Serum amino acid profiling in differentiating clinical outcomes of multiple sclerosis.

AIM OF THE STUDY: Amino acid metabolism is crucial for regulating immune responses and can be monitored in blood serum samples. This study aimed to analyse serum amino acid profiles in people with multiple sclerosis (pwMS), taking into account differences depending on the disease outcomes. CLINICAL RATIONALE FOR THE STUDY: Serum amino acid profiling is a promising, reproducible and minimally invasive technology, available at different stages of the disease, enabling the search for a specific biomarker to differentiate MS clinical outcomes. MATERIAL AND METHODS: The serum concentrations of 29 amino acids were determined using high-performance liquid chromatography mass spectrometry. RESULTS: A total of 121 pwMS (41 relapsing-remitting MS-RRMS; 55 secondary progressive MS - SPMS; and 25 primary progressive MS-RRMS) with a median Expanded Disability Status Scale (EDSS) score of 6 and 53 healthy controls (HCs) were included. We found significantly higher serum total amino acids concentrations in pwMS compared to HCs. Serum concentrations of arginine, 1-methyl-L-histidine and proline were higher in pwMS, while circulating citrulline, α-aminobutyric acid and tryptophan were lower in pwMS. We observed significant differences in serum total amino acids concentrations depending on MS type, with the highest level in the PPMS group and the lowest in the RRMS group. We found significantly higher serum levels of beta-aminoisobutyric acid in PPMS patients compared to those with RRMS and SPMS, and significantly higher serum levels of aspartic acid in PPMS patients compared to RRMS patients. From visual inspection, no trend was observed in total amino acids concentration with respect to the EDSS score. When analysing serum total amino acids concentration in pwMS with EDSS ≤ 5 compared to those with EDSS > 5, no significant differences were found. CONCLUSIONS AND CLINICAL IMPLICATIONS: Amino acid metabolism is altered in pwMS and depends on the clinical type of the disease. Further studies are needed to determine whether serum metabolomic profiling of amino acids may have an application in the search for clinical phenotype-specific MS biomarkers.

Serum amino acid profiles in patients with myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease characterized by weakness and rapid fatigue. Diagnostic methods used for myasthenia gravis are not conclusive and satisfactory, therefore it is necessary to develop reliable tools to help diagnose myasthenia gravis as early as possible. The aim of the study was to use HPLC-MS in conjunction with multivariate statistical analyses to investigate changes in the amino acid metabolic profiles between myasthenia gravis patients compared and controls. In addition, the effect of treatment regimens and myasthenia gravis type, on the observed changes in amino acid metabolic profiles were assessed. Serum levels of 29 amino acids were determined in 2 groups of individuals-28 patients with myasthenia gravis and 53 control subjects (CS). The results of our study indicate that serum levels of several amino acids in patients with myasthenia gravis changed significantly compared to the control group. Statistical analysis revealed differences between amino acids concentration in patients with different therapeutic scheme. In conclusion, amino acids may be involved in mechanisms underlying myasthenia gravis pathogenesis as well as may be potential biomarkers in MG patients diagnosis. However, considering the multifactorial, heterogenous and complex nature of this disease, validation on a larger study sample in further research is required before application into diagnostic practice.

Amino Acid Levels as Potential Biomarkers of Multiple Sclerosis in Elderly Patients: Preliminary Report.

BACKGROUND AND PURPOSE: Aging in multiple sclerosis is associated with both disease- and age-dependent neurodegeneration. Serum metabolomic profiling of amino acids seems to be a promising method for searching for biomarkers of neurodegenerative disorders. The aim of this study was to determine the profile of nonessential amino acids in the serum of elderly patients with secondary progressive multiple sclerosis (SPMS). METHODS: We used high-performance liquid chromatography to evaluate the serum concentrations of nonessential amino acids in subjects aged >65 years: six patients with SPMS and 20 control subjects (CS). RESULTS: The serine and alanine levels were significantly higher in SPMS patients than in CS, whereas the concentrations of aspartic acid, arginine, and cysteine were significantly lower in SPMS patients. These observations indicate that amino acids may be involved in SPMS neurodegeneration mechanisms. There were no significant differences in the serum concentrations of the other four amino acids investigated (glutamic acid, glycine, proline, and tyrosine) between patients with SPMS and CS. CONCLUSIONS: The preliminary results obtained in the study suggest that the metabolism of some amino acids is altered in patient with SPMS. We also conclude that amino acid profiling might be helpful in searching for putative biomarkers of central nervous system diseases. However, considering the multifactorial, heterogeneous, and complex nature of SPMS, further validation research involving larger study samples is required before applying these biomarkers in diagnostic practice.

Amino acids levels as a potential biomarker in myasthenia gravis.

The search for new diagnostic and therapeutic approaches for myasthenia gravis (MG) is highly desirable. Therefore, the aim of the present study is to assess the profile of non-essential amino acids in the serum of MG patients. We evaluated the serum levels of non-essential amino acids in MG patients (n = 10) and control subjects (CS, n = 10) using high-performance liquid chromatography (HPLC) method and assuming a two-fold concentration difference between the groups as significant. Serum levels of aspartic acid and glutamic acid in MG patients were significantly higher than in CS. There were no significant differences in mean serum levels of glycine, proline, alanine, serine, cysteine, arginine and tyrosine between MG patients and CS. The results indicate the need for further research to assess the role of non-essential amino acids in MG. Moreover, our preliminary results suggest that the metabolism of some amino acids seems to be changed in patients with MG. Therefore, we conclude that amino acids profiling might be helpful in searching for putative biomarkers of the central nervous system diseases such as myasthenia gravis.

Spectral-Domain Optical Coherence Tomography Assessment in Treatment-Naïve Patients with Clinically Isolated Syndrome and Different Multiple Sclerosis Types: Findings and Relationship with the Disability Status.

This study evaluates the peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular volume (TMV) using spectral-domain optical coherence tomography in treatment naïve patients with the clinically isolated syndrome (CIS) and different multiple sclerosis (MS) types. A total of 126 patients (15 CIS, 65 relapsing-remitting MS, 14 secondary progressive MS, 11 primary progressive MS, 21 benign MS) with or without optic neuritis (ON) history and 63 healthy age-similar controls were assessed. Concerning controls' eyes, pRNFL thickness was significantly reduced in CIS-ON eyes (p < 0.01), while both TMV and pRNFL thickness was decreased in all MS eyes regardless of ON history (p < 0.01). Significant differences in pRNFL thickness and TMV between MS variants were observed for non-ON eyes (p < 0.01), with the lowest values in benign and secondary progressive disease type, respectively. The pRNFL thickness was inversely correlated with Expanded Disability Status Scale (EDSS) score in non-ON subgroups (p < 0.01), whereas TMV was inversely correlated with EDSS score in both ON and non-ON subgroups (p < 0.01). Concluding, pRNFL thinning confirms optic nerve damage in CIS-ON eyes and appears to be disproportionately high with respect to the disability status of benign MS patients. The values of TMV and pRNFL in non-ON eyes significantly correspond to MS course heterogeneity and patients' disability than in ON eyes.

Early Clinical Features, Time to Secondary Progression, and Disability Milestones in Polish Multiple Sclerosis Patients.

Background and Objectives: Determining the clinical course of multiple sclerosis (MS) and prediction of long-term disability can be a big challenge. To determine early clinical features of MS, their influence on long-term disability progression, and time to transition from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS), a cohort of Polish patients was studied. Materials and Methods: We retrospectively evaluated 375 Polish MS patients based on data from available medical records. We assessed early clinical MS features and the relationship between demographics and time from disease onset to attainment of 4 and 6 points on the Expanded Disability Status Scale (EDSS), as well as time to conversion from RRMS to SPMS. Results: The differences between initial MS variants were significantly associated with gender, age at disease onset, number and type of the first symptoms, and rate of the disability accrual. Mean times from disease onset to attainment of EDSS 4 and 6 were significantly influenced by the disease variant, age at onset, gender, degree of recovery from the initial symptoms, and first inter-bouts interval. The mean time to secondary progression was significantly influenced by the number and type of the first symptoms of RRMS. Conclusions: Early clinical features of MS are important in determining the disease variant, the time to transition from RRMS to SPMS, as well as predicting the disability accumulation of patients. Despite the small differences regarding the first MS symptoms, the disability outcomes in the cohort of Polish patients are similar to other regions of the world.

Optical coherence tomography in diagnosis and monitoring multiple sclerosis.

This paper presents application of optical coherence tomography (OCT) for diagnosis and monitoring of multiple sclerosis (MS). The peripapillary retinal nerve fibre layer thinning and the reduced total macular volume analysis are shown. With the course of the MS, the severity of these abnormalities increases which reflects the progressive degeneration of retinal ganglion cells and nerve fibres. The OCT parameters are sensitive, non-invasive indicators useful in assessing the progression of inflammation and neurodegeneration in MS.

Evaluation of efficacy, safety and tolerability of fingolimod in patients with the relapsing form of multiple sclerosis - 12-month observation. A preliminary report.

BACKGROUND AND PURPOSE: Oral fingolimod 0.5 mg daily was approved in the European Union in 2011 for the treatment of relapsing multiple sclerosis in the aggressive form and as a second line treatment in patients with high disease activity despite interferon beta therapy. The aim of this study was the evaluation of efficacy, safety and tolerance of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) during a 12-month observation period. MATERIAL AND METHODS: The investigated group consisted of 11 patients aged between 23 and 63 years. All patients underwent immunomodulatory treatment (disease modifying drugs - DMD) or immunomodulatory treatment in combination with mitoxantrone (Mx) without a positive effect for 3-5 years. Patients received oral fingolimod 0.5 mg daily during 12 months. Disability was evaluated with Kurtzke Expanded Disability Status Scale (EDSS) scale. Safety and tolerability of fingolimod were evaluated by adverse events monitoring, laboratory tests, and ophthalmological and skin assessment. RESULTS: Before the initiation of fingolimod treatment all the patients progressed in disability and in MRI changes including five cases with gadolinium-enhancing lesions. During fingolimod treatment there was no new relapse in any patient and no patient stopped the treatment because of any adverse event. During the 12-month treatment, EDSS improvement was observed in seven patients, three patients were stable, and one patient progressed by 0.5 point in the EDSS. CONCLUSIONS: In our study patients fingolimod was effective, safe and well tolerated independently of disease activity and previous treatment.

Demyelinating lesions in the cervical cord in multiple sclerosis 10 years after onset of the disease. Correlation between MRI parameters and clinical course.

BACKGROUND AND PURPOSE: Demyelinating lesions in spinal cord in multiple sclerosis (MS) are found in magnetic resonance imaging (MRI) in 47-90% of patients; spinal cord atrophy, however, which is a measure of axonal loss and correlates with disability, is found in 13-41% of patients. Presence and character of lesions depend on the duration and progression of the disease. The aim of this study was to estimate the presence, character and location of lesions and cervical cord atrophy in MRI performed 10 years after the onset of MS in relation to the clinical course. MATERIAL AND METHODS: 60 patients (41 females and 19 males) with definite MS according to McDonald's criteria were studied. The age of patients ranged from 29 to 62 years and disease duration ranged from 11 to 40 years. The MS group comprised 20 patients with secondary progressive MS (SPMS), 20 patients with primary progressive MS (PPMS) and 20 patients with benign form of MS (BMS). Spinal cord MRI was performed in conventional T1 and T2-weighted sequences. RESULTS: Demyelinating lesions were found in 62% of patients (50% of patients with BMS, 60% with PPMS and 75% with SPMS). 42 intrinsic focal lesions were identified in 18 patients and diffuse lesions of spinal cord were noted in 19 patients. Focal lesions were seen in patients with BMS, whereas SPMS patients had diffuse cervical cord abnormalities, and PPMS patients exhibited both forms of changes. 60% of intrinsic focal lesions were located at C3-C5 levels. Medium-sized lesions prevailed in BMS form; in PPMS form small and medium-size lesions, and in SPMS form large lesions (>10 mm) were more frequent. The spinal cord was atrophic in 8% of patients (10% of patients with PPMS and 15% with SPMS). In BMS no atrophy of the cervical cord was observed. We did not find focal demyelinating lesions in the cervical segment of patients with spinal cord atrophy. CONCLUSIONS: Presence and character of demyelinating lesions in cervical cord ten years after onset of MS is significantly related to the clinical form of the disease. The mid-cervical region of the spinal cord appeared to be the commonest location of the focal lesions. Cervical cord atrophy was more frequent in patients with PPMS and SPMS, but it was not accompanied with intrinsic focal cord lesions.

[Demyelinating lesions in cervical spinal cord and disability in multiple sclerosis patients]. / Zmiany demielinizacyjne w rdzeniu szyjnym a niewydolnosc ruchowa w stwardnieniu rozsianym.

BACKGROUND AND PURPOSE: In multiple sclerosis (MS) lesions appear both in brain and cervical cord. The aim of this study was to estimate the presence of MRI changes in cervical cord depending on the course, duration of the disease and a disability. MATERIAL AND METHODS: Clinical measures included 66 patients suffering from MS, the diagnosis was made according to McDonald's criteria. Patients were aged from 18 to 62 (41 women and 25 men). RESULTS: In patients with relapsing-remitting form (EDSS 1-4) single lesions were seen whereas secondary progressive patients (EDSS 3-7) had diffuse demyelinating lesions and primary progressive patients (EDSS 4-8)--both kinds of changes. It has been shown that the lesions occurred as the disease proceeds. Patients without demyelinating lesions in cervical cord had EDSS from 1 to 3 and the duration of their disease was longer than 10 years (benign MS). CONCLUSIONS: The duration of the disease depends on the presence and character of demyelinating lesions in cervical cord to a large extent. That dependence was not noticed in a primary progressive form. In benign MS there were no lesions in cervical cord.