Ichiro Nakashima

Tohoku Medical and Pharmaceutical University · Division of Neurology

Objective To evaluate the degree of severity and disability progression in Japanese patients with multiple sclerosis (MS) using descriptive study methods.Methods Postal questionnaires were sent to patients through three Japanese MS patients' associations. Survey participants were asked to evaluate their disability and MS severity based on two scale...

Anti-myelin oligodendrocyte glycoprotein (MOG) antibody, which is specifically detected using a cell-based assay (CBA), has been identified in various demyelinating diseases, including neuromyelitis optica spectrum disorders (NMOSD), acute idiopathic optic neuritis (ON), and pediatric multiphasic disseminated encephalomyelitis. Although its pathoge...

The protein profiles in the cerebrospinal fluid of 10 patients with multiple sclerosis (MS), 10 patients with neuromyelitis optica (NMO), 8 inflammatory disease control patients, and 4 noninflammatory disease control patients were screened by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Peaks of 12.5 kDa were signi...

This study investigates the relation between the serological status of NMO (neuromyelitis optica)-IgG and the clinical and MRI features in Japanese patients with multiple sclerosis. Serum NMO-IgG was tested in 35 Japanese patients diagnosed with multiple sclerosis, including 19 with the optic-spinal form of multiple sclerosis (OSMS), three with the...

To evaluate the association between callosal or periventricular lesions, and the presence of oligoclonal IgG bands (OB) or the IgG index in Japanese patients with multiple sclerosis (MS). Brain magnetic resonance imaging (MRI) was studied in 34 Japanese clinically definite MS cases. Sagittal 2-mm fast fluid-attenuated inversion-recovery (FLAIR) ima...

Aims We conducted a questionnaire survey on Japanese MS patients to determine the relationship of fatigue, depression, and physical activity limitations with employment status. Materials and methods The study was conducted to assess the Patient Reported Outcome of MS patients treated with disease-modifying drug ≥6 months by recruiting MS patients...

Background and Purpose Slowly expanding lesions (SELs) have been proposed as novel MRI markers of chronic active lesions in multiple sclerosis (MS). However, the mechanism through which SELs affect brain volume loss in patients with MS remains unknown. Additionally, the prevalence and significance of SELs in Asian patients with MS remain unclear. T...

Objectives: In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD. Me...

Satralizumab, an anti-interleukin-6 receptor antibody, is approved in Japan for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD) and is undergoing post-marketing surveillance (PMS) of clinical use. We aimed to describe the real-world safety and effectiveness of satralizumab in Japanese patients with NMOSD. This is an ongoing PMS...

A 79-year-old woman presented with difficulty walking and disturbance of consciousness. Magnetic resonance imaging revealed diffuse white matter lesions and abnormal signals along the surface of the brain and sulci. A brain biopsy revealed granulomatous vasculitis with eosinophil infiltration. There was no peripheral blood eosinophilia or evidence...

Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years),...

Background To determine which disease-modifying therapies should be used in patients with multiple sclerosis (MS), identifying patients at high and low risk for brain volume loss (BVL) is important. Although the BVL rate in MS is nearly constant from early to late disease onset, regardless of the disease stage, individual differences have been note...

Objective To assess the pharmacokinetics and pharmacodynamics of the long-acting terminal complement 5 (C5) inhibitor ravulizumab in adults with anti-aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) in the phase 3, open-label CHAMPION-NMOSD trial (NCT04201262). Methods Patients aged 18 years or older received a...

Impaired cognitive processing speed is among the important higher brain dysfunctions in multiple sclerosis (MS). However, the exact structural mechanisms of the dysfunction remain uncertain. This study aimed to identify the brain regions associated with the impaired cognitive processing speed in MS by comparing the cognitive processing speed, measu...

In recent years, there is growing evidence of associations between antibodies against myelin oligodendrocyte glycoprotein (MOG) and several phenotypes of acute inflammatory demyelinating diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis, brainstem, and cerebral cortical encephalitis, called MOG antibody associated disorde...

Objective: Electrolyte disorders are among the important conditions negatively affecting the disease course of neuromyelitis optica spectrum disorder (NMOSD). Possible mechanisms may include renal tubular acidosis (RTA) accompanying Sjögren's syndrome (SS), syndrome of inappropriate antidiuretic hormone secretion (SIADH), and central diabetes insi...

Background The terminal complement C5 inhibitor eculizumab is approved in Japan for relapse prevention in aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and is undergoing mandatory post-marketing surveillance (PMS) of clinical use. Objectives The objective of the study is to assess the real-world, long-term sa...

Treatments for acute attacks of neuromyelitis optica (NMO) include steroid pulse therapy, plasma exchange, and intravenous immunoglobulin. Oral immunosuppressants, such as prednisolone and azathioprine, have also been used to prevent relapse. Recently, biologic agents such as eculizumab, satralizumab, inebilizumab, and rituximab have been approved...

Background: A few case reports have described patients with myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelinating syndrome who presented with symptoms of aseptic meningitis. All such patients required immunotherapy. We report a patient with MOG-Ab-associated disorder (MOGAD) who presented with symptoms of aseptic meningiti...

Anti-aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and Sjögren syndrome (SS) are likely comorbidities. However, the exact effects of age and disease duration on the positivity rates of serum anti-Ro/SSA and anti-La/SSB (anti-SSA/SSB) antibodies and the presence of sicca symptoms in patients with AQP4-IgG re...

White blood cell (WBC) count profiles in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are still unknown. This study evaluated the total WBC count, differential WBC counts, monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-l...

Background: To our knowledge, no nationwide epidemiological study of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been conducted. Objective: We examined the epidemiology and clinical features of MOGAD in Japan. Methods: We distributed questionnaires on the clinical characteristics of patients with MOGAD to neurol...

Objective: CHAMPION-NMOSD (NCT04201262) is a phase 3, open-label, externally controlled interventional study evaluating the efficacy and safety of the terminal complement inhibitor ravulizumab in adult patients with anti-aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). Ravulizumab binds the same complement comp...

A method that can be used in the early stage of multiple sclerosis (MS) to predict the progression of brain volume loss (BVL) has not been fully established. Thus, to develop a method of predicting progressive BVL in patients with MS (pwMS), eighty-two consecutive Japanese pwMS—with either relapsing-remitting MS (86%) or secondary progressive MS (1...

Background The autoantibody to myelin oligodendrocyte glycoprotein (MOG), a component of the central nervous system myelin, has been identified in a subset of demyelinating diseases. However, there is no convincing evidence to support the direct pathogenic contribution of this autoantibody. Objective To elucidate the role of anti-MOG autoantibodie...

Objective NA. Background Eculizumab is well tolerated and significantly reduces relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). We report eculizumab's long-term relapse-risk-reduction efficacy and safety in AQP4+ NMOSD during PREVENT ( NCT01892345 ) and its...

Objective NA. Background The terminal complement C5 inhibitor eculizumab is approved in Japan for the prevention of aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) relapse and undergoing mandatory post-marketing surveillance (PMS) of real-world use. Design/Methods This PMS interim analysis assessed eculizumab'...

Introduction This study aims to investigated for the first time the role of myeloid-derived suppressor cells (MDSCs) in metastatic-hormone sensitive prostate cancer (mHSPC), which has not been investigated previously. Materials and methods This was a prospective observational cohort study. MDSC subsets in peripheral blood samples were classified a...

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals wi...

More than 2 years have passed since the outbreak of coronavirus disease 2019 (COVID-19), but there is still no sign that the COVID-19 pandemic has ended. Although vaccines have shown high efficacy against severe acute respiratory syndrome coronavirus 2, a risk of adverse reactions and thrombosis has also been reported. Here we review the current kn...

Calculating the crude or adjusted annualized relapse rate (ARR) and its confidence interval (CI) is often required in clinical studies to evaluate chronic relapsing diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorders. However, accurately calculating ARR and estimating the 95% CI requires careful application of statistic...

Objective The patterns of relapse and relapse-prevention strategies for anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not completely investigated. We compared the patterns of relapse in later stages of MOGAD with those of anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD)....

Background Unilateral cerebral cortical encephalitis (UCCE) with myelin oligodendrocyte glycoprotein (MOG) antibody comprises a new spectrum of disease entities that are characterized by unilateral cerebral cortical T2-weighted fluid-attenuated inversion recovery (T2 FLAIR) hyperintense lesions on MRI. Methods In this retrospective study, the brai...

Background Retinal atrophy in the chronic phase of optic neuritis (ON) in anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains unclear. Methods Patients with these diseases were repeatedly evaluated using optical coherenc...

Introduction: This study aims to investigate the role of myeloid-derived suppressor cells (MDSCs) in metastatic-hormone sensitive prostate cancer (mHSPC). Materials and methods: MDSC subsets in peripheral blood samples were classified and evaluated by flow cytometry into early MDSCs (e-MDSCs), polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSC...

Objective The aim of the RIN-2 study was a compassionate use of rituximab (RTX) for patients who completed the RIN-1 study, a multicentre, randomised, double-blind, placebo-controlled trial of RTX. We also investigated the long-term safety and efficacy of RTX. Methods A study design was a prospective open-label extension study following the RIN-1...

Objectives To describe the case of an ischemic stroke patient with Klippel-Feil syndrome who developed multiple aneurysms and discuss the mechanism of aneurysm development. Materials and Methods A 44-year-old man presented with dizziness, left hemiparesis, and left-sided numbness and was admitted to our department. He developed multiple aneurysms...

Background: Two-dimensional (2D) measures have been proposed as potential proxy measures for whole-brain volume in multiple sclerosis (MS); however, cut-off values that determine the degree of brain volume loss (BVL) have not been established. Since we had previously developed a system to categorize MS patients into clusters with significantly dif...

Background Two-dimensional (2D) measures have been proposed as potential proxies for whole-brain volume in multiple sclerosis (MS). Objective To verify whether 2D measurements by routine MRI are useful in predicting brain volume or disability in MS. Methods In this cross-sectional analysis, eighty-five consecutive Japanese MS patients—relapsing-r...

Background and Objectives To analyze (1) the effect of immunoglobulin G (IgG) from patients with anti–myelin oligodendrocyte glycoprotein antibody (MOG-Ab)–associated disorder on the blood-brain barrier (BBB) endothelial cells and (2) the positivity of glucose-regulated protein 78 (GRP78) antibodies in MOG-Ab–associated disorders. Methods IgG was...

Introduction: We aimed to determine whether in vivo tau deposits and monoamine oxidase B (MAO-B) detection using ¹⁸ F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD) and whether ¹⁸ F-THK5351 retenti...

Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system; however, its exact mechanism is unknown. This study aimed to elucidate the profile of white blood cells (WBCs) in the acute phase of an MS attack. Sixty-four patients with MS at the time of diagnosis and 2492 age- and sex-adjusted healthy controls (HCs) were enr...

IntroductionNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease defined by attacks on the central nervous system that cause irreversible damage. Recent approval of NMOSD therapies warrants investigations of comparative efficacy to inform treatment decisions.MethodsA network meta-analysis (NMA) of all U.S. Food and Drug Administr...

Vaccine administration may be involved in the development of some central nervous system demyelinating diseases. The COVID-19 vaccine is being administered to the entire population, but to date, little association between vaccination and the risk of developing multiple sclerosis (MS) has been suggested, and only a few case reports have been publish...

Multiple sclerosis (MS) is an inflammatory disease of unknown etiology in the central nervous system characterized by dissemination in time and space. Difficulties are associated with definitively diagnosing MS early because there are no disease-specific symptoms or diagnostic markers; therefore, a comprehensive judgment to differentiate MS from ot...

During PREVENT (a phase 3, randomized, double-blind, placebo-controlled, time-to-event study) and its open-label extension (interim analysis), 33 adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD) received eculizumab monotherapy for a median of 2.8 years (range, 14 weeks–5.2 years). At 192 we...

A 74‐year‐old woman with a 13‐year history of pemphigoid under treatment with oral prednisolone suffered from left herpes zoster ophthalmicus (HZO) complicated by keratitis and started treatment with acyclovir. A few days later, she developed left‐sided ocular complications, including reduced visual acuity, fixed pupil, ptosis, and complete ophthal...

Introduction Optic neuritis (ON) is a major phenotype of clinical attack related to demyelinating neurological diseases of the central nervous system, including multiple sclerosis (MS), anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD), and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (...

Background: The clinical severity of Sandhoff disease is known to vary widely. Furthermore, long-term follow-up report is very limited in the literature. Case presentation: We present a long-term follow-up report of a patient with juvenile-onset Sandhoff disease with a motor neuron disease phenotype. The patient had compound heterozygous variant...

Objective To evaluate the degree of neuroaxonal injury in Japanese multiple sclerosis (MS) patients using serum neurofilament light (sNfL) and to investigate the relationship of sNFL with the degree of brain volume. Methods sNfL levels in 82 consecutive Japanese MS patients in remission were cross-sectionally evaluated using a single molecule arra...

Rheumatoid meningitis (RM) is a rare central nervous system manifestation of rheumatoid arthritis (RA). A meningeal biopsy is useful for diagnosis but is invasive and not very sensitive. We report about a patient with RM who was diagnosed using indices of anti‐cyclic citrullinated peptide (CCP) antibody and anti‐galactose‐deficient IgG antibody (ca...

Background : Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy characterized by aquaporin-4 antibodies, whose prognosis is influenced by onset age, race, environmental exposures and immunosuppression. Distinguishing the contribution of environment from genetics is challenging. We aimed to compare neuromyelitis optica sp...

Background Neuro-Behçet's disease (NBD) is typically characterized by inflammatory lesions with vasculitis in the brainstem and basal ganglia. Subcortical white matter lesions and linear lesions along the intramedullary trigeminal nerve are rare, and these lesions make NBD difficult to differentiate from other demyelinating diseases, such as multip...

Objective To elucidate the differences in the source and in the level of intrathecal synthesis between anti-aquaporin-4 antibodies (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). Methods Thirty-eight patients with MOG-IgG-associated disease and 36 with AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD)...

Anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease belongs to a new spectrum of disease entities that cause acute inflammatory demyelinating lesions in the central nervous system. MOG antibody-associated disease presents with several phenotypes including optic neuritis, myelitis, neuromyelitis optica spectrum disorder, brain...