Carolina Barnett

The quantitative myasthenia gravis score: comparison with clinical, electrophysiological, and laboratory markers.

Objective: To determine whether the quantitative myasthenia gravis score (QMGS) accurately represents disease severity in patients with myasthenia gravis (MG). Methods: One hundred thirty-five patients with MG from 2 previous randomized studies were included. QMGS correlation with the Myasthenia Gravis Foundation of America (MGFA) score, quality of life scale, acetylcholine receptor antibodies (AChRAbs), and electrophysiological parameters was studied. Results: The QMGS showed a good correlation with the MGFA scale (r2 = 0.54, P < 0.0001), jitter (rs = 0.40, P < 0.0001), and 15-item quality of life scale (rs = 0.41, P = 0.007) and was less well correlated with the 60-item myasthenia gravis–specific quality of life survey and other electrophysiological markers. No correlation was demonstrated with AchRAb titers, but AchRAb-positive patients had higher QMGS (14.2 ± 4.5) than AchRAb-negative patients (12.0 ± 3.7, P = 0.008). Conclusions: These results demonstrate that the QMGS is a valid marker for disease severity as shown by the MGFA scale, quality of life scale, and jitter, supporting the use of the QMGS as a primary outcome measure in clinical trials of MG.

Epidemiology of myasthenia gravis in Ontario, Canada.

Incidence and prevalence estimates in myasthenia gravis have varied widely. Recent studies based on administrative health data have large sample sizes but lack rigorous validation of MG cases, and have not examined the North American population. Our aim was to explore trends in MG incidence and prevalence for the years 1996-2013 in the province of Ontario, Canada (population 13.5 million). We employed a previously validated algorithm to identify MG cases. Linking with census data allowed for the calculation of crude- and age/sex-standardized incidence and prevalence rates for the years 1996-2013. The regional distribution of MG cases throughout the province was examined. Mean age at the first myasthenia gravis encounter was 60.2 ± 17.1 years. In 2013, there were 3611 prevalent cases in Ontario, and the crude prevalence rate was 32.0/100,000 population. Age- and sex-standardized prevalence rates rose consistently over time from 16.3/100,000 (15.4-17.1) in 1996 to 26.3/100,000 (25.4-27.3) in 2013. Standardized incidence rates remained stable between 1996 (2.7/100,000; 95% CL 2.3-3.0) and 2013 (2.3/100,000; 2.1-2.6). Incidence was highest in younger women and older men, and geographic variation was evident throughout the province. In conclusion, this large epidemiological study shows rising myasthenia gravis prevalence with stable incidence over time, which is likely reflective of patients living longer, possibly due to improved disease treatment. Our findings provide accurate information on the Canadian epidemiology of myasthenia gravis and burden for health care resources planning for the province, respectively.

Minimal clinically important difference in myasthenia gravis: Outcomes from a randomized trial

Introduction: The minimal clinically important difference (MCID) is the smallest outcome change that has clinical significance. Its use has not been established in the study of myasthenia gravis (MG). Methods: Patients from a published intravenous immunoglobulin (IVIg) vs. placebo study were studied. One anchor‐based and 3 distribution‐based techniques were used to identify quantitative myasthenia gravis score (QMGS), repetitive nerve stimulation (RNS), and single‐fiber electromyography (SFEMG) MCID cut‐offs. Patients with a change‐score exceeding MCID cut‐offs were compared. Results: MCID cut‐offs were below a QMGS change of 3.0. Anchor‐based and 1 × SEM cut‐offs showed 58.3% vs. 30.7% responders (P = 0.017), ½ SD 54.2% vs. 19.2% responders (P = 0.018), and effect size 0.519 vs. 0.164 (P = 0.011) in IVIg vs. placebo. Anchor‐based (P = 0.73) and effect‐size (P = 0.41) MCID cut‐offs did not show a difference between IVIg and placebo. MCID methods did not produce meaningful RNS cut‐offs. Conclusions: QMGS MCID values provide clinically relevant information and are recommended in MG trials. MCID analysis shows that improvement in MG patients treated with IVIg reflects clinically meaningful changes. Muscle Nerve 49: 661–665, 2014

The Characteristics of Chronic Inflammatory Demyelinating Polyneuropathy in Patients with and without Diabetes – An Observational Study

Introduction We aimed to determine whether the clinical characteristics and electrodiagnostic classification of nerve injury, and response to treatment differed in patients diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) with and without diabetes. Methods CIDP patients with diabetes (CIDP+DM) (n = 67) and without diabetes (CIDP-DM) (n = 67) underwent clinical examination and nerve conduction studies (NCS). CIDP-DM patients were selected using age and gender matching with the existing CIDP+DM cohort. Patients treated with immunotherapies were classified as responders (R) (n = 46) or non-responders (NR) (n = 54) based on clinical response to treatment. The groups were compared using analysis of variance, contingency tables and Kruskal-Wallis analyses. Results CIDP+DM subjects had more severe neuropathy based on higher lower limb vibration potential thresholds (VPT)(p = 0.004), higher Toronto Clinical Neuropathy Score (TCNS) (p = 0.0009), more proximal weakness (p = 0.03), more gait abnormality (p = 0.03) and more abnormal NCS. CIDP+DM subjects had more abnormal sural NCS with lower sural sensory nerve action potential amplitudes (2.4±3.0 µV, 6.6±6.0 µV, p<0.0001) and slower sural nerve conduction velocities (38.6±5.4 m/s, 41.0±5.3 m/s, p = 0.04). CIDP-DM subjects were more likely to receive immune therapies (93% vs 57%, p = <0.0001), despite no significant differences in treatment responder rates (p = 0.71). Patients who responded to therapy had shorter duration of CIDP than non-responders (8.0±6.0 y vs 11.9±7.6 y, p = 0.004). Discussion The clinical phenotype and electrophysiological profile of CIDP patients differs according to the presence or absence of diabetes. Despite CIDP+DM patients having more severe clinical and electrophysiological neuropathy, they are less likely to receive disease-modifying/specific therapy, yet have similar response rates to treatment as those without diabetes. Specifically, the duration of neuropathy - not diabetes status - was associated with treatment response.

Changes in quality of life scores with intravenous immunoglobulin or plasmapheresis in patients with myasthenia gravis

Background Intravenous immunoglobulin (IVIG) and plasmapheresis (plasma exchange (PLEX)) have comparable efficacy in reducing the Quantitative Myasthenia Gravis Score for disease severity (QMGS) in patients with moderate to severe myasthenia gravis (MG). Objective To determine if the improvement in the quality of life (QOL) after immunomodulation is comparable with either IVIG or PLEX. Methods 62 patients participated in the MG-QOL-60 study, completing the questionnaire at baseline and at day 14 after treatment. The MG-QOL-15 scores were computed from the MG-QOL-60 questionnaire responses. We analysed the change in the QOL scores from baseline to day 14 in both treatment groups. Results The scores in both QOL scales decreased at day 14 in the IVIG and PLEX groups, without significant difference between groups (QOL-15: IVIG −5.7±8.5, PLEX: −7.0±7.6, p=0.52; QOL-60: IVIG −13.3±16.9, PLEX −18.5±22.0, p=0.41). The improvement in QOL showed a good correlation with the decrease in QMGS. There was an excellent correlation between the MG-QOL-15 and MG-QOL-60 scores at baseline and at day 14. Conclusions This study of MG-QOL changes supports recent findings that IVIG and PLEX are comparable in the treatment of patients with moderate to severe MG and worsening symptoms. Furthermore, our study supports the use of the MG-QOL-15 as a secondary outcome measure in future clinical trials in MG.

Repetitive nerve stimulation cutoff values for the diagnosis of myasthenia gravis

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

International clinimetric evaluation of the MG-QOL15, resulting in slight revision and subsequent validation of the MG-QOL15r.

Introduction: The MG‐QOL15 is a validated, health‐related quality of life (HRQOL) measure for myasthenia gravis (MG). Widespread use of the scale gave us the opportunity to further analyze its clinimetric properties. Methods: We first performed Rasch analysis on >1,300 15‐item Myasthenia Gravis Quality of Life scale (MG‐QOL15) completed surveys. Results were discussed during a conference call with specialists and biostatisticians. We decided to revise 3 items and prospectively evaluate the revised scale (MG‐QOL15r) using either 3, 4, or 5 responses. Rasch analysis was then performed on >1,300 MG‐QOL15r scales. Results: The MGQOL15r performed slightly better than the MG‐QOL15. The 3‐response option MG‐QOL15r demonstrated better clinimetric properties than the 4‐ or 5‐option scales. Relative distributions of item and person location estimates showed good coverage of disease severity. Conclusions: The MG‐QOL15r is now the preferred HRQOL instrument for MG because of improved clinimetrics and ease of use. This revision does not negate previous studies or interpretations of results using the MG‐QOL15. Muscle Nerve 54: 1015–1022, 2016

Prevalence of Muscle Cramps in Patients With Diabetes

There are limited epidemiological studies addressing the prevalence of muscle cramps in the general population and diseases like diabetes (1). Common long-term complications of diabetes, such as neuropathy and nephropathy, have been associated with higher rates of muscle cramps (2). We aimed to determine the prevalence and characteristics of muscle cramps in patients with diabetes compared with healthy volunteers. Frequency, severity (using visual analog scale [VAS]), duration, and disability due to muscle cramps were evaluated, as is standard in clinical trials. Information about each patient’s clinical status was collected, including patient demographics, neuropathy (diagnosed using established clinical and electrophysiological criteria and quantitated using the Toronto Clinical Neuropathy Score) (3), diabetes complications, duration and type of diabetes, concurrent cramp-inducing (β-blockers, diuretics, statins) and cramp-protecting (quinine, calcium channel blockers, antiepileptics) medications, and markers of glycemic control (HbA1c). Baseline demographics and cramp characteristics for 269 patients with diabetes (type 1 diabetes, n = …

Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review

Objective: To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG). Methods: This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs. Results: Seventy-seven of 119 patients with anti-MuSK MG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome compared to 16% (5/31) of controls (p = 0.002). Number needed to treat for the primary outcome is 2.4. At last visit, 29% of rituximab-treated patients were taking prednisone (mean dose 4.5 mg/day) compared to 74% of controls (mean dose 13 mg/day) (p = 0.001 and p = 0.005). Classification of evidence: This study provides Class IV evidence that for patients with anti-MuSK MG, rituximab increased the probability of a favorable outcome.

Laser Doppler Flare Imaging and Quantitative Thermal Thresholds Testing Performance in Small and Mixed Fiber Neuropathies

Introduction Small fiber neuropathy might be a part of typical mixed small and large fiber neuropathy, or a distinct entity, affecting exclusively small nerve fibers. Objectives Explore the utility of small nerve fiber testing in patients with clinical presentation suggesting small fiber neuropathy, with and without evidence for concomitant large fiber neuropathy. Methods Patients attending the neuromuscular clinic from 2012 to 2015 with a clinical presentation suggesting small nerve fiber impairment, who had Laser Doppler flare imaging (LDIFlare) and quantitative thermal testing (QTT) were evaluated for this study. Patients with clinical or electrophysiological evidence for concomitant large fiber neuropathy were not excluded. Results The sensitivities of LDIFlare, cooling and heat threshold testing were 64%, 36%, and 0% respectively for clinically highly suggestive small fiber neuropathy, 64%, 56%, and 19% respectively for mixed fiber neuropathy, and 86%, 79%, and 29% respectively for diabetic mixed fiber neuropathy. Discussion LDIFlare and cooling thresholds testing are non-invasive small nerve fiber testing modalities, with moderate performance in patients with small and mixed fiber neuropathy, and excellent performance in diabetic mixed fiber neuropathy.