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.

Clinical characteristics and treatment outcomes in patients with double-seronegative myasthenia gravis.

BACKGROUND AND PURPOSE: Double-seronegative myasthenia gravis (dSNMG) is defined as myasthenia gravis (MG) without detectable or low affinity antibodies to acetylcholine receptor (AChR) and muscle-specific kinase (MuSK). There are limited data on detailed clinical features and outcomes after treatment in dSNMG patients. The aim was to describe the clinical characteristics and outcomes in dSNMG patients based on MG scales. METHODS: A retrospective study was performed of patients diagnosed with MG who had negative AChR or MuSK antibodies and they were compared with an AChR-positive MG cohort. Correlations were made with data from the first and last clinic visits, between demographics, clinical characteristics, treatment and disease severity, based on the Myasthenia Gravis Foundation of America category, Myasthenia Gravis Impairment Index (MGII), Patient Acceptable Symptom State and simple single question (SSQ). RESULTS: Eighty patients met the inclusion criteria for dSNMG. The baseline MGII and SSQ scores in the dSNMG cohort showed no significant differences from the AChR group (p = 0.94 and p = 0.46). The dSNMG cohort MGII and SSQ scores improved significantly at the last clinical evaluation (p = 0.001 and p = 0.047). The MGII improvement in the AChR cohort was significantly better (p = 0.003). CONCLUSIONS: The initial severity of dSNMG based on clinical scores is similar to antibody-positive MG patients. There is significant clinical improvement in dSNMG patients after therapy, measured in the last clinical evaluation. This supports an immune pathophysiology of many dSNMG patients.

Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study.

BACKGROUND AND PURPOSE: Generalized myasthenia gravis (gMG) is a rare, chronic, neuromuscular autoimmune disease mediated by pathogenic immunoglobulin G (IgG) autoantibodies. Patients with gMG experience debilitating muscle weakness, resulting in impaired mobility, speech, swallowing, vision and respiratory function. Efgartigimod is a human IgG1 antibody Fc fragment engineered for increased binding affinity to neonatal Fc receptor. The neonatal Fc receptor blockade by efgartigimod competitively inhibits endogenous IgG binding, leading to decreased IgG recycling and increased degradation resulting in lower IgG concentration. METHODS: The safety and efficacy of efgartigimod were evaluated in the ADAPT study. Key efficacy outcome measures included Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Efgartigimod demonstrated significant improvement in both the MG-ADL and QMG scores. This post hoc analysis aimed to determine whether all subdomains of MG-ADL and QMG improved with efgartigimod treatment. Individual items of MG-ADL and QMG were grouped into four subdomains: bulbar, ocular, limb/gross motor and respiratory. Change from baseline over 10 weeks in each subdomain was calculated for each group. RESULTS: Greater improvements from baseline were seen across MG-ADL subdomains in participants treated with efgartigimod compared with placebo. These improvements were typically observed 1 to 2 weeks after the first infusion and correlated with reductions in IgG. Similar results were observed across most QMG subdomains. CONCLUSIONS: These post hoc analyses of MG-ADL and QMG subdomain data from ADAPT suggest that efgartigimod is beneficial in improving muscle function and strength across all muscle groups, leading to the observed efficacy in participants with gMG.

Reliability of confocal corneal microscopy for measurement of dendritic cell density in suspected small fiber neuropathy.

INTRODUCTION/AIMS: Dendritic cells (DCs) and their contacts with corneal nerves are described in animal models of nerve damage. Dendritic cell density (DCD) is a potential marker of immune activity in suspected small-fiber neuropathy (SFN). Here, we aim to evaluate the intra- and inter-rater reliability of DCD measurements in suspected SFN. METHODS: This retrospective study collected DCD from confocal microscopy images from the corneal sub-basal epithelium of the eye from 48 patients (mean age 49.6 ± 12.1 y, 61% female). Two examiners, each blinded to the other's examinations and measurements, assessed DCD to evaluate inter-rater reliability. For intra-rater reliability, the first examiner performed a second measurement after 14 days. DCs were classified into two cell morphological subtypes: mature and immature. RESULTS: Test-retest reliability for total DCD showed excellent agreement, with an intraclass correlation coefficient of 0.96 and inter-rater reliability intraclass correlation coefficient of 0.77. The immature cell subtype showed excellent intra-rater reliability but lower inter-rater reliability. DISCUSSION: We found that DCD measurements in the corneal sub-basal epithelium are sufficiently reliable for consideration in clinical studies of patients with suspected SFN.

Optimal cut-off value of the modified Toronto Clinical Neuropathy Score in the diagnosis of polyneuropathy.

BACKGROUND AND PURPOSE: The modified Toronto Clinical Neuropathy Score (mTCNS) is a valid and reliable scale for the diagnosis and staging of diabetic sensorimotor polyneuropathy (DSP). The aim of this study was to determine the optimal diagnostic cut-off value of the mTCNS in diverse polyneuropathies (PNPs). METHODS: Demographics and mTCNS values were retrospectively extracted from an electronic database of 190 patients with PNP and 20 normal controls. Sensitivity, specificity, and likelihood ratios and area under the receiver-operating characteristic (ROC) curve were determined for each diagnosis and different cut-off values of the mTCNS. Patients underwent clinical, electrophysiological and functional assessments of their PNP. RESULTS: Forty-three percent of PNP was related to diabetes or impaired glucose tolerance. mTCNS was significantly higher in patients with PNP than in those without (15.27 ± 8 vs. 0.79 ± 1.4; p = 0.001). The cut-off value for diagnosing PNP was ≥3 (sensitivity 98.4%, specificity 85.7%, positive likelihood ratio 6.88). The area under the ROC curve was 0.987. CONCLUSION: A value of 3 or more on the mTCNS is recommended for the diagnosis of PNP.

Demographic and clinical determinants of the quality of life in adults with inherited and acquired myopathies.

BACKGROUND AND PURPOSE: Measuring health-related quality of life (QOL) is vital for understanding the disease impact, but the complex relationship between clinical parameters and QOL remains unclear. The objective was to determine the demographic and clinical factors that influence the QOL in adults with inherited and acquired myopathies. METHODS: The study was of cross-sectional design. Detailed demographic and clinical details were collected. Patients answered Neuro-QOL and Patient-Reported Outcomes Measurement Information System short-form questionnaires. RESULTS: Data was collected from 100 consecutive in-person patient visits. Mean age of the cohort was 49.5 ± 20.1 (18-85) years, and the majority were male (53, 53%). Bivariate analysis between the various demographic and clinical features with the QOL scales revealed single simple question (SSQ), handgrip strength, Medical Research Council (MRC) sum score, female gender, and age to be nonuniformly associated with the QOL scales. There was no difference between inherited and acquired myopathies for any of the QOL scores, except for the poorer lower limb function domain in inherited myopathies (36.7 ± 7.3 vs. 40.9 ± 11.2, p = 0.049). Linear regression models revealed lower SSQ, lower handgrip strength, and lower MRC sum score to independently predict poor QOL. CONCLUSIONS: Handgrip strength and SSQ serve as novel predictors of QOL in myopathies. Handgrip strength has a significant impact on physical, mental, and social domains and deserves special attention with respect to rehabilitation. SSQ correlates well with QOL and can be employed as a quick and global assessment of a patient's well-being. Differences in QOL scores between patients with inherited and acquired myopathies were minimal.

Phase 2 trial in acetylcholine receptor antibody-positive myasthenia gravis of transition from intravenous to subcutaneous immunoglobulin: The MGSCIg study.

BACKGROUND AND PURPOSE: Data on maintenance therapy with subcutaneous immunoglobulin (SCIg) in myasthenia gravis (MG) are limited. We report on transitioning acetylcholine receptor (AChR) antibody-positive (Ab+) MG patients on stable intravenous immunoglobulin (IVIg) regimens as part of routine clinical care to SCIg 1:1.2. METHODS: This multicenter North American open-label prospective investigator-initiated study had two components: the IVIg Stabilization Period (ISP) enrolling patients already on IVIg as part of routine clinical care (Weeks -10 to -1), followed by transition of stable MG subjects to SCIg in the Experimental Treatment Period (ETP; Weeks 0 to 12). We hypothesized that >65% of patients entering the ETP would have a stable Quantitative Myasthenia Gravis (QMG) score from Week 0 to Week 12. Secondary outcome measures included other efficacy measures, safety, tolerability, IgG levels, and treatment satisfaction. RESULTS: We recruited 23 patients in the ISP, and 22 entered the ETP. A total of 12 subjects (54.5%) were female, and 18 (81.8%) were White, with mean age 51.4 ± 17 years. We obtained Week 12 ETP QMG data on 19 of 22; one subject withdrew from ETP owing to clinical deterioration, and two subjects withdrew due to dislike of needles. On primary analysis, 19 of 22 participants (86.4%, 95% confidence interval = 0.72-1.00) were treatment successes using last observation carried forward (p = 0.018). Secondary efficacy measures supported MG stability. SCIg was safe and well tolerated, and IgG levels were stable. Treatment satisfaction was comparable between ISP and ETP. CONCLUSIONS: MG patients on IVIg as part of their routine clinical care remained stable on monthly IVIg dosage, and most maintained similar disease stability on SCIg.

Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial.

BACKGROUND AND AIMS: ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse. METHODS: ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0-7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints. RESULTS: Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: -21.8% [-34.5%, -7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common. INTERPRETATION: fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.

The Sensitivity and Specificity of Split-Hand Index Using Muscle Sonography.

BACKGROUND: The split-hand index (SHI) (first dorsal interosseous (FDI) × abductor pollicis brevis (APB)/abductor digiti minimi muscle (ADM)) has been suggested as a useful measure for amyotrophic lateral sclerosis (ALS) diagnosis, using electrophysiological and sonographic indices. In the present study, we aimed to explore the specificity of SHI derived by muscle ultrasound (MUS) for the diagnosis of ALS and spinal muscular atrophy (SMA). METHODS: Healthy controls (n = 65) were prospectively recruited at the Prosserman Family Neuromuscular clinic at Toronto General Hospital, from October to December 2018. In addition, 181 patients with ALS (n = 91), SMA (n = 33), polyneuropathy (n = 35), and myopathy (n = 22) were prospectively recruited at the neuromuscular clinic at Tel Aviv Sourasky Medical Center, from December 2018 to December 2020. All subjects underwent quantitative sonographic evaluation of muscle thickness, including the right APB, FDI, and ADM muscles. Area under curve (AUC), sensitivity, and specificity were determined for differentiating between groups. RESULTS: Although SHI showed good to excellent accuracy for differentiating each patient subgroup from controls (AUC 0.83-0.92), poorer diagnostic accuracy was shown for differentiating between different patient subgroups (AUC 0.54-0.74). CONCLUSIONS: Sonographic SHI is useful for differentiating patients from healthy controls, but might be not specific for motor neuron disease.

Retrospective study on the safety of COVID-19 vaccination in myasthenia gravis.

INTRODUCTION/AIM: Given the lack of information on safety of coronavirus disease 2019 (COVID-19) vaccination in myasthenia gravis (MG) patients, we aimed to review our experience after surveying patients, as part of routine clinical practice, to ensure that advice on safety is accurate. METHODS: We performed a retrospective chart review of MG patients from the Prosserman Family Neuromuscular Clinic at the Toronto General Hospital who received two injections of any COVID-19 vaccine from February to August 2021. Demographic data were abstracted from the patient medical records. We assessed changes in the severity of MG using the virtual Myasthenia Gravis Impairment Index (vMGII), the simple single question (SSQ), and Patient Acceptable Symptom State (PASS). We also assessed adverse effects after vaccination. RESULTS: We included 200 patients with a mean age of 64.3 ± 13.9 y, 51.5% were men, and 82% had generalized MG. The vMGII, SSQ, and PASS scores remained stable after each vaccine dose, and at last follow-up. Of the patients, 60% reported an adverse reaction after the first injection, and 56% after the second. The most common adverse reactions reported were local pain at the injection site, fatigue, headache, and fever. DISCUSSION: COVID-19 vaccinations were well tolerated in MG patients and were not associated with worsening severity of their MG. The prevalence of vaccine-related adverse reactions was the same as in the general population.

Pilot study of a novel transmembranous electromyography device for assessment of oral cavity and oropharyngeal muscles.

INTRODUCTION/AIMS: Electromyography (EMG) can provide valuable insights into the pathophysiology of oropharyngeal muscles in various disease states, but the invasive nature of the conventional needle EMG (nEMG) has its limitations in this setting. We aimed to examine the inter-rater reliability (IRR) of a novel transmembranous EMG (tmEMG) sensor as a non-invasive technique for assessment of oral cavity and oropharyngeal muscles for neuromuscular pathology. METHODS: The study was a prospective, cohort, pilot study with blinded data analysis in healthy participants (n = 6), patients with moderate to severe obstructive sleep apnea (OSA) (n = 5) and bulbar amyotrophic lateral sclerosis (ALS) (n = 5). Each patient underwent sampling from bilateral palatoglossus (PG) and genioglossus (GG), using both tmEMG and nEMG. IRR was expressed as percentage agreement and prevalence-adjusted bias-adjusted kappa coefficient (PABAK). RESULTS: Substantial IRR was found for participants with ALS (81.6%, PABAK 0.63) and OSA (78.8%, PABAK 0.61), and in healthy participants (87.1%, PABAK 0.74). A better IRR was seen with tmEMG (95.7%, PABAK 0.92) than with nEMG (73.9%, PABAK 0.48) for healthy participants and also for those with OSA. Studies from GG had higher IRR than PG. Only one participant had a minor adverse event (sore throat). DISCUSSION: The current study shows that analysis of PG and GG in both healthy and disease states using tmEMG has high IRR compared with nEMG analysis. Further validation studies can be undertaken to test its utility in analysis of oral cavity and oropharyngeal muscles.

Analysis of relapse by inflammatory Rasch-built overall disability scale status in the PATH study of subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy.

Clinical trials in chronic inflammatory demyelinating polyneuropathy (CIDP) often assess efficacy using the ordinal Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Here, data from the PATH study was reanalyzed using change in Inflammatory Rasch-built Overall Disability Scale (I-RODS) to define CIDP relapse instead of INCAT. The PATH study comprised an intravenous immunoglobulin (IVIG) dependency period and an IVIG (IgPro10 [Privigen]) restabilization period; subjects were then randomized to weekly maintenance subcutaneous immunoglobulin (SCIG; IgPro20 [Hizentra]) 0.2 g/kg or 0.4 g/kg or placebo for 24 weeks. CIDP relapse was defined as ≥1-point deterioration in adjusted INCAT, with a primary endpoint of relapse or withdrawal rates. This retrospective exploratory analysis redefined relapse using I-RODS via three different cut-off methods: an individual variability method, fixed cut-off of ≥8-point deterioration on I-RODS centile score or ≥4-point deterioration on I-RODS raw score. Relapse or withdrawal rates were 47% for placebo, 34% for 0.2 g/kg IgPro20 and 19% for 0.4 g/kg IgPro20 using the raw score; 40%, 28% and 15%, respectively using the centile score, and 49%, 40% and 27%, respectively using the individual variability method. IgPro20 was shown to be efficacious as a maintenance therapy for CIDP when relapse was defined using I-RODS. A stable response pattern was shown for I-RODS across various applied cut-offs, which could be applied in future clinical trials.

Practical Aspects of Transitioning from Intravenous to Subcutaneous Immunoglobulin Therapy in Neuromuscular Disorders.

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

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.

The complex association between pain and neuropathy.

BACKGROUND: Several studies of patients with polyneuropathy failed to show differences between patients with and without pain. In the current study, we aimed to explore the association between neuropathic symptoms, mainly pain, and polyneuropathy characteristics. METHODS: A prospective cross-sectional study recruiting 151 patients with non-diabetic polyneuropathy was performed between November 2016 and May 2017. A total of 38 patients with chronic inflammatory demyelinating neuropathy were excluded. Patients underwent clinical, electrophysiological and functional assessments of their polyneuropathy. Polyneuropathy characteristics were compared depending on the presence and severity of neuropathic symptoms. RESULTS: The presence and the severity of weakness were associated with a more severe neuropathy as measured by clinical, electrophysiological and functional assessments, while the presence of pain was associated with higher sural amplitudes, and the severity of pain showed a curvilinear association with neuropathy severity. CONCLUSIONS: Our study shows a novel finding of a curvilinear association between pain and polyneuropathy severity.

Fasciculation frequency at the biceps brachii and brachialis muscles is associated with amyotrophic lateral sclerosis disease burden and activity.

INTRODUCTION: Fasciculations are most commonly seen in the biceps brachii muscle in amyotrophic lateral sclerosis (ALS). In this study we have explored the association between fasciculation frequency in a single location-biceps brachii and brachialis muscles (BB), and disease burden and activity. METHODS: Sonographic muscle studies were performed in 90 ALS patients, 47 of whom were seen in subsequent follow-up. The association between fasciculations frequency at the BB and ALS Functional Rating Scale-Revised (ALSFRS-R) and manual muscle testing (MMT) scores was determined. RESULTS: High fasciculation frequency at the BB, where detection rate was the highest, was associated with shorter disease duration, greater muscle thickness, higher MMT scores, and faster rate of decline in ALSFRS-R initially, and MMT subsequently. DISCUSSION: High fasciculation frequency at the BB as determined by sonography, is associated with less impairment at time of examination, and a more active disease with a more rapid progression.

Clinical profile and impact of comorbidities in patients with very-late-onset myasthenia gravis.

INTRODUCTION/AIMS: The purpose of this study was to evaluate the clinical profile of myasthenia gravis (MG) in older patients and determine the impact of medical comorbidities on their MG status and outcome. METHODS: This was a retrospective chart review of patients with a symptom onset of MG at or after 65 years of age. Correlations were made between demographics, clinical characteristics, the Myasthenia Gravis Foundation of America (MGFA) severity scale scores, and Myasthenia Gravis Impairment Index (MGII) scores with two outcome measures: MGFA Post-Intervention Status (MGFA-PIS) and Simple Single Question (SSQ). RESULTS: The study population included 109 patients, with 90 of them having more than one follow-up visit. Their mean age was 75.3 ± 6.9 years and sex distribution was even. Of these patients, 67.7% had generalized MG. Nine-one percent of patients had one comorbidity. None of the demographic factors or comorbidities showed an association with MGFA-PIS, SSQ, or MGII after correction for multiple comparisons. Seventy-one percent of the patients improved with treatment, 12.4% remained unchanged, and 16.6% showed worsening at their last follow-up visit. DISCUSSION: Our study shows that patients with very-late-onset MG had a good prognosis and treatment response. None of the comorbidities had an impact on the severity of myasthenic symptoms or on outcome in these patients.

Telephone consultation for myasthenia gravis care during the COVID-19 pandemic: Assessment of a novel virtual myasthenia gravis index.

INTRODUCTION/AIMS: The aim of the study was to determine the association between the virtual Myasthenia Gravis Impairment Index (vMGII) with other patient-reported outcomes (PROs) of myasthenia gravis (MG) and its usefulness in telephone consultations with MG patients. METHODS: This was a retrospective case series in which vMGII score along with virtual Single Simple Question (vSSQ), virtual Patient-Acceptable Symptom State PASS (vPASS) response, and patient disease status based on Myathenia Gravis Foundation of America postintervention status were collected during telephone consultation along with the MGII, SSQ, and PASS responses during the preceding in-person clinic visits. RESULTS: In 214 patients, the mean difference of vMGII between the vPASS "Yes" and "No" groups was -14.2 ± 1.4 (95% confidence interval, -16.9 to -11.3; P < .001) with mean vMGII for vPASS "Yes" group being 6.4 ± 7.7 and vPASS "No" being 20.5 ± 11.5. A vMGII of 11.5 or higher predicted vPASS "yes" response with a sensitivity of 78.7% and specificity of 81.4%. A strong negative correlation was found between the vMGII and vSSQ (r = -.667; P < .001). The mean vMGII was 0.48 ± 1.42 for patients in remission, and 9.31 ± 10.93 for improved, 9.32 ± 8.79 for stable, and 22.58 ± 14.04 for worsened groups (P < .001). These associations were the same as those obtained during the preceding in-person clinic visit and the direction of change in MGII scores also indicated change in disease status. DISCUSSION: vMGII is an effective measure to assess an MG patient's disease status in telephone consultations and relates well with other PRO measures. The vMGII remains reliable for assessing MG disease status even with removal of the physical examination component.

Thymoma pathology and myasthenia gravis outcomes.

INTRODUCTION: There is limited evidence regarding the impact of World Health Organization (WHO) subtype of thymoma on post-thymectomy outcome of thymoma-associated myasthenia gravis (TAMG). The objective was to determine if the pathological subtypes of thymoma were associated with post-thymectomy outcomes of myasthenia gravis (MG), in patients with TAMG. METHODS: We performed a retrospective study of consecutive patients with TAMG who attended the neuromuscular clinic between January 2018 and December 2019 with a minimum follow-up of 1 y after thymectomy. Outcome measures were MG Impairment Index (MGII), single-simple question (SSQ), Myasthenia Gravis Foundation of America post-intervention status (MGFA PIS) and non-responder MG status at last assessment. RESULTS: Ninety-five patients were included; mean age at onset was 48.1 ± 12.1 y; 54(56.8%) were females. Thirteen patients developed MG post-thymectomy. The most common thymoma was WHO type B2 in 39 (41.1%). Most patients (40, 42.1%) had Masaoka stage II thymoma. There was no association of thymoma subtypes or Masaoka stage of disease with age, gender, MG phenotype, serology, post-thymectomy onset, interval from onset to thymectomy, MGII, SSQ, MGFA PIS, or non-responder status. Associations were found between positive serology and lower MGII (11.1 ± 14.2 vs 23 ± 12.9, P = .050), thymic follicular hyperplasia (TFH) and higher SSQ (89.3 ± 11.7 vs 80.1 ± 20.2, P-.043), and lack of recurrence and higher SSQ (84.1 ± 18 vs 72.5 ± 20, P = .037). DISCUSSION: The WHO pathological subtype of thymoma did not correlate with MG outcomes. However, positive acetylcholine antibody serology, presence of TFH, and non-recurrence of thymoma predict a favorable outcome.

Emerging drugs for the treatment of myasthenia gravis.

Introduction: Advances in understanding the immune pathomechanisms in myasthenia gravis (MG) allow for the development of novel targeted immune therapies. By working at specific points in the immunopathogenesis, these agents have the potential to provide rapid and efficacious responses compared to conventional immunosuppressive therapy (IST), addressing unmet needs and consequently are a research priority.Areas covered: This paper reviews the advances in MG treatment modalities with their scientific rationale. A search of clinicaltrials.gov and a literature search of PubMed from January 2015 to the end of June 2021 was done using the search terms: MG, treatment, immune targets to obtain information on recent developments of complement inhibitors, FcRn receptor inhibitors, direct and indirect B cell inhibitors, CAR and CAAR- T cell therapy, and hematopoietic stem cell transplantation. Specific agents in various phases of clinical development, evidence from ongoing trials and potential roadblocks are examined.Expert opinion: Despite several promising novel agents, existing data as to the timing of initiation and duration of treatment, long-term safety profile and utility in certain patient subsets are limited and require further research. Despite these considerations, the future of MG treatment is transitioning from broad-spectrum IST toward precise, target-driven and personalized immunotherapy.