Incidence and prevalence of neuromyelitis optica spectrum disorders in Slovakia.

OBJECTIVE: : Neuromyelitis optica spectrum disorders (NMOSDs) are a group of rare, inflammatory, demyelinating diseases that affect the central nervous system. Neither the incidence nor the prevalence of NMOSD has been determined in Slovakia thus far. The aim of this study was to determine both the incidence and the prevalence of NMOSD in Slovakia using the 2015 International Panel of NMOSD diagnosis (IPND) criteria. METHODS: : We performed a population-based study in Slovakia to estimate both the incidence and the prevalence of NMOSD during the period from 1 January 2006 through 31 December 2019. NMOSD cases were reported from multiple sources and the diagnosis was subsequently verified using the IPND criteria by a joint commitee of three neurologists. The prevalence is reported as number of cases per 100,000 inhabitans and the incidence as number of new cases per 1,000,000 person-years. Age-adjusted rates to the WHO standard population 2005-2025 were also calculated. RESULTS: : We identified 63 NMOSD cases. The crude point-prevalence rate was 1.37 (95% CI 1.03-1.71) per 100,000 inhabitants. The crude indidence rate was 0.88 (95% CI 0.65-1.12) per 1,000,000 person-years. The age-adjusted point-prevalence rate was 1.42 (95% CI 1.07-1.84) per 100,000 persons and the age-adjusted incidence rate was 0.96 (95% CI 0.72-1.25) per 1,000,000 person-years. CONCLUSION: : The NMOSD epidemiological situation in Slovakia is comparable to those reported from other Caucasian populations.

The association of rs703842 variants in CYP27B1 with multiple sclerosis susceptibility is influenced by the HLA-DRB1*15:01 allele in Slovaks.

In this study, we analysed the association of rs703842 in CYP27B1 gene with multiple sclerosis (MS) risk and disability progression in a group of 496 MS patients and 521 controls. For the first time in Central European Slovak population, we found the rs703842 allele C to be protective factor against MS development (p = 1.09 × 10-5). Moreover, the risky genotypes TT and TC were showed to be associated with an increased MS risk, and this was aggravated by the homozygous carriage of the HLA-DRB1*15:01 allele (OR = 2.82 vs. 4.86, p < .0001). No association of rs703842 with MS disability progression or calcidiol serum level was found.

A case of relapsing isolated neurosarcoidosis in an 18-year-old male patient successfully treated by corticosteroids.

Sarcoidosis is a granulomatous multisystemic disease of unknown cause most often affecting the lungs, lymph nodes of the pulmonary hilus, eyes, skin, and other structures including central (CNS) or peripheral nervous system (PNS). Isolated neurosarcoidosis is extremely rare. The diagnosis of isolated neurosarcoidosis is challenging because of its rarity, variety of manifestations, and the lack of systemic signs. We report relapsing and remitting isolated intracranial neurosarcoidosis in an 18-year-old male patient who undervent complex diagnostics including cerebral and meninges biopsy. Patient was succesfully treated with corticosteroids.

TNFRSF1A polymorphisms and their role in multiple sclerosis susceptibility and severity in the Slovak population.

Tumour necrosis factor (TNF)-mediated signalling plays a key role in inflammatory and neurodegenerative processes leading to the development of multiple sclerosis (MS). Recent studies have highlighted the role of tumour necrosis factor receptor superfamily member 1A (TNFRSF1A) gene encoding the type 1 TNF receptor in the genetic predisposition to MS. This study aimed to validate the association of TNFRSF1A rs1800693 and rs4149584 polymorphisms with susceptibility to MS in the Slovak population and analyse their influence on age at disease onset, severity, and disability progression. Polymerase chain reaction-restriction fragment length polymorphism method was used to genotype both TNFRSF1A polymorphisms in 541 MS patients and 724 healthy controls. Logistic regression analysis revealed a significantly increased risk of developing MS for the carriers of rs1800693 C allele (TC + CC vs. TT: pcorr = 0.005; OR = 1.61; 95% CI = 1.23-2.12), irrespective of sex and carriage of the major MS risk allele HLA-DRB1*15:01. On the other hand, no association could be found between rs4149584 and MS risk (GA + AA vs. GG: pcorr = 1.00; OR = 1.25; 95% CI = 0.71-2.21). Moreover, neither polymorphism was significantly associated with age at disease onset, MS Severity Score (MSSS) or MS Progression Index (PI) in any of the inheritance models. In conclusion, our results provide support for a sex- and HLA-DRB1*15:01-independent association of TNFRSF1A rs1800693 SNP with MS susceptibility, but not with age at disease onset, severity or rate of disability accumulation.

The HLA-DRB1 and HLA-DQB1 alleles are associated with multiple sclerosis disability progression in Slovak population.

OBJECTIVE: The aim of our present study was to analyse the association of HLA-DRB1 and -DQB1 alleles and genotypes with Multiple Sclerosis (MS) disability progression in a cohort of Central European Slovak population. METHODS: The allele and genotype variants were analyzed in 282 non-related MS patients. Rate of disease disability progression was evaluated using EDSS score in the 5th, 7th, 10th, and 15th year of disease duration, time to reach EDSS score 3 and 5, and MSSS score. Genotyping was performed by polymerase chain reaction with sequence-specific primers. RESULTS: We found that carriers of homozygous genotype for alleles DRB1*15 and DQB1*03 reached EDSS score 3 significantly earlier than non-carriers of these alleles (p = 0.0172; p = 0.00183, respectively). Genotype DQB1*03/03 carriage was also associated with significantly reduced time to reach EDSS score 5 (p = 0.00316). Lower EDSS score in the 5th year of disease duration was found in carriers of DRB1*07 allele (p cor = 0.028). When MSSS score was used, genotype DRB1*15/15 was found to be less frequent in slow progressing MS patients, when compared to MS patients with mid-rate and rapid disease disability progression (p cor = 0.0305). DISCUSSION: We showed for the first time that HLA-DRB1 and -DQB1 genotypes are genetic markers associated with disability progression in Slovak MS patients. Genotypes DRB1*15/15 and DQB1*03/*03 were identified as short-term clinical negative prognostic factors, while allele DRB1*07 carriage appeared to be a positive prognostic marker of better MS outcome.

Analysis of ICAM1 gene polymorphism in Slovak multiple sclerosis patients.

Infiltration of immune cells into CNS is one of the essential events in multiple sclerosis (MS) development. Adhesion molecules like the intercellular adhesion molecule 1 (ICAM-1) play critical role in this process. Therefore, the ICAM1 gene containing two important single-nucleotide polymorphisms (SNPs) belongs to candidate loci with possible involvement in MS susceptibility and/or severity. The objective of our case-control study was to analyze the association of two functional ICAM1 polymorphisms rs1799969 (or G241R) and rs5498 (or K469E) with susceptibility to MS and evaluate their influence on the age at disease onset, severity, neurological disability and progression rate. Two hundred forty-eight MS subjects (mean 39.2 years) and 208 age-matched controls (mean 35.6 years) were involved in the study. Genotyping of ICAM1 rs1799969 and rs5498 SNPs was performed by PCR-RFLP. Presence of the rs3135388 polymorphism tagging the major MS risk allele HLA-DRB1*15:01 allele was determined as well. Our analysis revealed no statistically significant association of ICAM1 polymorphisms with risk of MS development in the Slovak population. Stratification of study cohorts by gender, age at onset and presence of the HLA-DRB1*15:01 risk allele showed only moderate changes. Correlation of clinical findings as age at onset, Kurtzke Expanded Disability Status Scale, Multiple Sclerosis Severity Score and progression index with ICAM1 genotypes in MS patients revealed no significant association; however, patients with earlier onset of MS showed slightly higher frequencies of the homozygous G allele at rs5498 in comparison to other genotypes (P = 0.04), suggesting that GG carriers tend to induce MS at an earlier age.

ApaI, BsmI and TaqI VDR gene polymorphisms in association with multiple sclerosis in Slovaks.

OBJECTIVE: Vitamin D acts through vitamin D receptor (VDR) and has promising beneficial effects in the development and progression of multiple sclerosis (MS). The purpose of our study was to investigate the possible association of the VDR gene polymorphisms ApaI, BsmI and TaqI with the MS susceptibility and with the rate of disease disability progression in the Central European Slovak population. METHODS: The allele and genotype variants of ApaI, TaqI and BsmI VDR gene polymorphisms were analysed in 270 clinically diagnosed MS patients and 303 healthy controls. Genotyping was performed by polymerase chain reaction and restriction analysis. Patients were stratified by the rate of disease disability progression using MSSS scores. RESULTS: By logistic regression analysis, we revealed that genotype BB (AA) of BsmI VDR gene polymorphism is decreasing the risk of MS (BB (AA) vs Bb (AG) + bb (GG); OR = 0.59, 95% CI = 0.39-0.90, plog = 0.014). We did not identify any association of ApaI and TaqI polymorphisms neither with MS development nor with the disease progression. DISCUSSION: We showed for the first time that BsmI genotype BB (AA) is associated with the decreased susceptibility to MS in Slovak population. We propose the BsmI gene polymorphism to be one of the important genetic markers in evaluation of the risk of MS. However, our data suggest that VDR gene polymorphisms ApaI, BsmI and TaqI are not useful in the prediction of disease disability progression rate in MS in Slovaks.

Primary diffuse leptomeningeal gliomatosis as a rare cause of pain in cervical spine.

BACKGROUND: Primary diffuse leptomeningeal gliomatosis (PDLG) is a very rare neuro-oncological disease, with only 90 cases of PDLG described in medical literature so far. CASE PRESENTATION: We present a case report of a 56-years-old female patient, who was originally hospitalized due to cervical spine pain lasting several months. Despite complex diagnostics and treatment, the neurological state of the patient progressively deteriorated. Patient died 10 months after the first reported symptom. Postmortem pathological findings resulted in the diagnosis of PDLG. CONCLUSIONS: Affection of the cervical spine in early stages of PDLG is rare and has been described in only six patients so far. PDLG is a fatal neuro-oncological disease and it must be kept in mind in the differential diagnosis of persistent back pain syndromes.

Genetic variants in interleukin 7 receptor α chain (IL-7Ra) are associated with multiple sclerosis risk and disability progression in Central European Slovak population.

In this study, we determined the association between rs6897932 in interleukin 7 receptor α (IL7Ra) gene and the risk and disability progression of multiple sclerosis (MS) in 270 MS patients and 303 controls. We found allele C to be associated with the risk of MS and minor allele T to be protective against MS development. Moreover, we revealed for the first time that rs6897932 in IL7Ra gene is associated with the progression of MS, evaluated by MSSS scores. The minor allele T and genotype TT are protective against a rapid disability progression in MS in the Central European Slovak population.

The +190 G/A (rs1799864) polymorphism in the C-C chemokine receptor 2 (CCR2) gene is associated with susceptibility to multiple sclerosis in HLA-DRB1*15:01-negative individuals.

C-C chemokine receptor 2 (CCR2) is one of the key players involved in the transmigration of mononuclear cells into the central nervous system (CNS) and subsequent development of multiple sclerosis (MS). The aim of the current study was to analyse the association of CCR2 +190 G/A (rs1799864) polymorphism with susceptibility to MS and its influence on the age at onset, severity and neurological disability in MS. CCR2 genotyping was carried out by a polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) in 301 MS patients and 342 healthy controls. Logistic regression analysis suggested a marginally significant association between MS and rs1799864 A allele (AA+GA vs. GG, P=0.047, OR=1.50, 95% CI=1.00-2.25), however, after stratification of study groups for the presence of HLA-DRB1*15:01 risk allele, this association could be found in HLA-DRB1*15:01-negative individuals only (AA+GA vs. GG, P=0.014, OR=1.84, 95% CI=1.13-2.98). Furthermore, there was no association between CCR2 polymorphism and clinical features of MS. In conclusion, our results suggest that CCR2 +190 G/A polymorphism may increase the susceptibility to MS, but its action seems to be restricted to individuals who do not possess the major risk allele HLA-DRB1*15:01.

FokI vitamin D receptor gene polymorphism in association with multiple sclerosis risk and disability progression in Slovaks.

OBJECTIVE: It is still unclear as to why multiple sclerosis (MS) is so devastating and rapidly progressive in one patient and less so in another. Recent data implicate vitamin D in modulation of the risk as well as the clinical course of disease. Since vitamin D acts through the vitamin D receptor (VDR), association of single nucleotide polymorphisms (SNPs) in the VDR gene might account for variations in the MS risk within populations. The aim of our study was to determine the association between FokI gene polymorphism (rs10735810) and the risk of MS in a cohort of Slovak population and to investigate possible correlations of this SNP with the rate of disease disability progression. METHODS: FokI SNP was detected in 270 clinically diagnosed MS patients and 303 healthy control subjects. Genotyping was performed by polymerase chain reaction (PCR) and restriction analysis. We used multiple sclerosis severity score (MSSS) for patient's stratification by the rate of disease disability progression. RESULTS: We observed a significantly higher frequency of Ff genotype of FokI SNP (53·4 vs 43·7%, P  =  0·042) in women with MS compared to women of the control group. There was no significant association between FokI SNP and the rate of disease disability progression. DISCUSSION: Although our findings suggest a weak association between VDR SNP FokI and the MS risk in women, further studies are needed to explore the role of VDR polymorphic alterations in MS disease etiology and pathogenesis.

The association of HLA-DRB1 and HLA-DQB1 alleles with genetic susceptibility to multiple sclerosis in the Slovak population.

OBJECTIVE: The aim of the present study was to assess the association between HLA-DRB1 and -DQB1 allele groups with the genetic predisposition to multiple sclerosis (MS) in the Caucasian Central European Slovak population. METHODS: A total of 282 unrelated patients with sporadic MS were enrolled in this case-control study. HLA-DRB1 and HLA-DQB1 allele groups were genotyped using a polymerase chain reaction with sequence-specific primers. The DRB1 and DQB1 allele carrier frequencies, genotypes and haplotype frequencies were compared between MS cases and healthy controls. RESULTS: Positive association with MS was found for alleles HLA-DRB1*15 (OR = 3.64; Pcor = 6.9x10-11), DRB1*03 (after elimination of carriers of DRB1*15, OR = 2.8; Pcor = 0.0029), DQB1*06 (OR = 1.99; Pcor = 7.0x10-4), genotypes HLA-DRB1*15/*15 (OR = 7.6; Pcor = 0.001) and DQB1*06/*06 (OR = 3.81; Pcor = 4.0x10-4) and for haplotype DRB1*15-DQB1*06 (OR = 3.03; Pcor = 0.001). Carriage of alleles DRB1*07 (OR = 0.53; Pcor = 0.04), DRB1*13 (OR = 0.39; Pcor = 4.0x10-4), DQB1*03 (OR = 0.46; Pcor = 1.0x10-4), genotypes HLA-DRB1*13/*11 (OR = 0.12; Pcor = 0.004), DQB1*05/*03 (OR = 0.39; Pcor = 0.035), DQB1*03/*03 (OR = 0.38; Pcor = 0.029) and haplotypes DRB1*13-DQB1*06 (OR = 0.47; Pcor = 0.0128) and DRB1*11-DQB1*03 (OR = 0.58; Pcor = 0.0352) was found to be protective against MS development. DISCUSSION: This is the first study performed to analyse the association of HLA-DRB1/DQB1 with susceptibility to MS in Slovakia. The results of our study confirm that HLA class II alleles, genotypes and haplotypes are associated with MS risk.

Visual Evoked Potential and Magnetic Resonance Imaging are More Effective Markers of Multiple Sclerosis Progression than Laser Polarimetry with Variable Corneal Compensation.

BACKGROUND: The aim of our study was to assess the role of laser polarimetry and visual evoked potentials (VEP) as potential biomarkers of disease progression in multiple sclerosis (MS). PARTICIPANTS: A total of 41 patients with MS (82 eyes) and 22 age-related healthy volunteers (44 eyes) completed the study. MS patients were divided into two groups, one (ON) with a history of optic neuritis (17 patients, 34 eyes) and another group (NON) without it (24 patients, 48 eyes). The MS patients and controls underwent laser polarimetry (GDx) examination of the retinal nerve fiber layer (RNFL). In the MS group, we also examined: Kurtzke "expanded disability status scale" (EDSS), the duration of the disorder, VEP - latency and amplitude, and conventional brain magnetic resonance imaging (MRI). Our results were statistically analyzed using ANOVA, Mann-Whitney, and Spearman correlation analyses. RESULTS: In the MS group, brain atrophy and new T2 brain lesions in MRI correlated with both VEP latencies and amplitudes. Separate comparisons revealed VEP latency testing to be less sensitive in ON than in NON-patients. In ON patients, VEP amplitudes correlated mildly with brain atrophy (r = -0.15) and strongly with brain new MRI lesions (r = -0.8). In NON-patients, highly significant correlation of new MRI brain lesions with VEP latencies (r = 0.63, r = 0.6) and amplitudes (r = -0.3, r = -4.2) was found. EDSS also correlated with brain atrophy in this group (r = 0.5). Our study did not find a correlation of GDx measures with MRI tests. The GDx method was not able to detect whole brain demyelinization and the degeneration process, but was only able to reveal the involvement of optic nerves in ON and NON-patients. CONCLUSION: In our study, we found that both methods (VEP and GDx) can be used for the detection of optic nerve damage, but VEP was found to be superior in evaluating whole brain demyelinization and axonal degeneration. Both VEP and MRI, but not GDx, have an important role in monitoring disease progression in MS patients, independent of the ON history.