Clinical Focus
- Clinical Neurophysiology
Professional Education
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Internship: Medical College Of Wisconsin (2005) WI
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Board Certification: United Council for Neurologic Subspecialties, Autonomic Disorders (2011)
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Fellowship: Univ Of Texas Southwestern Medical Center (2009) TX
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Residency: Thomas Jefferson University Hospital (2008) PA
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Medical Education: Osmania Medical College (2000) India
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Board Certification: American Board of Psychiatry and Neurology, Neuromuscular Medicine (2009)
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Board Certification: American Board of Psychiatry and Neurology, Neurology (2008)
All Publications
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Smartphone-based App to Assess Diabetic Peripheral Neuropathy.
medRxiv : the preprint server for health sciences
2026
Abstract
Diabetic peripheral neuropathy (DPN) affects approximately 50% of individuals with diabetes and is a risk factor for amputations. Unfortunately, foot exams and screening tools are inconsistent and miss early-stage nerve damage. A smartphone-based application that delivers controlled vibrations, records patient responses, ands computes a vibration perception thresh-old (SVPT) may present an accessible, precise monitoring avenue. This study assesses the clinical relevance and precision of SVPTs for measuring large-fiber sensory deficits in patients with diabetes.We measured SVPTs in 71 patients with pre-diabetes or diabetes and compared their efficacy with tuning fork exams. We analyzed the correlation between SVPT and Rydel-Seiffer tuning fork (RSTF) scores, along with their relationship with clinical DPN markers such as hemoglobin A1c (HbA1c), age, and disease duration using multivariable linear regression.SVPTs moderately correlated with RSTF scores (Rs = -0.43, p = 0.0019). Among adults aged 50 to 69, SVPTs correlated significantly with clinical markers (F (4, 29) = 4.76, p = 0.00447, Multiple R 2 = 0.396, Adjusted R 2 = 0.313, ϵ = 0.167). The interaction between age and HbA1c was positively associated with SVPTs (β = 0.118, p = 0.001), while SVPTs were negatively associated with diabetes duration (β = -0.098, p = 0.003).We present a clinically relevant, patient-operated smartphone application for large-fiber sensory monitoring, tested on patients with varying DPN risk. This novel platform has the potential to provide a precise, reliable, and accessible avenue for identifying individuals at risk of developing DPN complications, prior to overt clinical manifestation.
View details for DOI 10.1101/2025.08.28.25333808
View details for PubMedID 41757168
View details for PubMedCentralID PMC12934888
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Update on the Phase 2 Part of Kysa-6, an Open-Label, Single-Arm, Multicenter Study of Kyv-101, a Fully Human CD19 Chimeric Antigen Receptor T-cell Therapy in Generalized Myasthenia Gravis
ELSEVIER SCIENCE INC. 2026
View details for Web of Science ID 001708751400085
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Reply to the Letter to the Editor: The Role of Patient-Reported Symptoms in Standardizing MGFA Class 0 and MGFA-PIS.
Muscle & nerve
2025
View details for DOI 10.1002/mus.70027
View details for PubMedID 40977477
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COVID-19 Vaccination and Infection in Myasthenia Gravis: A Longitudinal Patient Survey.
Muscle & nerve
2025
Abstract
INTRODUCTION/AIMS: Patients with myasthenia gravis (MG) often receive immunosuppressive treatments. While approved COVID-19 vaccines effectively prevent severe infections, the impact of vaccination among immunocompromised MG patients remains unclear. This study explored vaccination status, adverse events, and post-vaccination outcomes among MG patients.METHODS: A REDCap survey was conducted between September 21, 2021 and November 18, 2021 through the Myasthenia Gravis Foundation of America to collect data on demographic and disease characteristics, COVID-19 infections, vaccination status, and precaution strategies. A follow-up survey was available from January 11, 2022 to March 8, 2022.RESULTS: A total of 1205 participants [65.7% female, average age 59.6±15.4years] completed the survey. Most were White or Caucasian (87.9%), 63.6% held a bachelor's degree or higher, and 41.9% were retired. Acetylcholine receptor (AChR) antibody positivity was reported by 47%, MuSK-Ab positivity by 6.1%, and 19.6% were seronegative. Most (75%) were on immunosuppressive therapy, and the vaccination rate was 91.5%. Among COVID-19 vaccine recipients, 61.5% reported adverse effects, while 8.5% of participants remained unvaccinated due to concerns about side effects (65%) and potential worsening of MG symptoms (70.9%). Post-vaccination COVID-19 infection rates dropped from 9.7% to 2.4%. Hospitalization decreased from 2.3% to 0.3%, and MG exacerbation rates from 5.5% to 1.4%.DISCUSSION: COVID-19 vaccination acceptance is high among MG patients. Reported side effects in MG patients were comparable to those in the general population, and vaccination was associated with a reduced COVID-19 infection rate. Addressing concerns about vaccine side effects and providing efficacy data specific to MG could aid unvaccinated individuals in decision-making.
View details for DOI 10.1002/mus.28466
View details for PubMedID 40635622
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Standardization of Myasthenia Gravis Outcome Measures in Clinical Practice. A Report of the MGFA Task Force.
Muscle & nerve
2025
Abstract
INTRODUCTION/AIMS: Myasthenia gravis (MG) specific outcome measures are being used in clinical trials to evaluate therapeutic effectiveness. These validated tools are also becoming a necessity in clinical practice, with payors in the US market often requiring them to be used to monitor disease state. There is considerable variation and subjectivity regarding their use. This study aimed to develop consensus-based recommendations for the standardization of MG specific outcome measures in clinical practice.METHODS: A panel of 10US-based MG specialists developed consensus-based recommendations based on three rounds of formal voting using the UCLA-RAND appropriateness method after surveying myasthenia gravis clinicians and developing a focus group.RESULTS: Twenty one expert consensus statements based on six themes were developed following clinician survey result review and focus group theme development. Some key recommendations include: the MGFA Clinical Classification assesses disease at that examination and should be updated at intervals of 3-6months to reflect current clinical status. MGFA PIS represents the overall clinical judgment of the evaluator without the requirement for a defined change in scores on any outcome measure. Patient-reported items, such as MG-ADL and MGC, should be referenced to the previous 1week to optimize recall. Additional recommendations include scoring outcome measures in the presence of co-morbidity, scoring specific physical exam findings, and clarification regarding the administration of outcome measures.DISCUSSION: This method provided expert consensus-based recommendations for the use of MG-specific outcome measures and exam findings to help standardize how they are used in clinical practice.
View details for DOI 10.1002/mus.28417
View details for PubMedID 40260547
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US Clinical Practice Experience with Eculizumab in Myasthenia Gravis: Acute Clinical Events and Healthcare Resource Utilization.
Drugs - real world outcomes
2024
Abstract
BACKGROUND AND OBJECTIVE: The terminal complement inhibitor eculizumab is approved in the USA for the treatment of patients with acetylcholine receptor antibody-positive generalized myasthenia gravis (MG). The ELEVATE study aimed to examine clinical-practice outcome data on eculizumab effectiveness in US adults with MG (generalized or ocular). This paper reports the findings on MG exacerbations and crises and associated healthcare resource utilization, and the use of rescue therapy.METHODS: A retrospective chart review was conducted of US adults with MG who initiated eculizumab. Outcomes assessed for up to 2 years before and after eculizumab initiation included percentages and rates per patient per year (PPPY) of exacerbations and crises (the latter defined as intubation/impending intubation), healthcare resource utilization, and rescue therapy administration.RESULTS: A total of 119 patients diagnosed with MG were enrolled in the study; 92 patients had ≥3 months of data both before and during eculizumab therapy and were included in the analyses. The mean rate of MG exacerbations decreased from 0.385 PPPY before eculizumab initiation to 0.152 PPPY during eculizumab treatment (p = 0.0034); the mean rate of MG crises decreased from 0.411 to 0.056 PPPY (p = 0.0018). Rates of healthcare resource utilization and rescue therapy use also decreased significantly during eculizumab treatment.CONCLUSIONS: This retrospective chart review analysis provides evidence for a beneficial impact of eculizumab treatment on the incidence of MG exacerbations and crises and associated healthcare resource utilization in clinical practice, and on rescue therapy use. These data further support the therapeutic benefits of eculizumab in patients with MG.
View details for DOI 10.1007/s40801-024-00457-8
View details for PubMedID 39470958
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United States clinical practice experience with eculizumab in myasthenia gravis: symptoms, function, and immunosuppressant therapy use.
Journal of neurology
2024
Abstract
BACKGROUND/OBJECTIVES: The phase 3 REGAIN study and its open-label extension demonstrated the efficacy of the complement C5 inhibitor eculizumab in patients with treatment-refractory, acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG). The aim of the ELEVATE study was to assess the effectiveness of eculizumab in clinical practice in adults with MG in the United States.METHODS: A retrospective chart review was conducted in adults with MG who initiated eculizumab treatment between October 23, 2017 and December 31, 2019. Outcomes assessed before and during eculizumab treatment using a pre- versus post-treatment study design included Myasthenia Gravis-Activities of Daily Living (MG-ADL) total scores; minimal symptom expression (MSE); physician impression of clinical change; minimal manifestation status (MMS); and concomitant medication use.RESULTS: In total, 119 patients were included in the study. A significant reduction was observed in mean MG-ADL total score, from 8.0 before eculizumab initiation to 5.4 at 3months and to 4.7 at 24months after eculizumab initiation (both p<0.001). At 24months after eculizumab initiation, MSE was achieved by 19% of patients. MMS or better was achieved by 30% of patients at 24months. Additionally, 64% of patients receiving prednisone at eculizumab initiation had their prednisone dosage reduced during eculizumab treatment and 13% discontinued prednisone; 32% were able to discontinue nonsteroidal immunosuppressant therapy.DISCUSSION: Eculizumab treatment was associated with sustained improvements in MG-ADL total scores through 24months in adults with MG. Prednisone dosage was reduced in approximately two-thirds of patients, suggesting a steroid-sparing effect for eculizumab.
View details for DOI 10.1007/s00415-024-12569-w
View details for PubMedID 39052039
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Psychometric properties of MG-ADL items and MG-ADL score: An assessment of distributional characteristics, validity and factor structure in two large datasets.
Journal of the neurological sciences
2024; 463: 123135
Abstract
The Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) is an 8-item outcome measure to assess symptoms and functional limitations in myasthenia gravis (MG) patients. The MG-ADL score is an equally weighted level sum score that is used as primary outcome measures in clinical trials, in clinical practice, and as an end-point in health economic evaluation. This data analysis aims to obtain detailed knowledge of measurement properties of MG-ADL items and the MG-ADL score.Cross-sectional data from a real-world prospective study (MRW) were combined with longitudinal data from the ADAPT trial. Outcome measures included were MG-ADL, Quantitative Myasthenia Gravis score (QMG), MG 15-item Quality of Life (MG-QOL15r) and EQ-5D-5L. Patients were categorized by their Myasthenia Gravis Foundation of America (MGFA) clinical classification. The following measurement properties were assessed: distributional characteristics, inter-item correlation, convergent, known groups and construct validity and internal factor structure.Correlations of items within MG-ADL dimensions were moderate, while MG-ADL correlations between comparable MG-QOL15r and QMG items were mixed. Known groups validity for the MG-ADL score was demonstrated for MGFA class. Mean MG-ADL item level scores by MGFA class demonstrated construct validity. PCA, including all four outcome measures, resulted in a nine factor solution.Psychometric properties of individual MG-ADL items were moderate to good. This study showed that the MG-ADL adequately captures the multidimensional heterogeneous nature of MG. This is, however, accompanied by mixed psychometric performance of the MG-ADL score, which may complicate health economic modelling.MyRealWorld-MG was registered on November 25, 2019, with registration numberNCT04176211. The ADAPT randomized clinical trial is registered atClinicalTrials.gov(NCT03669588).
View details for DOI 10.1016/j.jns.2024.123135
View details for PubMedID 39068745
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Utilization of APE2 and RITE2 scores in autoimmune encephalitis patients with seizures.
Epilepsy & behavior : E&B
2024; 154: 109737
Abstract
PURPOSE: Immune-mediated seizures are rare but are increasingly recognized as an etiology of seizures resistant to anti-seizure medications (ASMs). Antibody Prevalence in Epilepsy 2 (APE2) and Response to Immunotherapy in Epilepsy 2 (RITE2) scores were developed recently to identify patients who may be seropositive for serum central nervous system (CNS) specific antibodies (Ab) and may benefit from immunotherapy (Dubey et al. 2018). The goal of this study was to apply APE2 and RITE2 scores to an independent cohort of patients with seizures secondary to autoimmune encephalitis (AE) and to further verify the sensitivity and specificity of the scores.PRINCIPAL RESULTS: We conducted a retrospective study at Stanford University Hospital between 2008 and 2021 and included patients who had acute seizures and AE using diagnostic criteria from Graus (n=34 definite AE, 10 probable AE, and 12 possible AE) (Graus et al. 2016). Patients were excluded if they did not have a serum Ab panel investigated or had alternate diagnoses (n=55). APE2 and RITE2 scores were calculated based on clinical and diagnostic data (n=56). Serum Ab were positive in 73% of patients, in which 63% cases carried CNS specific Ab. An APE2 score≥4 had a sensitivity of 97% and specificity of 14% to predict a positive serum CNS specific Ab. A RITE2 score≥7 had a sensitivity of 93% and specificity of 60% to predict seizure responsiveness to immunotherapy.CONCLUSION: APE2 and RITE2 scores had high sensitivities but low specificities to predict seropositivity and seizure responsiveness to immunotherapy in patients with autoimmune encephalitis with seizures.
View details for DOI 10.1016/j.yebeh.2024.109737
View details for PubMedID 38518672
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Ravulizumab use for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice.
Frontiers in neurology
2024; 15: 1378080
Abstract
Purpose: To describe the early experience of ravulizumab use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG).Methods: This multicenter retrospective study included AChR+ve gMG patients who were treated with ravulizumab and had both pre- and post-ravulizumab myasthenia gravis activities of daily living (MG-ADL) scores. Clinical information regarding MG history, concomitant treatment(s), MG-ADL, other MG-specific measures, and adverse events were recorded.Results: A total of 18 patients with mean age of 61.83 (±16.08, n=18) years were included in this cohort. In 10 complement inhibitor naive patients, a clinically meaningful reduction in mean Mg-ADL (baseline: 6.6 (±3.58) vs. 4.4 (±2.28), post ravulizumab) was seen. 6 out of 10 patients (60%) had clinically meaningful reduction post ravulizumab and two achieved minimum symptom expression (MSE). In 8 patients switched from eculizumab to ravulizumab, further reduction was noted in post ravulizumab mean MG-ADL (Baseline: 3.25 (±3.34) vs. 1.5 (±2.34) post ravulizumab). None of the patients who switched from eculizumab to ravulizumab experienced worsening symptoms. Eleven out of 14 (78.5%) patients on prednisone therapy were able to reduce their prednisone dose post-ravulizumab. None of the patients experienced any major side effects.Conclusion: In our clinical practice, 60% of AChR+ve gMG complement inhibitor naive patients experienced a clinically meaningful improvement in MG-ADL scores with ravulizumab. Patients were safely switched from eculizumab to ravulizumab and had further improvement in their mean MG-ADL scores. Of those on prednisone therapy, the majority were able to reduce their prednisone dosage.
View details for DOI 10.3389/fneur.2024.1378080
View details for PubMedID 38919970
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Plasma Exchange in Patients With Myositis due to Immune Checkpoint Inhibitor Therapy.
Journal of clinical neuromuscular disease
2023; 25 (2): 89-93
Abstract
ABSTRACT: Immune checkpoint inhibitors used to treat malignancies may lead to various immune-related adverse events (irAEs) including conditions such as myositis and myasthenia gravis (MG). Here, we describe 2 cases of myositis treated effectively with therapeutic plasma exchange (PLEX). A 64-year-old man with thymic cancer developed leg weakness and dyspnea 1 month after the second dose of nivolumab with moderate weakness in proximal and distal muscles, with elevated creatine kinase levels. Another 77-year-old man with Stage IIIB squamous cell carcinoma of the lung developed progressive proximal muscle weakness and became nonambulatory after cycle 2 of durvalumab with persistently high creatine kinase levels despite prednisone treatment. Electrophysiology revealed irritative myopathy without evidence of neuromuscular junction dysfunction and MG antibody testing was nonrevealing. With PLEX, both patients noticed rapid improvement in strength. PLEX in conjunction with other immunosuppressive agents can result in rapid improvement in irAE-myositis even in patients without associated MG.
View details for DOI 10.1097/CND.0000000000000457
View details for PubMedID 37962196
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Utility of Repetitive Nerve Stimulation in the Diagnosis of Myasthenia Gravis in the Inpatient Setting.
The Neurohospitalist
2023; 13 (4): 364-370
Abstract
Sensitivity and specificity of Repetitive Nerve Stimulation (RNS) is typically reported from outpatient centers, and we hypothesized that these values might not apply to hospitalized patients with higher grades of weakness. RNS may be helpful in rapidly confirming diagnosis of myasthenia gravis (MG) in the inpatient setting, as results from confirmatory antibody testing are often delayed. We sought to characterize the sensitivity and specificity of RNS in the inpatient setting to assist in the early diagnosis of MG.We performed a retrospective analysis of all adult patients who had inpatient RNS at our center from 2016 to 2021. Inclusion criteria included RNS performed at least at one site and a neurological evaluation which prompted an electrodiagnostic study to evaluate for neuromuscular junction (NMJ) pathology. Descriptive statistics and Fisher exact analysis were performed.Of the 32 identified hospitalized patients, 6 had greater than 10% decrement on slow RNS, confirming NMJ dysfunction. Five were diagnosed with MG, and 1 with Lambert-Eaton myasthenic syndrome. Of the 26 patients with normal RNS, 25 ultimately had alternative causes of weakness. One was later diagnosed as seronegative MG based on clinical improvement with acetylcholinesterase inhibitors. In our inpatient population, the overall sensitivity and specificity of RNS were 83.3% and 96.2% respectively. There was a statistically significant association between a positive RNS and diagnosis of MG (P = .0002).RNS is a highly sensitive and specific test for the diagnosis of MG in an inpatient setting, and these results are likely more rapidly available compared to antibody testing.
View details for DOI 10.1177/19418744231173829
View details for PubMedID 37701254
View details for PubMedCentralID PMC10494823
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Safety and outcomes with efgartigimod use for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice.
Muscle & nerve
2023
Abstract
Multiple novel therapies have been approved for patients with myasthenia gravis. Our aim is to describe the early experience of efgartigimod use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG).This multicenter retrospective study included AChR+ve gMG patients from five major neuromuscular centers who were treated with efgartigimod and had both pre- and post-efgartigimod myasthenia gravis activities of daily living (MG-ADL) scores. Information regarding MG history, concomitant treatment(s), MG-ADL and other MG-specific measures, laboratory data, and adverse events were recorded.A total of 37 patients (M:23, F:14) with a mean age of 65.56 (±14.74) y were included in this cohort. A total of 36/37 patients completed at least one cycle and 28 patients completed at least two cycles of efgartigimod. A total of 72% (26/36) of patients had a clinically meaningful reduction (≥2 point change) in MG-ADL after the completion of the first cycle of efgartigimod (mean pre-efgartigimod 8.02) (±3.09) versus post-efgartigimod 4.33 (±3.62). Twenty-five percent (9/36) achieved minimal symptom expression status after one cycle and 25% (7/28) after the second cycle. Treatment benefit was sustained after cycle 2. Three out of four patients with thymoma in this cohort had clinically significant reductions in MG-ADL scores. Immunoglobulin G (IgG) levels decreased by about 60% (n = 10). One patient had a relapse of Clostridium difficile infection resulting in the discontinuation of therapy. Four patients had mild side effects.Efgartigimod led to clinically meaningful improvement in MG-ADL in diverse AChR+ve gMG patients but treatment frequency to achieve optimal symptom control needs to be explored.
View details for DOI 10.1002/mus.27974
View details for PubMedID 37695277
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Differential Findings on Anorectal Manometry in Patients with Parkinson's Disease and Defecatory Dysfunction.
Movement disorders clinical practice
2023; 10 (7): 1074-1081
Abstract
Gastrointestinal dysfunction, particularly constipation, is among the most common non-motor manifestations in Parkinson's Disease (PD). We aimed to identify high-resolution anorectal manometry (HR-ARM) abnormalities in patients with PD using the London Classification.We conducted a retrospective review of all PD patients at our institution who underwent HR-ARM and balloon expulsion test (BET) for evaluation of constipation between 2015 and 2021. Using age and sex-specific normal values, HR-ARM recordings were re-analyzed and abnormalities were reported using the London Classification. A combination of Wilcoxon rank sum and Fisher's exact test were used.36 patients (19 women) with median age 71 (interquartile range [IQR]: 69-74) years, were included. Using the London Classification, 7 (19%) patients had anal hypotension, 17 (47%) had anal hypocontractility, and 3 women had combined hypotension and hypocontractility. Anal hypocontractility was significantly more common in women compared to men. Abnormal BET and dyssynergia were noted in 22 (61%) patients, while abnormal BET and poor propulsion were only seen in 2 (5%). Men had significantly more paradoxical anal contraction and higher residual anal pressures during simulated defecation, resulting in more negative recto-anal pressure gradients. Rectal hyposensitivity was seen in nearly one third of PD patients and comparable among men and women.Our data affirms the high prevalence of anorectal disorders in PD. Using the London Classification, abnormal expulsion and dyssynergia and anal hypocontractility were the most common findings in PD. Whether the high prevalence of anal hypocontractility in females is directly related to PD or other confounding factors will require further research.
View details for DOI 10.1002/mdc3.13755
View details for PubMedID 37476327
View details for PubMedCentralID PMC10354598
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NGLY1 deficiency: a prospective natural history study (NHS).
Human molecular genetics
2023
Abstract
N-glycanase 1 (NGLY1) Deficiency is a debilitating, ultra-rare autosomal recessive disorder caused by loss of function of NGLY1, a cytosolic enzyme that deglycosylates other proteins. It is characterized by severe global developmental delay and/or intellectual disability, hyperkinetic movement disorder, transient elevation of transaminases, (hypo)alacrima, and progressive, diffuse, length-dependent sensorimotor polyneuropathy. A prospective natural history study (NHS) was conducted to elucidate clinical features and disease course. Twenty-nine participants were enrolled (15 onsite, 14 remotely) and followed for up to 32 months, representing ~ 29% of the ~ 100 patients identified worldwide. Participants exhibited profound developmental delays, with almost all developmental quotients below 20 on the Mullen Scales of Early Learning, well below the normative score of 100. Increased difficulties with sitting and standing suggested decline in motor function over time. Most patients presented with (hypo)alacrima and reduced sweat response. Pediatric quality of life was poor except for emotional function. Language/communication and motor skill problems including hand use were reported by caregivers as the most bothersome symptoms. Levels of the substrate biomarker, GlcNAc-Asn (aspartylglucosamine; GNA), were consistently elevated in all participants over time, independent of age. Liver enzymes were elevated for some participants but improved especially in younger patients and did not reach levels indicating severe liver disease. Three participants died during the study period. Data from this NHS informs selection of endpoints and assessments for future clinical trials for NGLY1 Deficiency interventions. Potential endpoints include GNA biomarker levels, neurocognitive assessments, autonomic and motor function (particularly hand use), (hypo)alacrima, and quality of life.
View details for DOI 10.1093/hmg/ddad106
View details for PubMedID 37379343
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Neonatal Fc receptor blockade as emerging therapy in diseases with plasma exchange indications.
Journal of clinical apheresis
2023
Abstract
Neonatal Fc receptor (FcRn) blockade may represent a mechanism similar to plasma exchange (PLEX) in reducing immunoglobulin levels and thus have a broad implication for apheresis practitioners. Although only efgartigimod received FDA approval for myasthenia gravis in December 2021, multiple trials are currently underway with different FcRn therapies in a varied group of IgG antibody-mediated neurological and hematological disorders which are outlined in this review. In this review we discuss FcRn's mechanism of action, and its potential use in various neurological and non-neurological diseases. In addition, we further compare the kinetics and adverse events of PLEX and FcRn blockade. We encourage apheresis practitioners to be familiar with this class of drugs in order to better understand how these two therapies can be used either standalone, or in combination with other therapies as both FcRn antagonism and PLEX improve clinical state by reducing IgG levels and pathogenic antibodies.
View details for DOI 10.1002/jca.22055
View details for PubMedID 37183667
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Patient-reported impact of myasthenia gravis in the real world: findings from a digital observational survey-based study (MyRealWorld MG).
BMJ open
2023; 13 (5): e068104
Abstract
This study aims to explore the impact of myasthenia gravis (MG) - in terms of treatments, side effects, comorbidities, psychological health and work or study- in the real world from a patient perspective.This is a prospective, observational, digital, longitudinal study. Adults diagnosed with MG residing in the USA, Japan, Germany, the UK, Italy, Spain or Canada were eligible to participate in the study. There were no other exclusion criteria. Participants used a bespoke smartphone application to confirm eligibility, provide consent and enter data about their MG into a profile, a tracker to record MG-related events and a series of patient-reported outcome instruments. 1693 participants completed at least 1 survey and were included in this analysis.Results are presented as a percentage of respondents to each survey question. The study population was largely female (69% of 1586 respondents), with an average age of 49.9 years (SD 14.8). In the previous 12 months, 83.7% of 1412 respondents confirmed that they had received one or more routine treatments for MG, and 67.1% of 255 respondents confirmed that they had experienced a side effect in the previous month. Commonly experienced comorbidities reported by 966 respondents were thyroid problems, hypertension and anxiety, experienced by 37.5%, 31.4% and 28.0% of respondents, respectively.According to 889 respondents to the Hospital Anxiety and Depression Scale survey, 52.7% and 43.2% had a score indicative of at least mild anxiety and mild depression, respectively. Of 257 respondents, 33.0% reported experiencing a work or study impact in the past month.This analysis of baseline characteristics of the MyRealWorld MG study population indicates that, despite current treatments, patients experience notable burden. Further scheduled analyses will develop a longitudinal picture of MG burden.NCT04176211.
View details for DOI 10.1136/bmjopen-2022-068104
View details for PubMedID 37169499
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Utility of Repetitive Nerve Stimulation in the Diagnosis of Myasthenia Gravis in the Inpatient Setting
NEUROHOSPITALIST
2023
View details for DOI 10.1177/19418744231173829
View details for Web of Science ID 000985106200001
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Differential Findings on Anorectal Manometry in Patients with Parkinson's Disease and Defecatory Dysfunction
MOVEMENT DISORDERS CLINICAL PRACTICE
2023
View details for DOI 10.1002/mdc3.13755
View details for Web of Science ID 000982806800001
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Clinical Experience With Efgartigimod For Treatment Of Acetylcholine Receptor Antibody Positive Generalized Myasthenia Gravis
LIPPINCOTT WILLIAMS & WILKINS. 2023
View details for DOI 10.1212/WNL.0000000000202807
View details for Web of Science ID 001053672102284
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Myasthenia Gravis Activities of Daily Living (MG-ADL) Response to Eculizumab Treatment in Patients from the Generalized Myasthenia Gravis Registry
LIPPINCOTT WILLIAMS & WILKINS. 2023
View details for DOI 10.1212/WNL.0000000000202295
View details for Web of Science ID 001053672102253
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Risk of Infection in Patients with Myasthenia Gravis With and Without Thymoma
LIPPINCOTT WILLIAMS & WILKINS. 2023
View details for DOI 10.1212/WNL.0000000000202824
View details for Web of Science ID 001053672103135
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Achievement of Improved Post-Intervention Status in Patients with Generalized Myasthenia Gravis Treated with Ravulizumab during the CHAMPION MG Study
LIPPINCOTT WILLIAMS & WILKINS. 2023
View details for DOI 10.1212/WNL.0000000000202156
View details for Web of Science ID 001053672108071
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Patient-reported burden of myasthenia gravis: baseline results of the international prospective, observational, longitudinal real-world digital study MyRealWorld-MG.
BMJ open
2023; 13 (1): e066445
Abstract
Myasthenia gravis (MG) is a rare, chronic, autoimmune neuromuscular disease which can affect functional and mental aspects of health and health-related quality of life (HRQoL). This study aims to obtain detailed knowledge of the impact of MG on HRQoL in a broad population from the perspective of the patient.Prospective, observational, digital, longitudinal real-world study.Adult patients with MG from seven countries (USA, Japan, Germany, UK, Italy, Spain and Canada) downloaded a mobile application onto their phones and entered data about themselves and their MG.Data was collected using the following general and disease-specific patient-reported outcome measurements: EuroQol 5 Domains Health-Related Quality of Life Questionnaire (EQ-5D-5L), Myasthenia Gravis Activities of Daily Living (MG-ADL), Myasthenia Gravis Quality of Life 15-item revised scale (MG-QoL-15r), Hospital Anxiety and Depression Scale (HADS) and Health Utilities Index III (HUI3). Patients were categorised by their self-assessed Myasthenia Gravis Foundation of America (MGFA) class (I-V).Baseline results of 841 participants (mean age 47 years, 70% women) are reported . The distribution across the MGFA classes was: 13.9%, 31.0%, 38.1%, 15.5% and 1.6% for classes I-V. The MGFA class was a strong predictor of all aspects of HRQoL, measured with disease-specific and with generic instruments. The domains in which patients with MG most frequently mentioned problems were usual activities, anxiety and depression, tiredness, breathing and vision. The mean total MG-ADL Score was positively associated with increasing MGFA classes: 2.7, 4.4, 6.3 and 8.4 for MGFA classes I-IV. Mean baseline EQ-5D-5L utility was also associated with MGFA classes and was 0.817, 0.766, 0.648 and 0.530 for MGFA class I-IV.MG has a large impact on key aspects of health and HRQoL. The impact of this disease increases substantially with increasing disease severity.
View details for DOI 10.1136/bmjopen-2022-066445
View details for PubMedID 36720569
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Imaging in autonomic failure: a window into real-time physiological mechanisms and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2022
View details for DOI 10.1007/s10286-022-00910-0
View details for PubMedID 36409381
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Plasma Exchange for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitor Therapy: Implications for Clinical Care and Clinical Trial Design
AMER SOC HEMATOLOGY. 2022: 2835-2836
View details for DOI 10.1182/blood-2022-171037
View details for Web of Science ID 000893223202381
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Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea.
Nature genetics
2022; 54 (10): 1534-1543
Abstract
Sleep apnea is a common disorder that represents a global public health burden. KCNK3 encodes TASK-1, a K+ channel implicated in the control of breathing, but its link with sleep apnea remains poorly understood. Here we describe a new developmental disorder with associated sleep apnea (developmental delay with sleep apnea, or DDSA) caused by rare de novo gain-of-function mutations in KCNK3. The mutations cluster around the 'X-gate', a gating motif that controls channel opening, and produce overactive channels that no longer respond to inhibition by G-protein-coupled receptor pathways. However, despite their defective X-gating, these mutant channels can still be inhibited by a range of known TASK channel inhibitors. These results not only highlight an important new role for TASK-1 K+ channels and their link with sleep apnea but also identify possible therapeutic strategies.
View details for DOI 10.1038/s41588-022-01185-x
View details for PubMedID 36195757
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Comparison of Gastrointestinal Symptoms and Gastric Emptying Scintigraphy Between Postural Orthostatic Tachycardia Patients With and Without Small Fiber Neuropathy
LIPPINCOTT WILLIAMS & WILKINS. 2022: S408-S409
View details for Web of Science ID 000897916001175
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High Resolution Anorectal Manometry Findings in Men and Women With Parkinson's Disease, Using London Classification
LIPPINCOTT WILLIAMS & WILKINS. 2022: S407-S408
View details for Web of Science ID 000897916001174
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Autonomic function testing in multiple system atrophy: a prognostic biomarker? and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2022
View details for DOI 10.1007/s10286-022-00883-0
View details for PubMedID 35907042
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Implantable neurostimulators for neurogenic orthostatic hypotension: the wave of the future? and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2022
View details for DOI 10.1007/s10286-022-00871-4
View details for PubMedID 35655044
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Plasma exchange for severe immune-related adverse events from checkpoint inhibitors: an early window of opportunity?
Immunotherapy advances
2022; 2 (1): ltac012
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several advanced malignancies leading to durable remission in a subset of patients. Their rapidly expanding use has led to an increased frequency of immune-related adverse events (irAEs). The pathogenesis of irAEs is poorly understood but may involve aberrant activation of T cells leading to inflammatory cytokine release or production of pathogenic antibodies leading to organ damage. Severe irAEs can be extremely debilitating and, in some cases, life threatening. IrAEs may not always be corticosteroid responsive or may require excessively high, often toxic, corticosteroid doses. Therapeutic plasma exchange (PLEX) is a treatment modality that has shown promising results for the management of certain severe irAEs, including irAEs that are not mentioned in current treatment guidelines. PLEX may attenuate ongoing irAEs and prevent delayed irAEs by accelerating clearance of the ICI, or by acutely removing pathogenic antibodies, cytokines, and chemokines. Here, we summarize examples from the literature in which PLEX was successfully used for the treatment of irAEs. We posit that timing may be a critical factor and that earlier utilization of PLEX for life-threatening irAEs may result in more favorable outcomes. In individuals at high risk for irAEs, the availability of PLEX as a potential therapeutic mitigation strategy may encourage life-saving ICI use or rechallenge. Future research will be critical to better define which indications are most amenable to PLEX, particularly to establish the optimal place in the sequence of irAE therapies and to assess the ramifications of ICI removal on cancer outcomes.
View details for DOI 10.1093/immadv/ltac012
View details for PubMedID 35814850
View details for PubMedCentralID PMC9257781
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Real-World Eculizumab Effectiveness on US Patient Outcomes in Myasthenia Gravis (ELEVATE): a Retrospective Chart Review
LIPPINCOTT WILLIAMS & WILKINS. 2022
View details for Web of Science ID 000894020500409
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International COVID-19D AY, Vaccine Experience and Perceptions Survey In Patients with Myasthenia Gravis: An (P18-2.003)
LIPPINCOTT WILLIAMS & WILKINS. 2022
View details for Web of Science ID 000894020500295
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COVID-19 VACCINE SAFETY IN PATIENTS WITH MYASTHENIA GRAVIS
WILEY. 2022: S31
View details for Web of Science ID 000813311100068
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MGFA TASK FORCE FOR STANDARDIZATION OF MG OUTCOME MEASURES IN CLINICAL PRACTICE
WILEY. 2022: S15
View details for Web of Science ID 000813311100028
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Mechanisms of post-prandial symptoms in postural tachycardia syndrome and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2022
View details for DOI 10.1007/s10286-022-00863-4
View details for PubMedID 35316450
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Inappropriate sinus tachycardia in long-COVID and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2022
View details for DOI 10.1007/s10286-022-00854-5
View details for PubMedID 35129713
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Utilization of MG-ADL in myasthenia gravis clinical research and care.
Muscle & nerve
1800
Abstract
The Myasthenia Gravis Activities of Living (MG-ADL) scale is an 8-item patient-reported scale that measures myasthenia gravis (MG) symptoms and functional status. The objective of the current review is to summarize the psychometric properties of the MG-ADL and published evidence of MG-ADL use. A targeted literature review for published studies of the MG-ADL was conducted using a database and gray literature search. A total of 48 publications and 35 clinical trials were included. Studies indicated that the MG-ADL is a reliable and valid measure that has been used as an outcome in clinical trials and observational studies to measure MG symptoms and response to treatment. While most often used as a secondary endpoint in clinical trials, its use as a primary endpoint has increased in recent years. The most common MG-ADL endpoint is change in MG-ADL score from baseline, although there has been an increase in the analysis of a responder threshold using the MG-ADL. A new concept of minimal symptom expression (MSE) has emerged more recently. Duration of treatment effect is another important construct that is being increasingly evaluated using the MG-ADL. The use of the MG-ADL as a primary endpoint in clinical trials and in responder threshold analyses to indicate treatment improvement has increased in recent years. MSE using the MG-ADL shows promise in helping to determine success of treatment and may be the aspirational goal of MG treatment for the future once validated, particularly given the evolving treatment landscape in MG.
View details for DOI 10.1002/mus.27476
View details for PubMedID 34989427
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Characterization of autonomic symptom burden in long COVID: A global survey of 2,314 adults.
Frontiers in neurology
2022; 13: 1012668
Abstract
Background: Autonomic dysfunction is a known complication of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity are unknown.Objective: To assess the frequency, severity, and risk factors of autonomic dysfunction in PASC, and to determine whether severity of acute SARS-CoV-2 infection is associated with severity of autonomic dysfunction.Design: Cross-sectional online survey of adults with PASC recruited through long COVID support groups between October 2020 and August 2021.Participants: 2,413 adults ages 18-64 years with PASC including patients who had a confirmed positive test for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone.Main measures: The main outcome measure was the Composite Autonomic Symptom 31 (COMPASS-31) total score, used to assess global autonomic dysfunction. Test-confirmed hospitalized vs. test-confirmed non-hospitalized participants were compared to determine if the severity of acute SARS-CoV-2 infection was associated with the severity autonomic dysfunction.Key results: Sixty-six percent of PASC patients had a COMPASS-31 score >20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and test-confirmed non-hospitalized participants [28.95 (15.62, 46.60) vs. 26.4 (13.75, 42.10); p = 0.06].Conclusions: Evidence of moderate to severe autonomic dysfunction was seen in 66% of PASC patients in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and independent of the severity of acute COVID-19 illness.
View details for DOI 10.3389/fneur.2022.1012668
View details for PubMedID 36353127
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The 2021 Nobel Prize in Medicineandits relevance toautonomicmedicine-and otherupdates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2021
View details for DOI 10.1007/s10286-021-00838-x
View details for PubMedID 34751840
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Small nerve fiber involvement in chilblain lupus erythematosus (late breaking abstract)
WILEY. 2021: 440
View details for Web of Science ID 000696233800295
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Holiday heart syndrome: do not drink during this holiday! and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2021
View details for DOI 10.1007/s10286-021-00818-1
View details for PubMedID 34244877
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Non-invasive wearables for remote monitoring of HbA1c and glucose variability: proof of concept.
BMJ open diabetes research & care
2021; 9 (1)
Abstract
Diabetes prevalence continues to grow and there remains a significant diagnostic gap in one-third of the US population that has pre-diabetes. Innovative, practical strategies to improve monitoring of glycemic health are desperately needed. In this proof-of-concept study, we explore the relationship between non-invasive wearables and glycemic metrics and demonstrate the feasibility of using non-invasive wearables to estimate glycemic metrics, including hemoglobin A1c (HbA1c) and glucose variability metrics.We recorded over 25 000 measurements from a continuous glucose monitor (CGM) with simultaneous wrist-worn wearable (skin temperature, electrodermal activity, heart rate, and accelerometry sensors) data over 8-10 days in 16 participants with normal glycemic state and pre-diabetes (HbA1c 5.2-6.4). We used data from the wearable to develop machine learning models to predict HbA1c recorded on day 0 and glucose variability calculated from the CGM. We tested the accuracy of the HbA1c model on a retrospective, external validation cohort of 10 additional participants and compared results against CGM-based HbA1c estimation models.A total of 250 days of data from 26 participants were collected. Out of the 27 models of glucose variability metrics that we developed using non-invasive wearables, 11 of the models achieved high accuracy (<10% mean average per cent error, MAPE). Our HbA1c estimation model using non-invasive wearables data achieved MAPE of 5.1% on an external validation cohort. The ranking of wearable sensor's importance in estimating HbA1c was skin temperature (33%), electrodermal activity (28%), accelerometry (25%), and heart rate (14%).This study demonstrates the feasibility of using non-invasive wearables to estimate glucose variability metrics and HbA1c for glycemic monitoring and investigates the relationship between non-invasive wearables and the glycemic metrics of glucose variability and HbA1c. The methods used in this study can be used to inform future studies confirming the results of this proof-of-concept study.
View details for DOI 10.1136/bmjdrc-2020-002027
View details for PubMedID 36170350
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Do not sweat it: we test while you rest and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2021
View details for DOI 10.1007/s10286-021-00811-8
View details for PubMedID 33978866
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Telemedicine visits in myasthenia gravis: expert guidance and the myasthenia gravis core exam (MG-CE).
Muscle & nerve
2021
Abstract
Telemedicine may be particularly well-suited for myasthenia gravis (MG) due to the disorder's need for specialized care, its hallmark fluctuating muscle weakness and the potential for increased risk of virus exposure among patients with MG during the COVID-19 pandemic during in-person clinical visits. A disease-specific telemedicine physical examination to reflect myasthenic weakness does not currently exist. This paper outlines step-by-step guidance on the fundamentals of a telemedicine assessment for MG. The Myasthenia Gravis Core Exam (MG-CE) is introduced as a MG-specific, telemedicine, physical examination which contains 8 components (ptosis, diplopia, facial Strength, bulbar strength, dysarthria, single breath count, arm strength and sit to stand) and takes approximately 10 minutes to complete. Pre-visit preparation, remote ascertainment of patient-reported outcome scales and visit documentation are also addressed. Additional knowledge gaps in telemedicine specific to MG care are identified for future investigation.
View details for DOI 10.1002/mus.27260
View details for PubMedID 33959997
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Real-World Use of Eculizumab in Generalized Myasthenia Gravis in the United States: Results From a Pilot Retrospective Chart-Review Study
LIPPINCOTT WILLIAMS & WILKINS. 2021
View details for Web of Science ID 000729283601172
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Towards more evidenced-based therapies for postural tachycardia syndrome and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2021
View details for DOI 10.1007/s10286-021-00795-5
View details for PubMedID 33709266
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Orthostatic intolerance with Klippel-Trenaunay syndrome.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2021
View details for DOI 10.1007/s10286-021-00791-9
View details for PubMedID 33655381
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Myasthenia Symptom Burden, Fatigue, and Sleep: Are They Related?
Journal of clinical neuromuscular disease
2021; 22 (3): 123–28
Abstract
OBJECTIVE: Our aim is to explore the relationship between myasthenia gravis (MG)-related symptom burden, sleep quality, and fatigue in a diverse group of self-identified MG patients.METHODS: Patients provided relevant myasthenia disease data and completed the MG QOL-15, Epworth sleepiness scale, Pittsburgh Sleep Quality Index, and fatigue severity score (FSS) online. MG activities of daily living scale (MG-ADL) was completed on a follow-up telephone interview.RESULTS: One hundred ninety-six patients completed the online survey and 99 provided MG-ADL data. The mean age was 52 ± 15.34 years, 88 were acetylcholine receptor antibody positive, and 21 were muscle specific kinase positive. The mean MG-ADL was 6.81, indicating a moderate MG disease burden. Forty-seven (24%) reported high Epworth sleepiness scale scores, 152 (77%) reported high Pittsburgh Sleep Quality Index scores, and 162 (82%) reported high FSS scores. Correlation analysis correcting for body mass index and sleep apnea revealed a moderate positive correlation between MGQOL-15, MG-ADL, and FSS.CONCLUSIONS: There is a moderate positive correlation between various MG-specific outcome measures and fatigue severity.
View details for DOI 10.1097/CND.0000000000000321
View details for PubMedID 33595995
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RT-QUiC in multiple system atrophy: the biomarker of the future? and otherupdates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2021
View details for DOI 10.1007/s10286-021-00767-9
View details for PubMedID 33515140
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Antibody Prevalence in Epilepsy before Surgery (APES) in drug-resistant focal epilepsy.
Epilepsia
2021
Abstract
OBJECTIVE: There is a growing recognition of immune-mediated causes in patients with focal drug-resistant epilepsy (DRE); however, they are not systematically assessed in the pre-surgical diagnostic workup. Early diagnosis and initiation of immunotherapy is associated with a favorable outcome in immune-mediated seizures. Patients with refractory focal epilepsy with neuronal antibodies (Abs) tend to have a worse surgical prognosis when compared to other etiologies.METHODS: We studied the prevalence of serum Abs in patients ≥18years of age with DRE of unknown cause before surgery. We proposed and calculated a clinical APES (Antibody Prevalence in Epilepsy before Surgery) score for each subject, which was modified based on Dubey's previously published APE2 score. RESULTS`: A total of 335 patients were screened and 86 subjects were included in final analysis. The mean age at the time of recruitment was 44.84±14.86years, with age at seizure onset 30.89±19.88years. There were no significant differences among baseline clinical features between retrospective and prospective sub-cohorts. The prevalence of at least one positive Ab was 33.72%, and central nervous system (CNS)-specific Abs was 8.14%. APES score ≥4 showed slightly better overall prediction (area under the curve [AUC]: 0.84 vs 0.74) and higher sensitivity (100% vs 71.4%), with slightly lower but similar specificity (44.3% vs 49.4%), when compared to APE2 score ≥4. For subjects who had available positron emission tomography (PET) results and all components of APES score (n=60), the sensitivity of APES score ≥4 yielded a similar prediction potential with an AUC of 0.80.SIGNIFICANCE: Our findings provide persuasive evidence that a subset of patients with focal DRE have potentially immune-mediated causes. We propose an APES score to help identify patients who may benefit from a workup for immune etiologies during the pre-surgical evaluation for focal refractory epilepsy with unknown cause.
View details for DOI 10.1111/epi.16820
View details for PubMedID 33464599
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Autonomic function test during the COVID-19 pandemic: the Stanford experience.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2021
View details for DOI 10.1007/s10286-020-00752-8
View details for PubMedID 33387099
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Non-invasive wearables for remote monitoring of HbA1c and glucose variability: proof of concept
BMJ OPEN DIABETES RESEARCH & CARE
2021; 9 (1)
View details for DOI 10.1136/bmjdrc-2020-002027
View details for Web of Science ID 000662276300001
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COVID-19-associated risks and effects in myasthenia gravis (CARE-MG)
LANCET NEUROLOGY
2020; 19 (12): 970–71
View details for Web of Science ID 000599622000006
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COVID-19-associated risks and effects in myasthenia gravis (CARE-MG).
The Lancet. Neurology
2020; 19 (12): 970–71
View details for DOI 10.1016/S1474-4422(20)30413-0
View details for PubMedID 33212055
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Post-intervention status in patients with refractory myasthenia gravis treated with eculizumab during REGAIN and its open-label extension.
Neurology
2020
Abstract
OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) to achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN and its open-label extension.METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study.RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 87.1% of patients achieved improved status and 57.1% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected.CONCLUSIONS: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population.CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.TRIAL REGISTRATION: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624 (ClinicalTrials.gov).
View details for DOI 10.1212/WNL.0000000000011207
View details for PubMedID 33229455
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The shock of it: sympathetic activation promotes hair greying, and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2020
View details for DOI 10.1007/s10286-020-00746-6
View details for PubMedID 33210247
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A case report of postural tachycardia syndrome after COVID-19.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2020
View details for DOI 10.1007/s10286-020-00727-9
View details for PubMedID 32880754
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Can skin biopsy differentiate Parkinson disease from multiple system atrophy? And other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2020
View details for DOI 10.1007/s10286-020-00712-2
View details for PubMedID 32648015
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The quest for biomarkers in postural tachycardia syndrome and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2020
View details for DOI 10.1007/s10286-020-00694-1
View details for PubMedID 32418032
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Guidance for the management of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) during the COVID-19 pandemic.
Journal of the neurological sciences
2020; 412: 116803
View details for DOI 10.1016/j.jns.2020.116803
View details for PubMedID 32247193
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Synuclein in red blood cells: a potential biomarker for multiple system atrophy, and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2020
View details for DOI 10.1007/s10286-020-00680-7
View details for PubMedID 32189166
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Is postural tachycardia syndrome an autoimmune disorder? And other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2020
View details for DOI 10.1007/s10286-019-00661-5
View details for PubMedID 31938977
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Epidemiological evidence for a hereditary contribution to myasthenia gravis: a retrospective cohort study of patients from North America.
BMJ open
2020; 10 (9): e037909
Abstract
To approximate the rate of familial myasthenia gravis and the coexistence of other autoimmune disorders in the patients and their families.Retrospective cohort study.Clinics across North America.The study included 1032 patients diagnosed with acetylcholine receptor antibody (AChR)-positive myasthenia gravis.Phenotype information of 1032 patients diagnosed with AChR-positive myasthenia gravis was obtained from clinics at 14 centres across North America between January 2010 and January 2011. A critical review of the epidemiological literature on the familial rate of myasthenia gravis was also performed.Among 1032 patients, 58 (5.6%) reported a family history of myasthenia gravis. A history of autoimmune diseases was present in 26.6% of patients and in 28.4% of their family members.The familial rate of myasthenia gravis was higher than would be expected for a sporadic disease. Furthermore, a high proportion of patients had a personal or family history of autoimmune disease. Taken together, these findings suggest a genetic contribution to the pathogenesis of myasthenia gravis.
View details for DOI 10.1136/bmjopen-2020-037909
View details for PubMedID 32948566
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Clinical Reasoning: Therapeutic considerations in myasthenic crisis due to COVID-19 infection.
Neurology
2020
View details for DOI 10.1212/WNL.0000000000010651
View details for PubMedID 32817186
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Concomitant Immunosuppressive Therapy Use in Eculizumab-Treated Adults With Generalized Myasthenia Gravis During the REGAIN Open-Label Extension Study.
Frontiers in neurology
2020; 11: 556104
Abstract
Introduction: Chronic, broad-spectrum immunosuppressive therapy (IST) can be associated with side effects in many people with generalized myasthenia gravis (gMG), and treatment guidelines recommend that the IST dose be tapered once patients achieve a stable treatment response. We therefore examined IST use in eculizumab-treated patients with refractory gMG. Methods: The REGAIN open-label extension (OLE) enrolled 117 adults with refractory anti-acetylcholine receptor antibody-positive gMG who had completed the 6-month, randomized, double-blind, placebo-controlled REGAIN study of eculizumab. Eligible patients had received ≥2 ISTs for ≥1 year or ≥1 IST with intravenous immunoglobulin or plasma exchange ≥4 times in 1 year, without symptom control. During REGAIN, changes in concomitant MG therapies were not permitted; during the OLE, they were permitted at the investigators' discretion. Participants received eculizumab 1,200 mg every 2 weeks for up to 4 years; concomitant prednisone and related corticosteroids (PRED), azathioprine (AZA), and mycophenolate mofetil (MMF) use was recorded. Changes in MG Activities of Daily Living and Quantitative MG total scores, MG exacerbations, and adverse events were also recorded. Results: At last OLE assessment, 88.0% (103/117) of participants were using ≥1 IST vs. 98.3% (115/117) at OLE baseline. During the OLE, 76.9% (90/117) of patients experienced a total of 719 IST changes. Almost half of participants [48.7% (57/117)] stopped or decreased ≥1 IST owing to MG symptom improvement, representing 38.9% (280/719) of all changes. In patients who decreased and/or stopped ≥1 IST, mean daily doses of PRED, AZA, and MMF decreased between OLE baseline and last assessment by 60.8% [standard deviation (SD), 28.07; P < 0.0001], 89.1% (SD, 25.77; P < 0.0001), and 56.0% (SD, 32.99; P < 0.0001), respectively. Improved clinical outcomes were observed with eculizumab regardless of IST changes during the OLE, and eculizumab's safety profile was similar in patients who used PRED, AZA, and MMF. Conclusions: Use of ISTs by patients with previously refractory gMG decreased during eculizumab treatment in the REGAIN OLE. Clinical improvements with eculizumab were maintained by patients in all groups, including those who decreased and/or stopped concomitant ISTs. Trial registration: www.clinicaltrials.gov: NCT01997229, NCT02301624.
View details for DOI 10.3389/fneur.2020.556104
View details for PubMedID 33329303
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Seizures, Confusion, and Strokes in a Patient With AIDS.
The Neurohospitalist
2019; 9 (4): 209–14
View details for DOI 10.1177/1941874419830499
View details for PubMedID 31534610
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The microbiome in autonomic medicine and other updates in recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2019
View details for DOI 10.1007/s10286-019-00621-z
View details for PubMedID 31363881
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Long-term safety and efficacy of eculizumab in generalized myasthenia gravis
MUSCLE & NERVE
2019; 60 (1): 14–24
View details for DOI 10.1002/mus.26447
View details for Web of Science ID 000471831900011
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Do astronauts get postural tachycardia syndrome? And other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2019
View details for DOI 10.1007/s10286-019-00613-z
View details for PubMedID 31089931
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Response Rates in Placebo arm of MG Clinical Trials
LIPPINCOTT WILLIAMS & WILKINS. 2019
View details for Web of Science ID 000475965905213
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Changes in Concomitant Immunosuppressive Therapy Use During a Phase 3 Open-label Study of Eculizumab in Adults with Generalized Myasthenia Gravis: an Interim Analysis
LIPPINCOTT WILLIAMS & WILKINS. 2019
View details for Web of Science ID 000475965905091
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Improving 'neurologists' adherence to guidelines on prevention of possible complications of systemic corticosteroid therapy
LIPPINCOTT WILLIAMS & WILKINS. 2019
View details for Web of Science ID 000475965906040
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Dopamine transporter imaging versus myocardial MIBG scintigraphy for the diagnosis of prodromal synucleinopathies-and other updates on autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2019
View details for DOI 10.1007/s10286-019-00600-4
View details for PubMedID 30904961
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Long-term safety and efficacy of eculizumab in generalized myasthenia gravis.
Muscle & nerve
2019
Abstract
INTRODUCTION: Eculizumab is effective and well tolerated in patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN evaluating eculizumab's long-term safety and efficacy.METHODS: 117 patients received eculizumab (1,200 mg every 2 weeks) for 22.7 months (median).RESULTS: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. MG exacerbation rate was reduced by 75% from the year before REGAIN (p<0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (p<0.0001).DISCUSSION: These findings demonstrate the long-term safety and sustained efficacy of eculizumab for refractory gMG. This article is protected by copyright. All rights reserved.
View details for PubMedID 30767274
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Ion channels PIEZOs identified as the long-sought baroreceptor mechanosensors for blood pressure control, and other updates on autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2019
View details for DOI 10.1007/s10286-018-00588-3
View details for PubMedID 30604163
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A novel autosomal recessive orthostatic hypotension syndrome: and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2018
View details for DOI 10.1007/s10286-018-0578-z
View details for PubMedID 30415401
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FGFR3 Antibodies in Neuropathy: What to Do With Them?
Journal of clinical neuromuscular disease
2018; 20 (1): 35–40
Abstract
OBJECTIVES: To describe the variability of fibroblast growth factor receptor 3 (FGFR3) antibody titers in a small series of patients.METHODS: We performed a retrospective review of patients with neuropathy and positive FGFR3 antibodies.RESULTS: We report 7 patients (3 women) with an age range 44-81 years. Symptoms were acute onset in 3 and subacute onset in 4 patients. Five had neuropathic pain. Examination revealed normal large fiber function to mild/moderate predominantly sensory neuropathy and ataxia in one patient. Electrodiagnostic studies revealed normal large fiber function (3), demyelinating neuropathy (1), and mild/moderate axonal neuropathy (3). Four patients had high and 3 patients had low FGFR3 titers. Repeat testing revealed absence of antibodies in 2 patients and a significant reduction in one patient without any intervening immunotherapy.CONCLUSIONS: Our case series highlights the variability and inconsistency in FGFR3 antibody titers through enzyme-linked immunosorbent assay testing. These antibody titers should always be interpreted with caution in clinical context.
View details for DOI 10.1097/CND.0000000000000221
View details for PubMedID 30124558
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Autonomic dysfunction in multiple sclerosis and other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2018
View details for DOI 10.1007/s10286-018-0548-5
View details for PubMedID 30014341
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Reply to "Syncope is associated with electroencephalography changes" and to "Video-EEG during tilt-table testing is an invaluable aid for understanding syncope".
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
2018; 129 (7): 1500–1501
View details for DOI 10.1016/j.clinph.2018.04.601
View details for PubMedID 29729888
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Orthostatic hypotension: does the heart rate matter? And other updates on recent autonomic research.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2018
View details for DOI 10.1007/s10286-018-0532-0
View details for PubMedID 29779066
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Postural Orthostatic Tachycardia: The Stanford experience
LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000453090801125
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FGFR3 Antibodies in Neuropathy. What to do with them?
LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000453090800443
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Myasthenia Symptom Burden, Sleep and Fatigue: Are they related?
LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000453090805163
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The clinical utility of qualitative electroencephalography during tilt table testing - A retrospective study
CLINICAL NEUROPHYSIOLOGY
2018; 129 (4): 783–86
Abstract
To assess electroencephalography (EEG) changes during tilt table testing in syncope and other orthostatic syndromes.We retrospectively reviewed consecutive tilt table studies with simultaneous EEG from April 2014 to May 2016 at our center. All patients had video EEG during tilt table. All patients had at least 10 min of head up tilt unless they had syncope or did not tolerate the study. Video EEG was interpreted by epileptologists.Eighty-seven patients met the inclusion criteria. Mean age was 45 years, and 55 were women. Seven patients (∼8%) had syncope during tilt table, 11 patients (∼12%) had significant neurogenic orthostatic hypotension and a separate group of 11 patients (∼12%) had significant orthostatic tachycardia. Valsalva responses were abnormal in 7 of the 11 patients with orthostatic hypotension, suggesting an underlying neurogenic orthostatic hypotension. Visually discernable EEG changes were seen in only 3 patients (∼43%) who had syncope and in 1 patient (∼9%) with orthostatic tachycardia.Qualitative EEG analysis based on visual inspection during tilt table study revealed abnormalities in less than half the patients with syncope and a very small fraction with orthostatic tachycardia.Routine qualitative EEG recording might not be clinically useful during tilt table studies.
View details for DOI 10.1016/j.clinph.2018.01.058
View details for Web of Science ID 000427485900010
View details for PubMedID 29448152
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Is your autonomic function good enough to be an Olympian? And other updates on recent autonomic research
CLINICAL AUTONOMIC RESEARCH
2018; 28 (2): 177–79
View details for DOI 10.1007/s10286-018-0521-3
View details for Web of Science ID 000427880500006
View details for PubMedID 29541877
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Autonomic dysfunction predicts poor outcome in stroke: Updates on recent autonomic research
CLINICAL AUTONOMIC RESEARCH
2018; 28 (1): 9–11
View details for DOI 10.1007/s10286-017-0498-3
View details for Web of Science ID 000424641400004
View details for PubMedID 29305815
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Autoimmune autonomic neuropathies: time to look beyond autoimmune autonomic ganglionopathy
CLINICAL AUTONOMIC RESEARCH
2018; 28 (1): 7–8
View details for DOI 10.1007/s10286-017-0496-5
View details for Web of Science ID 000424641400003
View details for PubMedID 29305816
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Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study
LANCET NEUROLOGY
2017; 16 (12): 976–86
Abstract
Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial.We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229.Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy.The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed.Alexion Pharmaceuticals.
View details for PubMedID 29066163
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Postural tachycardia in hypermobile Ehlers-Danlos syndrome: A distinct subtype?
AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
2017; 208: 146–49
Abstract
It is not clear if patients with postural tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (hEDS) differ from patients with POTS due to other etiologies. We compared the results of autonomic testing and healthcare utilization in POTS patients with and without hEDS.Patients with POTS+hEDS (n=20) and POTS controls without hypermobility (n=20) were included in the study. All patients underwent autonomic testing, and the electronic medical records were reviewed to determine the number and types of medications patients were taking, as well as the number of outpatient, emergency department, and inpatient visits over the prior year.Patients with hEDS had twice as many outpatient visits (21 v. 10, p=0.012), were taking more prescription medications (8 vs. 5.5, p=0.030), and were more likely to see a pain physician (70% vs 25%, p=0.005). Autonomic testing demonstrated a slight reduction in heart rate variability and slightly lower blood pressures on tilt table testing in hEDS patients, however for most patients these variables remained within the range of normal. Orthostatic tachycardia on tilt table testing was greater in POTS controls (46bpm vs 39bpm, p=0.018). Abnormal QSweat responses were common in both groups (38% of POTS+hEDS and 36% of POTS controls).While autonomic testing results were not significantly different between groups, patients with POTS+hEDS took more medications and had greater markers of healthcare utilization, with chronic pain likely playing a prominent role.
View details for PubMedID 28986003
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Is pure autonomic failure an early marker for Parkinson disease, dementia with Lewy bodies, and multiple system atrophy? And other updates on recent autonomic research
CLINICAL AUTONOMIC RESEARCH
2017; 27 (2): 71-73
View details for DOI 10.1007/s10286-017-0408-8
View details for Web of Science ID 000399093100003
View details for PubMedID 28255741
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Outcome Measures in Myasthenia Gravis: Incorporation Into Clinical Practice.
Journal of clinical neuromuscular disease
2017; 18 (3): 135-146
Abstract
The development of validated assessment tools for evaluating disease status and response to interventions in patients with myasthenia gravis (MG) has been driven by clinical studies of emerging MG therapies. However, only a small proportion of MG-focused neurology practices have adopted these assessment tools for routine clinical use. This article reviews the suitability of 5 assessment instruments for incorporation into clinical practice, which should be driven by their ability to contribute to improved patient outcomes, and to be implemented within practice personnel and resource constraints. It is recommended that assessments based on both physician-evaluated and patient-reported outcomes be selected, to adequately evaluate both point-in-time symptom load and functional impact of MG symptoms over time. Provider resource allocation and reimbursement issues may be the most significant roadblocks to successful ongoing use of these tools; to that end, the addition of regular assessments to MG standards of care is recommended.
View details for DOI 10.1097/CND.0000000000000156
View details for PubMedID 28221304
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A case series of REM sleep behavior disorder in pure autonomic failure
CLINICAL AUTONOMIC RESEARCH
2017; 27 (1): 41-44
Abstract
Data on the prevalence of RBD in patients with PAF are limited, with discrepancies in the literature regarding prevalence. We aimed to provide further data on this association with a series of eight patients with PAF.We reviewed the electronic medical records of all patients seen at the Stanford neurology clinics from 2012 to 2016 who were given a provisional diagnosis of PAF (343 patients), and further screened by procedure codes to identify those patients who underwent both attended video-polysomonography and autonomic testing (18 patients), and met strict exclusionary criteria (8 patients).The mean age of our patients was 69 years, and 63 % were women. The mean duration of autonomic symptoms was 11.2 years, and the mean duration of dream enactment was 3.75 years. All patients demonstrated evidence of adrenergic failure on autonomic testing. Five out of 8 (63 %) met diagnostic criteria for RBD, confirmed on vPSG.Our series supports the concept that RBD in PAF may be more common than previously reported, and that the presence of RBD suggests brainstem involvement in some cases of PAF. In addition, the timing of RBD symptoms relative to the emergence of autonomic symptoms may be useful to help distinguish these conditions.
View details for DOI 10.1007/s10286-016-0386-2
View details for Web of Science ID 000394183100007
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A case series of REM sleep behavior disorder in pure autonomic failure.
Clinical autonomic research
2016: -?
Abstract
Data on the prevalence of RBD in patients with PAF are limited, with discrepancies in the literature regarding prevalence. We aimed to provide further data on this association with a series of eight patients with PAF.We reviewed the electronic medical records of all patients seen at the Stanford neurology clinics from 2012 to 2016 who were given a provisional diagnosis of PAF (343 patients), and further screened by procedure codes to identify those patients who underwent both attended video-polysomonography and autonomic testing (18 patients), and met strict exclusionary criteria (8 patients).The mean age of our patients was 69 years, and 63 % were women. The mean duration of autonomic symptoms was 11.2 years, and the mean duration of dream enactment was 3.75 years. All patients demonstrated evidence of adrenergic failure on autonomic testing. Five out of 8 (63 %) met diagnostic criteria for RBD, confirmed on vPSG.Our series supports the concept that RBD in PAF may be more common than previously reported, and that the presence of RBD suggests brainstem involvement in some cases of PAF. In addition, the timing of RBD symptoms relative to the emergence of autonomic symptoms may be useful to help distinguish these conditions.
View details for PubMedID 27757562
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Sleep disorders in patients with postural tachycardia syndrome.
Clinical autonomic research
2016; 26 (1): 67-73
Abstract
Patients with postural tachycardia syndrome (POTS) often describe symptoms of fatigue, sleepiness, and lack of refreshing sleep. We aimed to provide further objective measures of sleep in patients with POTS.POTS patients (n = 18) were selected based on autonomic testing and evaluation at our center. Controls (n = 16) of similar age, gender, and BMI were selected from new patients referred to the Stanford Sleep Disorders Clinic for any sleep-related complaint. All patients underwent polysomnography and completed several sleep questionnaires and a 2-week sleep diary.POTS patients and control subjects were of similar age (27 ± 10.2 vs. 29 ± 5.4 years, p = 0.92) and Body Mass Index (21 ± 3.8 vs. 24 ± 4.1, p = 0.14). The majority of subjects in both groups were females (72 % POTS vs. 81 % controls). POTS patients scored higher on subjective fatigue scales but not sleepiness scales. POTS patients scored in the normal range on the BDI and the "evening" category on the MEQ. Their sleep diaries were not different from controls. With the exception of mild OSA, slightly reduced %REM and prolonged REM latency, their PSG data were normal and no different from controls.It is unlikely that the sleep-related complaints of POTS patients are the result of a primary sleep disorder unique to POTS. We propose that a combination of factors such as body fatigue, chronic pain, and other somatic symptoms common in POTS patients might be the underlying reason for sleep-related symptoms in POTS.
View details for DOI 10.1007/s10286-015-0331-9
View details for PubMedID 26695400
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Disproportionate pupillary involvement in diabetic autonomic neuropathy
CLINICAL AUTONOMIC RESEARCH
2014; 24 (6): 305-309
Abstract
To study the degree of pupillary impairment in diabetic and non-diabetic autonomic neuropathy.We retrospectively sampled from all patients who underwent comprehensive autonomic testing and infrared pupillometry at UT Southwestern Medical Center. Composite autonomic severity score (CASS) and pupillary indices from the average of at least three pupillary response curves were recorded. We randomly matched patients with diabetic autonomic neuropathy (DAN) and patients with autonomic impairment unrelated to diabetes (non-DAN) based on gender, age (±5 years), and CASS (±1 point). We used the paired t test to analyze differences between the groups.We identified 40 patients with DAN and 40 matched controls with non-DAN. M:F ratio was 1:1. Mean CASS was 4.2 and mean age was 62.4 years. Six had type I and the rest had type II diabetes mellitus. Both absolute constriction amplitude (ACA) and maximum constriction velocity (MCV) were significantly lower in DAN compared to non-DAN; mean ACA was 0.9 mm vs. 1.17 mm (p = 0.0077) and mean MCV was 2.8 vs. 3.6 mm/s (p = 0.0039). Severely diminished MCV for age was noted in 48 % of diabetic and in only 28 % of non-DAN patients. The ACA-corrected time to 75 % re-dilation was significantly delayed in DAN vs. non-DAN [mean 3.2 vs. 1.7 s/mm (p = 0.025)]. A statistically significant decline was noted for both the MCV and ACA with higher cardiovagal subscores among DAN patients.Parasympathetic and sympathetic pupillary dysfunction appears to be a common feature of autonomic impairment in diabetes compared to non-diabetic causes of autonomic impairment.
View details for DOI 10.1007/s10286-014-0258-6
View details for Web of Science ID 000346021400010
View details for PubMedID 25377131