Is increased activator protein 1 in cerebrospinal fluid as a potential biomarker that distinguishes idiopathic intracranial hypertension from multiple sclerosis?

OBJECTIVES: To distinguish whether idiopathic intracranial hypertension (IIH) is a condition predisposing to multiple sclerosis (MS) or an isolated disease, the current gene transcription factor Activator Protein-1 (AP-1) was evaluated with its potential to differentiate both diseases. BACKGROUND: The aim of this study was to investigate the use of AP-1 as biomarkers for the discrimination of IIH and MS. METHODS: AP-1, TNF-α, and IL-6 protein values in the CSF of the cases were evaluated by the ELISA method. The numerical measures of the groups and the ability of AP-1 to distinguish the groups were analyzed with the ROC curve. RESULTS: There was no difference between the groups in CSF TNF-α, IL-6, CSF, and serum biochemistry analyses. However, it was determined that the AP-1 concentration (pg/ml) was significantly higher in the IIH group, the sensitivity of AP-1 in separating those with IIH was 75%, and the specificity in separating those with MS was 60% in those with an AP-1 concentration of 606.5 and above. CONCLUSION: According to our results, the fact that CSF TNF-α and IL-6 values did not differ in IIH compared to MS revealed that IIH could not methodologically control MS, and AP-1 was a supportive parameter in differentiating both diseases (Tab. 2, Fig. 1, Ref. 31).

Gas6/TAM system as potential biomarker for multiple sclerosis prognosis.

Introduction: The protein growth arrest-specific 6 (Gas6) and its tyrosine kinase receptors Tyro-3, Axl, and Mer (TAM) are ubiquitous proteins involved in regulating inflammation and apoptotic body clearance. Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system leading to progressive and irreversible disability if not diagnosed and treated promptly. Gas6 and TAM receptors have been associated with neuronal remyelination and stimulation of oligodendrocyte survival. However, few data are available regarding clinical correlation in MS patients. We aimed to evaluate soluble levels of these molecules in the cerebrospinal fluid (CSF) and serum at MS diagnosis and correlate them with short-term disease severity. Methods: In a prospective cohort study, we enrolled 64 patients with a diagnosis of clinical isolated syndrome (CIS), radiological isolated syndrome (RIS) and relapsing-remitting (RR) MS according to the McDonald 2017 Criteria. Before any treatment initiation, we sampled the serum and CSF, and collected clinical data: disease course, presence of gadolinium-enhancing lesions, and expanded disability status score (EDSS). At the last clinical follow-up, we assessed EDSS and calculated MS severity score (MSSS) and age-related MS severity (ARMSS). Gas6 and TAM receptors were determined using an ELISA kit (R&D Systems) and compared to neurofilament (NFLs) levels evaluated with SimplePlex™ fluorescence-based immunoassay. Results: At diagnosis, serum sAxl was higher in patients receiving none or low-efficacy disease-modifying treatments (DMTs) versus patients with high-efficacy DMTs (p = 0.04). Higher CSF Gas6 and serum sAXL were associated with an EDSS <3 at diagnosis (p = 0.04; p = 0.037). Serum Gas6 correlates to a lower MSSS (r2 = -0.32, p = 0.01). Serum and CSF NFLs were confirmed as disability biomarkers in our cohort according to EDSS (p = 0.005; p = 0.002) and MSSS (r2 = 0.27, p = 0.03; r2 = 0.39, p = 0.001). Results were corroborated using multivariate analysis. Conclusions: Our data suggest a protective role of Gas6 and its receptors in patients with MS and suitable severity disease biomarkers.

Antithrombin deficiency caused by SERPINC1 gene mutation in white matter lesions: A case report.

RATIONALE: White matter lesions (WMLs) are structural changes in the brain that manifest as demyelination in the central nervous system pathologically. Vasogenic WMLs are the most prevalent type, primarily associated with advanced age and cerebrovascular risk factors. Conversely, immunogenic WMLs, typified by multiple sclerosis (MS), are more frequently observed in younger patients. It is crucial to distinguish between these 2 etiologies. Furthermore, in cases where multiple individuals exhibit WMLs within 1 family, genetic testing may offer a significant diagnostic perspective. PATIENT CONCERNS: A 25-year-old male presented to the Department of Neurology with recurrent headaches. He was healthy previously and the neurological examination was negative. Brain magnetic resonance imaging (MRI) showed widespread white matter hyperintensity lesions surrounding the ventricles and subcortical regions on T2-weighted and T2 fluid-attenuated inversion recovery images, mimicking immunogenic disease-MS. DIAGNOSES: The patient was diagnosed with a patent foramen ovale, which could explain his headache syndrome. Genetic testing unveiled a previously unidentified missense mutation in the SERPINC1 gene in the patient and his father. The specific abnormal laboratory finding was a reduction in antithrombin III activity, and the decrease may serve as the underlying cause for the presence of multiple intracranial WMLs observed in both the patient and his father. INTERVENTIONS: The patient received percutaneous patent foramen ovale closure surgery and took antiplatelet drug recommended by cardiologists and was followed up for 1 month and 6 months after operation. OUTCOMES: While the lesions on MRI remain unchanging during follow-up, the patient reported a significant relief in headaches compared to the initial presentation. LESSONS: This case introduces a novel perspective on the etiology of cerebral WMLs, suggesting that hereditary antithrombin deficiency (ATD) could contribute to altered blood composition and may serve as an underlying cause in certain individuals with asymptomatic WMLs.

CD138 as a Specific CSF Biomarker of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The aim of this study was to identify novel biomarkers for multiple sclerosis (MS) diagnosis and prognosis, addressing the critical need for specific and prognostically valuable markers in the field. METHODS: We conducted an extensive proteomic investigation, combining analysis of (1) CSF proteome from symptomatic controls, fast and slow converters after clinically isolated syndromes, and patients with relapsing-remitting MS (n = 10 per group) using label-free quantitative proteomics and (2) oligodendrocyte secretome changes under proinflammatory or proapoptotic conditions using stable isotope labeling by amino acids in cell culture. Proteins exhibiting differential abundance in both proteomic analyses were combined with other putative MS biomarkers, yielding a comprehensive list of 87 proteins that underwent quantification through parallel reaction monitoring (PRM) in a novel cohort, comprising symptomatic controls, inflammatory neurologic disease controls, and patients with MS at various disease stages (n = 10 per group). The 11 proteins that passed this qualification step were subjected to a new PRM assay within an expanded cohort comprising 158 patients with either MS at different disease stages or other inflammatory or noninflammatory neurologic disease controls. RESULTS: This study unveiled a promising biomarker signature for MS, including previously established candidates, such as chitinase 3-like protein 1, chitinase 3-like protein 2, chitotriosidase, immunoglobulin kappa chain region C, neutrophil gelatinase-associated lipocalin, and CD27. In addition, we identified novel markers, namely cat eye syndrome critical region protein 1 (adenosine deaminase 2, a therapeutic target in multiple sclerosis) and syndecan-1, a proteoglycan, also known as plasma cell surface marker CD138 and acting as chitinase 3-like protein 1 receptor implicated in inflammation and cancer signaling. CD138 exhibited good diagnostic accuracy in distinguishing MS from inflammatory neurologic disorders (area under the curve [AUC] = 0.85, CI 0.75-0.95). CD138 immunostaining was also observed in the brains of patients with MS and cultured oligodendrocyte precursor cells but was absent in astrocytes. DISCUSSION: These findings identify CD138 as a specific CSF biomarker for MS and suggest the selective activation of the chitinase 3-like protein 1/CD138 pathway within the oligodendrocyte lineage in MS. They offer promising prospects for improving MS diagnosis and prognosis by providing much-needed specificity and clinical utility. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CD138 distinguishes multiple sclerosis from other inflammatory neurologic disorders with an AUC of 0.85 (95% CI 0.75-0.95).

Prognostic factors of tumefactive demyelinating lesions and differential features for multiple sclerosis in etiology.

BACKGROUND: Many different pathologies may underlie tumefactive demyelinating lesions. Identifying clinical and radiologic distinguishing features before pathologic examination is essential for diagnosis and treatment. In this study, we aimed to determine the clinical and radiologic features affecting the etiology and disease course of patients with tumefactive lesions (TDL). MATERIALS AND METHODS: We included 35 clinicoradiologically or histologically diagnosed TDL patients in our center over 11 years. Patient records were retrospectively evaluated and recorded. Clinical features, cerebral neuroimaging, and histologic biopsy preparations, if any, were assessed by three independent neurologists, two neuroradiologists, and two pathologists at admission and follow-up, respectively. RESULTS: The mean age of patients with TDL was 40.02±14.40 years. Symptom onset was 15 (1-365) days. The most common complaints at initial presentation were hemiparesis or hemiplegia, sensory complaints, and cognitive impairment (aphasia or apraxia). The lesions were most commonly localized in the frontal lobe (42.9 %). Mass effect was 17.1 %, edema 60 %, diffusion restriction 62.1 %, and contrast enhancement 71.9 % (mostly ring-shaped (68.8 %)) on MR images. Acute onset and OCB type-2 positivity were associated with MS diagnosis. On the other hand, CSF protein levels above 45 mg/dL were found to be related to non-MS etiologies. Only the predominance of aphasia or apraxia at onset was a risk factor for early high disability (EDSS>4; 3rd month). Subacute-chronic onset, being older than 40 years, or having brainstem symptoms at onset were independent risk factors for late high disability (2nd year). CONCLUSION: Acute onset or OCB type 2 positivity is a clue for early diagnosis of MS, while elevated CSF protein is a clue for demyelinating diseases other than MS. Presentation with cognitive dysfunction at onset is an independent risk factor for early disability, while age above 40 years, subacute-chronic presentation and brainstem findings at presentation are independent risk factors for late disability.

Primary cerebral immunoglobulin light chain amyloidoma in a patient with multiple sclerosis.

A man in his 60s, known with multiple sclerosis, presented with seizures and paresis of the left arm and leg. Brain imaging showed a white matter lesion, right parietal, which was progressive over the last 6 years and not typical for multiple sclerosis. Brain biopsy showed a B-cell infiltrate with IgA lambda monotypic plasma cell differentiation and amyloid deposits, typed as lambda immunoglobulin light chain (AL). Bone marrow biopsy and PET/CT ruled out a systemic lymphoma. Extended history taking, blood and urine testing (including cardiac biomarkers) identified no evidence of systemic amyloidosis-induced organ dysfunction.Primary cerebral AL amyloidoma is a very rare entity where optimal treatment is difficult to assess. The patient was treated with locally applied volumetric modulated arc radiotherapy, 24 Gy, divided in 12 fractions. Afterwards, the paresis of the left arm partially resolved, and the function of the left leg improved. Seizures did not occur anymore.

The consequences of delayed diagnosis and treatment in persons with multiple sclerosis given autologous hematopoietic stem cell transplantation.

OBJECTIVES: We have analyzed the association of delayed both diagnosis and treatment of persons with MS with the long-term results of patients given autologous hematopoietic stem cell transplantation (aHSCT). METHODS: Patients with MS referred to the HSCT-Mexico program were included in the study; in 103, detailed pre- and post-transplant evolution could be recorded. Two groups of patients were analyzed according to the time of evolution between the onset of symptoms and the definite diagnosis of MS: more than 8 months (delayed diagnosis, DD), or less than 8 months (non-delayed diagnosis, NDD). The progression of MS was assessed by changes in the expanded disability status scale (EDSS). RESULTS: The time elapsed between the onset of symptoms and the correct diagnosis was lower for the NDD group (1.55 vs. 35.87 months, p<0.05). Both groups of patients showed a similar EDSS score at diagnosis (1.5 vs. 1.5); however, the EDSS at the time of the transplant was higher in the DD group (4.5 vs. 3.0, p=0.3) and the response of the EDSS score to the transplant was significantly better for the NDD group, the last EDSS scores being 2.5 vs. 4.25 (p=0.03). Both groups of patients responded to aHSCT by diminishing the EDSS, but the response was significantly better in the NDD group. CONCLUSIONS: These data indicate that both the pre-transplant progression of the disease and the response to aHSCT were significantly worse in the DD group. An early diagnosis and an early aHSCT intervention are critical for a good prognosis, in terms of lowering and stabilizing the motor disability in MS patients given autografts.

Ophthalmoplegia with a focal lesion in the interpeduncular fossa as the initial symptoms of multiple sclerosis: 3-year follow-up.

The differential diagnosis of isolated ophthalmoplegia includes a range of pathologies. In this case, a 26-year-old man of Han nationality presented with ophthalmoplegia. Neuroimaging revealed an atypical focal lesion in the interpeduncular fossa. Initial systemic workup indicated intracranial Mycobacterium tuberculosis infection, but there was no evidence to support a diagnosis of other autoimmune diseases (e.g., myasthenia gravis or multiple sclerosis). Neuroimaging follow-up over the next 3 years revealed progression from atypical solitary lesions to multifocal lesions in the white matter of the brain. Key immunological markers were observed in cerebrospinal fluid during follow-up, suggesting the evolution of multiple sclerosis. Ophthalmoplegia with a focal lesion in the interpeduncular fossa was an unusual set of symptoms indicating multiple sclerosis onset. The findings in this case suggest that M. tuberculosis infection is an important but overlooked factor involved in the pathogenesis of multiple sclerosis. Upon initial detection, atypical lesions should receive sufficient attention and patients should undergo systematic screening to identify M. tuberculosis infection and its associated immunological abnormalities.

Multiple sclerosis in the elderly: a retrospective cohort study.

BACKGROUND: There is a lack of knowledge of disease course, prognosis, comorbidities and potential treatments of elderly MS patients. OBJECTIVE: To characterize the disease course including disability progression and relapses, to quantify the use of DMTs and to identify comorbidities and risk factors for progression in elderly multiple sclerosis (MS) patients. METHODS: This is a retrospective study of 1200 Austrian MS patients older than 55 years as of May 1st, 2017 representing roughly one-third of all the MS patients of this age in Austria. Data were collected from 15 MS centers including demographics, first symptom at onset, number of relapses, evolvement of disability, medication, and comorbidities. RESULTS: Median observation time was 17.1 years with 957 (80%) relapsing and 243 (20%) progressive onsets. Average age at diagnosis was 45 years with a female predominance of 71%. Three-hundred and twenty-six (27%) patients were never treated with a DMT, while most treated patients received interferons (496; 41%) at some point. At last follow-up, 420 (35%) patients were still treated with a DMT. No difference was found between treated and never-treated patients in terms of clinical outcome; however, patients with worse disability progression had significantly more DMT switches. Pyramidal onset, number of comorbidities, dementia, epilepsy, and psychiatric conditions as well as a higher number of relapses were associated with worse outcome. The risk of reaching EDSS 6 rose with every additional comorbidity by 22%. In late and very-late-onset MS (LOMS, VLOMS) time to diagnosis took nearly twice the time compared to adult and early onset (AEOMS). The overall annualized relapse rate (ARR) decreased over time and patients with AEOMS had significantly higher ARR compared to LOMS and VLOMS. Four percent of MS patients had five medications or more fulfilling criteria of polypharmacy and 20% of psychiatric drugs were administered without a matching diagnosis. CONCLUSIONS: In this study, we identified number of comorbidities, pyramidal and cerebellar signs, and a higher number of relapses as unfavorable prognostic factors in elderly MS patients filling gaps of knowledge in patients usually underrepresented in clinical trials and may guide future therapeutic studies.

Missed diagnosis of Fabry disease: should we screen patients with multiple sclerosis?

INTRODUCTION: Fabry disease (FD) can be undiagnosed in the context of multiple sclerosis (MS) due to similar clinical and paraclinical features. Our study aimed to determine the prevalence (and the necessity of screening) of FD among patients with possible or definite MS. METHODS: In this prospective monocentric observational study, we included consecutive patients enrolled between May 2017 and May 2019 after the first clinical event suggestive of MS. All patients underwent FD screening using dried blood spots in a stepwise manner combining genetic and enzyme testing. Patients were followed until May 2022. RESULTS: We included 160 patients (73.1% female, mean age 33.9 years). The 2017 revised McDonald's criteria for definite MS were fulfilled by 74 (46.3%) patients at the time of study recruitment and 89 (55.6%) patients after 3-5 years of follow-up. None of the patients had a pathogenic GLA variant, and four (2.5%) had a variant of unknown significance (p.A143T, p.S126G, 2 × p.D313Y). In two of these patients, the intrathecal synthesis of oligoclonal bands was absent, and none had hyperproteinorachia or pleocytosis in cerebrospinal fluid. Detailed examination of FD organ manifestations revealed only discrete ocular and kidney involvement in two patients. CONCLUSION: The prevalence of FD in the population of suspected or definite MS patients does not appear to be high. Our results do not support routine FD screening in all patients with a possible diagnosis of MS, but there is an urgent need to search for red flags and include FD in the differential diagnosis of MS.

Uveitis in the Setting of Co-Existing Systemic Sarcoidosis and Multiple Sclerosis.

We report a case of intermediate uveitis in the setting of both systemic sarcoidosis and multiple sclerosis. A 68-year-old female was diagnosed with bilateral granulomatous intermediate uveitis and cystoid macular edema. Initial systemic work-up was unrevealing. The uveitis was treated successfully with local corticosteroid injections. Eighteen months after presentation, the patient developed new systemic symptoms. Additional testing revealed systemic lymphadenopathy, with biopsy showing non-caseating granulomas, leading to a diagnosis of sarcoidosis. However, MRI of the brain and spinal cord along with cerebrospinal fluid analysis was consistent with MS. The management of the uveitis and systemic inflammation was co-managed by ophthalmology, neurology, and rheumatology, and eventually controlled with leflunomide and rituximab. Patients can rarely have co-existing systemic sarcoidosis and multiple sclerosis. Although challenging to diagnose, radiographic findings and cerebrospinal fluid analysis can be helpful to differentiate multiple sclerosis and neurosarcoidosis. Management of these patients requires coordination between multiple specialties.

Current use of fluid biomarkers as outcome measures in Multiple Sclerosis (MS): a review of ongoing pharmacological clinical trials.

The present study aims to describe the state of the art of fluid biomarkers use in ongoing multiple sclerosis (MS) clinical trials.A review of 608 ongoing protocols in the clinicaltrials.gov and EudraCT databases was performed. The trials enrolled patients with a diagnosis of relapsing remitting MS, secondary progressive MS, and/or primary progressive MS according to Revised McDonald criteria or relapsing MS according to Lublin et al. (2014). The presence of fluid biomarkers among the primary and/or secondary study outcomes was assessed.Overall, 5% of ongoing interventional studies on MS adopted fluid biomarkers. They were mostly used as secondary outcomes in phase 3-4 clinical trials to support the potential disease-modifying properties of the intervention. Most studies evaluated neurofilament light chains (NfLs). A small number considered other novel fluid biomarkers of neuroinflammation and neurodegeneration such as glial fibrillary acid protein (GFAP).Considering the numerous ongoing clinical trials in MS, still a small number adopted fluid biomarkers as outcome measures, thus testifying the distance from clinical practice. In most protocols, fluid biomarkers were used to evaluate the effectiveness of approved second-line therapies, but also, new drugs (particularly Bruton kinase inhibitors). NfLs were also adopted to monitor disease progression after natalizumab suspension in stable patients, cladribine efficacy after anti-CD20 discontinuation, and the efficacy of autologous hematopoietic stem cell transplant (AHSCT) compared to medical treatment. Nevertheless, further validation studies are needed for all considered fluid biomarkers to access clinical practice, and cost-effectiveness in the "real word" remains to be clarified.

Association Between Diseases and Symptoms Diagnosed in Primary Care and the Subsequent Specific Risk of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Previous studies have reported a possible prodrome in multiple sclerosis (MS) defined by nonspecific symptoms including mood disorder or genitourinary symptoms and increased health care use detected several years before diagnosis. This study aimed to evaluate agnostically the associations between diseases and symptoms diagnosed in primary care and the risk of MS relative to controls and 2 other autoimmune inflammatory diseases with similar population characteristics, namely lupus and Crohn disease (CD). METHODS: A case-control study was conducted using electronic health records from the Health Improvement Network database in the United Kingdom and France. We agnostically assessed the associations between 113 diseases and symptoms in the 5 years before and after diagnosis in patients with subsequent diagnosis of MS. Individuals with a diagnosis of MS were compared with individuals without MS and individuals with 2 other autoimmune diseases, CD and lupus. RESULTS: The study population consisted of patients with MS (n = 20,174), patients without MS (n = 54,790), patients with CD (n = 30,477), and patients with lupus (n = 7,337). Twelve ICD-10 codes were significantly positively associated with the risk of MS compared with controls without MS. After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, 5 ICD-10 codes remained significantly associated with MS: depression (UK: odds ratio 1.22, 95% CI 1.11-1.34), sexual dysfunction (1.47, 1.11-1.95), constipation (1.5, 1.27-1.78), cystitis (1.21, 1.05-1.39), and urinary tract infections of unspecified site (1.38, 1.18-1.61). However, none of these conditions was selectively associated with MS in comparisons with both lupus and CD. All 5 ICD-10 codes identified were still associated with MS during the 5 years after diagnosis. DISCUSSION: We identified 5 health conditions associated with subsequent MS diagnosis, which may be considered not only prodromal but also early-stage symptoms. However, these health conditions overlap with prodrome of 2 other autoimmune diseases; hence, they lack specificity to MS.

THE RELATIONSHIP BETWEEN THE DURATION OF REMISSIONS AFTER THE ONSET, THE SEVERITY OF THE RELAPSES AGAINST THE BACKGROUND OF DIFFERENT DURATION OF THE RELAPSING STAGE AND THE NATURE OF THE PROGNOSIS IN SECONDARY-PROGRESSIVE MULTIPLE SCLEROSIS.

Work objective - to study the relationship between the duration of remission after the onset, the severity of relapses against the background of different duration of the relapsing stage (RS) and the nature of the prognosis in the secondary progressive multiple sclerosis (SPMS) using clinical and mathematical analysis. Patients with different prognosis for SPMS; neurological examination using The Expanded Disability Status Scale (EDSS); a survey method. Mathematical methods: 'contingency tables 2x2' (determining the significance of the connection between a pair of two indicators - different duration of remission after the onset and RS in four groups of patients), Yule's Coefficient of Association (determining the magnitude of differences between the group and the studied indicator), a permutation test (defining clinical indicators on RS, which significantly differed in mild and severe relapses). Pairwise comparison in four groups of patients with different duration of remission after the onset and RS in SPMS showed that long-term remission after the onset and prolonged RS delay the transition of RS into secondary progression (SP). Short duration of these indicators revealed the opposite prognostic tendencies, indicating the further progression of the disease. The presence of severe relapses on RS in SPMS is predominantly associated with unfavorable prognostic indicators on RS and indicates the initiation of the transition into SP. Accordingly, the duration of remission after the onset, the severity of relapses against the background of different durations of RS should be regarded as prognostic clinical markers that play a key role in the switch of RS to SPS in SPMS. The results obtained should be used to assess the current clinical situation and timely prescribe an appropriate pathogenetic therapy on RS.

Performance of administrative databases for identifying individuals with multiple sclerosis.

Administrative databases are an alternative to disease registries as a research tool to study multiple sclerosis. However, they are not initially designed to fulfill research purposes. Therefore, an evaluation of their performance is necessary. Our objective was to assess the performance of the French administrative database comprising hospital discharge records and national health insurance databases in identifying individuals with multiple sclerosis, in comparison with a registry that exhaustively compiles resident multiple sclerosis cases in Lorraine, northeastern France, as reference. We recorded all individuals residing in the Lorraine region who were identified by the administrative database or the registry as having multiple sclerosis from 2011 to 2016. We calculated the Matthews correlation coefficient and other concordance indicators. For identifying individuals with multiple sclerosis, the Matthews correlation coefficient by the administrative database was 0.79 (95% CI 0.78-0.80), reflecting moderate performance. The mean time to identification was 5.5 years earlier with the registry than the administrative database. Administrative databases, although useful to study multiple sclerosis, should be used with caution because results of studies based on them may be biased. Our study highlights the value of regional registries that allow for a more exhaustive and rapid identification of cases.

The role of miRNAs in multiple sclerosis pathogenesis, diagnosis, and therapeutic resistance.

In recent years, microRNAs (miRNAs) have gained increased attention from researchers around the globe. Although it is twenty nucleotides long, it can modulate several gene targets simultaneously. Their mal expression is a signature of various pathologies, and they provide the foundation to elucidate the molecular mechanisms of each pathology. Among the debilitating central nervous system (CNS) disorders with a growing prevalence globally is the multiple sclerosis (MS). Moreover, the diagnosis of MS is challenging due to the lack of disease-specific biomarkers, and the diagnosis mainly depends on ruling out other disabilities. MS could adversely affect patients' lives through its progression, and only symptomatic treatments are available as therapeutic options, but an exact cure is yet unavailable. Consequently, this review hopes to further the study of the biological features of miRNAs in MS and explore their potential as a therapeutic target.

Evaluation of Inflammation in the Peripheral Multiple Sclerosis Retina Using Ultra-Widefield Optical Coherence Tomography: A Pilot Study.

BACKGROUND AND OBJECTIVE: Reports of fundus fluorescein angiography (FFA) in active multiple sclerosis (MS) have shown peripheral perivenous sheathing. We sought to assess the feasibility of ultra-widefield (UWF) FFA and optical coherence tomography (OCT) in assessing the peripheral retina in MS. MATERIALS AND METHODS: Participants with MS and healthy controls underwent bilateral UWF fundus photography and FFA. Swept-source OCTs were captured centrally, peripherally, and to delineate any abnormalities visualized. RESULTS: We recruited five people with relapsing remitting MS, with a mean age of 36.9 (± 9.9), mean disease duration of 11 years (± 6.3), and a median expanded disability status score of 0.75 (0 to 2.5). In all MS participants, the disease was not active clinically or radiologically. Using UWF-FFA and OCT, we did not detect clear evidence of peripheral retinal abnormalities, which is consistent with the participants having inactive MS. CONCLUSION: A pilot study using UWF-FFA and peripheral OCT to examine the retina in MS suggests that it may be useful to perform a larger prospective longitudinal study to establish its potential as a monitor of disease activity. [Ophthalmic Surg Lasers Imaging Retina 2023;54:586-588.].

Predictive value of α-synuclein expression in peripheral blood of multiple sclerosis patients: A two-dimensional assessment of a selected biomarker.

INTRODUCTION: Our study aimed to evaluate whether assessing α-synuclein expression levels in blood samples could provide a reliable and straightforward alternative to existing diagnostic and prognostic methods for neurodegenerative disorders, including multiple sclerosis (MS). We specifically investigated if α-synuclein and IL-6 expression levels from serum and peripheral blood mononuclear cells (PBMCs) could accurately predict MS severity in patients using a two-dimensional approach. METHODS: We designed a case-control study to analyze the expression of α-synuclein and IL-6 in the peripheral blood of an MS patient group (n = 51) and a control group (n = 51). We statistically evaluated the PBMCs and serum profiles of α-synuclein and IL-6 in MS patients, along with their age of onset, disease duration, tobacco exposure, and Expanded Disability Status Scale (EDSS) score, using SPSS V22.0 software and GraphPad Prism V9.0. RESULTS: Our findings indicate that α-synuclein production was significantly downregulated in MS patients. Principal component analysis also revealed distinct profiles between MS patients and controls. PBMCs and serum profiles of α-synuclein correlated with the EDSS score, suggesting that disease severity can be predicted using α-synuclein profiles. Moreover, α-synuclein showed a significant correlation with IL-6 and age of onset. Lastly, receiver operating characteristic curves of PBMCs and serum activity of α-synuclein profiles displayed discrimination with area under the curve values of 0.856 and 0.705, respectively. CONCLUSION: Our results imply that measuring α-synuclein levels in both serum and PBMCs could be a valuable method for diagnosing and predicting MS severity, potentially serving as a non-invasive biomarker for the disease.

Understanding who benefits most from cognitive rehabilitation for multiple sclerosis: A secondary data analysis.

BACKGROUND: Up to 70% of people with multiple sclerosis (MS) experience cognitive difficulties. Cognitive rehabilitation is a type of therapy that helps manage cognitive problems. OBJECTIVE: The Cognitive Rehabilitation for Attention and Memory in MS (CRAMMS) trial showed some evidence of effectiveness of cognitive rehabilitation in improving cognitive function, with some participants benefitting more than others. We therefore conducted a secondary analysis of the CRAMMS data to understand who benefits most. METHODS: We grouped baseline data into four categories of possible predictors. We used regression models to identify specific factors/characteristics that could predict the likelihood that an individual will benefit from cognitive rehabilitation. RESULTS: The models predicted whether a participant improved or did not improve in neuropsychological function following cognitive rehabilitation in up to 86% of participants. Results suggest that younger participants with medium to high education, diagnosed with relapsing-remitting multiple sclerosis (RRMS) and primary-progressive multiple sclerosis (PPMS) who have not experienced any recent relapses, with mild to moderate cognitive difficulties were most likely to benefit from cognitive rehabilitation. CONCLUSION: We can predict which participants are most likely to demonstrate significant improvements in neuropsychological function following group-based cognitive rehabilitation. Clinically, this allows us to optimise limited neuropsychology resources by offering such cognitive rehabilitation to those most likely to benefit.