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INTRODUCTION: Predicting the conversion of clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) is critical to personalizing treatment planning and benefits for patients. The aim of this study is to develop an explainable machine learning (ML) model for predicting this conversion based on demographic, clinical, and imaging data. METHOD: The ML model, Extreme Gradient Boosting (XGBoost), was employed on the public dataset of 273 Mexican mestizo CIS patients with 10-year follow-up. The data was divided into a training set for cross-validation and feature selection, and a holdout test set for final testing. Feature importance was determined using the SHapley Additive Explanations library (SHAP). Then, two experiments were conducted to optimize the model's performance by selectively adding variables and selecting the most contributive variables for the final model. RESULTS: Nine variables including age, gender, schooling, motor symptoms, infratentorial and periventricular lesion at imaging, oligoclonal band in cerebrospinal fluid, lesion and symptoms types were significant. The model achieved an accuracy of 83.6 %, AUC of 91.8 %, sensitivity of 83.9 %, and specificity of 83.4 % in cross-validation. In the final testing, the model achieved an accuracy of 78.3 %, AUC of 85.8 %, sensitivity of 75 %, and specificity of 81.1 %. Finally, a web-based demo of the model was created for testing purposes. CONCLUSION: The model, focusing on feature selection and interpretability, effectively stratifies risk for treatment decisions and disability prevention in MS patients. It provides a numerical risk estimate for CDMS conversion, enhancing transparency in clinical decision-making and aiding in patient care.

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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.

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BACKGROUND: Like MS prevalence, oligoclonal bands (OCB) frequency seems to follow a latitudinal gradient. Argentina is extensive, latitude-wise, and previous studies have not found an MS prevalence latitudinal gradient. Our aim is to describe OCB prevalence in MS, clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) patients included in the Argentinean MS and NMOSD registry (RelevarEM) and to investigate if it follows a latitudinal gradient. METHODS: For each province, an average latitude was calculated, and OCB frequency was investigated. Multivariate logistical regression analysis and linear correlation were performed. Statistical analysis was repeated after excluding patients from centers using isoelectric focusing (IEF) in less than 95% of patients (CwIEF<95). RESULTS: We included 2866 patients. OCB where positive in 73.9% of patients. No association or correlation were found between OCB and latitude of residence, even after excluding patients from (CwIEF<95). CONCLUSION: OCB positivity does not follow a latitudinal gradient in Argentina. Also, OCB positivity is lower than described in other world regions.

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Background: In CSF analysis for diagnostics we have knowledge-based software for numerical and graphical data interpretation, but software programs for statistics are scarce. Free, stand-alone software programs that calculate all individual functions of CSF protein analysis and allow the statistical treatment of groups of diseases numerically and graphically are presented for relevant examples. Methods: Diagnosis of an intrathecal synthesis refers to the upper limit of the reference range, Qlim = Qmean +3SD, but statistical evaluation of its frequency is referred to Qmean+2SD. When quantifying intrathecal synthesis for statistics, either the absolute amount (IgGloc) or the relative intrathecal fraction (IgGIF) can be reported with reference to the mean reference curve, Qmean. The free software CSF research Tool for immunoglobulins allows diagnostic and statistic evaluations with Reibergrams and calculation of mean values and standard deviations from disease groups. The software FLC-K statistics for free light chains Kappa offers for diagnostics and statistics the numerical and graphical interpretation basis for statistical processing in exported Excel tables. A free "CSF-App" for Smartphones provides data calculation for diagnostics of single patients with examples of disease-related data patterns. Results: Patients with clinically isolated syndrome (CIS) who were later diagnosed as MS showed no immunological differences to patients initially diagnosed as MS (same mean quantity of intrathecal synthesis in CIS and MS detectable for IgG and FLC-K). The frequently claimed diagnostically higher sensitivity of the FLCK analysis compared to IgG, can be explained by the up to 3-fold higher mean intrathecal fraction of FLC-K, corresponding to a higher frequency in the detection of intrathecal synthesis with FLCK analysis. Conclusions: With a knowledge-based quantification in CSF analysis, supported by knowledge-based software programs, scientifically and diagnostically important results can be obtained(AU)

Introducción: Los programas de software gratuitos y autónomos que calculan todas las funciones individuales del análisis de proteínas del líquido cefalorraquídeo (LCR) y permiten el tratamiento estadístico de grupos de enfermedades de forma numérica y gráfica se presentan como ejemplos relevantes. Métodos: Cuando se cuantifica la síntesis intratecal para la estadística, se puede informar la cantidad absoluta (IgGloc) o la fracción intratecal relativa (IgGIF) con referencia a la curva de referencia media, Qmean. El software gratuito "CSF research Tool" para inmunoglobulinas permite realizar evaluaciones diagnósticas y estadísticas con Reibergrams y calcular los valores medios y las desviaciones estándar de los grupos de enfermedades. El software FLC-K statistics para Free light chains Kappa ofrece para el diagnóstico y la estadística la base de interpretación numérica y gráfica para el procesamiento estadístico en tablas exportadas de Excel. El programa CSF-App para teléfonos inteligentes es gratuito y ofrece el cálculo de datos para el diagnóstico de pacientes individuales con ejemplos de patrones de datos relacionados con enfermedades. Resultados: Los pacientes con síndrome clínico aislado (SCA) que posteriormente fueron diagnosticados como EM no mostraron diferencias inmunológicas con respecto a los pacientes inicialmente diagnosticados como EM (la misma cantidad media de síntesis intratecal en el síndrome clínico aislado y EM detectable para IgG y FLC-K). La sensibilidad más elevada que se afirma con frecuencia en el diagnóstico del análisis de FLC-K en comparación con la IgG, puede explicarse por la fracción intratecal media hasta tres veces mayor de FLC-K, que corresponde a una mayor frecuencia en la detección de la síntesis intratecal con el análisis de FLC-K. Conclusiones: Con la cuantificación en el análisis del LCR se pueden obtener resultados importantes desde el punto de vista científico y diagnóstico(AU)

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The association between coronaviruses and central nervous system (CNS) demyelinating lesions has been previously shown. However, no case has been described of an association between the novel coronavirus (SARS-COV-2) and CNS demyelinating disease so far. SARS-COV-2 was previously detected in cerebrospinal fluid (CSF) sample of a patient with encephalitis. However, the virus identity was not confirmed by deep sequencing of SARS-COV-2 detected in the CSF. Here, we report a case of a patient with mild respiratory symptoms and neurological manifestations compatible with clinically isolated syndrome. The viral genome of SARS-COV-2 was detected and sequenced in CSF with 99.74-100% similarity between the patient virus and worldwide sequences. This report suggests a possible association of SARS-COV-2 infection with neurological symptoms of demyelinating disease, even in the absence of relevant upper respiratory tract infection signs.

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BACKGROUND: The objective was to evaluate the precision of kappa and lambda free light chains (KFLC and LFLC) in CSF for the diagnosis of multiple sclerosis (MS) and prognosis of clinically isolated syndrome (CIS). METHODS: CSF and serum samples from CIS, MS and other neurological non-MS disease were collected between 2015 and 2017. FLC concentrations were measured using immunoassay Freelite™. Results were correlated with the patients' diagnoses and ROC curve analysis was used to determine accuracy. In CIS patients, analysis of FLC were compared in CIS converters vs. non-converter during follow-up. RESULTS: In the MS group (n = 41), the optimal cut-off for KFLC determined was 7 mg/L, with a diagnostic sensitivity and specificity of 95% and 97%, respectively. The optimal cut-off for LFLC was 0.7 mg/L, with a diagnostic sensitivity and specificity of 71% and 81%, respectively. 36 CIS patients were included; mean follow-up time was 28 ± 9 months, and 22 (61.1%) patients converted to MS. The median concentration of CSF K and LFLCs at CIS diagnosis was slightly higher in CIS-converters compared to non-converters, but this did not reach statistical significance (KFLC: median 7 ± 5.3 mg/L vs. 5 ± 2.3 mg/L, p = 0.11; LFLC 0.7 ± 0.33 mg/L vs. 0.5 ± 0.23 mg/L p = 0.16). A strong correlation was observed between the concentration of K and L FLCs at diagnosis and the change in PBVC during follow-up (r = 0.72 and r = 0.65, respectively). CONCLUSION: KFLCs have a high sensitivity and specificity for the diagnosis of MS. FLC concentrations at CIS diagnosis were not significantly higher in CIS-converters.

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OBJECTIVE: To evaluate the quality of life (QoL) and potential QoL determinants in patients with clinically isolated syndrome (CIS). METHODS: Eighteen CIS patients and eighteen controls were submitted to QoL evaluation with Functional Assessment of Multiple Sclerosis QoL instrument (FAMS). Cognition was evaluated with specific battery tests; Anxiety and depression with Beck Anxiety (BAI) and Depression (BDI) Inventories and Neurological disability with Guy's Neurological Disability Scale (GNDS). RESULTS: There was a significant difference in QoL between CIS patients and controls. CIS patients had worse performance in Paced Auditory Serial Addition 2 seconds (p=0.009) and fluency tests (p=0.0038). There was a significant difference in BAI (p=0.003), but no significant difference in BDI between patients and controls. There were significant correlations between QoL measure and verbal fluency and Stroop's test. CONCLUSIONS: Cognition, but not anxiety, depression and disability, was associated with reduced quality of life.

OBJETIVO: Avaliar a qualidade de vida (QoL) e seus potenciais determinantes em pacientes com síndrome clinicamente isolada (SCI). MÉTODOS: Dezoito pacientes com SCI e 18 controles realizaram avaliação da QoL com Escala de Determinação da QoL na Esclerose Múltipla; cognição foi avaliada com bateria de testes específica; ansiedade e depressão com os Inventários de Beck de ansiedade (BAI) e de depressão (BDI) e a incapacidade neurológica com a Guy's Neurological Disability Scale. RESULTADOS: Houve diferença significativa na QoL avaliada entre pacientes com SCI e controles. Pacientes com SCI apresentaram pior desempenho no Pased Auditory Serial Addition 2 segundos (p=0,009) e na fluência verbal (p=0,0038). Houve diferença no BAI (p=0,003), entretanto sem diferença do BDI entre pacientes e controles. Houve correlações significativas entre QoL, fluência verbal e Stroop. CONCLUSÕES: Alterações cognitivas tiveram correlação com diminuição da QoL, o que não ocorreu com a depressão, ansiedade e incapacidade neurológica.

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Cognitive abnormalities have been extensively studied in Multiple Sclerosis (MS). However, little is known aboutthe cognitive involvement in patients with Clinically Isolated Syndrome (CIS). Objective: This study aimed to investigatecognitive impairment in patients with CIS compared with healthy subjects. Methods: 18 CIS patients and 18 controlswere subjected to the Wechsler memory scale, Rey Auditory Verbal Learning, Rey Complex Figure, Paced Auditory SerialAddition, Digit Span, verbal fluency, Stroop color card test, D2, and Digit Symbol tests. Results: CIS patients had significantlyworse performance on the Paced Auditory Serial Addition Test (PASAT) 2 seconds (P=0.009) and on verbal fluency tests(P=0.0038) than controls. Conclusion: CIS patients had worse cognitive performance than controls on neuropsychologicaltests evaluating executive functioning.

As alterações cognitivas na Esclerose Múltipla (EM) têm sido bastante estudadas. No entanto, ainda são poucosos estudos acerca do comprometimento cognitivo em pacientes com Síndrome Clinicamente Isolada (SCI). Objetivo:O objetivo deste estudo foi o de investigar funções cognitivas em pacientes com SCI em relação a um grupo controle.Métodos: Dezoito pacientes com SCI e 18 controles saudáveis foram submetidos à avaliação neuropsicológica, incluindoos seguintes testes: Escala Wechsler de Memória, ?Rey Auditory Verbal Learning Test?, Figura Complexa de Rey, ?PacedAuditory Serial Addition (PASAT) 2 e 3 segundos, ?Digit Span?, fluência verbal, teste de Stroop, D2 e ?Digit Symbol Test?.Resultados: Pacientes com SCI tiveram desempenho significativamente inferior nos testes PASAT 2 segundos (P=0.009)e fluência verbal (P=0.0038) quando comparados ao grupo controle. Conclusão: Pacientes com síndrome clinicamenteisolada apresentaram pior desempenho cognitivo em testes relacionados a funções executivas.

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Cognitive abnormalities have been extensively studied in Multiple Sclerosis (MS). However, little is known about the cognitive involvement in patients with Clinically Isolated Syndrome (CIS). OBJECTIVE: This study aimed to investigate cognitive impairment in patients with CIS compared with healthy subjects. METHODS: 18 CIS patients and 18 controls were subjected to the Wechsler memory scale, Rey Auditory Verbal Learning, Rey Complex Figure, Paced Auditory Serial Addition, Digit Span, verbal fluency, Stroop color card test, D2, and Digit Symbol tests. RESULTS: CIS patients had significantly worse performance on the Paced Auditory Serial Addition Test (PASAT) 2 seconds (P=0.009) and on verbal fluency tests (P=0.0038) than controls. CONCLUSION: CIS patients had worse cognitive performance than controls on neuropsychological tests evaluating executive functioning.

As alterações cognitivas na Esclerose Múltipla (EM) têm sido bastante estudadas. No entanto, ainda são poucos os estudos acerca do comprometimento cognitivo em pacientes com Síndrome Clinicamente Isolada (SCI). OBJETIVO: O objetivo deste estudo foi o de investigar funções cognitivas em pacientes com SCI em relação a um grupo controle. MÉTODOS: Dezoito pacientes com SCI e 18 controles saudáveis foram submetidos à avaliação neuropsicológica, incluindo os seguintes testes: Escala Wechsler de Memória, "Rey Auditory Verbal Learning Test", Figura Complexa de Rey, "Paced Auditory Serial Addition (PASAT) 2 e 3 segundos, "Digit Span", fluência verbal, teste de Stroop, D2 e "Digit Symbol Test". RESULTADOS: Pacientes com SCI tiveram desempenho significativamente inferior nos testes PASAT 2 segundos (P=0.009) e fluência verbal (P=0.0038) quando comparados ao grupo controle. CONCLUSÃO: Pacientes com síndrome clinicamente isolada apresentaram pior desempenho cognitivo em testes relacionados a funções executivas.

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Depression and anxiety have been reported in patients with multiple sclerosis (MS) and in patients with clinically isolated syndrome (CIS). However, the precise mechanisms that lead to depressive and anxiety symptoms in these patients are still unclear. In this study we evaluated with the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) patients with MS and CIS and compared them to controls. We also correlated BDI and BAI scores with clinical parameters. Kruskall-Wallis followed by Dunn's Multiple Comparison Test, Chi-square and Spearman test were used. Patients with MS had higher depressive and anxiety scores than controls. The BDI and BAI scores of patients with CIS were not significantly different from controls. There was a positive correlation between BDI, BAI and EDSS. Our results corroborate the view that MS patients have higher depression and anxiety levels than control subjects. Anxiety and depressive symptoms also seem to progress according to the severity of the disease.

A depressão e a ansiedade têm sido descritas em pacientes com esclerose múltipla (EM) e síndrome clinicamente isolada (CIS). Entretanto, os mecanismos precisos que determinam o surgimento de depressão e ansiedade ainda não estão elucidados. No presente estudo, foram utilizadas as escalas de Beck para depressão (BDI) e ansiedade (BAI) em pacientes com EM, CIS e controles. O grau de comprometimento funcional dos pacientes e o tempo de doença foram correlacionados com parâmetros clínicos. Foram utilizados os testes de Kruskall-Wallis seguido do teste de múltiplas comparações (Dunn's Test), qui-quadrado e o teste de Spearman. Pacientes com EM apresentam escores mais elevados de depressão e ansiedade do que controles. Houve correlação positiva entre os escores do BDI e do BAI com o grau de comprometimento funcional avaliado pela EDSS. Nossos resultados corroboram a visão de que pacientes com EM exibem mais ansiedade e depressão que controles. Sintomas ansiosos e depressivos parecem progredir com a gravidade da doença.

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The pattern of cognitive abnormalities in multiple sclerosis (MS) has been extensively studied and well characterized. However, little is known about the cognitive involvement in patients with the clinically isolated syndrome (CIS). Objectives: To perform a systematic review of the results of the studies on cognitive dysfunction in CIS patients. Methods: Cochrane, Lilacs, PubMed/Medline and SciELO databases were searched for studies involving patients with clinically isolated syndrome submitted to neuropsychological evaluation. Results: Seven studies fulfilled the selection criteria adopted in this review. The pattern of cognitive abnormalities in CIS resembles that found in patients with MS and is characterized by attention deficit, reduced information processing speed and impaired working memory and executive functions. The frequency of cognitive impairment in CIS seems to be lower than in MS. Conclusions: Cognition should be evaluated in patients with CIS. Future studies are required to evaluate the impact of cognitive abnormalities and to correlate them with axonal damage findings in patients with CIS.

As alterações cognitivas na esclerose múltipla (EM) são muito estudadas e bem caracterizadas. No entanto, pouco se sabe sobre o envolvimento cognitivo em pacientes com síndrome clínica isolada (SCI). Objetivos: Revisar sistematicamente resultados obtidos em estudos sobre cognição em pacientes com SCI. Métodos: Revisamos as seguintes bases de dados: Cochrane, Lilacs, Pubmed/Medline e Scielo buscando artigos em que pacientes com SCI foram submetidos à avaliação neuropsicológica. Resultados: Sete estudos preencheram critérios adotados pelos autores desta revisão. O padrão do prejuízo cognitivo em SCI é semelhante ao encontrado na EM, caracterizado por déficit de atenção, redução da velocidade de processamento, comprometimento da memória de trabalho e de funções executivas. A freqüência de disfunção cognitiva é inferior na SCI do que na EM. Conclusões: Pacientes com CIS devem ser avaliados quanto à cognição. Estudos futuros são necessários para avaliar o impacto do prejuízo cognitivo e correlacioná-lo com achados de dano axonal em pacientes com SCI.

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The pattern of cognitive abnormalities in multiple sclerosis (MS) has been extensively studied and well characterized. However, little is known about the cognitive involvement in patients with the clinically isolated syndrome (CIS). OBJECTIVES: To perform a systematic review of the results of the studies on cognitive dysfunction in CIS patients. METHODS: Cochrane, Lilacs, PubMed/Medline and SciELO databases were searched for studies involving patients with clinically isolated syndrome submitted to neuropsychological evaluation. RESULTS: Seven studies fulfilled the selection criteria adopted in this review. The pattern of cognitive abnormalities in CIS resembles that found in patients with MS and is characterized by attention deficit, reduced information processing speed and impaired working memory and executive functions. The frequency of cognitive impairment in CIS seems to be lower than in MS. CONCLUSIONS: Cognition should be evaluated in patients with CIS. Future studies are required to evaluate the impact of cognitive abnormalities and to correlate them with axonal damage findings in patients with CIS.

As alterações cognitivas na esclerose múltipla (EM) são muito estudadas e bem caracterizadas. No entanto, pouco se sabe sobre o envolvimento cognitivo em pacientes com síndrome clínica isolada (SCI). OBJETIVOS: Revisar sistematicamente resultados obtidos em estudos sobre cognição em pacientes com SCI. MÉTODOS: Revisamos as seguintes bases de dados: Cochrane, Lilacs, Pubmed/Medline e Scielo buscando artigos em que pacientes com SCI foram submetidos à avaliação neuropsicológica. RESULTADOS: Sete estudos preencheram critérios adotados pelos autores desta revisão. O padrão do prejuízo cognitivo em SCI é semelhante ao encontrado na EM, caracterizado por déficit de atenção, redução da velocidade de processamento, comprometimento da memória de trabalho e de funções executivas. A freqüência de disfunção cognitiva é inferior na SCI do que na EM. CONCLUSÕES: Pacientes com CIS devem ser avaliados quanto à cognição. Estudos futuros são necessários para avaliar o impacto do prejuízo cognitivo e correlacioná-lo com achados de dano axonal em pacientes com SCI.