Myasthenia gravis (MG) is an autoimmune-mediated neurological disorder. The relationship between MG and thymic abnormalities is well recognized, and thymectomy is one of the therapies for anti-acetylcholine receptor antibody-positive MG. The major pathogenic factor is anti-acetylcholine receptor antibody followed by anti-muscle-specific kinase antibody, and commercial kits are available to detect these antibodies. Several decades ago, the prognosis of MG was not favorable; therefore, the Ministry of Health and Welfare (predecessor of the Ministry of Health, Labor and Welfare) organized a Taskforce for Intractable Diseases, which included MG, in 1972. The Taskforce carried out consecutive epidemiological studies for MG in 1973, 1987, 2006 and 2018. The four studies found: (i) increasing prevalence; (ii) increasing late- and elderly-onset; (iii) decreasing female dominancy; (iv) decreasing infantile-onset (onset age of 0–4 years); and (v) decreasing frequencies of crisis. The latest epidemiological study in Japan and studies from other countries suggest an increasing number of patients with anti-acetylcholine receptor antibody-positive MG without thymoma in the elderly. It is important to find out the causes of this phenomenon, which will improve the prevention of MG.
To investigate the frequency of serum autoantibodies targeting contactin-associated protein 1 (Caspr1) and its complexes with other paranode antigens, contactin-1 (CNTN1) and neurofascin 155 (NF155), in Japanese patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
Sera from 26 CIDP patients, 35 patients with Guillain–Barré syndrome, and 31 healthy individuals participated. Paranodal immunoglobulin G antibodies were quantified using enzyme-linked immunosorbent assays with commercially available recombinant proteins as antigens.
Anti-Caspr1 antibodies were present in one participant (case 1, 3.8%) of CIDP, and negative in all Guillain–Barré syndrome patients and healthy participant. Case 1 was a man who developed subacute distal limb-predominant muscle weakness and sensory ataxia with postural hand tremor at 69 years-of-age, and therapeutic benefit of intravenous immunoglobulin and oral steroids was inadequate. The detected anti-Caspr1 antibodies predominantly belonged to the immunoglobulin G4 subclass, and the addition of CNTN1 to Caspr1 as an antigen increased antibody reactivity, although the increase was just 20–30% at most. The presence of autoantibodies against paranode protein complexes, including Caspr1/CNTN1, Caspr1/NF155 and Caspr1/CNTN1/NF155, was confirmed in several CIDP patients, although they also had anti-Caspr1 or anti-NF155 antibodies; thus, in our cohort, there were no patients with autoantibodies that specifically recognized paranode protein complexes.
This is the first confirmed Japanese case of anti-Caspr1 antibody-positive CIDP with a clinical signature similar to that of patients of Western origin. Our preliminary study did not identify the presence of specific antibodies against the paranode protein complexes, and the primary target antigen is likely Caspr1.
Details regarding the clinical course of natalizumab-associated progressive multifocal leukoencephalopathy (NAT-PML) have not been reported in Japanese patients. We experienced a Japanese NAT-PML case and report it for the purpose of clarifying the challenge it posed in medical treatment.
Herein, we describe a 58-y-old multiple sclerosis patient who had NAT-PML with immune reconstitution inflammatory syndrome (IRIS). Before NAT-PML developed, the patient's Expanded Disability Status Scale (EDSS) score was 5.5. She received natalizumab (300 mg) every 3–7 w, and her EDSS score had not changed for 9.1 y. The John Cunningham virus (JCV) index was 0.43 before NAT-PML developed. She developed a gait disturbance when NAT-PML emerged. Natalizumab was administered a total of 108 times. The patient was diagnosed with probable NAT-PML on the basis of punctate lesions on T2-weighted imaging and a JCV-PCR result of 29 copies/ml from cerebrospinal fluid (CSF) testing. Intravenous methylprednisolone (IVMP) was initiated when the contrast-enhanced lesion was first detected, but the NAT-PML lesion was rather enlarged despite the temporary disappearance of the contrast-enhanced lesion. An obvious increase in the IgG index and a slight increase in the CSF cell count were recognized at the time the immunological response was activated. Three cycles of a 3-d course of IVMP were administered every 2 w for IRIS, and the patient's worst EDSS score was 9.5.
Treatment sequencing should be executed before the onset of NAT-PML. Changes in CSF cell count and IgG index may be useful for treatment decision; further research is needed.
To examine the chemokine profile in the cerebrospinal fluid (CSF) of patients with glial fibrillary acidic protein astrocytopathy (GFAP-A), central nervous system immune-related adverse event (CNS-irAE), neurosarcoidosis (NS), neuromyelitis optica spectrum disorders (NMOSD), multiple sclerosis (MS), and human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy (HAM).
The study included 38 patients presenting to St. Marianna University Hospital between May 2013 and November 2021 with GFAP-A, CNS-irAE, NMOSD, MS, NS, HAM and noninflammatory neurological diseases (NIND). We recorded the age, sex, duration of disease, brain/spinal lesions on magnetic resonance imaging (MRI), blood data, and measured chemokines (CXCL9, −10, −13, CCL3, −4, −17, −20, −22) in CSF. In patients with GFAP-A, clinical symptoms, and CSF CXCL10 levels were compared before and after steroid treatment.
Patients with GFAP-A had higher CSF levels of CXCL10, CXCL13, and CCL22 (10736.1 [8786.7–149079.0] pg/ml (p < .05), 378.4 [239.9–412.2] pg/ml (p < .01) and 159.9 [130.5–413.9] pg/ml (p < .01), respectively). The CSF levels of CXCL10 improved from 10736.1 [8786.7–149079.0] pg/ml to 1879.0 [783.9–4360.0] pg/ml in patients with GFAP-A by steroid therapy.
CSF CXCL10 levels were particularly high in GFAP-A, and changes in levels after treatment correlated with clinical improvements, suggesting CXCL10 involvement in GFAP-A pathogenesis.
The primary purpose of the Japanese myasthenia gravis registry (JAMG-R) has been to research and promote high-quality medical care for MG patients in Japan. We reviewed the findings of surveys performed by JAMG-R over an ~10-y period. The first goal for favorable quality of life (QOL) is a status of minimal manifestations (MM) or better with an oral prednisolone (PSL) dose of 5 mg/d or less (MM-5 mg). Early and aggressive use of nonoral fast-acting treatment together with low-dose oral PSL (the “EFT strategy”) is recommended to reduce disease severity with minimal oral steroid use so that the MM-5 mg target can be met as soon as possible. We conducted the fourth largest multicenter survey ever in 2021, obtaining detailed clinical information from 1710 consecutive MG patients all over Japan, and compared the 2021 surveys with those from 2012 and 2015. The frequency of patients treated with EFT strategies showed a gradual increase, reaching 39% of the total MG patients in the 2021 survey. The current and maximum dose of PSL and the number of days at high-dose (>20 mg/d) PSL showed decreases. Survey results indicate that as EFT strategies have spread, the percentage of patients on MM-5 mg has increased. We again confirmed that MM-5 mg was associated with favorable QOL in the 2021 survey. Recent data regarding COVID-19 suggests that it did not seriously impact the MG population in Japan; unfortunately, refractory MG, observed in 21% of patients, is still an unresolved problem.
The mechanisms underlying therapeutic hypothermia, which protects neurons following severe brain damage, are only partially understood. We previously demonstrated that hypothermia reduced, whereas hyperthermia augmented, the release of tumor necrosis factor (TNF)-α and interleukin (IL)-17. Cerebral ischemia causes the loss of the blood–brain barrier (BBB) integrity, thereby increasing cerebral vascular permeability, which directly contributes to vasogenic edema, hemorrhagic transformation, and increased mortality. Brain microvascular endothelial cells (BMVECs) are a major component of BBB and tight junction proteins (TJPs) in these cells maintain the BBB integrity. In this study we determined the mechanisms underlying this treatment by measuring the effects of TNF-α and IL-17 on BMVEC barrier function and TJP expression in BMVECs, and by evaluating the effects of hypothermia and hyperthermia on TJP expression.
The barrier function of BMVECs was evaluated by measuring transepithelial electrical resistance (TEER). The expression of several TJPs, such as claudin-5 and junctional adhesion molecule (JAM)-B, was measured at the mRNA and protein levels using real-time polymerase chain reaction and immunocytochemistry, respectively.
TNF-α and IL-17 decreased TEER values, and TNF-α decreased claudin-5 and JAM-B mRNA and protein levels, whereas IL-17 decreased JAM-B mRNA and protein levels, and all of these effects were concentration-dependent. Compared with normothermia, claudin-5 and JAM-B proteins were not affected by hypothermia, whereas JAM-B protein was reduced by hyperthermia.
The hypothermic suppression of TNF-α and IL-17 release may contribute to the maintenance of BBB function by ameliorating the decrease of TJP(s). In contrast, hyperthermia may decrease barrier function through a decrease in JAM-B expression. However, the contribution of changes in the JAM-B expression to the barrier function of BMVECs remains to be clarified.
Myelin oligodendrocyte glycoprotein antibody-associated disease myelin oligodendrocyte glycoprotein antibody-associated disease is an emerging demyelinating condition distinct from neuromyelitis optica spectrum disorder and multiple sclerosis affecting both children and adults with a spectrum of clinical manifestations ranging from optic neuritis, myelitis and acute disseminated encephalomyelitis.
We describe the case of a 2 year-old girl diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease presenting as recurrent acute disseminated encephalomyelitis who showed suppression of disease activity after treatment with rituximab. This case represents the youngest Mexican patient with myelin oligodendrocyte glycoprotein antibody-associated disease reported to date.
Information regarding the clinical presentation and evolution among different population could help to a better understanding of the presentation of this entity.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：