Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study.

Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability. Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS. Methods: Patients with relapsing-remitting (RRMS) (n = 68) or secondary progressive MS (SPMS) (n = 15) underwent CCM and optical coherence tomography. Corneal nerve fibre density (CNFD-fibres/mm2), corneal nerve branch density (CNBD-branches/mm2), corneal nerve fibre length (CNFL-mm/mm2) and retinal nerve fibre layer (RNFL-µm) thickness were quantified along with neurological and radiological assessments at baseline and after 2 years of follow-up. Age-matched, healthy controls (n = 20) were also assessed. Results: In patients with RRMS compared with controls at baseline, CNFD (p = 0.004) and RNFL thickness (p < 0.001) were lower, and CNBD (p = 0.003) was higher. In patients with SPMS compared with controls, CNFD (p < 0.001), CNFL (p = 0.04) and RNFL thickness (p < 0.001) were lower. For identifying RRMS, CNBD had the highest area under the receiver operating characteristic (AUROC) curve (0.99); and for SPMS, CNFD had the highest AUROC (0.95). At follow-up, there was a further significant decrease in CNFD (p = 0.04), CNBD (p = 0.001), CNFL (p = 0.008) and RNFL (p = 0.002) in RRMS; in CNFD (p = 0.04) and CNBD (p = 0.002) in SPMS; and in CNBD (p = 0.01) in SPMS compared with RRMS. Follow-up corneal nerve loss was greater in patients with new enhancing lesions and optic neuritis history. Conclusion: Progressive corneal and retinal axonal loss was identified in patients with MS, especially those with more active disease. CCM may serve as an imaging biomarker of axonal loss in MS.

Impact of unilateral trigeminal neuralgia on bilateral ocular surface alterations.

OBJECTIVE: To evaluate ocular surface alterations in both eyes of patients with unilateral trigeminal neuralgia (TN) compared with controls. BACKGROUND: Corneal nerves mainly originate from the trigeminal nerve, and neurosensory abnormalities are important factors in ocular surface alterations and dry eye etiopathogenesis. METHODS: Twenty-four patients with idiopathic unilateral TN and 24 healthy controls with similar sex and age distributions were included in this cross-sectional study conducted from February 15 to September 15, 2021. The eyes on the affected sides of the patients with TN were treated as Group 1, their contralateral eyes as Group 2, and the right eyes of the controls as Group 3. All participants were evaluated for tear film and ocular surface using the Schirmer 1 test, tear breakup time (TBUT), Ocular Surface Disease Index (OSDI) score, and conjunctival impression cytology grading. RESULTS: The mean (SD) ages of the patients with TN (17 of 24 females, 70.8%) and controls (15 of 24 females, 62.5%) were 49.7 (11.7) and 48.5 (9. 6) years, respectively. The median [25th, 75th percentile] Schirmer 1 test results in Groups 1, 2, and 3 were 5.0 [4.0, 14.0], 7.0 [3.2, 11.7], and 10.0 [6.0, 15.7] mm, respectively, with no statistically significant differences between Groups 1 and 2 (p = 0.697), Groups 1 and 3 (p = 0.133), or Groups 2 and 3 (p = 0.129). The median TBUT scores in Groups 1, 2, and 3 were 7.0 [5.0, 10.0], 8.0 [5.2, 10.0], and 12.5 [8.0, 13.0] s, respectively, showing reduced times for both Groups 1 and 2 versus Group 3 (median difference = -3.0 [95% CI: -5.0, -1.0], p = 0.001, and median difference = -3.0 [95% CI: -5.0, -2.0], p = 0.001, respectively). Conjunctival impression cytology grades were significantly higher in Groups 1 and 2 versus Group 3 (median difference = 2.0 [95% CI: 1.0, 2.0], p < 0.001, and median difference = 1.0 [95% CI: 1.0, 2.0], p < 0.001, respectively). The median OSDI score in TN patients (30.2 [25.0, 34.9]) was significantly higher than in the controls (8.3 [0.0, 18.7]), with a median difference of 20.8 (95% CI: 14.7, 27.1), p < 0.001. CONCLUSION: Even if pain is unilateral in patients with TN, there are significant abnormalities in conjunctival cytology and tear functions in both eyes. There seem to be various pathophysiological mechanisms of TN that affect the bilateral ocular surface and lead to significant alterations.

Possible roles of sestrin2 in multiple sclerosis and its relationships with clinical outcomes / Possíveis papéis da sestrina2 na esclerose múltipla e suas relações com resultados clínicos

ABSTRACT Background: Characterized by demyelination, inflammation and axonal damage, multiple sclerosis (MS) is one of the most common disorders of central nervous system led by the immune system. There is an urgent and obvious need for biomarkers for the diagnosis and follow-up of MS. Objective: To investigate serum levels of sestrin2 (SESN2), a protein that responds to acute stress, in MS patients. Methods: A total of 85 participants, 40 patients diagnosed previously with relapsing-remitting MS and 45 healthy controls, were included. Serum SESN2 parameters were investigated in blood samples drawn from each participant in the patient and control groups. Results: SESN2 levels were significantly lower in MS patients than in controls (z: -3.06; p=0.002). In the ROC analysis of SESN2, the predictive level for MS was 2.36 ng/mL [sensitivity, 72.50%; specificity, 55.56%; p=0.002; area under the curve (AUC)=0.693]. For the cut-off value in both groups, SESN2 was an independent predictor for MS [Exp (B)=3.977, 95% confidence interval (95%CI) 1.507-10.494 and p=0.013]. Conclusions: The decreased expression of SESN2 may play a role in MS pathogenesis, and SESN2 could be used as a biomarker for MS and as immunotherapeutic agent to treat MS.

RESUMO Antecedentes: Caracterizada por desmielinização, inflamação e dano axonal, a esclerose múltipla (EM) é uma das doenças mais comuns do sistema nervoso central liderada pelo sistema imunológico. Há uma necessidade urgente e óbvia de biomarcadores para o diagnóstico e acompanhamento da EM. Objetivo: Investigar os níveis séricos de sestrina2 (SESN2), uma proteína que responde ao estresse agudo, em pacientes com EM. Métodos: Foram incluídos 85 participantes, 40 pacientes com diagnóstico prévio de EM recorrente-remitente e 45 controles saudáveis. Os parâmetros do SESN2 sérico foram investigados em amostras de sangue coletadas de cada participante nos grupos de paciente e controle. Resultados: os níveis de SESN2 foram significativamente mais baixos em pacientes com EM do que em controles (z: -3,06; p=0,002). Na análise ROC do SESN2, o nível preditivo para MS foi 2,36 ng/mL [sensibilidade, 72,50%; especificidade, 55,56%; p=0,002; área sob a curva (AUC)=0,693]. Para o valor de corte em ambos os grupos, SESN2 foi um preditor independente para MS [Exp (B)=3,977, intervalo de confiança de 95% (95%CI) 1,507-10,494; p=0,013]. Conclusões: A expressão diminuída de SESN2 pode desempenhar um papel na patogênese da EM, e SESN2 poderia ser usado como um biomarcador para EM e como agente imunoterapêutico para o tratamento de EM.

Evaluation of upper extremity ataxia through image processing in individuals with multiple sclerosis / Avaliação da ataxia da extremidade superior por processamento de imagem em indivíduos com esclerose múltipla

ABSTRACT Background: Impaired dexterity is a frequently reported disability among people with ataxic multiple sclerosis (MS). Objective: To quantify and standardize the evaluation of upper extremity coordination disorder among patients with multiple sclerosis (MS), using the Tablet Ataxia Assessment Program (TAAP). Methods: The X and Y axis movements of 50 MS patients and 30 healthy individuals who were evaluated using the International Cooperative Ataxia Rating Scale (ICARS) were also assessed using TAAP. The functional times of the participants' right and left hands were recorded using the nine-hole peg test (NHPT). The upper extremity coordination of individuals with MS was evaluated using the upper extremity kinetic functions section of ICARS. Results: The deviations for the X and Y axis movements of the MS group were greater than those of the control group (p<0.05). Significant correlations were shown between TAAP scores and NHPT and ICARS scores. The strongest correlation was found between NHPT and ICARS in the dominant hand (rnhpt=0.356, pnhpt=0.001; ricars=0.439, picars=0.000). In correlating the Y axis with ICARS, the deviations in the Y axis were found to be greater in the non-dominant hand than those in the X axis (ryright=0.402, pyright=0.004; ryleft=0.691, pyleft=0.000). Conclusion: Measurement using TAAP is more sensitive than other classical and current methods for evaluating ataxia. We think that TAAP is an objective tool that will allow neurorehabilitation professionals and clinicians to evaluate upper extremity coordination.

RESUMO Antecedentes: Destreza prejudicada é uma deficiência frequentemente relatada em pessoas com esclerose múltipla (EM) atáxica. Objetivo: Nosso objetivo é quantificar e padronizar a avaliação do distúrbio de coordenação da extremidade superior em pacientes com EM usando o Tablet Ataxia Assessment Program (TAAP). Métodos: Os movimentos dos eixos X e Y de 50 EM e 30 indivíduos saudáveis que foram avaliados com a International Cooperative Ataxia Rating Scale (ICARS) também foram avaliados com TAAP. Os tempos funcionais das mãos direita e esquerda dos participantes foram registrados usando o teste de nove pinos (NHPT). A coordenação da extremidade superior de indivíduos com EM foi avaliada com a seção de funções cinéticas da extremidade superior do ICARS. Resultados: Os desvios para os movimentos dos eixos X e Y do grupo MS foram maiores do que os do grupo controle (p <0,05). Correlações significativas foram mostradas entre os escores do TAAP e os escores do NHPT e do ICARS. A correlação mais forte foi encontrada entre NHPT e ICARS na mão dominante (rnhpt=0,356, pnhpt=0,001, ricars=0,439 e picars=0,000). Na correlação do eixo Y com ICARS, observou-se que os desvios no eixo Y foram maiores na mão não dominante do que no eixo X (ryright=0,402, pyright=0,004, ryleft=0,691 e pyleft=0,000). Conclusão: A medição com TAAP é mais sensível do que outros métodos clássicos e atuais de avaliação de ataxia. Acreditamos que o TAAP seja uma ferramenta objetiva que permitirá aos profissionais de neurorreabilitação e médicos avaliar a coordenação dos membros superiores.

Serum levels of irisin and nesfatin-1 in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune chronic neurological disease. Currently, there are no effective serum biomarkers to verify MS diagnosis, to assess disease prognosis, and evaluate response to MS treatment. OBJECTIVE: The present study is a preliminary assessment of irisin and nesfatin-1 serum levels in patients with relapsing- remitting MS (RRMS). METHODS: A total of 86 participants, 42 patients with RRMS diagnosis and 44 healthy controls were included in the study. The serum irisin and nesfatin-1 parameters of the patients and control group members were analyzed. RESULTS: Irisin and nesfatin-1 levels of the RRMS patients were significantly lower than the controls (z: -3.82, p<0.001; z: -4.79, p<0.001, respectively) The cut-off level of irisin is 10.390 (ng/mL) (sensitivity: 84.1%, specificity: 71.4%, AUC: 0.800), and the cut-off level of nestatin-1 is 7.155 (ng/mL) (sensitivity: 68.2%, specificity: 64.3%, AUC: 0.739) in the ROC analysis. For these cut-off levels in the case-control groups, the lower irisin and nesfatin-1 levels are the independent variables for MS patients (OR 9.723, 95%CI 2.884-32.785, p<0.001; OR 3.992, 95%CI 1.336-11.928, p<0.001) respectively. CONCLUSION: The present study revealed lower irisin and nesfatin-1 levels in patients with RRMS. These findings suggest that the decreased levels of irisin and nesfatin-1 peptides may contribute to MS pathogenesis such as inflammation, oxidative stress, and apoptosis in MS, leading to demyelination, axonal damage with neuronal loss, and gliosis.

Possible roles of sestrin2 in multiple sclerosis and its relationships with clinical outcomes.

BACKGROUND: Characterized by demyelination, inflammation and axonal damage, multiple sclerosis (MS) is one of the most common disorders of central nervous system led by the immune system. There is an urgent and obvious need for biomarkers for the diagnosis and follow-up of MS. OBJECTIVE: To investigate serum levels of sestrin2 (SESN2), a protein that responds to acute stress, in MS patients. METHODS: A total of 85 participants, 40 patients diagnosed previously with relapsing-remitting MS and 45 healthy controls, were included. Serum SESN2 parameters were investigated in blood samples drawn from each participant in the patient and control groups. RESULTS: SESN2 levels were significantly lower in MS patients than in controls (z: -3.06; p=0.002). In the ROC analysis of SESN2, the predictive level for MS was 2.36 ng/mL [sensitivity, 72.50%; specificity, 55.56%; p=0.002; area under the curve (AUC)=0.693]. For the cut-off value in both groups, SESN2 was an independent predictor for MS [Exp (B)=3.977, 95% confidence interval (95%CI) 1.507-10.494 and p=0.013]. CONCLUSIONS: The decreased expression of SESN2 may play a role in MS pathogenesis, and SESN2 could be used as a biomarker for MS and as immunotherapeutic agent to treat MS.

Serum levels of irisin and nesfatin-1 in multiple sclerosis / Níveis séricos de irisina e nesfatin-1 na esclerose múltipla

ABSTRACT Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune chronic neurological disease. Currently, there are no effective serum biomarkers to verify MS diagnosis, to assess disease prognosis, and evaluate response to MS treatment. Objective: The present study is a preliminary assessment of irisin and nesfatin-1 serum levels in patients with relapsing- remitting MS (RRMS). Methods: A total of 86 participants, 42 patients with RRMS diagnosis and 44 healthy controls were included in the study. The serum irisin and nesfatin-1 parameters of the patients and control group members were analyzed. Results: Irisin and nesfatin-1 levels of the RRMS patients were significantly lower than the controls (z: -3.82, p<0.001; z: -4.79, p<0.001, respectively) The cut-off level of irisin is 10.390 (ng/mL) (sensitivity: 84.1%, specificity: 71.4%, AUC: 0.800), and the cut-off level of nestatin-1 is 7.155 (ng/mL) (sensitivity: 68.2%, specificity: 64.3%, AUC: 0.739) in the ROC analysis. For these cut-off levels in the case-control groups, the lower irisin and nesfatin-1 levels are the independent variables for MS patients (OR 9.723, 95%CI 2.884-32.785, p<0.001; OR 3.992, 95%CI 1.336-11.928, p<0.001) respectively. Conclusion: The present study revealed lower irisin and nesfatin-1 levels in patients with RRMS. These findings suggest that the decreased levels of irisin and nesfatin-1 peptides may contribute to MS pathogenesis such as inflammation, oxidative stress, and apoptosis in MS, leading to demyelination, axonal damage with neuronal loss, and gliosis.

RESUMO Antecedentes: A esclerose múltipla (EM) é uma doença neurológica crônica autoimune inflamatória e neurodegenerativa. Atualmente, não há biomarcadores séricos eficazes para verificar o diagnóstico de EM, para avaliar o prognóstico da doença e avaliar a resposta ao tratamento de EM. Objetivo: O presente estudo é uma avaliação preliminar dos níveis séricos de irisina e nesfatina-1 em pacientes com EM recorrente-remitente (EMRR). Métodos: Um total de 86 participantes, 42 pacientes com diagnóstico de EMRR e 44 controles saudáveis, foram incluídos no estudo. Os parâmetros séricos de irisina e nesfatina-1 dos pacientes e membros do grupo controle foram analisados. Resultados: Os níveis de irisina e nesfatina-1 dos pacientes com EMRR foram significativamente mais baixos do que os dos controles (z: -3,82, p <0,001; z: -4,79, p <0,001, respectivamente). O nível de corte de irisina é 10,390 (ng/mL) (sensibilidade: 84,1%, especificidade: 71,4%, AUC: 0,800), e o nível de corte de nestatina-1 é 7,155 (ng/mL) (sensibilidade: 68,2%, especificidade: 64,3%, AUC: 0,739) na análise ROC. Para esses níveis de corte nos grupos de caso-controle, os níveis mais baixos de irisina e nesfatina-1 são as variáveis independentes para pacientes com EM (OR 9,723, IC95% 2,884-32,785, p <0,001; OR 3,992, IC95% 1,336-11,928, p <0,001) respectivamente. Conclusão: O presente estudo revelou níveis mais baixos de irisina e nesfatina-1 em pacientes com EMRR. Esses achados sugerem que os níveis diminuídos de peptídeos irisina e nesfatina-1 podem contribuir para a patogênese da EM, como inflamação, estresse oxidativo e apoptose na EM, levando à desmielinização, dano axonal com perda neuronal e gliose.

Conjunctival impression cytology and tear film parameters in patients with multiple sclerosis.

PURPOSE: To evaluate conjunctival impression cytology (CIC) findings and tear film parameters in patients with multiple sclerosis (MS) compared with controls. METHODS: Thirty-three patients with MS (MS group) and 33 age- and sex-matched healthy subjects (control group) were included in this cross-sectional comparative study. CIC grades, tear break-up time (TBUT), Schirmer 1 test results, and Ocular Surface Disease Index (OSDI) scores were compared between the two groups, and correlations between CIC grade, TBUT, Schirmer 1 test result, OSDI score, Expanded Disability Status Scale score, and disease duration were analyzed. RESULTS: Mean CIC grade was higher in the MS group than in the control group (1.48 ± 0.71 and 0.39 ± 0.56, respectively; p < 0.001). In the MS group, CIC of the 14 participants (42.4%) was grade 2-3. In the control group, CIC of the only one participant (3.3%) was grade 2, and none of them was grade 3. TBUT (8.12 ± 3.16, 13.06 ± 4.23 s in MS and control groups, respectively; p < 0.001) and Schirmer 1 test results (8.45 ± 5.75, 17.36 ± 10.89 mm in MS and control groups, respectively; p < 0.001) were lower, and OSDI score (36.36 ± 19.19, 13.70 ± 15.36 in MS and control groups, respectively; p < 0.001) was higher in the MS group compared to the control group. CONCLUSION: In patients with MS, objective findings of dry eye, subjective symptoms related to dry eye, and CIC abnormalities, including high grades of conjunctival squamous metaplasia and goblet cell loss, are more common. Patients with MS should be monitored for ocular surface alterations and dry eye disease.

Evaluation of upper extremity ataxia through image processing in individuals with multiple sclerosis.

BACKGROUND: Impaired dexterity is a frequently reported disability among people with ataxic multiple sclerosis (MS). OBJECTIVE: To quantify and standardize the evaluation of upper extremity coordination disorder among patients with multiple sclerosis (MS), using the Tablet Ataxia Assessment Program (TAAP). METHODS: The X and Y axis movements of 50 MS patients and 30 healthy individuals who were evaluated using the International Cooperative Ataxia Rating Scale (ICARS) were also assessed using TAAP. The functional times of the participants' right and left hands were recorded using the nine-hole peg test (NHPT). The upper extremity coordination of individuals with MS was evaluated using the upper extremity kinetic functions section of ICARS. RESULTS: The deviations for the X and Y axis movements of the MS group were greater than those of the control group (p<0.05). Significant correlations were shown between TAAP scores and NHPT and ICARS scores. The strongest correlation was found between NHPT and ICARS in the dominant hand (rnhpt=0.356, pnhpt=0.001; ricars=0.439, picars=0.000). In correlating the Y axis with ICARS, the deviations in the Y axis were found to be greater in the non-dominant hand than those in the X axis (ryright=0.402, pyright=0.004; ryleft=0.691, pyleft=0.000). CONCLUSION: Measurement using TAAP is more sensitive than other classical and current methods for evaluating ataxia. We think that TAAP is an objective tool that will allow neurorehabilitation professionals and clinicians to evaluate upper extremity coordination.

Cystatin C as a potential biomarker to evaluate migraine.

BACKGROUND: Migraine is a multifactorial neurovascular syndrome and closely associated to inflammation. Cystatin C (Cys C) is a neuroendocrine polypeptide which also plays a role in inflammation. Objective: To investigate the levels of Cys C in migraine patients without aura. METHODS: A total of 80 participants were included in the study; 40 patients and 40 healthy controls. Serum Cys C levels were investigated by using enzyme-linked immunosorbent assay (ELISA). Statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Inc, IL, USA). RESULTS: Serum Cys C levels were found as 73.88 ng/mL in the patient group and 24.92 ng/mL in the healthy control group, being significantly higher among patients (p=0.000). Serum Cys C levels were significacntly different across age subgroups among patients (p=0.049), but not among controls. However, visual analog scale (VAS) (p=0.707), disease duration time (p=0.725) and body mass index (p=0.136) were not significantly different between the two groups. CONCLUSION: Our findings demonstrate that high serum Cys C levels are independently associated to migraine without aura. To the best of our knowledge, this is the first study to determine the serum levels of Cys C in patients with migraine. Thus, serum Cys C may be a potential biomarker of migraine.

Cystatin C as a potential biomarker to evaluate migraine / Cistatina C como potencial biomarcador para avaliação de enxaqueca

ABSTRACT Background: Migraine is a multifactorial neurovascular syndrome and closely associated to inflammation. Cystatin C (Cys C) is a neuroendocrine polypeptide which also plays a role in inflammation. Objective: To investigate the levels of Cys C in migraine patients without aura. Methods: A total of 80 participants were included in the study; 40 patients and 40 healthy controls. Serum Cys C levels were investigated by using enzyme-linked immunosorbent assay (ELISA). Statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Inc, IL, USA). Results: Serum Cys C levels were found as 73.88 ng/mL in the patient group and 24.92 ng/mL in the healthy control group, being significantly higher among patients (p=0.000). Serum Cys C levels were significacntly different across age subgroups among patients (p=0.049), but not among controls. However, visual analog scale (VAS) (p=0.707), disease duration time (p=0.725) and body mass index (p=0.136) were not significantly different between the two groups. Conclusion: Our findings demonstrate that high serum Cys C levels are independently associated to migraine without aura. To the best of our knowledge, this is the first study to determine the serum levels of Cys C in patients with migraine. Thus, serum Cys C may be a potential biomarker of migraine.

RESUMO Introdução: A enxaqueca é uma síndrome neurovascular multifatorial e está intimamente associada à inflamação. A cistatina C (Cys C) é um polipeptídeo neuroendócrino que também desempenha papel importante na inflamação. Objetivo: Investigar os níveis de Cys C em pacientes com enxaqueca sem aura. Métodos: Foram incluídos no estudo 80 participantes; 40 pacientes e 40 controles saudáveis. Os níveis séricos de Cys C foram investigados usando o ensaio de imunoabsorção ligado à enzima (enzyme-linked immunosorbent assay - ELISA). A análise estatística foi realizada utilizando o Statistical Package for the Social Sciences (SPSS), versão 22.0 (SPSS Inc, IL, EUA). Resultados: Em nosso estudo, os níveis séricos de Cys C foram encontrados em 73,88 ng/mL no grupo de pacientes e 24,92 no grupo de controle saudável, sendo os níveis significativamente maiores nos pacientes (p=0,000). Os níveis séricos de Cys C foram significativamente diferentes entre faixas etárias no grupo de pacientes (p=0,049). No entanto, a escala visual analógica (EVA) (p=0,707), o tempo de duração da doença (p=0,725) e o índice de massa corporal (p=0,136) não foram significativamente diferentes entre os dois grupos. Conclusão: Nossos achados demonstram que altos níveis séricos de Cys C estão independentemente associados à enxaqueca sem aura. Até onde sabemos, este é o primeiro estudo a determinar os níveis séricos de Cys C em pacientes com enxaqueca e os resultados sugerem que o Cys C sérico pode ser um potencial biomarcador nessa condição clínica.

Progressive Loss of Corneal and Retinal Nerve Fibers in Patients With Multiple Sclerosis: A 2-Year Follow-up Study.

Purpose: To determine longitudinal alterations in corneal nerve fiber morphology, dendritic cell (DC) density, and retinal nerve fiber layer (RNFL) thickness over 2 years in patients with multiple sclerosis (MS). Methods: Thirty-one consecutive patients with relapsing-remitting MS (RRMS) underwent assessment of the Kurtzke Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS), corneal confocal microscopy to quantify corneal subbasal nerve morphology and DC density, and spectral-domain optical coherence tomography to quantify RNFL thickness at baseline and after 2 years. Results: There was a significant reduction in corneal nerve fiber area (CNFA) (P = 0.003), nerve fiber width (CNFW) (P = 0.005), and RNFL thickness (P = 0.004) with an increase in EDSS (P = 0.01) over 2 years. The change in corneal nerve fiber density (CNFD) correlated with the change in EDSS (ρ = -0.468; P = 0.008), MSSS (ρ = -0.442; P = 0.01), DC density (ρ = -0.550; P = 0.001), and RNFL (ρ = 0.472; P = 0.007). The change in corneal nerve fiber length (CNFL) correlated with the change in EDSS (ρ = -0.445; P = 0.01) and MSSS (ρ = -0.490; P = 0.005). Furthermore, there was a significant decrease in CNFL (P < 0.001), CNFA (P = 0.02), CNFW (P = 0.04), corneal total branch density (P = 0.01), and RNFL thickness (P = 0.02) and a significant increase in DC density (P = 0.04) in patients with worsening EDSS (n = 15). Conclusions: Corneal confocal microscopy can be used to detect progressive corneal nerve fiber loss that relates to a progression of disability in patients with RRMS. Translational Relevance: Corneal confocal microscopy acts as a sensitive imaging biomarker for progressive nerve degeneration in patients with MS.

A cross-sectional study to assess the association between major depression and inflammatory markers in patients with acute ischemic stroke.

BACKGROUND: Increased interest in the relationship between affective disorder and long-term health consequences has generated recent examinations of depression and stroke. Observations suggest that depressive disorder is associated with abnormal physiological and immunological responses and a resultant increase in inflammatory markers. Given the high prevalence of stroke and associated costs for the community, it is important to understand the mechanisms that may impact on the outcome to achieve the best possible prognosis. AIMS: The view that inflammatory factors contribute to depression is predicated on findings that circulating cytokines and other inflammatory factors are increased in depressed patients. Therefore, it has been hypothesized that inflammation could be one of the mechanisms by which depression increases risk for ischemic stroke. Our aim was to determine whether there is any relationship between major depression and tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), IL-18, brain-derived neurotrophic factor (BDNF), and neuron-specific enolase (NSE) in patients with acute ischemic stroke (AIS). STUDY DESIGN: This was as a cross-sectional design. MATERIALS AND METHODS: This study has a cross-sectional design, and it was conducted in Necmettin Erbakan University, the Meram Faculty of Medicine in Konya, Turkey, between 2014 and 2015. Fifty-three AIS patients admitted to the hospital within the first 24 h after stroke onset were recruited. Major depression was ascertained by means of the structured clinical interview for the diagnostic and statistical manual of mental disorders, Fourth Edition/Clinical Version. The enzyme-linked immunosorbent assay was used to measure the serum levels of TNF-α, IL-1 ß, IL-18, BDNF, and NSE at admission. RESULTS: A total of 53 patients with a mean age of 65.9 years were recruited. Of these patients, 17 (32.1%) had major depression. Depressive and nondepressive patients had similar demographical and clinical features. There was no significant statistical difference between depressive and nondepressive patients with AIS with respect to levels of TNF-α, IL-1 ß, IL-18, BDNF, and NSE. CONCLUSION: This study suggests that in patients who have experienced AIS, there is no significant relationship between major depression and basal proinflammatory cytokines (TNF-α, IL-1 ß, IL-18), BDNF, and NSE.

The prevalence of bruxism and related factors in patients with multiple sclerosis: a comparative study.

OBJECTIVE: To determine the prevalence of bruxism and related factors in patients with multiple sclerosis (MS). METHODS: Diagnosed with relapsing-remitting MS under the 2010-revised McDonald diagnostic criteria, 182 patients without MS exacerbations during the previous three months were included in the patient group, and 145 healthy individuals made up the control group in the study. Demographic data of the participants in both groups were determined. In the patient and control groups, the diagnosis of definite bruxism was made using the International Classification of Sleep Disorders (Diagnosis and Coding Manual, Second Edition). RESULTS: Bruxism was found in 29.7% (n = 54) of the patients and in 12.4% (n = 18) of the controls, and the difference was statistically significant (p < 0.001). Of all patients, the onset of bruxism was found in 70.4% (n = 38) after the diagnosis and in 29.6% (n = 169) prior to the diagnosis of MS. Compared with those without bruxism, the mean age (p = 0.031) and the score of the Expanded Disability Status Scale (p = 0.001) were also significantly higher among MS patients with bruxism. Between MS patients with and without bruxism, no significant differences were found in terms of sex, marital status, educational status, employment, cigarette smoking, total number of exacerbations, number of exacerbations within the previous year, and drugs used. CONCLUSIONS: The frequency of bruxism was found to be higher in the patients with MS than in the controls. Bruxism is associated with age and the Expanded Disability Status Scale score in MS patients.

The prevalence of bruxism and related factors in patients with multiple sclerosis: a comparative study / A prevalência do bruxismo e fatores relacionados em pacientes com esclerose múltipla: um estudo comparativo

ABSTRACT Objective: To determine the prevalence of bruxism and related factors in patients with multiple sclerosis (MS). Methods: Diagnosed with relapsing-remitting MS under the 2010-revised McDonald diagnostic criteria, 182 patients without MS exacerbations during the previous three months were included in the patient group, and 145 healthy individuals made up the control group in the study. Demographic data of the participants in both groups were determined. In the patient and control groups, the diagnosis of definite bruxism was made using the International Classification of Sleep Disorders (Diagnosis and Coding Manual, Second Edition). Results: Bruxism was found in 29.7% (n = 54) of the patients and in 12.4% (n = 18) of the controls, and the difference was statistically significant (p < 0.001). Of all patients, the onset of bruxism was found in 70.4% (n = 38) after the diagnosis and in 29.6% (n = 169) prior to the diagnosis of MS. Compared with those without bruxism, the mean age (p = 0.031) and the score of the Expanded Disability Status Scale (p = 0.001) were also significantly higher among MS patients with bruxism. Between MS patients with and without bruxism, no significant differences were found in terms of sex, marital status, educational status, employment, cigarette smoking, total number of exacerbations, number of exacerbations within the previous year, and drugs used. Conclusions: The frequency of bruxism was found to be higher in the patients with MS than in the controls. Bruxism is associated with age and the Expanded Disability Status Scale score in MS patients.

RESUMO Objetivo: Neste estudo, pretendeu-se determinar a prevalência de bruxismo e fatores relacionados em pacientes com esclerose múltipla (EM). Métodos: Diagnosticados com EM remitente recidivante sob os critérios de McDonald Diagnostic revisados em 2010, 182 pacientes sem ataques de EM durante os últimos três meses foram incluídos no grupo de pacientes, e 145 indivíduos saudáveis constituíram o grupo de controle no estudo. Os dados demográficos dos participantes dos dois grupos foram determinados. Nos grupos de pacientes e controle, o diagnóstico de bruxismo definitivo foi feito usando a Classificação Internacional de Distúrbios do Sono (1) (Manual de Diagnóstico e Codificação Segunda Edição). Resultados: O bruxismo foi detectado em 29,7% (n = 54) dos pacientes e observado dentro de 12,4% (n = 18) dos controles, e a diferença foi estatisticamente significante (p <0,001). De todos os pacientes, o tempo inicial de bruxismo foi encontrado em 70,4% (n = 38) após o diagnóstico e em 29,6% (n = 169) antes do diagnóstico. Em comparação com aqueles sem bruxismo, os níveis de idade média (p = 0,031) e o escore da Escala de Status de Incapacidade Expandida (p = 0,001) também foram significativamente maiores entre os pacientes com esclerose múltipla com bruxismo. Entre os pacientes com esclerose múltipla com e sem bruxismo, não foi encontrada diferença significativa em termos de sexo, estado civil, status educacional, emprego, tabagismo, número total de ataques, número de ataques no último ano e medicamentos utilizados. Conclusões: A freqüência de bruxismo foi maior em pacientes com esclerose múltipla do que nos controles. O bruxismo está associado à idade e ao escore da Escala de Status de Incapacidade Expandida (EDSS) em pacientes com EM.

Anxiety, Mood, and Personality Disorders in Patients with Benign Paroxysmal Positional Vertigo.

INTRODUCTION: This study presents the current prevalence of anxiety, mood, and personality disorders as well as factors associated with the existence of psychiatric disorders in patients with benign paroxysmal positional vertigo (BPPV). METHODS: The study sample comprised 46 patients with BPPV and 74 control subjects. Anxiety and mood disorders were ascertained via the Structured Clinical Interview for the Diagnostic and Statistical Manual (DSM) of Mental Disorders, Fourth Edition/Clinical Version. Personality disorders were diagnosed via the Structured Clinical Interview for DSM, Revised Third Edition, Personality Disorders. RESULTS: Of the 46 patients, 18 (39.1%) had at least one mood or anxiety disorder and 13 (28.3%) had at least one personality disorder. The most common Axis I and Axis II disorders in the patient group were major depression in 8 (17.4%) and obsessive-compulsive personality disorder in 10 (21.7%) patients, respectively. It was found that major depression (p=0.021), generalized anxiety disorder (p=0.026) and obsessive- compulsive personality disorder (p=0.001) were more prevalent in the BPPV group compared with the control group. CONCLUSION: Results suggest that psychiatric disturbances should be carefully checked in patients with BPPV due to the relatively high rate of comorbidity.

The Assessment of Sexual Dysfunction in Male Patients with Multiple Sclerosis.

INTRODUCTION: To investigate the effects of multiple sclerosis (MS) on male sexuality. METHODS: While 61 men with MS were included into the study group, 60 healthy men constituted the control group in the study. In MS patients, such parameters as functional status and depression levels were assessed with the Expanded Disability Status Scala (EDSS) and the Beck Depression Scale (BDS), other parameters such as pain levels, sexual function and quality of life (QoL) were evaluated with the Visual Analog Scala (VAS), the International Index of Erectile Function (IIEF) and the short form-36 (SF-36), respectively. RESULTS: Patients with MS were classified as 45 with EDSS <5.5 and 19 with EDSS >5.5. Mean VAS and BDI scores patients with MS were found statistically significantly higher, compared with those of the controls (p<0.05). Mean IIEF and all sub-group scores of SF-36 of patients with MS were found to be statistically significantly lower, compared with those of the control group (p<0.05). Mean EDSS in patients with MS was 2.75±2.42. While there was a positive correlation between IIEF scores of patients with MS, and mean mental and physical components of SF-36, a negative correlation was found between IIEF scores in MS patients, and age, disease duration, number of attacks, number of marital years and scores of EDSS, VAS and BDI (p<0.00). When BDI ≥17 was accepted as the threshold for depression, the depression was detected in 62.5% of patients with MS and 11.7% of the controls (p<0.001). CONCLUSION: Sexual functions are affected negatively in male patients with MS and seem to be associated with increased disability, pain and accompanying depression. Therefore, male patients with MS should also be evaluated with regard to sexual function, as well as disability during their follow-ups.

Sleep quality, morningness-eveningness preference, mood profile, and levels of serum melatonin in migraine patients: a case-control study.

The melatonin as the pineal gland's secretory product is implicated in the pathophysiology of migraine. Melatonin has critical functions in human physiology, and research underscores the importance of melatonin in circadian rhythm, sleep, and mood regulation. Clinical observations have indicated that migraine attacks have a seasonal, menstrual, and circadian timing, suggesting that chronobiological mechanisms and their alterations may causally involve in the etiology of the disease. However, the topic has received relatively little attention in the migraine literature. Associations between melatonin, circadian preference, sleep, and mood states were investigated in the current study. Fifty-five patients (47 females and 8 males) were compared to 57 gender and age-matched control subjects (40 females and 17 males). A socio-demographical questionnaire, the Beck Depression Inventory, Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), Profile of Mood States (POMS), and Morningness-Eveningness Questionnaire were administered to volunteers. Blood samples were taken from all participants at about 1:00 AM in an unlit room not to hamper melatonin secretion, and blood melatonin levels were measured using quantitative ELISA test. In comparison with controls, melatonin levels were significantly lower among migraine patients. Migraineurs reported significantly greater scores on the BAI, confusion-bewilderment subscale of the POMS, and total and sleep latency subscale of the PSQI. Migraine patients who had nausea during the migraine attacks and who reported bouts relevant to certain food consumption, such as cheese or chocolate, had significantly lower levels of melatonin. Contrarily, groups did not reveal statistically substantial difference in circadian preferences.

Delirium in patients with acute ischemic stroke admitted to the non-intensive stroke unit: Incidence and association between clinical features and inflammatory markers.

BACKGROUND: Stroke patients with development of delirium have unfavorable outcomes, higher mortality, longer hospitalizations, and a greater degree of dependence after discharge. Studies suggest that delirium is associated with abnormal immunological responses and a resultant increase in inflammatory markers. OBJECTIVE: Our aim was to determine whether there is an entity relationship between delirium, inflammation and acute ischemic stroke (AIS). METHODS: Sixty AIS patients admitted to the hospital were consecutively recruited. Delirium was diagnosed with the clinical assessment according to the Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of Interleukin-1 beta (IL-1 beta), Interleukin 18 (IL-18), Tumor Necrosis Factor-alpha (TNF-alpha), Brain-Derived Neurotrophic Factor (BDNF), and Neuron Specific Enolase (NSE) at admission. RESULTS: Eleven (18.3%) of 60 patients were diagnosed with delirium, and the majority (n=8, 72.7%) was the hypoactive type. Delirious and non-delirious patients had similar demographic and clinical features. Delirious patients had significantly higher lengths of hospital stay, National Institutes of Health Stroke Scale (NIHSS) at admission and discharge compared to non-delirious patients. In addition, there was no significant statistical difference between delirious and non-delirious patients with AIS in respect of levels of TNF-alpha, IL-1 beta, IL-18, BDNF and NSE. This study suggests that delirium is not scarce in patients with AIS admitted to the non-intensive stroke unit, and that delirium developing after AIS seems not to be associated with serum TNF-alpha, IL-1 beta, IL-18, BDNF and NSE but is associated with length of hospital stay and stroke severity.

Myasthenia gravis with acute respiratory failure in the emergency department.

Acute respiratory failure (ARF) is defined as a sudden malfunction in the ability of respiratory system to maintain adequate gas exchange. Acute hypercapnic respiratory failure develops as a result of ventilation deficiency and it is defined as an increase of PaCO2 above 45 mmHg. Myasthenia Gravis (MG) is a sporadically developing auto-immune deficiency where the neuro-muscular transmission is affected and it is one of the important reasons for neurologically-induced respiratory distress. Here, we report a case of a 75-year-old male patient previously undiagnosed MG, who presented with ARF. MG is not a common entity that we encounter daily. Patients on occasions may present to the emergency department because of acute exacerbation. Though most of them were known cases, we should be aware of some unrecognized cases and should consider MG as a differential diagnosis for patients with acute respiratory failure.