Search

The central nervous system (CNS) has long been considered as an immunological privileged site where the surveillance of the immune system does not reach out. However, it is now recognized that this CNS homeostasis is collapsed by neuroinflammation such as influx of proinflammatory factors and cells, neuronal dysfunction, and glial activation. Currently, CNS neuroinflammation is considered as a main pathomechanism to mediate disease progression in not only neurotrauma and neuroinflammatory disorders but also neurodegenerative diseases including dementia. Moreover, growing evidence indicates that chronic CNS neuroinflammation is also involved in the pathogenesis of psychiatric disorders such as autism spectrum disorders, depression, and schizophrenia. This paper reviews the current proposed pathomechanisms and therapeutic strategies of neurological and psychiatric disorders from a point of view of chronic neuroinflammation. [ABSTRACT FROM AUTHOR]

Background: To date, there is no journal that reports the coexistence of thymoma‐associated myasthenia gravis, alopecia areata, and twenty‐nail dystrophy. This paper hypothesizes that the presence of thymoma increases the risk of these conditions. Case presentation: The patient was a 37‐year‐old Filipino who came in for a year of history of fluctuating, but progressive, left‐sided ptosis and diplopia; difficulty swallowing; dysarthria; and aspiration and symmetric proximal muscle weakness confirmed to be myasthenia gravis by abnormal repetitive nerve stimulation and the presence of thymoma on histology. Before his thymectomy, he also developed gradually worsening thinning and longitudinal ridging of all fingernails and toenails; and patches of bald areas on the scalp; diagnosed to be twenty‐nail dystrophy and alopecia areata, respectively, by a board‐certified dermatologist. Conclusion: Thymoma is the possible risk factor and link for the co‐occurrence of the three conditions in the present patient. [ABSTRACT FROM AUTHOR]

What is important, I think, is to examine typical complications that are reported relatively frequently and to discuss the effects of COVID-19 infection on the brain, nerves, and muscles from their pathogenesis. If you read the article straightforwardly, you will easily understand that they refer to symptoms or complications found in the brain, nerves, and muscles associated with COVID-19. Even Guillain-Barré syndrome (GBS), the International GBS Outcome Study reported that there has been no significant increase in patient enrollment.3 In addition, the significance of discussing the subtypes of GBS in detail in this paper is not clear. [Extracted from the article]

Multiple sclerosis (MS) is an inflammatory disease defined by damage to the myelin sheaths of neurons. MS is classified into different subtypes including relapsing–remitting MS, secondary progressive MS and primary progressive MS. The present study aimed to estimate the prevalence of different forms and clinical symptoms of MS among Iranian people using meta‐analysis. We searched all available databanks, such as SID, Magiran, PubMed, Google scholar, Scopus and Science, directly to identify relevant evidence. All findings were reviewed and eligible articles were selected. The standard error of prevalence was calculated based on binomial distribution formula. The heterogeneity between the results of primary studies was detected using Cochrane (Q) and I2 indices. The primary results were combined according to a random effects model. The effect of related factors in heterogeneity was investigated using a meta‐regression model. During the primary search, 17 352 articles were identified. After limiting the search strategy, and excluding duplicates and irrelevant papers, finally, 21 primary studies were entered into the final meta‐analysis. The total prevalences of relapsing–remitting MS, primary progressive MS and secondary progressive MS types among Iranian people were estimated to be 69.7% (95% CI 63.7–75.8), 7.01% (95% CI 4.05–9.96) and 17.8% (95% CI 11.7–23.9) respectively. In addition, prevalences of fatigue and motor dysfunction were estimated to be 71.1% (95% CI 60.9–81.3) and 56.3% (95% CI 27.9–84.6), respectively. Our meta‐analysis showed that relapsing–remitting MS is the most common type of MS, and fatigue is the most common clinical manifestation in patients. Motor dysfunction and balance disorder are the other common problems in patients. [ABSTRACT FROM AUTHOR]

Background: Acute encephalitis refers to inflammation of the brain that develops as a rapidly progressive encephalopathy. It usually has an infectious origin, but an increasing number of autoimmune etiologies have been identified recently. Keeping a high index of suspicion is of great importance, because delayed diagnosis and delayed initiation of appropriate therapy may lead to poor outcome. Case presentation: This paper describes a case of anti‐N‐methyl‐D‐aspartate receptor (anti‐NMDAR) encephalitis in a young female who presented with a short prodrome; had a rapidly progressive illness; and could not be saved even after early, optimal, and aggressive immunomodulatory therapy. Conclusions: Despite early diagnosis, and prompt therapy, anti‐NMDAR encephalitis may progress and remain refractory to treatment. More studies are needed for further therapeutic avenues in treatment‐refractory cases of anti‐NMDAR encephalitis not responding even to cyclophosphamide as highlighted by our case. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is the prototypic autoimmune connective tissue disorder (CTD) usually affecting young females. Central nervous system lupus is a serious complication encountered in SLE cases. Predominant involvement of rhombencephalon in patients of SLE at the first contact with health care professional has not been seen and described frequently in the literature. It still remains a diagnostic and therapeutic challenge. Case presentation: This paper describes a case of SLE in an adolescent female who was diagnosed as having rhombencephalitis, which is a rare presentation of SLE. Conclusions: Central nervous system lupus should be included in the provisional diagnosis of any young female patient presenting with complicated neurologic manifestations over the background of joint pain or fever or headache or confusion or psychosis, to avoid misdiagnosis and aid in timely institution of aggressive immunotherapy. [ABSTRACT FROM AUTHOR]

Guillain-Barré syndrome ( GBS) is an acute self-limited polyneuropathy. The original paper was reported by Guillain, Barré and Strohl in 1916. GBS was considered to be a demyelinating disease of the peripheral nervous system, called acute inflammatory demyelinating polyneuropathy. In the 1980s, the acute axonal type of GBS was first reported. This subtype was later called acute motor axonal neuropathy. In addition to acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy, several subtypes including Miller Fisher syndrome were reported. GBS was shown to be an immune-mediated disease. The frequent presence of antibodies against various glycolipids have been reported in the acute-phase sera from GBS patients since the end of the 1980s, including anti- GM1 antibody in acute motor axonal neuropathy and anti- GQ1b antibody in Miller Fisher syndrome. The efficacy of plasmapheresis and intravenous immunoglobulin therapy has been established since the mid 1980s. However, despite those therapies, there are still severe or refractory cases. Further investigation is necessary for the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Among the different forms of cerebellar ataxia, autoimmune cerebellar ataxia (ACA) or immune‐mediated cerebellar ataxia (IMCA), which appears to be based on an autoimmune mechanism, has long been considered important from the viewpoint of paraneoplastic syndrome. With the expansion of the concept of immune‐mediated neurological diseases and the identification of many novel autoantibodies, ACA has recently become an important neurological syndrome. Although no definitive diagnostic criteria of ACA exist, Hadjivassilou et al suggested diagnostic criteria for primary ACA in 2020 and Dalmau and Graus showed proposed diagnostic criteria for ACA in 2022. The proposed diagnostic criteria for ACA by Dalmau and Graus emphasize the importance of antibody reliability. In the future, additional studies should be conducted to identify new antibodies associated with ACA and to clarify the importance of each antibody. Moreover, ACA is a disease for which immunological therapeutic intervention is feasible and requires early treatment to maintain cerebellar function. Many cases with ACA have reported the efficacy of immunotherapy. The concept of ACA may have the potential for further expansion and becomes increasingly important in the diagnosis of cerebellar ataxia. [ABSTRACT FROM AUTHOR]

The Japanese Society for Neuroimmunology has been honoring the I Clinical and Experimental Neuroimmunology i (CENI) Best Article Award to encourage young members of the society to submit their excellent papers to CENI since 2013. The award nominee is selected from the original articles or case reports in regular issues or supplements of CENI, written by members of the society. In this article, we clarified the differential roles of colony-stimulating factors and transforming growth factor-beta (TGF-beta) in the differentiation of hematopoietic cells to microglia-like cells. [Extracted from the article]

Objective: 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). Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

The Japanese Society for Neuroimmunology has been honoring I Clinical and Experimental Neuroimmunology i (CENI) Best Article Award to encourage members of the society to submit their excellent papers to CENI since 2013. The article entitled "Quotient of cerebrospinal fluid/serum immunoglobulin G as a predictive factor for non-responders to intravenous methylprednisolone therapy in patients with relapsing neuromyelitis optica spectrum disorder: Implication for early initiation of plasmapheresis", which appears in I Clin Exp Neuroimmunol i 7: 272-280, 2016, was written by Dr Satoru Oji. In this article, we described that the quotient of cerebrospinal fluid/serum IgG was a predictive factor for the efficacy of intravenous methylprednisolone in patients with relapsing neuromyelitis optica spectrum disorders (NMOSD), which implied the early institution of plasmapheresis. [Extracted from the article]

Objective: There is little research on the relationship between self‐concept, psychiatric symptoms and quality of life among multiple sclerosis (MS) patients. We assessed the impact of disease perception (expectation and knowledge) on these metrics according to time from diagnosis. Methods: This was an observational, cross‐sectional, multicenter study. Group 1 included patients up to 3 months from MS diagnosis, whereas group 2 included patients with MS diagnosis established for >12 months and <36 months. A 19‐item true/false questionnaire developed by the investigators to assess disease perception, Hospital Anxiety and Depression Scale (HADS), Fatigue Severity Scale and three‐level level version of EQ‐5D questionnaires were used. Results: A total of 90 patients from six centers were included (38 in group 1). A total of 80% had a good disease knowledge, whereas just 48% reported positive expectations. There were no differences in disease knowledge, disease expectations, HADS, Fatigue Severity Scale and EQ‐5D. We found an inverse correlation between disease knowledge and problems in self‐care (P = 0.018) and fatigue (P = 0.032). Patients with the worst expectations about the disease were more anxious (P = 0.012 on HADS and P < 0.001 on EQ‐5D). They also reported more problems in mobility (P = 0.002), self‐care (P = 0.005), usual activities (p = 0.009) and pain (P = 0.001), and a worst health status compared with the past 12 months (P < 0.001) and with the best imaginable status (P < 0.001). Conclusions: Our study showed no association between disease duration and disease perception. Patients with less disease knowledge reported more problems in self‐care and higher fatigue scores. Patients with the worst disease expectations were more anxious and reported a worse health status. More attention should be paid to perceived health status in MS patients. [ABSTRACT FROM AUTHOR]

Background: Stiff Person Syndrome (SPS), a rare immune‐mediated neuromuscular disorder, is characterized by rigidity, stiffness, and intermittent spasms of axial and extremity muscles. Various immunotherapies including intravenous immunoglobulin (IVIG) have been used for this autoimmune condition. Here we aim to review the role of IVIG in the treatment of SPS along with its outcome. Methods: A systematic literature search of PubMed and Embase was conducted to identify the relevant published articles against the predefined criteria using suitable keywords combinations till September 20, 2021. Data were extracted to produce descriptive information of SPS patients on demographics, diagnostics, treatment with IVIG, and outcome. Results: Twelve studies with 216 patients were included in the review and 63.89% of them had classical SPS. Glutamic acid decarboxylase (GAD) autoantibodies were present in 72.68% of the patients and 57.89% in whom electromyography (EMG) was performed had continuous motor activity. IVIG therapy was given to 95 patients in different regimens in various studies and varying scoring systems were used to assess the outcome, and 83.16% showed some form of improvement, 14.74% showed no improvement, while 2.10% worsened. None of the included studies mentioned an adverse effect of IVIG in the patients. Conclusion: IVIG may benefit patients with SPS along with other medications. Owing to the rarity of the disease and insufficient studies on the assessment of immunotherapy in SPS, longitudinal studies with a sizable number of patients are required to clarify clinical course, treatment, and outcome in SPS with the use of IVIG. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment (CI) is common in multiple sclerosis. We assessed the relationship between CI and demographic, motor disability, and volumetric brain atrophy in relapsing remitting multiple sclerosis (RRMS). Methods: In all, 43 RRMS patients and 40 age‐ sex‐, and education‐matched normal volunteers were enrolled. Assessments included: demographic, Expanded Disability Status Scale (EDSS); Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS); and brain volumetric assessment. Results: The mean age of onset of RRMS patients was 25.72 y and the mean number of attacks was 3.30 ± 2.33/year. The total brain volume, cerebral, and cerebellar hemispheres, brainstem as well as thalamic and hippocampal gray matter were significantly reduced in RRMS patients compared with controls. CI was detected in 41.9% of patients. Patients with CI had fewer years of education (P =.001), a higher number of attacks (P =.002), worse EDSS scores (P =.030); reduced gray matter volume, particularly of the thalamus, and hippocampus compared with patients without CI. There were significant negative correlations between CI with duration of illness, number of attacks, time elapsed between onset and diagnosis, and EDSS. Thalamic volume showed strong positive correlations with CI (P <.0001). The best predictors of CI were thalamic atrophy, duration of illness, and years of education (P =.001,.010, and.035 respectively). Conclusion: We confirmed the presence of gray matter atrophy of the brain in RRMS patients. Volumetric magnetic resonance imaging measures of thalamus, duration of illness, and years of education could be useful biomarkers of CI in RRMS. [ABSTRACT FROM AUTHOR]

Objective: This is a critical review of studies aiming to assess the safety and efficacy of monoclonal antibodies as compared with the classical regimen in patients with neuromyelitis optica spectrum disorder. Methods: Various electronic databases were searched for original articles reporting results from the use of monoclonal antibodies in neuromyelitis optica spectrum disorder. The Expanded Disability Status Scale and annualized relapse rate score before and after treatment were the primary effect measures. The pooled standardized mean difference with 95% CI was calculated using the random effects model. The heterogeneity of the included studies was calculated using Cochran's Q test and I2 statistics. Results: Of 36 included studies, meta‐analysis was carried out from 27 studies. The pooled analysis of 1010 patients showed a mean reduction in the mean annualized relapse rate ratio after tocilizumab therapy −2.45 (95% CI −3.13 to −1.77) to be higher compared with rituximab −1.49 (95% CI −1.81 to −1.17). Likewise, the mean reduction in the Expanded Disability Status Scale after tocilizumab was higher −1.10 (95% CI −1.75 to −0.44) compared with rituximab −0.80 (95% CI −1.11 to −0.48). Conclusion: Tocilizumab has a greater effect than rituximab in terms of the reduction of the annualized relapse rate and Expanded Disability Status Scale in neuromyelitis optica spectrum disorder patients. The greater efficacy of tocilizumab could result from its multiple dynamic pharmacodynamics (i.e. its effect on interleukin‐6‐dependent inflammatory processes, involving CD20‐negative plasmablasts, pathogenic T cells and regulatory T cells) and to some degree due to heterogeneity in our study. Satralizumab (monotherapy or add‐on), eculizumab and inebilizumab (monotherapy) are effective in aquaporin‐4‐positive cases with good safety profiles. Ublituximab, bortezomib, bevacizumab and C1‐esterase inhibitors are both effective and safe add‐on drugs. [ABSTRACT FROM AUTHOR]

The article offers information on the papers presented at the 2nd MS Summer College held in Sapporo, Japan on August 1-2, 2015 on topics including genetic and environmental influence on multiple sclerosis (MS), neuromyelitis optica, and astrocyte injury and secondary demyelination. It informs that opening remarks were made by Seiji Kikuchi, and researchers Douglas S. Goodin and Tatsuro Misu delivered lectures on the epidemiology of MS.

Information about several papers discussed at the annual meeting of American Academy of Neurology held in Philadelphia, USA, during April 26 to May 3, 2014 is presented. Epidemiological studies offer evidence that smoking, low vitamin D levels and infection with the Epstein-Barr virus increase the risk of multiple sclerosis (MS). Topics discussed include Progressive multifocal leukoencephalopathy, autoimmune encephalomyelitis (EAE) and biomarkers.

Background: Cryopyrin‐associated periodic syndrome (CAPS) is an autoinflammatory disorder with a spectrum ranging from the milder familial cold auto‐inflammatory syndrome (FCAS) phenotype to the more severe Muckle–Wells Syndrome. Although headaches are the most common neurological symptoms, neuroinflammatory diseases such as multiple sclerosis (MS) have only been reported in the more severe phenotypes. Case Presentation: We describe a 43‐year‐old male diagnosed with relapse‐remitting MS who developed cold‐induced arthralgias and urticaria. He initially presented with facial numbness and arthralgias in his late teenage years, and brain magnetic resonance imaging (MRI) demonstrated multiple lesions with periventricular white matter extension. Oligoclonal bands were detected in the cerebrospinal fluid (CSF). Symptoms gradually improved, and a decade later he presented with numbness at upper limbs and tongue. Brain and spine MRI showed new lesions, but CSF was unremarkable. He was started on interferon β‐1a with symptomatic improvement until another flare around 13 years later. Treatment was changed to dimethyl fumarate. During this hospitalization, urticaria was problematic and particularly associated with cold temperatures. This raised suspicion for possible CAPS and subsequently confirmed with an A439V mutation in the NLRP3 gene, consistent with FCAS. Anakinra was started but was not tolerated because of localized reactions despite desensitization. His serum amyloid A was mildly elevated at 9 mg/L (reference range 0–6). He remains stable from a neurological perspective, including imaging, and continues dimethyl fumarate. Conclusions: To date, FCAS and possible association with MS has not been described. The case raises challenges in the diagnosis of concurrent disease processes. It also highlights that neurological sequelae should be considered in all spectrums of CAPS, and distinctions with MS should be made where possible. [ABSTRACT FROM AUTHOR]

Human prion diseases (HPDs) are progressive and fatal neurodegenerative diseases caused by abnormal prion protein (PrPSc). They can be sporadic, genetic or acquired. Sporadic HPDs include sporadic Creutzfeldt–Jakob disease (CJD) and sporadic fatal insomnia. Genetic HPDs include genetic CJD, Gerstman–Sträussler–Scheinker disease and fatal familial insomnia. Acquired HPDs include Kuru, variant CJD and iatrogenic CJD. The World Health Organization clinical diagnostic criteria for HPDs include clinical findings, cerebrospinal fluid protein markers and electroencephalography, and the UK and European clinical diagnostic criteria include a combination of clinical findings, 14‐3‐3 protein in the cerebrospinal fluid, magnetic resonance imaging diffusion‐weighted imaging and electroencephalography. Recently, the development and clinical application of real‐time quaking‐induced conversion has allowed pre‐mortem diagnosis of sporadic CJD. The real‐time quaking‐induced conversion assay allows detection of >1 fg of PrPSc in diluted CJD brain homogenate, as well as a variety of biological tissues and cerebrospinal fluid. However, the real‐time quaking‐induced conversion assay does not provide prognostic data and has lower diagnostic accuracy for some rarer, atypical prion diseases. Furthermore, recent advancements in laboratory testing and magnetic resonance imaging diffusion‐weighted imaging have shown improved diagnostic accuracy for prion diseases. Clinical trials of prion disease treatments have recently begun in many countries. The therapeutic window consists mainly of the early stage of disease, and few clinical studies have examined the role of biomarkers at this stage. Therefore, biomarkers, imaging and clinical symptoms might be extremely important for the diagnosis of prion diseases. Clinical trials of prion disease treatments have recently begun in many countries. The therapeutic window mainly consists of the early stage of disease, and few clinical studies have examined the role of biomarkers at this stage. Therefore, biomarkers, imaging and clinical symptoms might be extremely important for the diagnosis of prion diseases. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor–induced hypophysitis is a rare complication of pembrolizumab, but the effects of drug‐induced hypophysitis on preexisting pituitary lesions are unknown. The authors treated an unusual case of pembrolizumab‐induced hypophysitis that resulted in acute exacerbation of a preexisting pituitary cystic lesion causing severe intractable headaches. Before initiation of pembrolizumab therapy, magnetic resonance imaging should be carefully reviewed for sellar pathology. Patients demonstrating a Rathke's cleft cyst should consider other forms of treatment first or be carefully counseled before pembrolizumab initiation, because the advent of hypophysitis could result in symptomatic progression of an existing lesion, necessitating urgent surgical intervention. [ABSTRACT FROM AUTHOR]

Neurocognitive compromise, neuropsychiatric symptoms and psychopathology are all evident in the acute stages of autoimmune encephalitides. These factors considerably affect functional independence after discharge. Drawing on psychometric assessments and qualitative descriptions, this review explores the nature, extent and diagnosis of cognitive disorder in autoimmune encephalitides. Potential pathophysiological and neuroanatomical architecture related to neurocognitive compromise in the acute and chronic stages of this illness is examined. In regard to outcomes, the review highlights clinicodemographic factors currently known to be associated with poorer cognitive outcome. Finally, the review delves into neuropsychiatric symptomology and psychological concerns that should be considered at diagnosis and during follow up of these patients. [ABSTRACT FROM AUTHOR]

Objectives: Immune checkpoint inhibitor (ICI) therapy has revolutionized the management of multiple cancers with previously poor prognosis. Despite its efficacy the therapy is associated with a wide spectrum of immune‐related adverse events (irAEs) including neurological deficits ranging from peripheral neuropathy, myopathy, and myasthenic syndromes to encephalopathy or meningitis. Up to now, neurological irAEs, especially those with central nervous system (CNS) involvement, have been reported rather sporadically. Symptoms can be unspecific, which results in a diagnostic challenge. Methods: In the study at hand, we report 5 patients who presented with symptoms of the CNS during ICI therapy indicating autoimmune encephalitis. Results: Symptoms ranged from headache and hallucinations to symptoms of the brainstem to cerebellar syndrome. Radiological findings according to brain magnetic resonance imaging were unspecific, and analysis of autoantibodies remained negative in all cases. All patients underwent lumbar puncture, and examination of the cerebrospinal fluid revealed an elevated cell count, and thus an indication of inflammation, in 4 cases (80%). Consequently, all patients received high‐dose steroid treatment, and symptoms of all patients with elevated cerebrospinal fluid cell count significantly improved. Conclusions: We demonstrate that symptoms of immune checkpoint inhibitor–induced encephalitis can be unspecific, and radiological findings are often inconspicuous. Thus, cerebrospinal fluid analysis is the most important examination to achieve a correct diagnosis, which in turn is decisive for a rapid start of therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe two cases of Baló's concentric sclerosis, and to review the state‐of‐the‐art literature. This dissertation is the result of a critical analysis matching the literature and our professional experience. Data were synthesized into a narrative review. BCS is often referred to as a variant of multiple sclerosis (MS). It is still unclear whether BCS is an acute variant of MS or a distinct entity that happens to coexist with MS. BCS and MS‐like lesions might be present at the same time. BCS lesions are characterized by a large concentric "onion‐like" shape on MRI T2‐weighted images composed of alternating hypointense and hyperintense layers. On contrast‐enhanced T1‐weighted images, BCS active lesions usually show an enhancing and non‐enhancing pattern. The advancing edge of demyelination could be represented by peripheral restricted diffusion and contrast enhancement. Baló's lesions is mainly found in the supratentorial white matter; however; the cerebellum, the brainstem and the spinal cord might be affected as well. The present two cases both showed onion‐like lesions; case 1 showed typical BCS features, whereas case 2 was atypical and could be classified as probably BCS or as a BCS‐like lesion in the course of MS. It is important for radiologists to be able to recognize this type of lesion and to cooperate with clinicians to help them carry out earlier diagnosis and treatment, determining a better clinical outcome for patients affected by BCS, even without histological confirmation, which is still considered the gold standard. [ABSTRACT FROM AUTHOR]

The article offers information on the Clinical and Experimental Neuroimmunology (CENI) Best Article Award launched by the Japanese Society for Neuroimmunology to encourage members of the society to submit their excellent work to CENI. It states that two articles are awarded each year which include one from basic science and one from a clinical field. It adds that award winners are encouraged to submit a congress report and to attend the international meeting.

The brain interacts with the immune system under inflammatory and non‐inflammatory conditions. Brain cells have the capacity to produce a variety of cytokines in response to systemic immune activation. Therefore, we hypothesized that brain cells and immune cells move close to each other, so that they can carry out intercellular interactions. In the present article, I review our studies to determine the site for the brain–immune cell–cell interactions. The leptomeninges, choroid plexus stroma and epithelium, attachments of the choroid plexuses, vascular endothelial cells, cells of the perivascular space, and astrocytic end‐feet compose the histological architecture that supports interactions between bone marrow‐derived myeloid cells and brain parenchymal cells under non‐inflammatory conditions. This architecture also functions as the interface at which systemic inflammation‐induced responses can be conveyed to the brain parenchyma under inflammatory conditions. It should be noted that such brain–immune interactions occur in the absence of florid inflammatory cell infiltrates in the brain parenchyma, and with relative preservation of the blood‐brain barrier. Rather, cells comprising the blood‐brain barrier act as the interface linking peripheral immune activation and brain responses. These responses, known as "neuroinflammation", are unique to the brain. Neuroinflammation differs from the histological inflammation that is accompanied by a florid infiltration of the leptomeninges (meningitis) and/or brain parenchyma (encephalitis) by inflammatory cells. In this review, the relevance of histological studies to unravel the mechanisms linking systemic inflammation, brain–immune interface cells and brain parenchymal cells, with a special emphasis on sepsis‐associated encephalopathy, is discussed. [ABSTRACT FROM AUTHOR]

Objective: Clinically isolated syndrome (CIS) is a first demyelinating episode targeting the central nervous system. It can later fulfill the diagnostic criteria for multiple sclerosis (MS) or remain as a single event with no further clinical or paraclinical evidence of disease. Given the difficulty of predicting the long‐term course of the disease at the moment of the first episode, we intended to examine clinical and laboratory features associated with MS conversion, underlining the prognostic value of oligoclonal bands (OCBs) determination. Methods: We analyzed patients with an episode compatible with CIS (not fulfilling the 2010 McDonald criteria) as the first manifestation of MS (according to the same criteria), observed in our MS clinic (n = 82). Results: From our cohort, 76.8% of patients converted to MS. OCBs were present at baseline in 68.0% of MS patients, but also in 73.7% of stable CIS patients (P =.77). After stratification of the results by treatment, there was also no statistically significant association between the presence of OCBs and conversion to MS. Additionally, positive OCBs did not predict earlier conversion to MS. Conclusions: Our study outlines the high prevalence of positive OCBs in patients with CIS, even in those who, until now, do not fulfill the 2010 diagnostic criteria for MS. This raises questions about the early assumption of MS diagnosis based on OCB status. A very hasty diagnosis could result in chronic treatment initiation and a possibly lifelong stigma in patients who might never develop new lesions or have a second attack. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editor discusses various papers within the issue on topics including connexins of astroglia, immune cell trafficking, and the 12th Annual Meeting of the Multiple Sclerosis (MS) Workshop held in Fukuoka, Japan from August 3-4, 2013.

Hashimoto encephalopathy (HE) is an autoimmune encephalopathy associated with autoimmune chronic thyroiditis. The clinical entity and nosology of HE have long been debated. Recently, new autoantibodies associated with autoimmune encephalitis have been discovered. With accumulated reported cases, and our discovery of serum autoantibody against NH2‐terminal of alpha‐enolase as a specific diagnostic marker, HE has been recognized as a distinct clinical entity. The condition appears dominant in females. The clinical features of HE are characterized by various neuropsychiatric symptoms, such as altered consciousness, psychosis and seizures, the presence of serum anti‐thyroid antibodies, normal or non‐specific changes in brain magnetic resonance imaging, diffuse slow wave activities in electroencephalogram and responsiveness to immunotherapy. A few pathological studies showed a lymphocytic infiltration of the small and medium‐sized vessels of the brain, which suggested vasculitis. Non‐specific neurological symptoms, laboratory findings and neuroimaging of HE make its diagnosis an oversight and difficult, whereas antibodies against NH2‐terminal of alpha‐enolase can be useful as a diagnostic biomarker for HE. In this review, we describe the current state of knowledge about HE and discuss progress in the diagnosis of HE. [ABSTRACT FROM AUTHOR]

Non‐infectious encephalitis has been a recognized entity for many years; however, its pathophysiology was not fully understood. Patients (usually women) presented with acute behavioral changes and were admitted to mental hospitals, without a correct diagnosis. With the new advances on antibody detection, the non‐infectious encephalitis panorama has been changing. Immune‐mediated diseases of the central nervous system encompass a variety of disorders, including the classic paraneoplastic encephalitis and the more recently discovered autoimmune encephalitis. Recognition of the new syndromes and antigens, in addition to the advances in diagnostic methods, such as antibody detection and imaging, and early implementation of immunotherapy, have changed the field of autoimmune encephalitis significantly over the past two decades. The best recognized form of autoimmune encephalitis is anti‐N‐methyl‐D‐aspartate receptor encephalitis, which usually presents with neuropsychiatric changes, seizures, autonomic dysfunction and usually a decreased level of consciousness. Nevertheless, the panorama for other types of receptors, such as anti‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor, anti‐gamma‐aminobutyric acid and, most recently, anti‐glycine receptor, anti‐metabotropic glutamate receptor 5, dopamine receptor D2 and dipeptidyl‐peptidase‐like protein 6, which can present clinically as encephalitis, is currently changing, meaning that the panorama for diagnosis and treatment is broadening every day. [ABSTRACT FROM AUTHOR]

Cognitive impairment is one of the most important non‐physical symptoms of patients with multiple sclerosis (MS), and few studies have reported on cognitive impairments in patients with neuromyelitis optica spectrum disorders. Adequate batteries are required to assess cognitive function in MS, and cognitive impairments in patients with MS are likely not adequately evaluated. As cognitive impairment usually affects employment status and activities of daily living in patients with MS and neuromyelitis optica spectrum disorders, the effect of this symptom on daily activities should be closely examined. The present review focuses on the prevalence and characteristics of cognitive impairments in patients with MS and neuromyelitis optica spectrum disorders, as well as the methods used to evaluate cognitive function in such patients. As cognitive impairment usually affects employment status and activities of daily living in patients with multiple sclerosis and neuromyelitis optica spectrum disorders, the effect of this symptom on daily activities should be closely examined. This review focuses on the prevalence and characteristics of cognitive impairments in patients with multiple sclerosis and neuromyelitis optica spectrum disorders, as well as the methods used to evaluate cognitive function in such patients. [ABSTRACT FROM AUTHOR]

Objective: We investigated the association of magnetic resonance imaging (MRI) findings and social activities with cognition in Japanese patients with multiple sclerosis (MS). Methods: Cognition was evaluated by the Brief International Cognitive Assessment for MS (BICAMS), using previously published data for 156 Japanese patients with MS. The BICAMS results were analyzed with available MRI data, focusing on hyperintense lesions on T2/fluid‐attenuated inversion recovery images. Logistic regression analysis was used to assess associations between the BICAMS scores and social activities (i.e. "student," "employed full time," "employed part time," "homemaker" and "unemployed because of MS"). The independent variables were the BICAMS scores, and the Expanded Disability Status Scale, sex, age at examination, education and disease duration. The dependent variable was the "social activity." Results: Analysis of variance showed that patients with MS and more cerebral lesions on MRI had lower scores in all three domains of the BICAMS (the Symbol Digit Modalities Test, the second edition of the California Verbal Learning Test and the revised Brief Visuospatial Memory Test). Scores of all three domains were also significantly lower in patients with cerebellar lesions. Regarding social activities, patients who were unemployed because of MS had lower BICAMS scores compared with employed patients. However, the BICAMS domain scores did not independently affect the other social activities. Conclusions: Higher numbers of cerebral lesions and the presence of cerebellar lesions evaluated by MRI affect cognitive function based on the BICAMS. Cognitive function might affect social activities in patients with MS. Higher numbers of cerebral lesions evaluated by MRI affect cognitive function based on the BICAMS. Cognitive function might affect social activities in patients with MS. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the epidemiology and characteristics of transverse myelitis (TM) and neuromyelitis optica spectrum disorders (NMOSD) in Abu Dhabi, United Arab Emirates. Methods: Retrospective chart review at four large government‐run hospitals in Abu Dhabi between 2010 and 2016. Data collected included year of onset, presentation, laboratory results including aquaporin‐4 immunoglobulin G (IgG)/myelin oligodendrocyte glycoprotein IgG antibodies and the occurrence of any relapses. Results: A total of 46 individuals were identified. Of these, 23 (50%) were Emirati citizens. Within the overall group including pediatrics, the crude prevalence rate for monophasic TM was 1.0 per 100 000, and for NMOSD was 0.34 per 100 000. Incidence rates within the overall group for TM and NMOSD were 0.18 per 100 000 and 0.05 per 100 000, respectively. For Emirati citizens aged ≥20 years, the prevalence rate for monophasic TM was 2.46 per 100 000 and 1.76 per 100 000 for NMOSD, and the incidence was 0.57 per 100 000 and 0.17 per 100 000, respectively. The incidence of monophasic TM and NMOSD within the Emirati pediatric population (aged ≤19 years) was 0.18 per 100 000 and 0.06 per 100 000, respectively. The mean age of onset for monophasic TM was 36 years, and for NMOSD was 43 years. Nine patients had a positive aquaporin‐4 IgG or anti‐myelin oligodendrocyte glycoprotein IgG antibody result. Of the 30 participants with available laboratory cerebrospinal fluid analysis, 36.6% had elevated white blood counts (>5.0 × 106/L), and 43% had elevated protein levels. A total of 19 participants had documentation of oligoclonal bands or IgG index, and just four (21%) had either oligoclonal bands or elevated IgG index. Conclusion: The present study describes the epidemiology and characteristics of TM and NMOSD among populations in Abu Dhabi. The adult prevalence rate for Emirati citizens was 2.46 per 100 000 for monophasic TM, and 1.76 per 100 000 for NMOSD. The overall incidence was 0.18 per 100 000 and 0.05 per 100 000, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Gap junctions or hemichannels are expressed on all cells in our body, and have a highly significant role in homeostasis and in disease states. There are 21 connexins found in humans and they have distinct characteristics that compensate for each other. The anatomical expression pattern also differs between each connexin; some of them are expressed together and some are not. Genetically mutated connexin genes induce inheritable diseases, but acquired disorders can also be caused by primary or secondary connexin dysfunctions. In the central nervous system, glial cells are the main connexin‐expressing cells. They utilize connexin gap junctions to assemble glial networks. The present review not only describes the basic structures and functions of connexins, it also examines the relationships between connexins and their role in disease pathology. [ABSTRACT FROM AUTHOR]

Abstract: With the massive digitalization of many processes involved in human activities, electronic medical records (EMR) are being increasingly deployed in medical centers. EMR have the potential to become a main major real‐life data source for future medical research and evaluation of practice. Multiple sclerosis is a paradigmatic example of a complex disease that can benefit from this new source of information. Today, researchers and clinicians alike have access to tools allowing an en masse identification of multiple sclerosis patients, and extraction of demographics and clinical variables with high accuracy. However no matter how “big” the (EMR) data might be, biases are inherent to EMR data generation. These have to be studied and eventually accounted for in analysis in order to fulfill the promise of personalized medicine for all, and carrying out large clinical and research studies in multiple sclerosis. [ABSTRACT FROM AUTHOR]

I joined the Japanese Society for Neuroimmunology at its establishment in 1988. Now, I am going to step down from the Executive Committee of the Society. I sincerely thank all the members for support. Dr Kira gave me a great opportunity to make suggestions on improving the Society. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency might be a risk factor for multiple sclerosis ( MS). The active form of vitamin D has some protective effects on MS. The study by Takahashi et al. in this issue addressed the question of how vitamin D works on MS pathology. Using a human brain microvascular endothelial cell line, they showed that vitamin D attenuated the damage of barrier function of the cell line after exposure to either MS sera or tumor necrosis factor-α. The study along with their previous study suggests that vitamin D might protect blood-brain barrier function, and could give us a rationale for the use of vitamin D in MS patients. [ABSTRACT FROM AUTHOR]

The article discusses the 32nd European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and 21st Annual Conference of Rehabilitation in Multiple Sclerosis held at ExCeL London event venue in London, England from September 14-17, 2016. It mentions the presentation of several researches on topics including the cerebral cortical lesions assessment among clinical isolated syndrome (CIS) patients, the multiple sclerosis (MS) diagnosis, and imaging neuroprotection and repair.

Magnetic resonance imaging has improved the diagnosis and evaluation of disease activity in multiple sclerosis ( MS), and its widespread use has contributed to creating the concept of radiologically isolated syndrome ( RIS) to describe patients without symptoms of MS whose magnetic resonance imaging findings suggest they might be at risk of future demyelinating events. Indeed, using the revised McDonald criteria now allows some patients who would have been diagnosed with clinically isolated syndrome ( CIS) in the era of Poser criteria to be diagnosed as having MS before a second episode. The present review discusses the current concepts of RIS and CIS, and the risk factors for conversion from these conditions to MS. Clinical trials involving participants with CIS at high risk of developing clinically definite MS have shown that disease-modifying drugs significantly suppressed the conversion from CIS to MS, and that early treatment with these drugs could improve future disease prognosis in patients who subsequently developed MS. When a patient presents with RIS or CIS, the primary concern for the physician and patient should be the probability of conversion to MS, and the patient should be followed up taking into consideration the risk factors for conversion from RIS or CIS to MS. [ABSTRACT FROM AUTHOR]

Two reports published in Nature provided provocative data implicating 'salt' as an important exacerbating factor in the development of autoimmune diseases. High-salt conditions enhanced the differentiation of pathogenic interleukin-17-producing helper T cells and accelerated the pathology of experimental autoimmune encephalomyelitis mice. [ABSTRACT FROM AUTHOR]

We describe a 69-year-old woman with dermatomyositis who presented with asymmetric peripheral neuritis. The patient first developed dermatomyositis at 39 years-of-age; her symptoms improved several years later with oral prednisolone treatment. A year and a half before admission to our hospital, she developed a sensory disturbance in her feet that gradually expanded to both legs with left dominance. Six months later, bilateral leg muscle weakness and proximal muscle tenderness appeared. Neurological examination at admission revealed proximal muscle weakness and atrophy of all four limbs. Ankle jerk was absent bilaterally. There was sensory impairment in the left hand and both lower limbs, with more severe involvement of the left side and the medial side. Electrophysiological tests showed decreased sensory nerve action potentials in the left superficial fibular nerve and bilateral sural nerves, and decreased motor action potentials in the bilateral fibular nerves. We diagnosed mononeuritis multiplex as a complication of dermatomyositis. Her symptoms of mononeuritis multiplex and dermatomyositis were successfully treated with intravenous methylprednisolone pulse therapy followed by oral prednisolone therapy. Although our literature search found nine cases of dermatomyositis with polyneuropathy/polyradiculoneuropathy, most of which involved axonal neuropathy, this is the first case report of dermatomyositis presenting with mononeuritis multiplex. [ABSTRACT FROM AUTHOR]

Cholesterol and lipid are essential component of nerve cells. They are found in abundant quantities in the brain, with the largest pool of free cholesterol in the myelin sheath, a crucial component taking part in electrochemical conduction along the axons. However, disruption in cholesterol homeostasis becomes detrimental, as seen in multiple sclerosis ( MS) at its various stages. MS is a complex disorder that is characterized by ongoing inflammatory, demyelinating and neurodegenerative processes. With an extensive literature search and critical review, we found that emerging epidemiological and molecular evidence suggests that cholesterol might have: (i) a causal relationship with MS; (ii) a positive association with the progression in disability in MS with an increase in cholesterol level; and (iii) an important role to play as a biomarker predicting MS disease course and the therapeutic response. The present review also highlights the possible therapeutic role of cholesterol and lipids in MS. [ABSTRACT FROM AUTHOR]

Objective To assist policymakers as they reflect on treatment protocols and approaches for the efficient delivery of medical care for multiple sclerosis (MS) patients in Japan. Methods We analyzed data from a large Japanese health insurance claims database. Using an algorithm based on diagnosis codes, all patients with a diagnosis of MS were identified; patients having a non- MS demyelinating disease were excluded from the population. MS patient data were used for cross-sectional analysis carried out on the data collected at a certain period. We identified a total of 1808 MS patients, and we analyzed data for 1133 patients with an observation period of ≥6 months from October 2013 to September 2014. Newly diagnosed MS patients were identified within the MS patients, and their data were used for longitudinal analysis, tracking each patient over a period of time. Results The total per patient per month cost for MS was ¥93 542 ( US$781, €695 as of October 2015). Disease-modifying therapy drugs costs constituted half of the overall medical costs. For newly diagnosed MS patients, hospitalization costs were the largest component in the initial month, while drug costs were the largest component more than several months after the initial visit. There was a positive correlation between relapse frequency and medical cost. Conclusions These results provide up-to-date information on the demographics, medical treatment and cost status of MS in almost real-time by using a claims database. They suggest that claims data analysis can effectively support medical policymaking. [ABSTRACT FROM AUTHOR]

The development of multiple sclerosis ( MS) is based on complex interactions between genetic and environmental factors. Epigenetic regulation is a biological phenomenon defined as the modification of gene expression without alteration of the DNA sequence, and is currently thought to underlie the interactions between the genetic and environmental risks of MS. The molecular mechanisms of epigenetics include DNA methylation, histone modification, and micro RNAs. Observational data obtained from epidemiological studies of MS, such as the parent-of-origin effect and the longitudinal increase in female patients, suggest that epigenetic mechanisms are involved in MS development, although the molecular basis remains unclear. Interestingly, environmental factors related to the development of MS, such as Epstein-Barr virus, smoking, and vitamin D, have been shown to regulate gene expression through epigenetic mechanisms in some experimental settings. One study showed no reproducible differences among DNA methylation profiles in peripheral blood CD4+ T cells between three monozygotic twin pairs discordant for MS. However, several studies have shown that dysregulated DNA methylation of genes is related to abnormal immune reactions and post-translational modifications of myelin proteins in MS brain samples. In addition, abnormal micro RNA profiles have been reported in brain tissues and peripheral blood immune cells obtained from MS patients. In this article, we will review the studies on the epigenetics of MS and discuss the perspectives for future research. [ABSTRACT FROM AUTHOR]

Objectives To evaluate pregnancy outcomes in Japanese patients with multiple sclerosis (MS) enrolled in a postmarketing surveillance study of intramuscular interferon beta-1a (IM IFN beta-1a). Methods Safety data were collected from Japanese patients receiving 30 lg weekly IM IFN beta-1a. Pregnancy outcomes and annualized relapse rates (ARR) were analyzed retrospectively in patients who registered into the postmarketing surveillance study. Results A total of 1110 of 1638 patients registered in the postmarketing surveillance study were women. A total of 21 pregnancies (20 patients) resulted in 17 live births, 2 induced abortions, one spontaneous abortion and one unknown outcome. Weights and lengths of the 17 newborns were similar to newborns in the general Japanese population. No complications or malformations were reported. Of these 20 patients, nine experienced relapses in the year after childbirth, two experienced relapses in the year before pregnancy, and one experienced relapses before and during pregnancy. The mean (standard deviation) ARR was 0.94 (2.18) in the year before pregnancy, 0.25 (1.00), 0 (0) and 0 (0) in the three trimesters of pregnancy, and 1.05 (1.81), 0.84 (1.68), 0.63 (2.01) and 0.21 (0.92) in the first four quarters postpartum. Of the five patients who relapsed during the first quarter postpartum, only one had resumed IFN beta-1a treatment for 35 days. Conclusions Although sample size limits our ability to draw definitive conclusions, we did not find evidence that IFN beta-1a has adverse effects on pregnancy outcomes in Japanese patients with MS. Early IFN beta-1a resumption might reduce the risk of relapse within the first quarter postpartum. [ABSTRACT FROM AUTHOR]

Objective Enzyme-linked immunosorbent assay ( ELISA) is the conventional technique for antiglycolipid antibody testing in inflammatory neuropathy sera. Miniaturized array-based assays (glycoarrays) have also been used to detect these antibodies. As previous studies have focused on specific disease categories, such as Guillain-Barré syndrome, the array has never been tested on an unselected population in a routine diagnostic laboratory setting. Methods In the present prospective study, we compared the results of the glycoarray with data obtained with a standardized inflammatory neuropathy cause and treatment- ELISA. A total of 300 sera sent to the Glasgow Neuroimmunology Laboratory for routine antiglycolipid antibody testing during a 6-month period were tested both with ELISA and glycoarray. Results The two techniques were significantly correlated and showed good agreement. By ELISA, six sera were positive for immunoglobulin G antibodies against GM1 or GD1a, 11 for immunoglobulin G anti- GQ1b antibodies, five for immunoglobulin M anti- GM1 antibodies and three for immunoglobulin M antibodies against disialosyl gangliosides. The glycoarray had a sensitivity of 92% to detect ELISA-positive sera with a specificity above 92% for all the different ELISA patterns. Conclusions The glycoarray allows testing of large panels of antibodies against single glycolipids and complexes of glycolipids on a very small scale. Its technical characteristics make it suitable as a diagnostic screening test. As data provided by the glycoarray and ELISA were reliably correlated in the present study, the glycoarray can be used in a routine setting to detect antiglycolipid antibodies. Further studies, including more positive samples, are required to clarify the future position of the array in the biological investigation of inflammatory neuropathies. [ABSTRACT FROM AUTHOR]

Pediatric myasthenia gravis (P- MG) is an autoimmune disease affecting the neuromuscular junction ( NMJ), and is rare in children. The roadmap of the research carried out for P- MG in Hong Kong over the past 30 years was reviewed. Currently, there is a lack of epidemiological studies in comparing clinical data or the outcome for people of different ethnic origins. P- MG is more common in Asians, especially Chinese and Japanese. Because of the lack of comparison studies for P- MG worldwide, the author initiated collaboration with international colleagues in 2008, and set up 'The International Paediatric Myasthenia Gravis Registry Focus Group ( FG)' in 2009. We then established an 'International Pediatric Myasthenia Gravis Registry ( IPMGR)' to review the current knowledge of P- MG in children. We designed an e- MG questionnaire for 'Myasthenia Syndromes in Children,' and launched through the website ( ICNAPaedia) of the International Child Neurology Association ( ICNA) in 2009-2010. As of 2014, we had collected 121 replies from clinicians-researchers in 43 countries. In 2013, we started a Delphi process for obtaining a consensus for diagnosis, management and treatment of P- MG. Despite the lack of research funding support as a result of the rarity of P- MG, and the lack of innovative pharmaceutical research and development, we still stress that we set up a foundation as a small step towards consolidating international collaboration to carry out epidemiological studies, genetic studies and randomized controlled trials of all the current available treatments, especially steroids for ocular P- MG, and indications for thymectomy. [ABSTRACT FROM AUTHOR]

The article discusses the 9th Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS) meeting held at the Millennium Hilton Bangkok Hotel in Bangkok, Thailand from October 27-29, 2016. Topics include the presentation of several topics including the outcomes of neuromyelitis optica spectrum disorders (NMOSD) treatment through rituximab, the T cell repertoire on multiple sclerosis (MS) patients, and neuroimaging approach for demyelinating disease.

Monocytes and microglia both originate from myeloid precursor cells and share common characteristics even after differentiation. Recent studies have shown functional differences between these cell types, indicating their unique roles in lesion formation in neurodegenerative diseases. The present review summarizes the functional characteristics of these 'similar but different' macrophages in both health and disease. [ABSTRACT FROM AUTHOR]

Autoimmunity in the central nervous system ( CNS) seems to be a physiological process that might normally occur from the very early stages of fetal development. There is some evidence suggesting that CNS autoimmunity could participate in brain structuring, early antigen recognition and immune tolerance. Interestingly, clues to the occurrence of such early events can be discovered in cord blood samples from newborns and peripheral blood, as well as cerebrospinal fluid samples from adults by means of antibody profiling, through antigen microarray technology. In the past, results from those studies raised the possibility for the existence of a physiological autoantibody network recognizing self-key antigens, as proposed by Irun Cohen many years ago. After examining those findings, I suggest the existence of a specific autoantibody network recognizing resident antigens, which would eventually behave as a two-sided sword in the CNS. It might act as a framework for the organization of local immune homeostasis, which is necessary for the maintenance of neurophysiological processes. On the contrary, it might also participate in the pathogenesis of abnormal autoimmunity after the loss of tolerance to resident antigens. The disturbance of this synchronic homeostasis by environmental stimuli might trigger abnormal reactivity, influenced by favorable genetic conditions. In this regard, the evidence supporting some cutting-edge concepts that are intended to comprehensively characterize the molecular and cellular mechanisms likely implicated in abnormal CNS autoimmunity (primarily in multiple sclerosis) is presented. Finally, the usefulness of the detection of specific disease-associated autoantibodies and autoantibody profiling as clinical tools is also approached. [ABSTRACT FROM AUTHOR]