In Hye Jeong

Comparative analysis of treatment outcomes in patients with neuromyelitis optica spectrum disorder using multifaceted endpoints

Background: There is still an unmet need for comparative analyses of available treatment options for neuromyelitis optica spectrum disorder (NMOSD). Objective: We aimed to compare the efficacies of the immunosuppressants most commonly prescribed for patients with NMOSD using multifaceted endpoints. Methods: We conducted a retrospective analysis of treatment outcomes in 138 NMOSD patients treated with azathioprine, mycophenolate mofetil (MMF), or rituximab. The primary outcome measures were the annualized relapse rate (ARR), annualized severe relapse rate, time to first relapse, and time to first severe relapse. Results: A comparison of any relapse among the groups revealed that the azathioprine had a significantly higher risk of relapse relative to the rituximab (hazard ratio: 1.82; 95% CI: 1.1–3.1; p=0.03). A comparison of severe relapse among the groups revealed that the hazard ratios of severe relapse for the azathioprine and MMF relative to the rituximab were 11.66 (95% CI: 2.6–52.3; p=0.001) and 5.96 (95% CI: 1.0–35.1; p=0.048), respectively. The times to first relapse and first severe relapse were also significantly different among the treatment groups Conclusions: The present study showed that reductions in the risks of relapse and severe relapse differed among patients who were initially treated with azathioprine, MMF, and rituximab.

Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases.

Background We evaluated the seroprevalence of myelin oligodendrocyte glycoprotein immunoglobulin G1 (MOG-IgG) and associated clinical features of patients from a large adult-dominant unselected cohort with mainly relapsing central nervous system (CNS) inflammatory diseases. We also investigate the clinical relevance of MOG-IgG through a longitudinal analysis of serological status over a 2-year follow-up period. Methods Serum samples from 505 patients with CNS inflammatory diseases at the National Cancer Center were analysed using cell-based assays for MOG-IgG and aquaporin-4 immunoglobulin G (AQP4-IgG). MOG-IgG serostatus was longitudinally assessed in seropositive patients with available serum samples and at least 2 years follow-up. Results Twenty-two of 505 (4.4%) patients with CNS inflammatory diseases were positive for MOG-IgG. Patients with MOG-IgG had neuromyelitis optica spectrum disorder (NMOSD, n=10), idiopathic AQP4-IgG-negative myelitis (n=4), idiopathic AQP4-IgG-negative optic neuritis (n=4), other demyelinating syndromes (n=3) and multiple sclerosis (n=1). No relapses were seen in patients when they became MOG-IgG seronegative, whereas a persistent positive serological status was observed in patients with clinical relapses despite immunotherapy. Conclusions In a large adult-predominant unselected cohort of mainly relapsing CNS inflammatory diseases, we confirmed that NMOSD phenotype was most commonly observed in patients with MOG-IgG. A longitudinal analysis with 2-year follow-up suggested that persistence of MOG-IgG is associated with relapses.

A Longitudinal Brain Magnetic Resonance Imaging Study of Neuromyelitis Optica Spectrum Disorder

Brain involvement is commonly seen in patients with neuromyelitis optica spectrum disorder (NMOSD). However, little is known about the chronic changes of acute brain lesions on MRI over time. Here, our objective was to evaluate how acute brain MRI lesions in NMOSD changed on follow-up MRI. We reviewed the MRIs of 63 patients with NMOSD who had acute brain lesions and follow-up MRI over an interval of at least 3 months. Of the 211 acute brain lesions, 24% of lesions disappeared completely on T2-weighed images (WI) and a decrease in size ≥50% on T2-WI was observed in 58% of lesions on follow-up MRI. However, 47% of lesions revealed focal T1-hypointensity and, in particular, 18% showed focal cystic changes. Cystic changes were observed most commonly in corticospinal tract and corpus callosal lesions whereas the vast majority of lesions in the cerebellum, basal ganglia and temporal white matter resolved completely. MRI remission on T2-WI occurred in 82% of lesions, while approximately half of the lesions presented foci of T1-hypointensity, which may be considered a severe tissue injury over time. The extent of brain injury following an acute brain lesion in NMOSD may depend on the location of the lesion.

Tumefactive demyelinating lesions as a first clinical event: Clinical, imaging, and follow-up observations.

BACKGROUND Tumefactive demyelinating lesions (TDLs) are associated with a variety of demyelinating diseases in the central nervous system (CNS). However, there are no current guidelines describing how to classify and treat patients with this rare phenotype. Thus, the present study aimed to determine the long-term evolution and disease course of patients initially presenting with TDLs and to describe their clinical and radiographic characteristics. METHODS From the National Cancer Center registry of inflammatory diseases of the CNS, 31 patients initially presenting with TDLs with follow-up for at least 12 months were enrolled and their demographic, clinical, and radiographic characteristics were evaluated. RESULTS The median follow-up duration was 37.6 months, during which time 11 patients were diagnosed with neuromyelitis optica spectrum disorder (NMOSD), seven with multiple sclerosis (MS), and 11 remained idiopathic; six did not experience any further clinical events (isolated demyelinating syndrome), and five patients experienced recurrent demyelinating events that were not consistent with either MS or NMOSD. Of the remaining two patients, one was diagnosed with hyperthyroidism-associated demyelination and one with tacrolimus-induced demyelination. CONCLUSIONS The majority of TDLs evolve into MS or NMOSD. However, despite extensive diagnostic work-ups and long-term follow-ups, the etiology of TDLs was unknown for some patients.

Short segment myelitis as a first manifestation of neuromyelitis optica spectrum disorders

Background: Some patients with neuromyelitis optica spectrum disorders (NMOSD) present with spinal cord lesions extending fewer than three vertebral segments (short transverse myelitis, STM), hindering an early diagnosis. Objective: We investigated the frequency and imaging characteristics of STM lesions in patients presenting with myelitis as an initial manifestation of NMOSD. Methods: Patients seen at three referral hospitals in Korea between June 2005 and March 2015 who met the following inclusion criteria were recruited for review: seropositivity for aquaporin-4 antibody, initial presentation with myelitis and spinal cord magnetic resonance imaging (MRI) performed within 1 month of initial myelitis onset. Results: Of the 76 enrolled patients, 65 (85.5%) collectively had 69 longitudinally extensive transverse myelitis lesions, while the remaining 11 (14.5%) had a total of 15 STM lesions. Of the 15 STM lesions, 5 spanned 2.5 vertebral segments, 6 were continuous over two segments, 3 showed a length of 1.5 segments and 1 was confined to a single segment. On axial imaging, all of the STM lesions involved the central grey matter. Conclusion: These MRI findings suggested that STM does not preclude the possibility of an NMOSD diagnosis.

Bright spotty lesions on the spinal cord: an additional MRI indicator of neuromyelitis optica spectrum disorder?

Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disease of the central nervous system (CNS), thus, an early and accurate diagnosis is important.1 The aquaporin-4 (AQP4) antibody is a specific marker of NMOSD that has generally modest sensitivity but is not always available in time. The radiological characteristics, such as longitudinally extensive transverse myelitis (LETM), are helpful in the diagnosis, but LETM is not a pathognomonic feature of NMOSD. Therefore, it would be good to identify the other specific features associated with NMOSD. Bright spotty lesions (BSLs) on spinal MRIs have recently been identified as a discriminative feature that distinguishes NMOSD from multiple sclerosis (MS).2 However, previous study was conducted with a small number of patients and the timing of the MRIs was not controlled. Furthermore, it has not been investigated whether BSLs may help to discriminate NMOSD from other entities, such as idiopathic transverse myelitis (ITM), which share many similar features with NMOSD. Thus, the present study investigated whether BSLs can be utilised as a discriminative feature of NMOSD to distinguish it from MS and ITM in a large cohort of patients with myelitis, particularly during the acute phases. A total of 114 patients, who presented with acute myelitis and underwent spinal MRIs (≤3 weeks since the latest clinical attack), were enrolled from the National Cancer Centre registry of CNS idiopathic inflammatory diseases between 2005 and 2014. Of 114 patients, 59 patients with NMOSD were positive for AQP4 antibody, 31 patients met the McDonald criteria for MS and 24 patients fulfilled the criteria for ITM.3 All patients with MS and ITM were negative for AQP4 antibody following repeated assays of three different methods.4 Myelin-oligodendroglycoprotein (MOG) antibodies were also tested using a cell-based assay at Tohoku University and all patients were negative for MOG antibodies.4 …

Utility of the rio score and modified rio score in korean patients with multiple sclerosis.

Objectives Early identification of suboptimal responders to multiple sclerosis (MS) treatment is critical for optimizing therapeutic decisions. The Rio score (RS) and modified Rio score (MRS) were developed to discriminate the responses to interferon-beta (IFNB) treatment in MS patients. This study was performed to evaluate the utility of RS and MRS in daily clinical practice in Korea. Methods This was a real-world setting, multicenter, retrospective study of MS patients treated with IFNB from 10 hospitals in Korea. We investigated whether the RS and MRS at the early stage of IFNB therapy could predict treatment responses over 3 years. Suboptimal treatment responses at 3 years were defined as the presence of clinical relapse and/or EDSS progression and/or patients who had been treated with INFB for at least for 1 year and therapy was switched due to perceived treatment failure during the 2 years of follow-up. Results Seventy patients (50 females and 20 males) were enrolled; 92% (12/13) of patients with high RS and 86% (12/14) of patients with high MRS (score 2 or 3) were suboptimal responders, whereas 93% (53/57) of patients with low RS and 93% (52/56) patients with low MRS (score 0 or 1) showed optimal responses. New active lesions on MRI with clinical relapse in high RS and MRS were the most common combination in suboptimal responders. Conclusions We confirmed that RS and MRS at 6–15 months of IFNB therapy were useful for predicting poor responders over 3 years.

Cerebral Cortex Involvement in Neuromyelitis Optica Spectrum Disorder

Background and Purpose Brain lesions involving the cerebral cortex are rarely described in patients with neuromyelitis optica spectrum disorder (NMOSD), in contrast to multiple sclerosis. We investigated cerebral cortex involvement using conventional brain magnetic resonance imaging (MRI) in anti-aquaporin-4 (AQP4)-antibody-positive NMOSD patients. Methods The study enrolled 215 NMOSD patients who were seropositive for the anti-AQP4 antibody from 5 referral hospitals, and retrospectively analyzed their demographic, clinical, and MRI findings. Abnormal cerebral cortex lesions on brain MRI were identified by a neuroradiologist and two neurologists using consensus. Results Most of the 215 enrolled patients (87%) were female. The median age at onset was 22.5 years (range: 15–36 years) and the mean follow-up duration was 123 months. Brain lesions were found in 143 of 194 patients (74%) in whom MRI was performed during follow-up. Brain lesions involving the cerebral cortex were identified in 6 of these 194 patients (3.1%). Five of the patients were female, and the six patients together had a median age of 29 years (range: 15–36 years) at the time of lesion presentation. Three of them showed leptomeningeal enhancement in the lesions. At presentation of the cortex-involving lesions, five of these patients were not being treated at the time of presentation, while the sixth was being treated with interferon-beta. Conclusions Although rare, cortical involvement occurs in NMOSD and is commonly combined with leptomeningeal enhancement. We speculate that this occurs only in patients who are not treated appropriately with immunosuppressant drugs.

Metabolomic profiling of CSF in multiple sclerosis and neuromyelitis optica spectrum disorder by nuclear magnetic resonance

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are inflammatory diseases of the central nervous system. Although several studies have characterized the metabolome in the cerebrospinal fluid (CSF) from MS and NMOSD patients, comparative analyses between them and between the relapse and the remission of each disease have not been performed. Both univariate and multivariate analyses were used to compare 1H-NMR spectra of CSF from MS, NMOSD, and healthy controls (HCs). The statistical analysis showed alterations of eight metabolites that were dependent on the disease. Levels of 2-hydroxybutyrate, acetone, formate, and pyroglutamate were higher and levels of acetate and glucose were lower in both MS and NMOSD. Citrate was lower in MS patients, whereas lactate was higher in only NMOSD specifically. The shared feature of metabolic changes between MS and NMOSD may be related to altered energy metabolism and fatty acid biosynthesis in the brain. Another analysis to characterize relapse and remission status showed that isoleucine and valine were down-regulated in MS relapse compared to MS remission. The other metabolites identified in the disease comparison showed the same alterations regardless of disease activity. These findings would be helpful in understanding the biological background of these diseases, and distinguishing between MS and NMOSD, as well as determining the disease activity.

Increased frequency and severity of restless legs syndrome in patients with neuromyelitis optica spectrum disorder.

OBJECTIVES To investigate the comorbidity of restless legs syndrome (RLS) and neuromyelitis optica spectrum disorder (NMOSD). METHODS This study enrolled 159 NMOSD patients and 153 age- and gender-matched healthy controls. All participants completed a questionnaire based on the updated International Restless Legs Syndrome Study Group consensus criteria, the International RLS Severity scale, Epworth Sleepiness Scale, Fatigue Severity Scale, and Pittsburgh Sleep Quality Index, and were subsequently interviewed by a neurologist. The frequency and features of RLS were compared between NMOSD patients and healthy controls. The clinical and radiological characteristics of the NMOSD patients with and without RLS were also compared. RESULTS The frequency and severity of RLS were significantly higher in NMOSD patients than in healthy controls (p = 0.015 for both) and NMOSD patients with RLS had a longer disease duration and more severe disability than those without RLS. CONCLUSIONS This study indicated importance of considering RLS in NMOSD patients.