Neuroimmunological Conditions Research Articles

Dopamine-driven Increase in IL-1β in Myeloid Cells is Mediated by Differential Dopamine Receptor Expression and Exacerbated by HIV.

The catecholamine neurotransmitter dopamine is classically known for regulation of central nervous system (CNS) functions such as reward, movement, and cognition. Increasing evidence also indicates that dopamine regulates critical functions in peripheral organs and is an important immunoregulatory factor. We have previously shown that dopamine increases NF-κB activity, inflammasome activation, and the production of inflammatory cytokines such as IL-1β in human macrophages. As myeloid lineage cells are central to the initiation and resolution of acute inflammatory responses, dopamine-mediated dysregulation of these functions could both impair the innate immune response and exacerbate chronic inflammation. However, the exact pathways by which dopamine drives myeloid inflammation are not well defined, and studies in both rodent and human systems indicate that dopamine can impact the production of inflammatory mediators through both D1-like dopamine receptors (DRD1, DRD5) and D2-like dopamine receptors (DRD2, DRD3, and DRD4). Therefore, we hypothesized that dopamine-mediated production of IL-1β in myeloid cells is regulated by the ratio of different dopamine receptors that are activated. Our data in primary human monocyte-derived macrophages (hMDM) indicate that DRD1 expression is necessary for dopamine-mediated increases in IL-1β, and that changes in the expression of DRD2 and other dopamine receptors can alter the magnitude of the dopamine-mediated increase in IL-1β. Mature hMDM have a high D1-like to D2-like receptor ratio, which is different relative to monocytes and peripheral blood mononuclear cells (PBMCs). We further confirm in human microglia cell lines that a high ratio of D1-like to D2-like receptors promotes dopamine-induced increases in IL-1β gene and protein expression using pharmacological inhibition or overexpression of dopamine receptors. RNA-sequencing of dopamine-treated microglia shows that genes encoding functions in IL-1β signaling pathways, microglia activation, and neurotransmission increased with dopamine treatment. Finally, using HIV as an example of a chronic inflammatory disease that is substantively worsened by comorbid substance use disorders (SUDs) that impact dopaminergic signaling, we show increased effects of dopamine on inflammasome activation and IL-1β in the presence of HIV in both human macrophages and microglia. These data suggest that use of addictive substances and dopamine-modulating therapeutics could dysregulate the innate inflammatory response and exacerbate chronic neuroimmunological conditions like HIV. Thus, a detailed understanding of dopamine-mediated changes in inflammation, in particular pathways regulating IL-1β, will be critical to effectively tailor medication regimens.

Real-world efficacy, roll-out and uptake of intramuscular tixagevimab/cilgavimab as COVID-19 pre-exposure prophylaxis in people with multiple sclerosis and neuroimmunological conditions during the COVID-19 pandemic

BackgroundIn Australia, tixagevimab/cilgavimab 150 mg/150 mg was a government-funded pre-exposure prophylaxis for COVID-19 people with multiple sclerosis (pwMS) and other neuroimmunological conditions (pwNIc) treated with anti-CD20 antibodies or sphingosine-1-phosphate receptor...

Safety and tolerability of intravenous immunoglobulin infusion in Down syndrome regression disorder.

Three large multi-center studies have identified the clinical utility of intravenous immunoglobulin (IVIg) in the treatment of Down syndrome regression disorder (DSRD). Yet the tolerability of infusions in individuals with DS and the safety of IVIg remains unknown in this population. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD compared to a real-world cohort of individuals with pediatric onset neuroimmunologic disorders. A single-center, retrospective chart review evaluating clinically documented infusion reactions was performed for individuals meeting international consensus criteria for DSRD and having IVIg infusions between 2019 and 2023. Infusion reactions were evaluated for severity and need for alterations in infusion plan. This cohort was compared against an age and sex matched cohort of children with neuroimmunologic conditions who had also received IVIg infusions. In total, 127 individuals with DSRD and 186 individuals with other neuroimmunologic disorders were enrolled. There was no difference in the overall rate of adverse reactions (AEs) between the DSRD and general neuroimmunology cohorts (p = 0.31, 95% CI: 0.80-2.00), but cardiac-related AEs specifically were more common among the DSRD group (p = 0.02, 95% CI: 1.23-17.54). When AEs did occur, there was no difference in frequency of pharmacologic intervention (p = 0.12, 95% CI: 0.34-1.13) or discontinuation of therapy (p = 0.74, 95% CI: 0.06-7.44). There was a higher incidence of lab abnormalities on IVIG among the general neuroimmunology cohort (p = 0.03, 95% CI: 0.24-0.94) compared to the DSRD cohort. Transaminitis was the most common laboratory abnormality in the DSRD group. In a large cohort of individuals with DSRD, there were no significant differences in the safety and tolerability of IVIg compared to a cohort of children and young adults with neuroimmunologic conditions.

Sleep Disturbances in Autoimmune Neurological Diseases.

To summarize the current evidence on the associations between autoimmune neurological diseases (e.g., multiple sclerosis, myasthenia gravis) and sleep disturbances (e.g., insomnia, parasomnias), as well as to review the main characteristics of sleep disorders with an immune-related pathophysiology (e.g., narcolepsy, anti-IgLON5 disease). An immune-mediated damage of the areas in the central nervous system that control sleep and wake functions (e.g., hypothalamus, brainstem) can lead to sleep disorders and sleep symptoms. Sleep disturbances are the reason to seek for medical attention in certain neuroimmunological conditions (e.g., narcolepsy, anti-IgLON5 disease) where sleep-related alterations are the main clinical feature. The assessment of sleep-related symptomatology and disorders should be included in the routine evaluation of patients with autoimmune neurological diseases. Clinicians should be aware of the typical clinical presentation of certain neuroimmunological disorders mainly affecting sleep.

Differential Diagnosis of Tumor-like Brain Lesions.

Tumor-like brain lesions are rare and commonly suggest a neoplastic etiology. Failure to rapidly identify non-neoplastic causes can lead to increased morbidity and mortality. In this review, we describe 10 patients who presented with atypical, non-neoplastic tumor-like brain lesions in which brain biopsy was essential for a correct diagnosis and treatment. There has been increasing recognition of autoimmune conditions affecting the nervous system, and many of those diseases can cause tumor-like brain lesions. Currently available reports of non-neoplastic tumor-like brain lesions are scarce. Most case series focus on tumefactive demyelinating lesions, and a comprehensive review including other neuroimmunological conditions such as CNS vasculitis, neurosarcoidosis, histiocytic and infectious etiologies is lacking. We review the literature on tumor-like brain lesions intending to increase the awareness and differential diagnosis of non-neoplastic brain tumor mimics. We advocate for earlier brain biopsies, which, in our case series, significantly changed diagnosis, management, and outcomes.

Facilities, selection, outcome measurement, and limitations of therapeutic plasma exchange for neuroimmunological disorders: The South East Asian survey study.

Therapeutic plasma exchange (TPE) for neuroimmunological disorders has played an important role in the Southeast Asian region. This study investigates the challenges of performing TPE within the region. A questionnaire-based survey was conducted and launched to 15 South East Asian Therapeutic Plasma Exchange Consortium (SEATPEC) members from seven countries in January 2021. It included demographics, TPE techniques, indications, challenges, timing, outcome measurement, and access to laboratory testing in each local center. A total of 15 neurologists from 12 participating centers were included. They usually perform five sessions of TPE (100.0%), with 1 to 1.5 plasma volume (93.3%), and exchanges via the central catheter (100.0%). Acute relapses of neuromyelitis optica spectrum disorder and myasthenia gravis are the most common indications. They used a combination of normal saline and 5% albumin (60.0%) as replacement fluid. Most (66.7%) used TPE as an add-on treatment in steroid-refractory cases or as first-line treatment for severe attacks. They suggested assessing the TPE efficacy of TPE by the interval to the next attack, post-TPE relapse rates, and TPE-related complications. The major challenges within our region are expense, reimbursibility, and access to TPE. Although countrywise differences exist, all share similarities regarding methods, indications, timing, obstacles, and challenges of TPE for neuroimmunological conditions. Regional collaboration will be essential to identify strategies to reduce these barriers to access to TPE in the future.

Piloting an Advanced Neuroimmunology Elective for Neurology Residents

Objective To describe the creation of an Advanced Neuroimmunology elective for residents with a special interest in clinical neuroimmunology. Background There has been a dramatic change in the landscape of neuroimmune conditions with the discovery of new pathogenic autoantibodies, disease modifying therapies and wider availability of multidisciplinary care systems for patients. Most residencies do offer exposure to multiple sclerosis but with increasing interest in neuroimmunology and autoimmune neurological conditions, there is a gap in resident education to meet needs of this changing landscape. Design/Methods A curriculum for advanced neuroimmunology (NI) was developed for residents with special interest in clinical neuroimmunology. This two-week elective consisted of rotations through NI and affiliated multidisciplinary clinics to increase exposure to immune mediated neurological illnesses, appreciate their heterogeneity, and aid multi-disciplinary approach. Department experts in various disease states related to neuroimmunology were contacted and based on interest and resident elective time, a schedule was set up for rotations through neuroinfectious diseases, pulmonary sarcoidosis clinic, neuro-oncology, neuropathology and rheumatology. An additional expectation was to work with the fellow on inpatient consults that came in through the 2 weeks. In addition to multiple sclerosis/neuroimmunology division didactics, residents are encouraged to attend other affiliated department conferences as well as present at interdepartmental meetings, such as neuro-rheumatology conference. Results The availability of this elective allowed increased exposure to neuroimmunological conditions outside the typical Multiple Sclerosis elective at UTHealth. It also has allowed for additional inter-departmental collaboration clinically. Since the initial pilot elective, more residents have requested this as an elective and will be surveyed about their experience. Conclusions There is an unmet need for MS and NI subspecialists. Exposure to the broad spectrum of neuroimmunological conditions through multi-disciplinary collaborations during residency is instrumental to ensure future specialists have the foundations to adapt to this rapidly advancing field.

Curriculum Innovations: Virtual Didactics as a Tool for Harmonizing Education About Rare Topics in Neuroimmunology.

Neuroimmunology is a rapidly evolving subspecialty. At this time, fellowship training is not standardized. Discrepancies exist in fellowship programs across the United States, including in faculty expertise in rarer neuroimmunologic conditions. Many graduating fellows feel uncomfortable managing the full spectrum of diseases within neuroimmunology. To evaluate the feasibility and efficacy of a series of live, virtual, interinstitutional seminars educating neuroimmunology fellows on topics that may be infrequently encountered by trainees. A steering committee of 6 neuroimmunology and multiple sclerosis fellowship program directors selected 18 topics felt to be high yield but representing unique areas of expertise. A live, interactive seminar series was organized. Recognized experts on each topic led seminars using a teleconferencing platform over the 2020-2021 academic year. Recordings were subsequently made available for asynchronous learning. Trainees were surveyed before and after the seminar series and comfort levels with each topic were recorded. An average of 41 trainees participated in each live seminar and an additional average of 17 trainees viewed each seminar on demand. Trainee comfort levels with each topic increased after the seminar series was completed. An average of 72% of trainees self-identified as at least "comfortable" with each topic after the series compared with 26% beforehand (p < 0.0001). A year-long series of live, interactive, interinstitutional seminars focusing on unique topics within a single subspecialty represents an effective way to increase trainee comfort levels with such topics.

Intravenous Immune Globulins vs Plasma Exchange Usage in Patients with Neuromuscular and Neuro-immunological Conditions (P4-13.007)

Intravenous Immune Globulins vs Plasma Exchange Usage in Patients with Neuromuscular and Neuro-immunological Conditions (P4-13.007)

Anti-Spike IgG in multiple sclerosis patients after BNT162b2 vaccine: An exploratory case-control study in Italy

BackgroundPatients with neuroimmunological conditions such as multiple sclerosis (MS) often receive disease-modifying therapies (DMTs) or immunosuppressants which may reduce the response to vaccines. BNT162b2 (Pfizer-BioNTech) is the first COVID-19 vaccine authorized in Italy. Its clinical efficacy and serological response were not evaluated in MS patients receiving DMTs or immunosuppressants. This early multicenter study evaluated serological response to BNT162b2 and safety in these patients. MethodsFrom February 2021 we enrolled consecutive MS patients, treated with at least one DMT and all healthcare workers (HCWs), having received or being scheduled to receive the first dose of BNT162b2. Blood samples were collected after the second vaccine dose and analyzed to quantitatively detect the presence of anti-Spike antibodies. Serological response was compared to the one from a control population of HCWs, with neither neuroimmunological conditions nor receiving immunosuppressants. Patients receiving treatments associated with a possible reduced response (Under-scrutiny treatment group) were also compared to those undergoing other treatments. Anti-Spike levels were described as median and interquartile range (IQR). Comparisons were performed with Wilcoxon-Mann-Whitney test. Solicited and unsolicited adverse events (AEs) were collected. Results39 MS patients and a control population of 273 HCWs were included. One patient, under treatment with ocrelizumab, did not respond to BNT162b2, while all the remaining patients and all controls developed a serological response to the vaccine. Median anti-Spike levels were similar between patients (1471.0 BAU/ml; IQR 779.7 to 2357.0) and controls (1479.0 BAU/ml; IQR 813.1 to 2528.0) (p = 0.53). Patients included in the Under-scrutiny treatments group showed reduced anti-Spike levels (156.4 BAU/ml; IQR 33.4 to 559.1) compared to those receiving other treatments (1582.4 BAU/ml; IQR 1296.5 to 2219.0) (p = 0.001). Solicited AEs were all mild to moderate in severity, generally reported in the first days after vaccination, and resolved in the following days. Two MS patients reported a clinical relapse after the second vaccine dose. ConclusionBNT162b2 induced a serological response in MS patients treated with DMTs similar to controls not receiving DMTs or immunosuppressants. Some treatments were associated with reduced levels of anti-Spike antibodies in patients. These observations have relevant implications for treated patients receiving BNT162b2 and the community.

Low-dose intrathecal rituximab is a safe and potentially effective treatment for pediatric neuroimmunologic disorders

Historically, treatment options for refractory neuroimmunologic disorders have been limited. Use of intrathecal rituximab has been described in a few case reports but experience in pediatric patients is limited. Here, we report our experience with intrathecal rituximab in 5 pediatric patients with refractory neuroimmunologic conditions. Patients were identified based on treatment-refractory symptoms despite first and second-line therapies and treated according to a standardized protocol. Although individual outcomes varied, intrathecal rituximab showed a favorable safety profile and was well-tolerated. Three out of five patients showed evidence of a positive clinical response assessed by modified Rankin score or Mitchell-Pike Opsoclonus-Myoclonus score. Findings from this retrospective observational study suggest that intrathecal rituximab is a safe and potentially effective therapy in carefully selected patients with refractory neuroimmunologic disorders despite appropriate first and second-line therapies.

Emerging role of white matter lesions in cerebrovascular disease.

White matter lesions have been implicated in the setting of stroke, dementia, intracerebral haemorrhage, several other cerebrovascular conditions, migraine, various neuroimmunological diseases like multiple sclerosis, disorders of metabolism, mitochondrial diseases and others. While much is understood vis a vis neuroimmunological conditions, our knowledge of the pathophysiology of these lesions, and their role in, and implications to, management of cerebrovascular diseases or stroke, especially in the elderly, are limited. Several clinical assessment tools are available for delineating white matter lesions in clinical practice. However, their incorporation into clinical decision-making and specifically prognosis and management of patients is suboptimal for use in standards of care. This article sought to provide an overview of the current knowledge and recent advances on pathophysiology, as well as clinical and radiological assessment, of white matter lesions with a focus on its development, progression and clinical implications in cerebrovascular diseases. Key indications for clinical practice and recommendations on future areas of research are also discussed. Finally, a conceptual proposal on putative mechanisms underlying pathogenesis of white matter lesions in cerebrovascular disease has been presented. Understanding of pathophysiology of white matter lesions and how they mediate outcomes is important to develop therapeutic strategies.

Utilization of Visual Acuity Retroilluminated Charts for the Assessment of Afferent Visual System Dysfunction in a Pediatric Neuroimmunology Population

Visual acuity has been a significant outcome measure in clinical trials for patients suffering from neuro-ophthalmological diseases and multiple sclerosis; however, there are limited data on the comparison of various testing strategies in pediatric patients with these disorders. Clinical trials using vision as an outcome could include a variety of tools to assess the acuity, including 2-m and 4-m standardized retroilluminated charts. We investigated the difference in Early Treatment Diabetic Retinopathy Study (ETDRS) scores obtained using 2-m and 4-m charts, as well as the impact of optic neuritis, use of vision correction, age, and gender on visual acuity data from 71 patients with pediatric neuroimmunological conditions in a cross-sectional study. We determine that the ETDRS letter scores obtained using 4-m charts are on average 3.43 points less (P = 0.0034) when testing monocular ETDRS letter scores and on average 4.14 points less (P = 0.0008) when testing binocular ETDRS letter scores, relative to that obtained using the 2-m charts. However, we find that when performing monocular testing, optic neuritis in the eye being tested did not result in a statistically significant difference between 2-m and 4-m ETDRS letter scores. Although visual acuity charts are formatted by the distance, there are significant differences in the number of letters correctly identified between 2-m and 4-m charts. Although the differences may not impact the clinical acuity, research protocols should consider these differences before collapsing data across disparate studies.

Neuroimmunogastroenterology: At the Interface of Neuroimmunology and Gastroenterology.

The central nervous system (CNS) is an important regulator of the gastrointestinal tract, and CNS dysfunction can result in significant and disabling gastrointestinal symptom manifestation. For patients with neuroimmunologic and neuroinflammatory conditions, the recognition of gastrointestinal symptoms is under-appreciated, yet the gastrointestinal manifestations have a dramatic impact on quality of life. The current treatment strategies, often employed independently by the neurologist and gastroenterologist, raise the question of whether such patients are being treated optimally when siloed in one specialty. Neuroimmunogastroenterology lies at the borderlands of medical specialties, and there are few resources to guide neurologists in this area. Here, we provide an overview highlighting the potential mechanisms of crosstalk between immune-mediated neurological disorders and gastrointestinal dysfunction.

Chapter 6 - Neuroimmunologic disorders in pregnancy

Pregnancy influences the course of neuroimmunologic conditions, which include multiple sclerosis (MS), neuromyelitis optica spectrum disorder, and autoimmune encephalitis. The outcomes differ significantly for each disorder, reflecting the impact of hormonal changes, T-cell subsets, and placental factors on disease pathogenesis. In recent years, numerous data have emerged regarding MS activity throughout pregnancy and postpartum. Historically, the misconception that pregnancy worsens MS outcomes led patients to abstain from childbearing. Now, more women with these disorders, empowered by up-to-date information and better baseline disease control, are choosing to conceive. Nevertheless, the management of MS and related disorders in the pregnancy and postpartum period is complicated and requires a nuanced approach. Since standardized treatment guidelines around pregnancy are currently lacking, neurologists, together with obstetricians, must engage patients in a shared decision-making process that weighs the benefits to the mother and risks to the fetus. This chapter outlines the pathophysiology of neuroimmunologic disorders during pregnancy and postpartum, the impact of these diseases on childbearing, including fertility, pregnancy, delivery, and peurperium, as well as existing recommendations for treatment.

Clinic to in-home telemedicine reduces barriers to care for patients with MS or other neuroimmunologic conditions.

ObjectiveTo describe the routine use of telemedicine-enabled neurologic care in an academic outpatient MS and neuroimmunology clinic and quantify its role in reducing patient burden.MethodsBetween January 2017 and December 2017, we surveyed patients and MS neurologists after 50 consecutive routinely scheduled televideo visits and a convenience sample of 100 in-clinic visits. Summary statistics were calculated and comparisons performed.ResultsOverall, 98% televideo participants found the technology easy to use, and only 17% believed that an in-person examination would have more effectively addressed their needs for the visit. MS neurologists reported achieving their clinical goals in 47/48 (98%) of televideo visits and an adequate physical examination with 2 exceptions (possible cauda equina syndrome and visual field loss). Three emergency department referrals were avoided due to televideo availability. Telemedicine reduced travel burden, including a mean (±SD) travel distance of 160 (±196) miles and avoiding overnight lodging and air travel. Telemedicine also reduced indirect costs, including time off work (65% of employed patients) and caregiver burden (30% avoided caregiver time off from work/obligations). Across 8 domains of provider interpersonal communication skills, telemedicine and in-clinic participants rated only 1 domain to be different (eye contact), and overall, 96% of in-clinic and 100% of telemedicine participants agreed/strongly agreed that their clinical goals had been met.ConclusionsWhen incorporated as part of the continuum of MS/neuroimmunology care, clinic to in-home telemedicine reduces travel and caregiver burden and enables efficient, convenient, and effective follow-up.

Ribonucleic acid sequencing data mining: A new tool for understanding neuroimmunological conditions

AbstractRNA sequencing is a next‐generation sequencing‐based approach for comprehensive gene expression analysis. The “big data’’ of RNA sequencing have been deposited in public databases. Two recent studies attempted to use such data to answer clinically relevant questions pertaining to neuroimmunology.

A neurologist's guide to safe use of immunomodulatory therapies.

Increased understanding of the pathogenesis of immune-mediated neurologic conditions with concomitant development of new therapeutic agents modulating various aspects of the immune system has resulted in the use of innovative therapies in the treatment of these diseases. These novel immunomodulatory therapeutic regimens also augment the potential for complications, including severe adverse effects.In this review, the authors address practical issues regarding management of patients with neuroimmunological conditions treated with immunomodulatory therapies, including glucocorticoids, methotrexate, azathioprine, mycophenolate, cyclophosphamide, rituximab, tumor necrosis factor-α inhibitors, and intravenous immunoglobulins. Particular focus is placed on their infectious and noninfectious adverse effects, contraindications, safety monitoring, risk surveillance, and preventive strategies in clinical practice.

Will anti-neuronal antibody biomarkers make neuropsychiatric systemic lupus erythematosus no longer a diagnosis of exclusion?

Development of the American College of Rheumatology (ACR) criteria for neuropsychiatric systemic lupus erythematosus (NPSLE) was a major step in understanding these disorders. Without biomarkers confirming a direct relationship between systemic lupus erythematous and the neuropsychiatric diagnoses, skeptics may view the ACR classification as mere semantics. However, by allowing neurologists and rheumatologists in different centers to use standardized terms, the criteria are useful in caring for patients and in assembling homogeneous groups of research participants. In pediatric systemic lupus erythematous cohorts, the prevalence of NPSLE in general, and movement disorders in particular, ranged from 34.6% and 0% in a retrospective study in Taiwan1 to 95% and 7% in a prospective study in the United States.2 For many patients, diagnosis and treatment are delayed as mimicking infectious, toxic, and metabolic conditions are ruled out. A diagnostic biomarker would be immensely helpful. Although history, examination, magnetic resonance imaging, cerebrospinal fluid (CSF) analysis, and standard autoantibody profiles are important, none are sufficiently sensitive or specific to be considered a diagnostic biomarker for NPSLE. The search for informative biomarkers in neuro-immunological conditions including NPSLE has been hampered by the use of techniques which alter the target antigen’s structure. Studies using cell-based assays, which preserve antigenic structure, have produced more clinically useful and scientifically valid results. At least two prior studies have used cell-based, flow cytometry assays in NPSLE. In adult patients with NPSLE, Alosachie et al.3 found antibodies to a neuroblastoma cell line in 63% (36/57) of serum samples and 83% (5/6) of CSF samples, but none using a glioma cell line. In a cohort of 17 adult patients with NPSLE, Kang et al.4 detected antibodies to the same neuroblastoma cell line in 77% (13) of serum and 88% (15) of CSF samples. In the latter study, abnormalities in magnetic resonance imaging and CSF anti-ribosomal P antibody assays were found in only 59% and 18% of patients with NPSLE respectively. In both studies, patients with systemic lupus erythematous without neuropsychiatric symptoms, and disease and healthy controls rarely harbored such antibodies, thus yielding good positive and negative predictive values, particularly for the CSF assays.3,4 Dale et al.,5 the first group to apply these techniques to pediatric NPSLE patients, found elevated serum immunoglobulin G binding to the surface of cells with dopaminergic neuronal characteristics in six females with chorea (n=4) or parkinsonism (n=2) associated with lupus and/or anti-phospholipid antibodies compared with healthy and disease controls. The fact that similar levels of antibodies were detected in patients with lupus without neuropsychiatric symptoms contrasts with the prior reports and is somewhat troubling. This finding suggests a difference between pediatric and adult NPSLE and/or the requirement for a ‘second hit’ to cause clinical expression, but ultimately remains unexplained in the current study. From the above studies, several points emerge. First, anti-neuronal autoantibodies appear to be important in NPSLE. Secondly, based on the two adult studies, measurement of such antibodies in CSF may be more meaningful than in serum. The lack of testing in CSF in the current study is an important limitation. Lastly, the target cell type chosen for the antibody assays may be critically important. An elegant feature of the current study is that the authors used a cell line with dopaminergic characteristics to detect antibodies in the subgroup of patients with movement disorders within NPSLE. This raises several questions. Does this approach explain why Dale et al. found elevated antibodies in all of the patients, compared with prior studies with lower sensitivity? Would the dopaminergic cell assay detect antibodies in other NPSLE subgroups? What is the best cell type to use for other, more common NPSLE diagnoses, such as headaches, seizures, and mood disorders? Future research will hopefully identify the specific antigen targeted by the autoantibodies in patients with NPSLE, perhaps within diagnostic subgroups. Such identification is necessary to elevate the status of the currently identified autoantibodies from an informative, but not definitive, finding, to the next big diagnostic biomarker in the field.

NEUROIMAGING OF DEMYELINATING DISEASES

ABSTRACTThe availability of advanced imaging techniques, especially that of MRI, has truly revolutionized the field of clinical neuroimmunology. MRI is extensively used in the diagnosis, prognostication, and disease monitoring of neuroimmunologic conditions. MRI biomarkers are integral parts of the