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.

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.

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.

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.

Temporal evolution of nerve conduction study abnormalities in anti-myelin-associated glycoprotein neuropathy.

BACKGROUND: A distal-predominant demyelinating symmetric pattern is most frequent in patients with neuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies. The literature however lacks longitudinal data to describe whether this is consistent over time. METHODS: From the Ottawa Neuromuscular Center database, we identified 23 patients with both immunoglobulin M gammopathy and anti-MAG antibodies. For median, ulnar and fibular motor conduction studies, we analyzed distal latency and amplitude, negative peak duration, terminal latency index (TLI), and conduction velocity. For median, ulnar, sural, and superficial fibular sensory conduction studies, we analyzed distal latency and amplitude. Results were compared for the earliest and the latest data sets. RESULTS: The mean time interval between the two assessment points was 6.5 years. Median and ulnar motor nerve conduction studies did not show a significant change for any of the parameters tested. There was disproportionate prolongation of median distal motor latency and reduction in TLI, compared to the ulnar nerve. Deep fibular motor conduction studies showed a marked reduction in amplitudes over time. Sensory potentials were recordable in the upper limb in less than 50% at the first study and less than 25% on the most recent study. There was an even larger attrition of recordable sural and superficial fibular sensory potentials. CONCLUSIONS: Our results highlight the stability of median and ulnar motor conduction study results over a mean observation period of 6.5 years. In contrast, lower limb motor and all sensory potentials show a marked trend toward becoming unrecordable.

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.

Impact of disuse muscular atrophy on the compound muscle action potential.

BACKGROUND: Disuse atrophy from immobilization is the result of decreased neural activity and muscle unloading. METHODS: We studied the impact of disuse on hand intrinsic compound muscle action potentials (CMAPs) in a cohort of 39 patients with unilateral 6-week immobilization of the hand in a cast, after distal radius fracture. We excluded patients with nerve injury. We compared side-to-side CMAP characteristics at the time of cast removal and at a subsequent follow-up visit, after a mean interval of 7.8 weeks. RESULTS: Statistically significant reductions in CMAP amplitude were noted for the abductor pollicis brevis (29.2%), abductor digiti minimi (19.0%), and first dorsal interosseus (24.9%). There was partial repair of the relative CMAP reduction at the follow-up visit (20.1%, 10.7%, and 8.7%, respectively). There was no significant change in CMAP duration. CONCLUSIONS: These results provide a framework for quantifying the degree of hand intrinsic CMAP amplitude reduction attributed to disuse.

Updated cerebrospinal fluid total protein reference values improve chronic inflammatory demyelinating polyneuropathy diagnosis.

INTRODUCTION: Recent literature has concluded that cerebrospinal fluid total protein (CSF-TP) upper reference limits (URL) should be higher than 45 mg/dl and stratified by age. METHODS: Data-driven URLs were applied to the analysis of a cohort of patients with correctly and incorrectly diagnosed chronic inflammatory demyelinating polyneuropathy (CIDP). Descriptive statistics were calculated, and exploratory analyses were used to test the impact of different CSF-TP URLs on sensitivity and specificity of CIDP diagnosis. RESULTS: The adoption of higher and age-dependent CSF-TP URLs reduced the sensitivity of CSF analysis slightly (from 95% to 84%-86%); however, the overall CIDP detection rate was unchanged. Twelve of 36 (33%) false-positive diagnoses occurred with CSF-TP elevation as the sole supportive criteria. By applying updated CSF-TP URLs, the specificity of CSF analysis increased from 39% to 57%-64%. DISCUSSION: Implementation of data-driven CSF-TP URLs improves CIDP diagnostic specificity without compromising sensitivity, thereby lessening CIDP misdiagnosis. Muscle Nerve 60: 180-183, 2019.

Ultrasound-Assisted Lumbar Puncture in a Neuromuscular Clinic has a High Success Rate and Less Pain.

BACKGROUND: Lumbar puncture (LP) performed with the assistance of ultrasound (US) may improve success rate, with fewer puncture attempts and less pain. OBJECTIVES: To explore the utility of US-assisted LP in a neuromuscular clinic. METHODS: We performed a prospective, randomized, open-label study between May 2016 and January 2017. The primary outcome measure was LP success rate, and the secondary outcome measures included procedure time, number of attempts, and the levels of pain, anxiety, and satisfaction. RESULTS: Lumbar puncture was performed in 40 consecutive patients. Ultrasound-assisted LP had a 100% success rate, compared with 85% (95% confidence interval: 58%-96%) without US assistance, although this difference failed to reach statistical significance. Ultrasound-assisted LP was associated with less pain and, also in patients >60 years of age, with fewer needle insertions. Both groups reported high satisfaction rates, regardless of the use of US. CONCLUSION: Ultrasound-assisted LP has a high success rate and less pain than unassisted LP, and can be accomplished easily in the outpatient neuromuscular clinic setting equipped with US.

CONTEXTE: En plus de diminuer le nombre de tentatives de ponction alors nécessaires et la douleur qui en résulte, il est possible qu'un examen de ponction lombaire effectué avec l'aide d'appareils à ultrasons obtienne un plus haut taux de réussite. OBJECTIFS: Dans le cadre d'une clinique neuromusculaire, se pencher sur l'utilité des examens de ponction lombaire assistés par des appareils à ultrasons. MÉTHODES: De mai 2016 à janvier 2017, nous avons mené une étude prospective sans insu à répartition aléatoire. La principale mesure de nos résultats a porté sur le taux de succès des examens de ponction lombaire. D'autres mesures de résultats ont inclus les aspects suivants: la durée des examens, le nombre de tentatives de ponction ainsi que les niveaux de douleur, d'anxiété et de satisfaction des patients. RÉSULTATS: Des examens de ponction lombaire ont été effectués chez 40 patients consécutifs. Ceux menés à l'aide d'appareils à ultrasons ont donné à voir un taux de succès de 100 % comparativement à 85 % (IC 95 % : 58 % - 96 %) dans le cas de ceux effectués sans ces appareils. Rappelons toutefois que cette différence ne s'est pas révélée significative sur le plan statistique. Les examens de ponction lombaire au moyen d'appareils à ultrasons ont aussi été associés à moins de douleurs ressenties et, chez des patients âgés de plus de 60 ans, à moins d'insertions d'aiguilles. Enfin, ces deux groupes ont rapporté des taux de satisfaction élevés, et ce, sans égard à l'utilisation d'appareils à ultrasons. CONCLUSIONS: Les examens de ponction lombaire assistés par des appareils à ultrasons possèdent un haut taux de succès et entraînent moins de douleurs que ceux menés sans ces appareils. Ils peuvent aussi être effectués facilement dans le cadre de cliniques neuromusculaires externes qui en sont munies.

A Survey of Cerebrospinal Fluid Total Protein Upper Limits in Canada: Time for an Update?

BACKGROUND: The antiquated standard reference range of 0.15-0.45 g/L for cerebrospinal fluid total protein (CSF-TP) is well entrenched in medical literature and laboratory operating procedures across the world. METHODS: We conducted a web-based survey with a response rate of 34.9% through the listserv of the Canadian Neurological Sciences Federation. Additional laboratory reference data were collated by telephone interview of hospital laboratory technologists across Canada. RESULTS: A total of 142 site responses were obtained: 64.1% from academic/tertiary hospitals and 35.9% from community hospitals. A strong majority (80.4%) of both types of institutions reported using a CSF-TP upper reference limit of 0.45 g/L or less. As a rule, no age adjustments were implemented in CSF-TP-level interpretation. CONCLUSIONS: Recent well-powered laboratory reference studies have documented CSF-TP upper reference limits that are above 0.6 g/L starting at age 50, with incremental limits partitioned by subsequent decades of age. The conventional 0.45 g/L limit could lead to false positive results. Our survey suggests there is a need to consider a wide adoption of data-driven, rather than historical, reference values.

The utility of a single simple question in the evaluation of patients with myasthenia gravis.

INTRODUCTION: Assessing myasthenia gravis (MG) can be challenging, and multiple scales are available to evaluate disease severity. We evaluated the utility of a single, simple question, as part of the MG evaluation: "What percentage of normal do you feel regarding your MG, 0%-100% normal?" METHODS: A retrospective chart review of patients attending the neuromuscular clinic from January 2014 to December 2015 was performed. Responses were correlated with symptoms and signs, the Quantitative Myasthenia Gravis Score (QMGS), the Myasthenia Gravis Impairment Index (MGII), and the 15-item Myasthenia Gravis Quality of Life scale (MG-QOL15). RESULTS: The total cohort included 169 patients. The percentage of normal correlated strongly with limb muscle weakness and MG scales, moderately with bulbar and respiratory symptoms, and weakly with ocular manifestations. DISCUSSION: The question, "What percentage of normal do you feel regarding your MG?" is feasible and valid, and can be incorporated easily into routine clinical evaluation. Muscle Nerve 57: 240-244, 2018.

Quantitative sonographic assessment of myotonia.

INTRODUCTION: This study explores ultrasound imaging for qualitative and quantitative assessment of myotonia. METHODS: Sixteen patients with myotonia and 16 controls underwent sonographic evaluation of the thenar eminence muscles to assess the relaxation time after muscle percussion. RESULTS: The mean time for complete muscle relaxation in patients with myotonia was longer than that of controls. A cutoff of > 0.9 s for myotonia detection had a sensitivity of 88% and a specificity of 100%. The interrater reliability was moderate for qualitative assessment but was high for quantitative assessment. The relaxation time did not correlate with the number of trinucleotide repeats in patients with myotonic dystrophy. DISCUSSION: Sonographic evaluation for the presence of myotonia is feasible, sensitive, and specific but does not correlate with disease severity in myotonic dystrophy. Muscle Nerve 57: 146-149, 2018.

Laboratory Abnormalities in Polyneuropathy and Electrophysiological Correlations.

To study the frequency of laboratory test abnormalities, and electrophysiological correlations, we performed a retrospective chart review of 226 patients with polyneuropathy. The frequency of laboratory test abnormalities, and correlations with electrophysiological findings were explored. Abnormal glucose handling tests were the most common findings (54%), followed by paraproteinemia (21%) and anemia (21%). The frequencies of paraproteinemia and anemia in our cohort were significantly higher than previously reported. In addition, several laboratory abnormalities correlated with electrophysiological findings of median neuropathy at the wrist, expanding current knowledge about the deleterious effects of various metabolic and hematologic derangements at this site.

Electrophysiological testing is correlated with myasthenia gravis severity.

INTRODUCTION: Electrophysiological studies play an important role in the diagnosis of myasthenia gravis (MG). The objectives of this study was to explore the correlation of jitter and decrement with various clinical symptoms and signs and disease severity. METHODS: We performed a retrospective chart review of 75 MG patients who attended the neuromuscular clinic from April 2013 to May 2014. We compared clinical characteristics between patients with high jitter (>100 µs) and decrement (>10%), and patients with lower values to explore the correlations and optimal thresholds of jitter and decrement for different clinical features. RESULTS: High jitter and decrement values were associated with more severe disease, manifested by more frequent symptomatic bulbar and limb muscle weakness, more frequent ocular and limb muscle weakness on examination, higher quantitative MG score, and generalized disease. CONCLUSIONS: The yield of the electrophysiological assessment in MG extends beyond disease diagnosis and correlates with disease severity and the presence of generalized disease. Muscle Nerve 56: 445-448, 2017.

Repetitive nerve stimulation cutoff values for the diagnosis of myasthenia gravis.

INTRODUCTION: Repetitive nerve stimulation (RNS) showing ≥ 10% decrement is considered the cutoff for myasthenia gravis (MG), but this has never been validated. The objective of this study was to find an optimal validated cutoff value for decrement on RNS. METHODS: We performed retrospective chart review of patients who had electrophysiological assessment for possible MG from 2013 to 2015. RESULTS: A total of 122 patients with MG and 182 controls were identified. RNS sensitivities for generalized and ocular MG using the traditional ≥10% cutoff value were 46% and 15%, respectively, for frontalis recordings, and 35% and 19%, respectively, for nasalis recordings. Using a decrement cutoff value of 7% for frontalis and 8% for nasalis increased the sensitivities by 6-11%, with specificities of 95-96%. CONCLUSIONS: For RNS in facial muscles, we suggest a cutoff value of 7-8%, which increases test sensitivity by 6-11%, while preserving high specificity for the diagnosis of MG. Muscle Nerve, 2016 Muscle Nerve 55: 166-170, 2017.

Peripheral nerve high-resolution ultrasound in diabetes.

INTRODUCTION: High-resolution ultrasound (HRU) is used in the diagnosis of peripheral neuropathies. There are conflicting data regarding HRU findings in patients with diabetic sensorimotor polyneuropathy (DSP). Our purpose in this study was to measure nerve cross-sectional areas (CSAs) in patients with diabetes, with and without DSP. METHODS: We performed a prospective peripheral nerve HRU study of 100 diabetic subjects, assessed the CSA at predefined sites, and compared the results with those of 100 normal subjects. We evaluated the use of individual CSA values and various summary scores for diagnosis of DSP. RESULTS: Diabetic subjects had higher CSA values than healthy volunteers, and those with DSP had higher CSA values. Three or more enlarged CSA sites predicted DSP with 64% sensitivity and 77% specificity. CONCLUSIONS: Peripheral nerves are enlarged diffusely in diabetic patients, including sites not susceptible to bony compression. The number of enlarged CSA values can help predict the presence of DSP. Muscle Nerve, 2016 Muscle Nerve 55: 171-178, 2017.

Reference values for ultrasonograpy of peripheral nerves.

INTRODUCTION: High-resolution ultrasonography (HRU) is a novel method that provides morphological information about peripheral nerves. We aimed to determine reference values for nerve cross-sectional area (CSA) on HRU. METHODS: One hundred healthy volunteers had HRU of median, radial, ulnar, fibular, tibial, sural, and superficial fibular nerves at defined sites. The CSA was measured and the effects of age, gender, and body mass index (BMI) were evaluated. RESULTS: CSA values in healthy subjects are described. CSA is larger in lower limb motor nerves than in sensory nerves at similar sites, and the CSA tends to be symmetrical. The strongest effect on CSA was for age, although gender and BMI had some effects. CONCLUSIONS: This study provides normative values for HRU, and it suggests that further research with age- and gender-specific distributions must be a key priority in the development of HRU for use as a diagnostic test for peripheral nerve diseases.