Search

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

© 2020 Elsevier Ltd. All rights reserved., Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.

Progressive multifocal leukoencephalopathy (PML) is a rare viral demyelinating disease of central nervous system. Immunosuppression is a significant risk factor for the disease. Previously, PML developed more commonly in patients of hematological malignancy and acquired immune deficiency syndrome (AIDS). In the era of biological disease modifying anti-rheumatic drugs, PML is more frequently reported in patients of autoimmune diseases. However, for its rarity and unspecific clinical presentations, accurate diagnosis and immediate immune restoration might be difficult in clinical practice, and the outcome might thus be miserable. Herein we present a 27-year-old lady of systemic lupus erythematosus (SLE) – rheumatoid arthritis overlap syndrome with suspected involvement of central nervous system. Neuropsychiatric SLE was suspected first. However, after intensive immunosuppressive treatment, the condition kept deteriorating. An alternative diagnosis was thus considered. PML was suspected for her immunosuppressive status and suggestive radiological findings, and the diagnosis was confirmed by a polymerase chain reaction of JC virus from cerebrospinal fluid. After restoring the immune status by decreasing the dose of immunosuppressants, the condition of the patient improved significantly. We report this case to raise the importance of clinical alertness for the rare but possibly underdiagnosed disease. Keywords: Antirheumatic agents, Rheumatoid arthritis, Immunosuppressive agents, Progressive multifocal leukoencephalopathy, Systemic lupus erythematosus

A case report with a review of the current literature concerning cutaneous necrosis has occasionally been reported in interferon therapy.We report a 19-year-old woman diagnosed multiple sclerosis for three years. She selfinjected the standard dose of recombinant interferonβ-1a (12 million units) subcutaneously three times a week. Severe necrotizing cutaneous reactions over abdomen Happened and she must receive parental antibiotics and surgical debridement.Our observation emphasizes the importance of educating patients on the proper selfadministration of subcutaneous injections of interferon β.

BackgroundThe indications for lumbar puncture in non-HIV-infected, non-transplant (NHNT) patients with cryptococcosis without meningeal signs need to be more fully defined.ObjectivesThis study was designed to determine the optimal predictors of central nervous system (CNS) involvement in adult NHNT patients with cryptococcosis.MethodsThe study population consisted of adult NHNT patients with culture-confirmed cryptococcosis who sought care at a university hospital in Taiwan from 2002 to 2016. We used a case-control method to identify the clinical characteristics and laboratory findings associated with CNS involvement in patients who underwent a diagnostic lumbar puncture. In the sensitivity analysis, we included additional control patients who did not undergo lumbar puncture, but were followed beyond 12 months without the development of CNS involvement in the absence of exposure to any fungicidal agents.ResultsWe entered 270 NHNT adult patients into the study during the 15-year period. CNS involvement was confirmed in 66 (71.0%) of 93 patients who underwent lumbar puncture. A multivariable analysis revealed that presence of neurological manifestations and elevated serum CRAG titers were independently associated with a 23.97-fold (95% confidence interval [CI], 4.37-182.23) and 1.53-fold (per 2-fold increment, 95% CI 1.26-1.92) increased odds ratio for CNS involvement, respectively. Headache and focal neurologic signs were independently associated with CNS involvement. A cut-off serum CRAG titer of ≥1:64 provided the highest diagnostic performance by Youden index (sensitivity 83% and specificity 65%). Similar findings were noted in the sensitivity analysis including 198 (73%) patients.ConclusionLumbar puncture is indicated for NHNT patients with cryptococcosis who have neurologic manifestations or a serum CRAG titer of ≥1:64.

Persistent Helicobacter pylori (H. pylori) infection is a chronic inflammatory stimulus to hosts with an inverse correlation to atopic disorders. In this study, a total of 105 consecutive multiple sclerosis (MS) patients were divided into 52 opticospinal MS (OSMS) and 53 conventional MS (CMS), and their sera, along with those from 85 healthy controls (HC), were examined by an enzyme-linked immunosorbent assay using antibodies against H. pylori. H. pylori seropositivity was significantly lower in patients with CMS (22.6%) compared with HC (42.4%) and patients with OSMS (51.9%) (p=0.0180 and p=0.0019, respectively). In patients with CMS, H. pylori seropositivity showed a significant inverse association with mean EDSS score and fulfillment of McDonald MRI criteria for space (OR=0.61, p=0.0344 and OR=0.11, p=0.0297). These findings suggest that H. pylori infection is a protective factor against CMS in Japanese.

Vascular permeability changes precede the development of demyelinating lesions in multiple sclerosis (MS), and vessel wall thickening and capillary proliferation are frequently seen in autopsied MS lesions. Although vascular growth factors are critical for inducing such vascular changes, their involvement in MS has not been extensively studied. Thus, we examined the involvement of various vascular growth factors in MS according to their clinical phase and subtype. We measured serum levels of vascular endothelial growth factor (VEGF), acidic and basic fibroblast growth factors (FGF) and platelet-derived growth factors (PDGFs)-AA, -AB and -BB in 50 patients with MS (27 opticospinal MS and 23 conventional MS patients) and 33 healthy controls using sandwich enzyme immunoassays. Correlations between growth factor changes and brain and spinal cord MRI findings were then analyzed. Serum VEGF concentrations were significantly higher in MS patients in relapse than in controls (p = 0.0495) and in MS patients in remission (p = 0.0003), irrespective of clinical subtype. Basic FGF was significantly increased in conventional MS patients, but not opticospinal MS patients compared with controls (p = 0.0291), irrespective of clinical phase. VEGF at relapse showed a significant positive correlation with the length of spinal cord lesions on MRI (r = 0.506, p = 0.0319). The results suggest that an increase in serum VEGF concentration might be involved in MS relapse and the formation of longitudinally extensive spinal cord lesions.

Andersen-Tawil syndrome (ATS) is a rare familial potassium channelopathy characterized by the clinical triad of periodic paralysis, cardiac arrhythmia and dysmorphic facial/skeletal features. The majority of ATS patients are caused by mutations of the KCNJ2 gene, which encodes the inward-rectifying potassium channel protein Kir2.1. However, the effects of the KCNJ2 mutation on the central nervous system are rarely studied. In this report, we describe a heterozygous missense mutation (p.Thr192Ile) in the KCNJ2 gene, which segregates with the disease phenotype in an ATS family. It is noted that in addition to the classical clinical phenotypes of ATS, the index patient exhibited major depression and pyramidal tract signs with diffuse periventricular white matter lesions without contrast enhancement. This mutation and the unusual clinical manifestations observed underscore the phenotypic complexity underlying ATS. Our observations expand the current knowledge of the phenotypic variability of ATS caused by the KCNJ2 mutation. Patients with ATS, especially those carrying the KCNJ2 mutations, should be monitored for their potential neuropsychiatric system involvement.

Case reports with a comprehensive review of the current literature concerning subacute combined degeneration induced by nitrous oxide inhalation. A differential diagnosis should be considered when young patients present with progressive myelopathy because that the misuse of nitrous oxide has potentially serious outcomes.Three young patients aged from 18 to 24, one male and two females, were diagnosed with progressive ascending numbness in four limbs or both legs and ataxia. They all had been inhaling nitrous oxide from whipped-cream containers for several months. A cervicothoracic magnetic resonance imaging scan revealed long segmental hyperintensity changes at the posterior column of the spinal cord. Serological examination showed a low level of vitamin B12. Subacute combined degeneration of the spinal cord was diagnosed and the etiology was considered related to nitrous oxide misuse. Their neurological status, neuroimage, and neurophysiologic condition improved after vitamin B12 supplementation and cessation of nitrous oxide inhalation.Iatrogenic usage of nitrous oxide apparently resulted in subacute combined degeneration in our three patients. Recently, nitrous oxide misuse has increased among young people. Subacute combined degeneration of the spinal cord should be considered as a possible outcome of such abuse.

We present a case report and a comprehensive review of the literature concerning aseptic meningoencephalitis and Sjögren's syndrome (SS).We report a 44-year-old woman of primary SS with initial presentation of aseptic meningoencephalitis and a reversible magnetic resonance image (MRI) lesion in the medulla. The diagnosis of primary SS based on ocular dryness, lacrimal hyposecretion, secretory and excretory dysfunction from sialocintigraphy, and positive anti-SS-A antibodies. Corticosteroid and cyclophosphamide therapies reversed the neurological deficits and the MRI lesion.Primary SS may have variable manifestations in the central nervous system which may precede the classic sicca symptoms. SS should be investigated in cases of aseptic meningoencephalitis even without clinical signs of xerostomia or xerophthalmia. MRI is useful in demonstrating brain lesions and in evaluating treatment efficacy of the SS.

There are two distinct subtypes of multiple sclerosis (MS) in Asians: opticospinal (OSMS) and conventional (CMS). OSMS has similar features to neuromyelitis optica (NMO) and half of OSMS patients have the NMO-Immunoglobulin G (IgG)/ anti-aquaporin-4 (AQP4) antibody. We reported that Helicobacter pylori (H. pylori) infection was significantly less common in CMS patients than controls. To reveal the immune responses to the H. pylori neutrophil-activating protein (HP-NAP) in Japanese MS patients, according to anti-AQP4 antibody status, sera from 162 MS patients, 37 patients with other inflammatory neurological diseases (OIND), and 85 healthy subjects were assayed for anti-H. pylori antibodies, anti-HP-NAP antibodies, and myeloperoxidase (MPO) by enzyme immunoassays. H. pylori seropositivity rates were significantly higher in anti-AQP4 antibody-positive MS/NMO (AQP4 + /MS) patients (19/27, 70.4%) than anti-AQP4 antibody-negative CMS (AQP4 — /CMS) patients (22/83, 26.5%). Among H. pylori-infected individuals, the anti-HP-NAP antibody was significantly more common in AQP4 + /MS and AQP4 — /OSMS patients than healthy subjects (36.8%, 34.6% versus 2.8%). Among the AQP4 + /MS patients, a significant positive correlation between anti-HP-NAP antibody levels and the final Kurtzke’s Expanded Disability Status Scale scores was found, and MPO levels were higher in anti-HP-NAP antibody-positive patients than anti-HP-NAP antibody-negative ones. Therefore, HP-NAP may be associated with the pathology of anti-AQP4 antibody-related neural damage in MS/NMO patients.

Cerebral venous thrombosis (CVT) has a wide spectrum of symptoms and is therefore difficult to diagnose. CVT has been reported to be associated with various etiologies. There are, however, very few reported cases of CVT associated with iron deficiency anemia (IDA), especially in adults.We reported the case of a female patient with seizure and hemorrhagic infarction due to sagittal sinus thrombosis. She had severe hypochromic microcytic anemia due to iron deficiency, and had a good prognosis after iron supplementation and oral anticoagulation therapy.The present case indicates that iron deficiency is a risk factor for CVT.