Clinical and paraclinical characteristics of optic neuritis in the context of the McDonald criteria 2017.

Optic neuritis is often an initial symptom in multiple sclerosis (MS) or clinically isolated syndrome (CIS), yet comprehensive studies using the 2017 McDonald criteria for MS are scarce. Patient records from our academic centre (2010-2018) were reviewed. Using the 2017 McDonald criteria, three groups were formed: MS optic neuritis (optic neuritis with confirmed MS), CIS optic neuritis (optic neuritis without confirmed MS) and suspected optic neuritis (sON). We compared clinical and paraclinical findings among the groups to identify predictors for CIS- or MS-optic neuritis. The study included 129 MS, 108 CIS, and 44 sON cases. The combination of visual impairment, dyschromatopsia, and retrobulbar pain was observed in 47% of MS patients, 42% of CIS patients, and 30% of sON patients. Dyschromatopsia was the strongest indicator of MS or CIS diagnosis in the backward regression model. 56% of MS patients had relative afferent pupillary defect, 61% optic nerve anomalies within magnetic resonance imaging, and 81% abnormal visual evoked potentials. Our results emphasize the challenges in diagnosing optic neuritis, as not all patients with objectively diagnosed MS exhibit the triad of typical symptoms. To address potentially missing clinical features, incorporating additional paraclinical findings is proposed.

Differential diagnosis between multiple sclerosis and leukodystrophies - A scoping review.

Multiple Sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) characterized by damage to the myelin sheaths of oligodendrocytes. Currently, there is no specific biomarker to identify the disease; however, a diagnostic criterion has been established based on patient's clinical, laboratory, and imaging characteristics, which assists in identifying this condition. The primary method for diagnosing MS is the McDonald criteria, first described in 2001 and revised in the years 2005, 2012, and 2017. These criteria have been continuously reviewed to enhance specificity and sensitivity in the diagnosis of MS, thereby reducing errors in its differential diagnosis. An important differential diagnosis that shares overlapping features with MS, mainly the progressive forms, are leukodystrophies with demyelination as underlying pathology. Leukodystrophies comprise a rare group of genetically determined disorders that lead to either demyelination or hypomyelination of the central nervous system that can result neuroimaging changes as well as clinical findings similar to those observed in MS. Thus, systematic evaluation encompassing clinical presentation, neuroimaging findings, and laboratory metrics proves indispensable for a differential diagnosis. As such, this study aimed to establish, clearly and objectively, the similarities and differences between MS and the main demyelinating leukodystrophies. The study analyzed the parameters of the McDonald criteria, including clinical, laboratory, and magnetic resonance imaging aspects, as found in patients with leukodystrophies through scoping literature review. The data were compared with the determinations of the revised 2017 McDonald criteria to facilitate the differential diagnosis of these diseases in clinical practice.

Tumefactive demyelinating lesions: a retrospective cohort study in Thailand.

Tumefactive demyelinating lesions (TDL), characterized by large (≥ 2 cm) demyelinating lesions mimicking tumors, are a rare manifestation of the central nervous system inflammatory demyelinating diseases (CNS-IDD). Distinguishing TDL from other brain lesions can be challenging, often necessitating biopsy or advanced diagnostics. The natural history of TDL varies among races. This study aimed to assess demographics, clinical and radiological features, laboratory findings, management, and outcomes of Thai patients with TDL. We retrospectively reviewed records of twenty-six patients with TDL from the Multiple Sclerosis and Related Disorders registry from two tertiary medical centers. Among 1102 CNS-IDD patients, 26 (2.4%) had TDL. The median age at TDLs onset was 34.5 years (range 17-75); 69.2% were female. Over 70% manifested TDL as their initial CNS-IDD presentation. Common presenting symptoms included motor deficits, sensory disturbances, and cognitive problems. About two-fifths exhibited multiple lesions, most frequently in the frontoparietal region (46.2%). Half of the patients showed an incomplete ring on post-contrast T1-weighted imaging, with peripheral diffusion-weighted imaging restriction in twenty-one patients. T2-hypointense rims were present in thirteen (56.5%) patients. Brain biopsy was performed in 12 cases (46.1%). Serum aquaporin-4 immunoglobulin was positive in 16.7% of tested (4/24) cases. Serum myelin oligodendrocyte glycoprotein immunoglobulin was negative in all thirteen patients tested. Twenty patients (76.9%) received intravenous corticosteroids for TDL attacks. After the median follow-up period of 48 months (range 6-300), 23.1% experienced CNS-IDD relapses. Median Expanded Disability Status Scale at TDL diagnosis was 4.3 (range 0.0-9.5), and improved to 3.0 (range 0.0-10.0) at the last follow-up. This study suggested that TDL were rare among Thai CNS-IDD patients, frequently presenting as a monophasic condition with a favorable outcome.

Clinically isolated syndrome: Diagnosis and risk of developing clinically definite multiple sclerosis.

INTRODUCTION: In most cases, multiple sclerosis (MS) initially presents as clinically isolated syndrome (CIS). Differentiating CIS from other acute or subacute neurological diseases and estimating the risk of progression to clinically definite MS is essential since presenting a second episode in a short time is associated with poorer long-term prognosis. DEVELOPMENT: We conducted a literature review to evaluate the usefulness of different variables in improving diagnostic accuracy and predicting progression from CIS to MS, including magnetic resonance imaging (MRI) and such biofluid markers as oligoclonal IgG and IgM bands, lipid-specific oligoclonal IgM bands in the CSF, CSF kappa free light-chain (KFLC) index, neurofilament light chain (NfL) in the CSF and serum, and chitinase 3-like protein 1 (CHI3L1) in the CSF and serum. CONCLUSIONS: Codetection of oligoclonal IgG bands and MRI lesions reduces diagnostic delays and suggests a high risk of CIS progression to MS. A KFLC index > 10.6 and CSF NfL concentrations > 1150 ng/L indicate that CIS is more likely to progress to MS within one year (40%-50%); 90% of patients with CIS and serum CHI3L1 levels > 33 ng/mL and 100% of those with lipid-specific oligoclonal IgM bands present MS within one year of CIS onset.

Clinical characteristics and long-term follow-up outcomes of myelin oligodendrocyte glycoprotein antibody-associated disease in Han Chinese participants.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated inflammatory demyelinating disease of the central nervous system. This study aimed to delineate the clinical manifestations, imaging features, and long-term outcomes in Chinese patients with MOGAD and analyze the recurrence-associated factors. The phenotypic and neuroimaging characteristics of 15 Han Chinese patients with MOGAD were retrospectively analyzed. Demyelinating attacks, MOG antibodies in the cerebrospinal fluid/serum, response to immunotherapy, follow-up outcomes, and recurrence-associated factors were recorded. The median age at disease onset was 34 years (range, 4-65 years). The most common initial presentations included vision loss (10/15, 66.7%) and seizures (5/15, 33.3%). Serum MOG-Ab titers in 14/15 cases were higher than those in the cerebrospinal fluid and were detected in 3/6 relapsed patients. Brain magnetic resonance imaging during acute attacks showed lesions in 10/15 patients (66.7%), mostly in the cortex/subcortical white matter (5/15, 33.3%). Recurrence occurred in 6/15 patients (40.0%); in 4 patients, recurrence occurred shortly after immunotherapy discontinuation. Residual neurological deficits were present in 5/15 patients (33.3%), including visual impairment, incapacitation, cognitive impairment, and speech reduction. Optic neuritis was the most common clinical manifestation of MOGAD. magnetic resonance imaging findings were heterogeneous and the cerebral cortex/subcortical white matter was the most susceptible brain region. Although patients in the acute phase responded well to methylprednisolone pulse therapy, the long-term recurrence rate was high. Consistently detected serum MOG antibodies and inappropriate maintenance immunotherapy may be associated with recurrence, and residual neurological deficits should not be ignored.

Kidney Transplant Recipient With Tumefactive Demyelinating Lesions: A Case Report and Literature Review.

Tumefactive demyelinating lesions (TDLs) are rare and specific types of inflammatory demyelinating lesions. Its clinical manifestations are nonspecific, and the imaging findings are similar to those of other intracranial space-occupying lesions, which are usually misdiagnosed as tumors or abscesses and require a pathologic examination to confirm the diagnosis. Tumefactive demyelinating lesions after kidney transplantation are even rarer. This article reports a case of TDLs after kidney transplantation. A 60-year-old female patient underwent kidney transplantation 15 years ago and took anti-rejection drugs such as tacrolimus, tacrolimus, and corticosteroids after surgery. The patient was admitted with headache and left limb weakness, and magnetic resonance imaging of the head showed multiple space-occupying lesions with surrounding edema. The patient underwent a stereotactic biopsy of the encephalopathy lesion, and postoperative pathology confirmed TDLs. She was treated with corticosteroids and discharged after the improvement of her symptoms. Here, to our knowledge, we report the first case of TDLs after kidney transplantation. We report this case to provide clinicians with useful information on intracranial demyelinating disease after kidney transplantation.

[A patient with anti-myelin oligodendrocyte glycoprotein antibody-associated combined central and peripheral demyelination with anti-galactocerebroside and anti-GM1 antibodies].

A 48-year-old male was admitted to our hospital because of chronic progressive demyelination of the peripheral nerves of the upper limbs, as well as acute myelitis presenting with sensory disturbance from the left chest to the left leg. We established a diagnosis of combined central and peripheral demyelination (CCPD). The patient was positive for serum anti-myelin oligodendrocyte glycoprotein (MOG), anti-galactocerebroside IgG, and anti-GM1 IgG antibodies. Intravenous methylprednisolone therapy and plasma exchange improved myelitis, and the subsequent administration of oral prednisolone yielded a gradual improvement of the peripheral nerve damage with a mostly negative result for the antibodies. However, the patient experienced a relapse of radiculitis eight months later. Relapses of anti-MOG antibody-associated disease can provoke new immune reactions, leading to CCPD.

Monophasic Acquired Demyelinating Syndromes of the Central Nervous System in Children.

Acquired demyelinating syndromes of the central nervous system are immune-mediated demyelinating disorders that can affect the brain, optic nerves, and spinal cord. These disorders have become increasingly recognized in children due to advances in imaging techniques, improvements in diagnostic testing, extensive research into understanding the pathophysiology underlying these disorders, and collaborative multi-institutional efforts to raise awareness of these disorders in children. Moreover, developments in the field of neuroimmunology have allowed us to identify autoantibodies that have presumed causal roles in acquired demyelinating syndromes. Identification of these autoantibodies helps determine clinical course (ie, monophasic vs relapsing course), prognosis, and treatment approach. Acquired demyelinating disorders can affect both children and adults. However, the clinical features, disease course, and treatments are often unique in the pediatric population. Thus, it is important to understand the spectrum of these disorders in children to help provide a timely diagnosis and prompt treatment to achieve optimal outcomes. In this article, the epidemiology, clinical features, diagnosis, treatment, and outcomes of the most common monophasic acquired demyelinating syndromes in children will be reviewed.

Conversion Predictors of Clinically Isolated Syndrome to Multiple Sclerosis in Mexican Patients: A Prospective Study.

BACKGROUND: Clinically Isolated Syndrome (CIS) is the first clinical episode suggestive of Clinical Definite Multiple Sclerosis (CDMS). There are no reports on possible predictors of conversion to CDMS in Mexican mestizo patients. AIM OF THE STUDY: To investigate immunological markers, clinical and paraclinical findings, and the presence of herpesvirus DNA to predict the transition from CIS to CDMS in Mexican patients. METHODS: A single-center prospective cohort study was conducted with newly diagnosed patients with CIS in Mexico between 2006 and 2010. Clinical information, immunophenotype, serum cytokines, anti-myelin protein immunoglobulins, and herpes viral DNA were determined at the time of diagnosis. RESULTS: 273 patients diagnosed with CIS met the enrolment criteria; after 10 years of follow-up, 46% met the 2010 McDonald criteria for CDMS. Baseline parameters associated with conversion to CDMS were motor symptoms, multifocal syndromes, and alterations of somatosensory evoked potentials. The presence of at least one lesion on magnetic resonance imaging was the main factor associated with an increased risk of conversion to CDMS (RR 15.52, 95% CI 3.96-60.79, p = 0.000). Patients who converted to CDMS showed a significantly lower percentage of circulating regulatory T cells, cytotoxic T cells, and B cells, and the conversion to CDMS was associated with the presence of varicella-zoster virus and herpes simplex virus 1 DNA in cerebrospinal fluid and blood. CONCLUSION: There is scarce evidence in Mexico regarding the demographic and clinical aspects of CIS and CDMS. This study shows several predictors of conversion to CDMS to be considered in Mexican patients with CIS.

Clinical spectrum and prognosis of pathologically confirmed atypical tumefactive demyelinating lesions.

To describe the clinical spectrum and prognosis of atypical tumefactive demyelinating lesions (TDLs), which were confirmed by pathology. A total of 11 patients were diagnosed with atypical TDLs confirmed by brain biopsy and surgery between January 2006 and December 2017. The clinical spectrum and prognosis in these patients were analyzed. The patients' ages ranged from 29 to 62 years, with a mean age of 48.9 years; 72.7% were males. The Expanded Disability Status Scale (EDSS) of the patients with first onset was 2.36. Most of the patients started with limb numbness and weakness (45.5%) or alalia (27.2%). The mean time from symptom onset to biopsy or surgery was 12.9 days (3-30 days). Most of the patients had solitary lesions (72.7%), supratentorial lesions (90.9%, particularly predominant in the frontal, temporal, and parietal lobes), moderate edema (63.6%), mild mass effect (54.5%), and patchy lesions (54.5%). Among them, three patients were positive for myelin basic protein (MBP) and one patient was positive for myelin oligodendrocyte glycoprotein (MOG). The patients were followed up for an average of 6.9 years (2-14 years), and recurrent TDLs were observed in 2 patients. Except for the 2 patients who relapsed, only 1 of the 9 patients died; the other 8 patients improved or maintained the status quo (the EDSS scores were lower or unchanged). The patients did not have any serious nervous system injury at onset, and the main presentation included extremity weakness, headache or dizziness, and alalia. The most common form was patchy on MRI enhancement. Cerebrospinal fluid and demyelination test can be an indicator of TDLs, and seizures may be a poor prognostic indicator. Most atypical TDLs have monophasic courses and good outcomes. The effect of neurosurgery alone was good in our group, and the effect of surgery on atypical TDLs can be further studied.

Myelin Oligodendrocyte Glycoprotein as an Autoantigen in Inflammatory Demyelinating Diseases of the Central Nervous System.

Demyelinating diseases of the central nervous system are caused by an autoimmune attack on the myelin sheath surrounding axons. Myelin structural proteins become antigenic, leading to the development of myelin lesions. The use of highly specialized laboratory diagnostic techniques for identification of specific antibodies directed against myelin components can significantly improve diagnostic approaches. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) currently includes demyelinating syndromes with known antigens. Based on the demonstrated pathogenic role of human IgG against MOG, MOGAD was classified as a distinct nosological entity. However, generation of multiple MOG isoforms by alternative splicing hinders antigen detection even with the most advanced immunofluorescence techniques. On the other hand, MOG conformational changes ensure the structural integrity of other myelin proteins and maintain human-specific mechanisms of immune autotolerance.

Predictive factors of multiple sclerosis relapse after the first demyelinating event: A 5-year follow-up.

There is a growing need to discover the characteristics that predict prognostic factors after the first demyelinating event. In this study of 141 patients that met the 2017 McDonald criteria, a higher number of oligoclonal bands, cervical spinal cord demyelinating lesions, and sensory involvement were identified as independent predictors of the second demyelinating event during the 5-year follow-up period in patients who experienced the first demyelinating event. The identification of the aforementioned risk variables will make it possible to identify patients who are more likely to exhibit early second demyelinating event, implying more frequent monitoring and consideration of early application of highly effective disease-modifying treatment.

Magnetic resonance imaging of disorders with white matter changes in children and adolescents: a pictorial essay.

White matter changes are seen in a spectrum of disorders in children and adolescents. Understanding their distribution and appearance helps to reach diagnoses in daily radiologic practice. This pictorial essay will outline the magnetic resonance imaging (MRI) appearances of diseases with white matter changes including demyelinating diseases, dysmyelinating disorders/leukodystrophies, infections, autoimmune diseases, vascular causes, mitochondrial disorders and neurocutaneous syndromes, along with a brief overview of clinical aspects of the diseases such as typical age of presentation, etiology, symptoms and signs and treatment options. This article highlights important features in common white matter diseases in children and adolescents.

Sixteen syndrome: a rare presentation of central demyelination.

This case illustrates two diagnostic challenges for clinicians: the rarely described sixteen syndrome and the relationship between tumour necrosis factor (TNF)-alpha inhibitors and central demyelination. Sixteen syndrome affects horizontal eye movements and the facial nerve bilaterally reflecting a lesion in the posterior pontine tegmentum, adjacent to the fourth ventricle. Given its rarity and complexity of clinical signs, this syndrome risks misdiagnosis and mismanagement. The relationship between TNF-alpha inhibitors and demyelination is a complex issue in which causality is yet to be established. This diagnostic challenge poses a management dilemma for clinicians.

Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: Kappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS. METHODS: We conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC). RESULTS: One thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (p = 0.123 and p = 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (p < 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (p < 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (p = 0.065). In the multivariate analysis model, female gender (p = 0.003), young age (p = 0.013), and evidence of disease activity (p < 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index. DISCUSSION: KFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders.

[Osmotic demyelination syndrome and overly rapid correction of hyponatremia]. / Syndrome de démyélinisation osmotique : quelle vitesse de correction de la natrémie ?

Hyponatremia is a frequent condition in hospitalized patients and is associated with significant morbidity and mortality. An association between rapid correction of hyponatremia and the occurrence of osmotic demyelination syndrome has been reported. Osmotic demyelination syndrome may present with severe neurologic symptoms, including in rare cases locked-in. Therefore, rapid correction of hyponatremia is recommended only in the presence of severe symptoms. In those cases, hypertonic saline (NaCl 3% 2 ml/Kg over 20 minutes) is recommended with close plasma sodium monitoring. After symptoms improvement, increases in sodium concentration should not exceed 8 mmol/l/24h. In cases without severe neurologic symptoms, the use of 3% NaCl solution should be avoided, and management should target the underlying causes of hyponatremia.

L'hyponatrémie est fréquente à l'hôpital avec une morbimortalité significative. Une association entre la vitesse de correction d'une hyponatrémie et la survenue d'un syndrome de démyélinisation osmotique (SDO) a été mise en évidence dans des études observationnelles. Dès lors, une correction rapide d'une hyponatrémie doit être réservée aux patients avec des symptômes sévères d'hyponatrémie. Dans ces situations, l'utilisation de NaCl 3 % (2 ml/kg) en bolus est recommandée avec des contrôles rapprochés de la natrémie. Après l'amélioration des symptômes, une vitesse de correction inférieure à 8 mmol/24 heures est indiquée. En l'absence de symptômes sévères, il est préférable d'éviter l'utilisation du NaCl 3 % et de traiter selon le mécanisme sous-jacent.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease: Presentation and outcomes of adults at a single center.

BACKGROUND/INTRODUCTION: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a chronic demyelinating disorder that has been increasingly recognized since the serum antibody became commercially available in 2017. The most common clinical presentation is optic neuritis, and first line acute treatment is intravenous (IV) steroids. However, there are many questions that remain unanswered. For clinicians and patients, the primary question is whether relapses will occur and whether to treat with chronic therapy. METHODS: This retrospective chart review examined characteristics of thirty-three known adult MOGAD cases at a single institute. Data was collected on patient demographics, clinical presentation, objective diagnosis with MRI and serum antibody levels, acute and chronic treatment and disease outcomes. RESULTS: Our MOGAD cases revealed a slight female to male predominance of 1.5:1. No racial groups were affected disproportionately, and age of symptom onset spanned a large range with a median of 40 years. The most common clinical and radiologic presentation was optic neuritis followed by transverse myelitis and brainstem symptoms/lesions. IV methylprednisolone was used in the vast majority of cases for acute treatment. 83.3% of our patients were treated with chronic therapy at some point during their disease course. Therapies include rituximab, IVIG, ocrelizumab, mycophenolate mofetil and ofatumumab. The majority of our patients were treated with rituximab and we did not see a significant benefit of yearly relapse reduction for rituximab versus other therapies. Our cohort had a higher-than- expected percentage of cases with relapsing disease (56.3%) compared to monophasic (43.8%). DISCUSSION/CONCLUSION: Our study confirms prior data regarding the demographics, clinical presentation and radiologic presentation of MOGAD. There is no consensus on whether maintenance therapy should be started for MOGAD cases with a single clinical event. Our cohort showed a higher relapse rate than has been reported previously and all known relapses occurred within one year of diagnosis. More data is necessary to confirm risk of relapse in the years following diagnosis. In addition, further data on biomarkers are needed to predict the disease course could help guide management.