BDNF and Tau as biomarkers of severity in Multiple Sclerosis

AbstractAimsDetermine if serum levels of tau and brain-derived neurotrophic factor (BDNF) can be used as severity biomarkers in multiple sclerosis (MS).Patients and methodsSubjects with MS, older than 18 and younger than 55 years were included; 74 patients with a diagnosis of relapsing-remitting MS (RRMS), 11 with secondary-progressive MS (SPMS), and 88 controls were included. Total tau and BDNF were measured by western blot.ResultsIncreased tau and decreased BDNF in MS patients compared to controls was found. Total-tau has a peak in RRMS, the second decile of the Multiple Sclerosis Severity Score, and in the lowest Expanded Disability Status Scale and is no different than controls for SPMS patients and the most severe cases of MS.ConclusionBDNF is a good biomarker for diagnosis of MS but not for severity or progression. Tau appears to have a more active role in the progression of MS.

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Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration

Biological Chemistry ◽

10.1515/bc.2008.085 ◽

2008 ◽

Vol 389 (6) ◽

Cited By ~ 48

Author(s):

Isobel A. Scarisbrick ◽

Rachel Linbo ◽

Alexander G. Vandell ◽

Mark Keegan ◽

Sachiko I. Blaber ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cortical Neurons ◽

Serine Proteases ◽

Serum Levels ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive ◽

Neurite Retraction ◽

Disability Status ◽

Relapsing Remitting ◽

Potential Activity

Abstract Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2–15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p≤0.027), with highest levels associated with secondary progressive disease. Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and KLK6 with future EDSS worsening in relapsing remitting patients (p≤0.007). Supporting the concept that KLK1 and KLK6 promote degenerative events associated with progressive MS, exposure of murine cortical neurons to either kallikrein promoted rapid neurite retraction and neuron loss. These novel findings suggest that KLK1 and KLK6 may serve as serological markers of progressive MS and contribute directly to the development of neurological disability by promoting axonal injury and neuron cell death.

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The 1,000th Transplant for Multiple Sclerosis and Other Autoimmune Disorders at the HSCT-México Program: A Myriad of Experiences and Knowledge

Frontiers in Neurology ◽

10.3389/fneur.2021.647425 ◽

2021 ◽

Vol 12 ◽

Author(s):

Iván Murrieta-Álvarez ◽

Yahveth Cantero-Fortiz ◽

Andrés A. León-Peña ◽

Juan C. Olivares-Gazca ◽

José Manuel Priesca-Marín ◽

...

Keyword(s):

Multiple Sclerosis ◽

Response Rate ◽

Expanded Disability Status Scale ◽

Hematological Diseases ◽

Secondary Progressive ◽

Disability Status ◽

Relapsing Remitting ◽

New Knowledge ◽

Autoimmune Conditions ◽

Increased Activity

After gaining experience conducting both auto and allografts in persons with hematological diseases in the HSCT programs in Puebla and Monterrey, México, this study outlines subsequent program autografting patients with autoimmune conditions. The first transplant in multiple sclerosis was conducted in Puebla on July 5, 2006. From 2015 we increased activity autografting persons with autoimmune conditions in the two campuses of the HSCT-México program: Puebla and Monterrey. By December 6, 2020, patient number 1,000 in the program was autografted. In our experience, a significant reduction in the expanded disability status scale score was achieved in all of the three phenotypes of the disease (from a median of 5.1 to 4.5 points), whereas the response rate (defined as a decrease of at least 0.5 of EDSS score regardless of baseline EDSS, or unchanged EDSS) was 83, 78, and 73% after 12 months in the relapsing-remitting, primary-progressive and secondary-progressive forms of multiple sclerosis, respectively. In addition to analyzing the viability, safety, and efficacy of our method, this study contributes new knowledge to the field of both stem cell transplantation and multiple sclerosis.

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CCR5Δ32 Polymorphism Associated with a Slower Rate Disease Progression in a Cohort of RR-MS Sicilian Patients

Multiple Sclerosis International ◽

10.1155/2011/153282 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6

Author(s):

Rosalia D'Angelo ◽

Concetta Crisafulli ◽

Carmela Rinaldi ◽

Alessia Ruggeri ◽

Aldo Amato ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Onset ◽

Expanded Disability Status Scale ◽

Ccr5 Gene ◽

Secondary Progressive ◽

Inflammatory Mechanism ◽

Disability Status ◽

Relapsing Remitting ◽

Cc Chemokines ◽

Sicilian Population

Multiple sclerosis (MS) disease is carried through inflammatory and degenerative stages. Based on clinical feaures, it can be subdivided into three groups: relapsing-remitting MS, secondary progressive MS, and primary progressive MS. Multiple sclerosis has a multifactorial etiology with an interplay of genetic predisposition, environmental factors, and autoimmune inflammatory mechanism in which play a key role CC-chemokines and its receptors. In this paper, we studied the frequency of CCR5 gene Δ32 allele in a cohort of Sicilian RR-MS patients comparing with general Sicilian population. Also, we evaluate the association between this commonly polymorphism and disability development and age of disease onset in the same cohort. Our results show that presence of CCR5Δ32 is significantly associated with expanded disability status scale score (EDSS) but not with age of disease onset.

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T2 hypointense rims and ring-enhancing lesions in MS

Multiple Sclerosis Journal ◽

10.1177/1352458510377905 ◽

2010 ◽

Vol 16 (11) ◽

pp. 1317-1325 ◽

Cited By ~ 7

Author(s):

Sara Llufriu ◽

Teresa Pujol ◽

Yolanda Blanco ◽

Karolina Hankiewicz ◽

Mattia Squarcia ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Characteristics ◽

Clinically Isolated Syndrome ◽

Routine Clinical Practice ◽

The Other ◽

Expanded Disability Status Scale ◽

Secondary Progressive ◽

Disability Status ◽

Relapsing Remitting ◽

Mri Scans

Background: Hypointense rims peripherally on T2-weighted MRI (rim lesions) have been associated with gadolinium ring-enhancing lesions in multiple sclerosis (MS) in pathological studies. However, little is known about their frequency, we analyzed clinical significance in a cohort of MS sufferers according to routine clinical practice. Methods: We retrospectively reviewed all available MRI scans performed on our MS patients between 2000 and 2009. A total of 580 MRI scans from 257 patients were analyzed. The presence of rim lesions and ring enhancement was assessed and counted blind. Furthermore, the correlation between both patterns, and with clinical characteristics, was evaluated. Results: Thirty-five rim lesions were identified and 9% (24/257) of the patients showed at least one of these lesions. Forty ring-enhancing lesions were counted and 12% (29/245) of the patients who had undergone gadolinium MRI presented at least one such lesion. Thirteen lesions co-localized both patterns (40% of the rim lesions and 33% of the ring-enhancing lesions). Rim lesions and ring-enhancing lesions were observed in patients with clinically isolated syndrome (7%, 7%), relapsing—remitting (11%, 15%) and secondary progressive (13%, 9%) but none with primary progressive MS. Presence of ring-enhancing lesions was significantly associated with a shorter time to reach EDSS (Expanded Disability Status Scale) 4.0 and 6.0 (hazard ratio 7.6, 95% confidence interval 2.3—24.6). Conclusions: Rim lesions and ring-enhancing lesions are present in close to 10% of patients with MS, and frequently both lesions appear independently one to the other. The association of ring enhancement with worst prognosis needs to be confirmed in prospective studies.

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Transbulbar B-Mode Sonography for Clinical Phenotyping Multiple Sclerosis

Applied Sciences ◽

10.3390/app8112177 ◽

2018 ◽

Vol 8 (11) ◽

pp. 2177 ◽

Cited By ~ 1

Author(s):

Roberto De Masi ◽

Stefania Orlando ◽

Aldo Conte ◽

Sergio Pasca ◽

Rocco Scarpello ◽

...

Keyword(s):

Multiple Sclerosis ◽

Optic Nerve ◽

Optic Nerve Sheath Diameter ◽

Expanded Disability Status Scale ◽

Secondary Progressive ◽

Nerve Sheath ◽

Transitional Group ◽

Disability Status ◽

Relapsing Remitting ◽

Clinical Phenotyping

The aim of this study was to assess putative differences in optic nerve sheath diameter (ONSD) and associated clinical/paraclinical variables between relapsing remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) patients. We examined 60 relapse-free MS patients and 35 healthy controls by means of transbulbar B-mode sonography (TBS). Expanded disability status scale (EDSS) values were from 3 to 4 indicated patients with a transitional RR to SP phenotype. Mean ONSD was significantly lower in MS patients. Mean ONSD measured at 5 mm from the eyeball (ONSD5) was significantly lower in SP than in RR patients, while ONSD measured at 3 mm from the eyeball (ONSD3) was statistically higher in RR than in the transitional group. The myelination index (MI), i.e., the ratio of ONSD3 to ONSD5, was used to assess the relative myelination of the optic nerve (ON). Higher ONSD5 and MI (0.90) corresponded to patients with the RR phenotype having a mean EDSS of 2.0; lower MI (0.84) clustered the transitional patients having a mean EDSS of 3.7. Finally, lower MI with low ONSD3 identified the SP phenotype having a mean EDSS ≥ 4.0. The TBS in MS highlights chronic optic neuropathy, caused by early subclinical axonal loss and demyelination.

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Manometric correlations of anorectal dysfunction and biofeedback outcome in patients with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458507082606 ◽

2007 ◽

Vol 14 (2) ◽

pp. 237-242 ◽

Cited By ~ 19

Author(s):

E. Munteis ◽

M. Andreu ◽

JE Martinez-Rodriguez ◽

A. Ois ◽

F. Bory ◽

...

Keyword(s):

Multiple Sclerosis ◽

Expanded Disability Status Scale ◽

Maximal Contraction ◽

Anorectal Dysfunction ◽

Secondary Progressive ◽

Disability Status ◽

Relapsing Remitting ◽

Maximal Pressure ◽

Reflex Threshold ◽

Inhibitory Reflex

Objective To evaluate clinical and manometric characteristics of multiple sclerosis (MS) patients with anorectal dysfunction (ARD) and their influence on biofeedback outcome.Patients and methods Patients were clinically and manometrically studied and compared with controls. Patients were subsequently offered to initiate biofeedback manoeuvres to improve ARD.Results Fifty-two patients with ARD, 39 women, mean age 44.96 ± 9.26 years, mean Expanded Disability Status Scale 4.13 ± 1.72, were evaluated. Thirty-one patients had relapsing-remitting (RR), 16 secondary progressive and five primary progressive MS. ARD complaints were constipation (67.3%), double ARD (23.1%) and isolated incontinence (9.6%). The manometric study showed significant differences in patients compared with controls in maximal contraction pressures (98.1 ± 44.2 mm Hg versus 152.05 ± 66.9 mm Hg, P < 0.001) and anal inhibitory reflex threshold (92.9 ± 63.4 mL versus 40.45 ± 11.3 mL, P < 0.001). Maximal pressure was lower in progressive forms compared with RR forms (83.1 ± 36.2 mm Hg versus 108.2 ± 46.7 mm Hg, P < 0.05) in relation to higher disability. Patients with paradoxical contraction (PC) (35 patients, 67.3%) showed more manometric disturbances. From a total of 18 patients performing biofeedback, those reporting some improvement (six complete, two partial) had milder manometric abnormalities.Conclusions The most frequent manometric abnormalities in our MS patients with ARD were alterations of maximal pressures, anal inhibitory reflex and PC. Biofeedback could be more useful in patients with lower disability and manometric alterations. Multiple Sclerosis 2008; 14: 237—242. http://msj.sagepub.com

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Relationship between Expanded Disability Status Scale scores and the presence of temporomandibular disorders in patients with multiple sclerosis

European Journal of Dentistry ◽

10.4103/ejd.ejd_91_17 ◽

2018 ◽

Vol 12 (01) ◽

pp. 144-148 ◽

Cited By ~ 2

Author(s):

Lucas Senra Correa Carvalho ◽

Osvaldo José Moreira Nascimento ◽

Luciane Lacerda Franco Rocha Rodrigues ◽

Andre Palma Da Cunha Matta

Keyword(s):

Multiple Sclerosis ◽

Temporomandibular Disorders ◽

Control Group ◽

Expanded Disability Status Scale ◽

Exact Test ◽

Disability Status ◽

Relapsing Remitting ◽

Scale Scores ◽

Axis I ◽

Relapsing Remitting Multiple Sclerosis

ABSTRACTObjectives: The objectives of this study were to assess the prevalence of temporomandibular disorders (TMDs) in patients with relapsing-remitting multiple sclerosis (MS) and to investigate whether an association exists between the presence of TMD symptoms and the degree of MS-related disability. Materials and Methods: In all, 120 individuals were evaluated: 60 patients with a diagnosis of relapsing-remitting MS and 60 age- and sex-matched controls without neurological impairments. A questionnaire recommended by the European Academy of Craniomandibular Disorders for the assessment of TMD symptoms was administered. For those who answered affirmatively to at least one of the questions, the RDC/TMD Axis I instrument was used for a possible classification of TMD subtypes. The Expanded Disability Status Scale (EDSS) was the measure of the degree of MS-related disability. Statistical Analysis Used: Fisher’s exact test was used to analyze the data. ANOVA was used to detect significant differences between means and to assess whether the factors influenced any of the dependent variables by comparing means from the different groups. Results: The prevalence of TMD symptoms in patients with MS was 61.7% versus 18.3% in the control group (CG). A diagnosis of TMD was established for 36.7% in the MS group and 3.3% in the CG (P = 0.0001). There were statistically significant differences between degrees of MS-related disability and the prevalence of TMD (P = 0.0288). Conclusions: The prevalence of both TMD and TMD symptoms was significantly greater in the MS group. EDSS scores and TMD prevalence rates were inversely related.

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A Pilot Study of 24-h Motor Activity Patterns in Multiple Sclerosis: Pre-Planned Follow-Up at 2 Years

Clocks & Sleep ◽

10.3390/clockssleep3030023 ◽

2021 ◽

Vol 3 (3) ◽

pp. 366-376

Author(s):

Lorenzo Tonetti ◽

Federico Camilli ◽

Sara Giovagnoli ◽

Vincenzo Natale ◽

Alessandra Lugaresi

Keyword(s):

Multiple Sclerosis ◽

Motor Activity ◽

Activity Pattern ◽

Activity Patterns ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Relapsing Remitting ◽

Edss Score ◽

Activity Prognosis

Early multiple sclerosis (MS) predictive markers of disease activity/prognosis have been proposed but are not universally accepted. Aim of this pilot prospective study is to verify whether a peculiar hyperactivity, observed at baseline (T0) in early relapsing-remitting (RR) MS patients, could represent a further prognostic marker. Here we report results collected at T0 and at a 24-month follow-up (T1). Eighteen RRMS patients (11 females, median Expanded Disability Status Scale-EDSS score 1.25, range EDSS score 0–2) were monitored at T0 (mean age 32.33 ± 7.51) and T1 (median EDSS score 1.5, range EDSS score 0–2.5). Patients were grouped into two groups: responders (R, 14 patients) and non-responders (NR, 4 patients) to treatment at T1. Each patient wore an actigraph for one week to record the 24-h motor activity pattern. At T0, NR presented significantly lower motor activity than R between around 9:00 and 13:00. At T1, NR were characterized by significantly lower motor activity than R between around 12:00 and 17:00. Overall, these data suggest that through the 24-h motor activity pattern, we can fairly segregate at T0 patients who will show a therapeutic failure, possibly related to a more active disease, at T1. These patients are characterized by a reduced morning level of motor activation. Further studies on larger populations are needed to confirm these preliminary findings.

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Reduced peripheral blood regulatory B cell levels are not associated with the Expanded Disability Status Scale score in multiple sclerosis

Journal of International Medical Research ◽

10.1177/0300060518783083 ◽

2018 ◽

Vol 46 (9) ◽

pp. 3970-3978 ◽

Cited By ~ 4

Author(s):

Shujun Guo ◽

Qingqing Chen ◽

Xiaoli Liang ◽

Mimi Mu ◽

Jing He ◽

...

Keyword(s):

Multiple Sclerosis ◽

B Cells ◽

Peripheral Blood ◽

Plasma Cells ◽

Serum Levels ◽

Memory B Cells ◽

Healthy Controls ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Edss Score

Objective To investigate levels of regulatory B (Breg) cells, plasma cells, and memory B cells in the peripheral blood, and interleukin (IL)-10 in the serum of multiple sclerosis (MS) patients, and to determine the correlation between Breg cell levels and the Expanded Disability Status Scale (EDSS) score. Methods Levels of Breg cells, plasma cells, and memory B cells in the peripheral blood of 12 MS patients were measured using flow cytometry. IL-10 serum levels were measured by enzyme-linked immunosorbent assay. The correlation between Breg cell levels and MS EDSS score was measured using Pearson’s correlation coefficient. Results Compared with healthy controls, MS patients had decreased levels of CD19+CD24hiCD38hi Breg cells in their peripheral blood and reduced serum levels of IL-10; however, the ratios of CD19+CD27hiCD38hi plasma cells and CD19+CD27+CD24hi memory B cells to total B cells did not differ significantly between healthy controls and MS patients. CD19+CD24hiCD38hi Breg cell levels in the peripheral blood of MS patients were not significantly correlated with MS EDSS score. Conclusion Peripheral blood CD19+CD24hiCD38hi Breg cell levels and serum IL-10 levels were reduced in MS patients compared with controls, but Breg cell levels were not correlated with MS EDSS score.

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Patients with neuromyelitis optica have a more severe disease than patients with relapsingremitting multiple sclerosis, including higher risk of dying of a demyelinating disease

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130020 ◽

2013 ◽

Vol 71 (5) ◽

pp. 275-279 ◽

Cited By ~ 15

Author(s):

Denis Bernardi Bichuetti ◽

Enedina Maria Lobato de Oliveira ◽

Nilton Amorin de Souza ◽

Mar Tintoré ◽

Alberto Alain Gabbai

Keyword(s):

Multiple Sclerosis ◽

Neuromyelitis Optica ◽

Disease Duration ◽

Demyelinating Disease ◽

Age Of Onset ◽

Severe Disease ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Relapsing Remitting ◽

Relapsing Remitting Multiple Sclerosis

Although neuromyelitis optica (NMO) is known to be a more severe disease than relapsing-remitting multiple sclerosis (RRMS), few studies comparing both conditions in a single center have been done.Methods:Comparison of our previously published cohort of 41 NMO patients with 177 RRMS patients followed in the same center, from 1994 to 2007.Results:Mean age of onset was 32.6 for NMO and 30.2 for RRMS (p=0.2062) with mean disease duration of 7.4 years for NMO and 10.3 years for RRMS. Patients with NMO had a higher annualized relapse rate (1.0 versus 0.8, p=0.0013) and progression index (0.9 versus 0.6, p≪0.0001), with more patients reaching expanded disability status scale (EDSS) 6.0 (39 versus 17%, p=0.0036). The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15.Conclusion:Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease.

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