心血管领域-心律失常方向

METHODS::Guillain-Barré syndrome (GBS) is an acute, monophasic, polyradiculoneuropathy usually provoked by a preceding infection. The cardinal features are progressive weakness in the upper and lower limbs accompanied by loss of deep tendon reflexes. The diagnosis is made on the basis of the clinical history and examination findings, supported by typical cerebrospinal fluid and electrophysiology findings. Trauma and surgery are well understood but rare precipitants of GBS, which clinicians should be aware of, in order not to miss an opportunity to use immunomodulatory therapies. Furthermore, the presence of postsurgical or post-traumatic GBS should prompt careful assessment for underlying malignancy or autoimmune disease associated with an acute demyelinating polyradiculoneuropathy. Here, we present a case of post-traumatic GBS and discuss the potential mechanisms that might underlie this, as well as the investigations and treatment that should be considered.

METHODS::Cerebral vasculitis is a serious complication of bacterial meningitis that can cause significant morbidity and mortality due to stroke. Currently, there are no treatment guidelines or safety and efficacy studies on the management of cerebral vasculitis in this context. Herein, we report a case of a previously well 11-year-old girl who presented with acute otitis media that progressed to mastoiditis and fulminant meningitis. Group A Streptococcus was found in blood and ear-fluid cultures (lumbar puncture was unsuccessful). Her decreased level of consciousness persisted despite appropriate antimicrobial treatment, and repeat MRI revealed extensive large vessel cerebral vasculitis. Based on expert opinion and a presumed inflammatory mechanism, her cerebral vasculitis was treated with 7 days of pulse intravenous methylprednisolone followed by oral prednisone taper. She was also treated with intravenous heparin. Following these therapies, she improved clinically and radiographically with no adverse events. She continues to undergo rehabilitation with improvement.

METHODS:BACKGROUND/PURPOSE:Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan. METHODS:In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR). RESULTS:Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 103/uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353. CONCLUSION:Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan.

METHODS:OBJECTIVE:To explore the clinical efficacy and safety of subcutaneous (SC) rozanolixizumab, an anti-neonatal Fc receptor humanized monoclonal antibody, in patients with generalized myasthenia gravis (gMG). METHODS:In this phase 2a, randomized, double-blind, placebo-controlled, 2-period, multicenter trial (NCT03052751), patients were randomized (1:1) in period 1 (days 1-29) to 3 once-weekly (Q1W) SC infusions of rozanolixizumab 7 mg/kg or placebo. In period 2 (days 29-43), patients were re-randomized to either rozanolixizumab 7 mg/kg or 4 mg/kg (3 Q1W SC infusions), followed by an observation period (days 44-99). Primary endpoint was change from baseline to day 29 in Quantitative Myasthenia Gravis (QMG) score. Secondary endpoints were change from baseline to day 29 in MG-Activities of Daily Living (MG-ADL) and MG-Composite (MGC) scores and safety. RESULTS:Forty-three patients were randomized (rozanolixizumab 21, placebo 22 [period 1]). Least squares (LS) mean change from baseline to day 29 for rozanolixizumab vs placebo was as follows: QMG (LS mean -1.8 vs -1.2, difference -0.7, 95% upper confidence limit [UCL] 0.8; p = 0.221; not statistically significant), MG-ADL (LS mean -1.8 vs -0.4, difference -1.4, 95% UCL -0.4), and MGC (LS mean -3.1 vs -1.2, difference -1.8, 95% UCL 0.4) scores. Efficacy measures continued to improve with rozanolixizumab 7 mg/kg in period 2. The most common adverse event in period 1 was headache (rozanolixizumab 57%, placebo 14%). CONCLUSION:Whereas change from baseline in QMG was not statistically significant, the data overall suggest rozanolixizumab may provide clinical benefit in patients with gMG and was generally well tolerated. Phase 3 evaluation is ongoing (NCT03971422). CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that for patients with gMG, rozanolixizumab is well-tolerated, but did not significantly improve QMG score.

METHODS:OBJECTIVE:To test the hypothesis that autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) is safe and shows efficacy in the treatment of stiff-person spectrum disorder (SPSD). METHODS:Twenty-three participants were treated in a prospective open-label cohort study of safety and efficacy. After stem cell mobilization with cyclophosphamide (2 g/m2) and filgrastim (5-10 µg/kg/d), participants were treated with cyclophosphamide (200 mg/kg) divided as 50 mg/kg IV on day -5 to day -2; rabbit anti-thymocyte globulin (thymoglobulin) given intravenously at 0.5 mg/kg on day -5, 1 mg/kg on days -4 and -3, and 1.5 mg/kg on days -2, and -1 (total dose 5.5 mg/kg); and rituximab 500 mg IV on days -6 and +1. Unselected peripheral blood stem cells were infused on day 0. Safety was assessed by survival and National Cancer Institute common toxicity criteria for adverse events during HSCT. Outcome was assessed by ≥50% decrease or discontinuation of antispasmodic drugs and by quality of life instruments. RESULTS:There was no treatment-related mortality. One participant died 1 year after transplantation of disease progression. Of the 74% of participants who responded, 47% have stayed in remission for a mean of 3.5 years; 26% did not respond. Compared to nonresponders, responders were more likely to have pretransplantation intermittent muscle spasms (16 of 17 vs 0 of 6), normal reflexes (12 of 17 vs 0 of 6), and positive CSF anti-glutamic acid decarboxylase serology (12 of 14 vs 2 of 6). Compared to responders, nonresponders were more likely to have lead pipe rigidity (4 of 6 vs 0 of 17) and EMG-documented simultaneous contraction of agonist/antagonist limb muscles (4 of 6 vs 1 of 17). Pre-HSCT use of prescription serotonin selective receptor inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) was more common in those who relapsed or never responded (9 of 12) compared to those responders who never relapsed (0 of 11). CONCLUSION:In this cohort, HSCT was safe, but the beneficial effect of HSCT was variable and confined predominately to participants with episodic spasms and normal tendon reflexes without simultaneous cocontraction of limb agonist/antagonist muscles who were not taking SSRI or SNRI antidepressants. CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that, for a subset of people with SPSD, autologous nonmyeloablative HSCT improves outcomes. CLINICALTRIALSGOV IDENTIFIER:NCT02282514.

METHODS:OBJECTIVE:To determine whether hospital-diagnosed and community-treated infections are important Guillain-Barré syndrome (GBS) risk factors, we investigated the magnitude and duration of associated GBS risk. METHODS:We conducted a nationwide population-based case-control study of all patients with first-time hospital-diagnosed GBS in Denmark between 1987 and 2016 and 10 matched population controls per case. Hospital-diagnosed infections were determined in the 1987-2016 period and community antibiotic prescriptions in the 2004-2016 period. We used conditional logistic regression to examine the relative risk of GBS associated with having a recent infection. RESULTS:Hospital-diagnosed infections within 60 days were observed in 4.3% of 2,414 GBS cases vs 0.3% of 23,909 controls, with a matched odds ratio (OR) of 13.7 (95% confidence interval [CI], 10.2-18.5). The strongest association with subsequent GBS was observed for lower respiratory tract infection, gastrointestinal tract infection, and septicemia. Community antibiotic prescriptions within 60 days were observed in 22.4% of 1,086 GBS cases and 7.8% of 10,747 controls, with a matched OR of 3.5 (95% CI, 3.0-4.1). The risk of GBS declined considerably with time since infection, with high ORs of 21.3 (95% CI, 14.5-31.2) and 4.7 (95% CI, 3.9-5.7) observed within the first month after a hospital-diagnosed infection and a community antibiotic prescription, respectively. However, GBS risk remained increased 2.4-fold (95% CI, 1.1-5.5) and 1.5-fold (95% CI, 1.2-2.0) even in the fifth month after infection. CONCLUSION:There is a strong, temporal association between community antibiotic use and especially infections necessitating hospitalization and risk of subsequent GBS.

METHODS::An 80-year-old, previously healthy patient presents with acute transverse myelitis with sensory level at T8. The MRI scan of the spinal cord showed longitudinal extensive transverse myelitis, and she tested positive for aquaporin 4 antibodies in serum. She received treatment with intravenous and oral steroids, with no improvement and then underwent plasma exchange. She was then started on azathioprine for prevention of relapses, while continuing physiotherapy and occupational therapy. Eventually, she was transferred to a specialised spinal cord centre for long-term rehabilitation.

METHODS::Miller Fisher syndrome (MFS), an acute demyelinating neuropathy, is characterised by a triad of areflexia, ataxia and ophthalmoplegia. It is the most common variant of Guillain-Barre Syndrome (GBS). In about 5.6%-7.1% of MFS cases, patients also suffer from progressive motor weakness of the limbs. This condition is termed MFS/GBS overlap syndrome. Whether it is in MFS or GBS, bilateral vocal cord paralysis (BVCP) is a rare manifestation with limited cases reported in the literature. We report an extremely rare case where a 65-year-old man developed BVCP in an MFS/GBS overlap syndrome. We have also reviewed previous case reports in the literature for comparison.

METHODS::Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are considered 2 diseases on the same spectrum due to their many underlying similarities. In recent years, both diseases have witnessed both diagnostic and treatment advances, which shaped the way we manage them. In this article, the authors focus on different diagnostic modalities in GCA as well as the presence of different clinical phenotypes and the role of screening for aortic involvement. The authors also discuss traditional treatments and the role of evolving steroid-sparing agents in the management of both GCA and PMR.

METHODS::A previously fit and well 53-year-old man was referred to the otolaryngology clinic with intermittent stridor and was found to have bilateral vocal fold paresis. Subsequent airway compromise necessitated emergency surgical tracheostomy. The man was discharged home with tracheostomy in situ and a diagnosis of idiopathic bilateral vocal cord palsy, as all primary investigations were negative. Neurological disease was suspected following readmission to hospital several weeks later with diplopia. Electromyography and serum antibody testing confirmed a diagnosis of anti-muscle-specific tyrosine kinase antibody positive myasthenia gravis (MuSK-MG); a subset of MG where autoantibodies are directed against MuSK. Resolution of bilateral vocal fold paresis was found 8 months after a short course of immunoglobulin (intravenous immunoglobulin (IVIg)) and daily mycophenolate therapy was commenced. Multidisciplinary teamwork between ear, nose and throat surgeons, neurologists and speech therapists enabled successful decannulation of tracheostomy. The patient has recovered well and remains minimally symptomatic.