidiously-progressive, non-fatigable and non-fluctuating ocular, bulbar and oesophageal weakness, with a normal frontalis single fibre EMG. This case clinically resembled a mitochondrial myopathy (Mitochondrial Neurogastrointestinal Encephalopathy-MNGIE) with a poor prognosis. Because of the atypical presentation, MuSK antibodies were identified very late in the disease course, at which point the patient responded very well to immunotherapy. We report an unusual presentation of an uncommon but treatable condition, illustrating significant phenotypic heterogeneity possible in MuSK-antibody myasthenic syndrome.

Autologous Hematopoietic Stem Cell Transplantation for Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) refractory to conventional therapy can lead to marked disability and represents a therapeutic challenge. OBJECTIVE: To report five cases of treatment-refractory disabling CIDP treated with autologous hematopoietic stem cell transplantation (AHSCT). METHODS: This was a retrospective cohort study from a tertiary care referral center for both neuromuscular disease and AHSCT. Patients with CIDP treated with AHSCT between 2008 and 2020 were included. All patients had major persistent and disabling neuropathic deficits despite combinations of intensive immunosuppressive therapy. The primary outcome measures were: Medical Research Council sum score, Overall Neuropathy Limitations Scale and requirement for ongoing CIDP immunotherapy after transplantation. We also analyzed safety outcomes by documenting all severe AHSCT-related complications. RESULTS: Five patients with refractory CIDP underwent AHSCT. Three were classified as manifesting a typical syndrome, two were classified as the multifocal Lewis Sumner variant. The mean age at time of CIDP diagnosis was 33.4 years (range 24-46 years), with a median delay of 46 months (range 21-135 months) between diagnosis and AHSCT. The median follow-up period was 41 months. All five patients were able to wean off CIDP-related immunotherapy. Marked improvements in Medical Research Council scale and overall Neuropathy Limitations Scale were noted in 4/5 patients. One patient with longstanding neurogenic atrophy showed no improvement in disability scales. There were no treatment-related deaths or critical illnesses. CONCLUSIONS: AHSCT can achieve marked sustained clinical improvement of refractory CIDP and may allow for weaning off long-term complex immunotherapies.

Fracture Risk in Patients with Myasthenia Gravis: A Population-Based Cohort Study.

BACKGROUND: Prednisone is a common treatment for myasthenia gravis (MG), and osteoporosis is a known potential risk of chronic prednisone therapy. OBJECTIVE: Our aim was to evaluate the risk of serious fractures in a population-based cohort of MG patients. METHODS: An inception cohort of patients with MG was identified from administrative health data in Ontario, Canada between April 1, 2002 and December 31, 2015. For each MG patient, we matched 4 general population comparators based on age, sex, and region of residence. Fractures were identified through emergency department and hospitalization data. Crude overall rates and sex-specific rates of fractures were calculated for the MG and comparator groups, as well as rates of specific fractures. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. RESULTS: Among 3,823 incident MG patients (followed for a mean of 5 years), 188 (4.9%) experienced a fracture compared with 741 (4.8%) fractures amongst 15,292 matched comparators. Crude fracture rates were not different between the MG cohort and matched comparators (8.71 vs. 7.98 per 1000 patient years), overall and in men and women separately. After controlling for multiple covariates, MG patients had a significantly lower risk of fracture than comparators (HR 0.74, 95% CI 0.63-0.88). CONCLUSIONS: In this large, population-based cohort of incident MG patients, MG patients were at lower risk of a major fracture than comparators. The reasons for this finding are unclear but may highlight the importance osteoporosis prevention.