A population-based epidemiological study of neuromyelitis optica spectrum disorder in Hungary.

BACKGROUND AND PURPOSE: The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO Diagnosis (IPND) criteria. METHODS: A retrospective population-based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016. Possible NMOSD patients were selected via multistage re-evaluation from multiple sources. Crude and sex- and serostatus-specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person-years) from 2006 to 2015 were estimated and age-adjusted rates were determined. RESULTS: Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 [95% confidence interval (CI) 1.52-2.28] per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person-years provided an incidence rate of 1.32 (95% CI 1.08-1.61) per 1 000 000 person-years. Age-adjusted prevalence was 1.87 (95% CI 1.56-2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98-1.46) per 1 000 000 person-years. CONCLUSIONS: In this first report of a large population-based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.

Prevalence of multiple sclerosis in Csongrád County, Hungary.

OBJECTIVE: Recent epidemiological studies were mainly based on the Poser or other diagnostic criteria. There have been no previous data from Hungary, which were assessed with the more up-to-date McDonald criteria and which give comparable standardized data from the region. MATERIALS AND METHODS: Data were collected from the MS Register of the Department of Neurology at the University of Szeged. All possible and definitive patients with MS living in the county on the prevalence day were included in the study. Direct standardization was based on the European standard population. RESULTS: On 1 January 2013, 379 registered patients with MS were alive in the county, that is, a crude MS prevalence of 89.8/100,000, 46.6/100,000 in males and 128.6/100,000 in females; standardized prevalence: 83.7/100,000 (42.3/100,000 for males, 122.6/100,000 for females). The distribution of the clinical forms: 11% clinically isolated syndrome, 69% relapsing-remitting form, 14% secondary progressive form, 6% primary progressive form. Patients with no or only mild symptoms comprised 91.9% of the relapsing-remitting population. CONCLUSIONS: This is the first standardized epidemiological study based on the McDonald criteria in Central Europe. Hungary is a medium-risk country as concerns the prevalence of MS. The crude prevalence appears to have increased relative to previous reports from the county.

Factors influencing the health-related quality of life in Hungarian multiple sclerosis patients.

BACKGROUND: The 'Multiple Sclerosis Quality of Life Instrument' (MSQOL-54) was recently validated in Hungarian, on more than 400 multiple sclerosis (MS) patients. The aim of the present study was to examine the impact on their overall quality of life (QoL) of the demographic and clinical data on these patients, and their scores on different QoL scales. METHODS: The Hungarian version of MSQOL-54 was given to patients at the outpatient units at the Department of Neurology, University of Szeged, and two other Hungarian MS centres. Additional data, including the EDSS scores of the patients, and relevant clinical and demographic data, were also collected. RESULTS: The questionnaire scales relating to social function, general health, mental health and satisfaction with the sexual function mostly determined the overall QoL ratings. 62.1% of the patients indicated at least one comorbid condition. Depressed patients had a significantly worse quality of life (p<0.0001). CONCLUSIONS: MSQOL-54 is a useful tool for the recognition of possibly treatable factors influencing the QoL, but not assessed by the EDSS. Quality of life data have emerged on more than 400 patients, i.e. a considerable proportion of the Hungarian MS patient population.

Cross-cultural adaptation and validation of the 'Multiple Sclerosis Quality of Life Instrument' in Hungarian.

Health-related quality of life measurements are gaining more importance in the study and clinical practice of multiple sclerosis. The aim of our study was the adaptation of the Multiple Sclerosis Quality of Life Instrument (MSQOL-54) in Hungarian. The study was carried out at the Department of Neurology, University of Szeged and two other multiple sclerosis centers. The Hungarian translation of the questionnaire was given to patients at the outpatient units of the neurology departments. The EDSS score of the patients were determined and data concerning the onset and the clinical form of the disease was collected. Altogether 438 patients filled out the questionnaire. We enrolled patients with all clinical forms of the disease. Cronbach's alpha coefficients were over 0.8 in case of all scales except ;Rolelimitations - emotional' (0.794), indicating a good internal consistency reliability for group comparisons. The instrument was able to distinguish between known clinical group differences. The Hungarian version of the MSQOL-54 instrument shows good psychometric properties similar to the original questionnaire.

Epidemiology of familial multiple sclerosis in Hungary.

The prevalence of familial aggregation of multiple sclerosis (MS) is estimated between 5 and 10%. Studies emphasize the effect of genetic factors over the environment of the patients in the development of the disease. We investigated familial accumulation of MS in the cases of 1500 patients in five Hungarian MS centers. According to our data, the risk of familial MS in Hungary is lower than in other countries for which literature data are accessible. The literature does not contain any data for the prevalence of familial MS in Hungary and middle-eastern Europe.

Familial effects on the clinical course of multiple sclerosis.

BACKGROUND: Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease. METHOD: We evaluated 1,083 families with > or =2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent-child pairs. RESULTS: There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent-child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings (correlation coefficient 0.18; p < 0.001) but not the parent-child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children (kappa -0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups (correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent-child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent-child pairs and no evidence for anticipation or effects of genetic loading. CONCLUSION: Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.

The norepinephrine level is decreased in the lymphocytes of long-term interferon-beta-treated multiple sclerosis patients.

The mutual involvement of dopamine and its metabolites in the nervous and immune systems has the potential to provide information on the interaction of these two systems. During a 24-hour period, we used capillary electrophoresis with electrochemical detection to repeatedly measure the intracellular catecholamine concentrations in the peripheral blood lymphocytes of relapsing-remitting multiple sclerosis (RRMS) patients receiving interferon (IFN)-beta-1b (n = 13), and those of IFN-naïve RRMS patients receiving their first IFN-beta-1a injection (n = 19) during this study, and compared them with the levels in healthy controls (n = 12). At baseline, the norepinephrine level was significantly decreased (P =0.003) in the long-term IFN MS patients compared with the controls. The Time x Group interactions for dopamine (P=0.5854) and norepinephrine (P=0.6192) were not significant. The group effects for the individual drugs were P=0.3529 and 0.1282, respectively. The lower norepinephrine level at baseline in the long-term IFN MS group suggests an immunologically stable phase, in line with our previous findings. This is the first report of the effects of IFN-beta administration on intracellular catecholamines in MS patients. Further studies are necessary to elucidate the immune reactions affected by the catecholamines in MS and to evaluate the roles of these potential immunotransmitters.

Interferon-beta affects the tryptophan metabolism in multiple sclerosis patients.

Tryptophan and its metabolites are of great interest in understanding the pathogenesis of multiple sclerosis (MS). The total levels of tryptophan and its metabolites, kynurenine and kynurenic acid were determined in plasma by capillary liquid chromatography electrospray ionisation tandem mass spectrometry. This is the first report of the plasma levels of these analytes in healthy controls and relapsing-remitting MS patients receiving long-term and acute interferon-beta (IFN-beta) treatment. Twenty-four hours post-administration increased kynurenine levels (first IFN MS versus healthy, P = 0.042) and kynurenine/tryptophan ratio (K/T; first IFN MS versus healthy, P =0.027; first IFN MS versus long-term IFN MS, P = 0.036) were found. The long-term IFN MS group had higher K/T ratios at 4 and 12 h post-administration (P = 0.015 and 0.009, respectively). The increase of K/T ratio in the first IFN MS group indicate an induction of the enzyme indolamine-2,3-dioxygenase (IDO), as reported earlier in experimental allergic encephalomyelitis. As IDO is participating in both inflammatory and neurodegenerative processes, further knowledge of its involvement in the pathogenesis of MS is of great importance.

Familial multiple sclerosis: case study of three affected siblings.

We report on three sisters with new-onset multiple sclerosis (MS). The symptoms of the eldest sister began in 1993 with lower-limb weakness and paraesthesia. In 1998, she had limb weakness, nystagmus and ataxia. Magnetic resonance imaging (MRI) of the brain, the cerebrospinal fluid (CSF) examinations, and evoked potentials verified MS. The middle sister exhibited left-side optic neuritis in 1998. All findings pointed to MS. The third sister had subjective complaints such as paraesthesias and vertigo. MRI and CSF results supported the diagnosis. Both parents and all four grandparents are without neurological signs; the brain MRI examinations on the parents were negative. The prevalence of familial MS in first-degree relatives is 5-10%, while that in twins is 20-30%. In this case, environmental factors seem to play the crucial role. Although the anamnesis as concerns MS proved negative in the other family members examined here, further genetic examination of the sisters is needed.

The prevalence of multiple sclerosis, distribution of clinical forms of the disease and functional status of patients in Csongrád County, Hungary.

OBJECTIVE: The aim of this study was to determine the prevalence of multiple sclerosis (MS) in the population of Csongrád County, Hungary (400,128 inhabitants) and to determine the functional status (based on the Expanded Disability Status Scale; EDSS) of the patients according to the clinical forms of the disease. METHODS: The diagnosis was established with the aid of the Poser diagnostic criteria, and the degree of physical disability was determined using the Kurtzke EDSS. RESULTS: In Csongrád County, the prevalence of MS is 62/100,000. The distribution of patients according to the clinical forms of MS was as follows: 15% had the benign form, 54% had relapsing-remitting MS, 20% had secondary chronic progressive MS and 11% had the primary chronic progressive form of MS. Sixty percent of relapsing-remitting MS patients had an EDSS score of 0-4 points and 33% had an EDSS score of 4.5-6.5 points. CONCLUSION: The distribution of patients according to the clinical forms of the disease in this representative population is comparable to results in other regions of the world.

Nonenzymatic antioxidants of blood in multiple sclerosis.

Free radical action has been suggested as a causal factor in multiple sclerosis. We investigated the plasma level of lipid peroxides expressed in terms of malone dialdehyde and changes in blood nonenzymatic antioxidants (glutathione, alpha-tocopherol, retinol, plasma sulfhydryl groups, and uric acid) in multiple sclerosis patients with exacerbation or in remission, including a group treated with beta-interferon. The malone dialdehyde level was increased by 38% (n.s.) during exacerbations. The blood concentration of oxidized glutathione was likewise elevated (P<0.05), while the ratio of plasma alpha-tocopherol to cholesterol plus triglyceride was decreased (P<0.001). These changes suggest increased free radical production and consumption of the scavenger molecules during the active phase of the disease. Blood reduced glutathione level was increased (P<0.01) during exacerbation and remission as well. The rise in this thiol is likely to be a compensatory mechanism defending the cells from further oxidant injuries. Beta-interferon increased plasma alpha-tocopherol levels (P<0.001) but not the lipid corrected alpha-tocopherol value. Other parameters were not influenced by the drug.

[Treatment of relapsing-remitting multiple sclerosis with interferon beta type 1-b]. / A relapszus-remisszió kórformájú sclerosis multiplexes betegek kezelése interferon-béta-1b-vel.

Interferon-beta-1b was the first drug found to slow the progression of relapsing-remitting multiple sclerosis, with a reported decrease in the relapse rate of up to 34%. The present study involved 35 patients treated with interferon-beta-1b for one year. The aims of the study were: a) to compare the changes in the relapse rate and the number of days of hospitalization with other data, b) to compare the steroid needs required to treat relapses for one year before and in the year of interferon-beta-1b treatment. Our data indicated that the relapse rate may decrease as much as 77% following the introduction of interferon-beta-1b treatment. The adverse effects and the changes in the EDSS grades were similar to the published data. The duration of hospitalization decreased by 84% and the amount of methylprednisolone needed for remission by 78%. This data suggest that the impairment of the condition of the patients may be delayed considerably, while some of them can continue to work for a longer period, the standard of life of these patients therefore being more tolerable.

Effects of methylacetylenic putrescine, an ornithine decarboxylase inhibitor and potential novel anticancer agent, on human and mouse cancer cell lines.

Sensitivity of several human and mouse cancer cell lines to methylacetylenic putrescine (MAP) was evaluated using clonogenic, sulforhodamine B and cell counting assays. The effects of MAP on cell morphology, cell cycle phase distribution and changes in polyamine metabolism of xenografted MCF-7 and MDA-MB-231 human mammary tumor cells were also investigated. On the basis of IC50 values, BHT-101 human thyroid carcinoma cells were the most sensitive (9 micrograms/ml), followed by P388 mouse lymphoma (32 micrograms/ml), MCF-7 (48 micrograms/ml) and MDA-MB-231 (110 micrograms/ml) human breast carcinoma cell lines. MAP treatment led to accumulation of P388 cells in G1 phase. At higher doses, the cytoplasm of the cells became vacuolated followed by apoptosis. The foamy cytoplasm may suggest a rare type of cell death (Clarke III type) called non-apoptotic programmed cell death. MAP treatment resulted in a total inhibition of ornithine decarboxylase (ODC) activity with a concomitant decrease of intracellular polyamine (mostly putrescine and spermidine) content in the breast cancer cells, whilst the spermine concentration was shown to increase. MAP proved at least 10 times more potent than the formerly studied DL-alpha-difluoromethylornithine making it an attractive candidate for clinical testing.

[Diagnostic studies of cerebrospinal fluid in patients with multiple sclerosis]. / Liquordiagnosztikai vizsgálatok sclerosis multiplexes betegekben.

The diagnostic criteria postulated by Poser necessitate clinical and laboratory CSF analysis for establishment of the diagnosis of definitive multiple sclerosis. The present paper reports methods for CSF examinations relating to multiple sclerosis with regard to the examinations suggested by the Charcot Foundation. In the course of CSF analysis, it is important to discriminate between the immunoglobulins present in normal amounts, those synthesized locally in pathological quantities and those penetrating across the damaged blood-CSF barrier. Normally, a parallel assay of CSF and serum specimens is carried out in the course of quantitative and qualitative protein analysis. In 37 patients with clinical multiple sclerosis, we determined the albumin and the immunoglobulin classes IgG, IgA and IgM, using laser nephelometry. An elevated IgG index was found in 76% of the cases, which points to local IgG snythesis and might be proof of the humoral immune response. The albumin quotient, which is suitable for examination of the integrity of the blood-CSF barrier, was within the reference range. Qualitative protein analysis was performed by means of electrophoresis on agarose-gel and isoelectric focusing. Agarose-gel electrophoresis revealed oligoclonal gammopathy in 68%, in contrast with the 91% demonstrated by isoelectric focusing. Comparison of the two kids of qualitative protein analyses indicated that isoelectric focusing was more sensitive for the detection of oligoclonal bands, in support of the literature finding.

The prevalence of multiple sclerosis in the Hungarian city of Szeged.

OBJECTIVES: The aim of this study was to determine the prevalence of multiple sclerosis in a population in South Hungary. METHODS: The diagnosis was established with the aid of the Poser diagnostic criteria and the degree of physical disability was determined on the Kurtzke expanded disability status scale (EDSS). The present medical state (EDSS score) was determined from outpatient clinical control tests. The prevalence, the average age at onset of the disease and the proportions of the various clinical forms were calculated, and the patients' disability status was estimated. RESULTS: In 1996, the prevalence was 65/100,000, and the incidence from January 1, 1995 through December 31, 1996 was 7/100,000/year. DISCUSSION: During a period of 2 years, the number of diagnosed patients has almost doubled. The disease can be recognized in an early stage with a minimal neurological deficit. The development of the diagnostics necessitates re-examinations with modern diagnostic procedures. During the last 3 years, the general practitioner system has been reorganized, and the working relationships between the clinic and family doctors have developed considerably. A comparison of the present findings with those in other countries with a similar climate revealed very similar prevalence data.

Apolipoprotein E allele frequencies in patients with late-onset sporadic Alzheimer's dementia in Hungary.

INTRODUCTION: The presence of the apolipoprotein E4 allele (apoE4) has been recognized as a risk factor for the development of presenile and senile forms of Alzheimer's dementia (AD). MATERIAL AND METHODS: The apoE alleles frequency of 71 normal controls (NC), 60 demented controls (DC) and 50 senile type AD subjects was determined by polymerase chain reaction in order to get data about the apoE polymorphism of the Hungarian AD population. RESULTS: The apoE3/3 genotype was the most common in all groups. The apoE4 frequency was significantly higher (28%) in the AD group than that was (7% and 9%) in the NC and DC populations, respectively. No apoE4 homozygotes were found in the DC group and the number of heterozygotes was lower in the DC than in the AD group. CONCLUSION: The results are in good agreement with others in the literature and support the occurrence of an increased apoE4 allele frequency in Hungarian senile AD population.

Pharmacological inhibition of brain carbonic anhydrase protects against 4-aminopyridine seizures.

The effects of the inhibition of carbonic anhydrase on the manifestation of tonic-clonic seizures were investigated in freely-moving rats. 4-Aminopyridine, a specific blocker of the neuronal K+ channels was used to produce generalized convulsions. After pretreatment of adult male rats with 20 or 40 mg/kg acetazolamide, 3, 5, 7 or 9 mg/kg 4-aminopyridine was injected intraperitoneally and the latencies of the symptoms were measured. Pharmacological inhibition of brain carbonic anhydrase significantly increased the latency of onset of seizures. Bolus administration of acetazolamide decreased the incidence of generalized convulsions and protected against status epilepticus. Chronic acetazolamide treatment for 2 days affected only the generalized convulsions. The results suggested that alterations of the extracellular and intracellular pH by acetazolamide decreased the efficacy of synaptic transmission in several areas of the brain. The possible effects of the HCO3- ions on the sensitivity of synaptic and nonsynaptic neuronal receptors are discussed.

Naltrexone potentiates 4-aminopyridine seizures in the rat.

The effects of a pharmacological blockade of the mu opiate receptors on the manifestation of tonic-clonic seizures were investigated in freely moving animals. 4-aminopyridine, a specific blocker of the neuronal K+ channels was used to produce generalized convulsions. After pretreatment of adult rats with 1 mg/kg naltrexone HCl, 3, 5, 7, 9, 14 mg/kg 4-aminopyridine was injected intraperitoneally, and the latencies of the symptoms generated by 4-aminopyridine were measured. Naltrexone HCl decreased these latencies and enhanced the seizures significantly. The experiments provided further evidence for the existence of a tonic anticonvulsant opioid system in the brain.

A modified semipermeable membrane technique for carbonic anhydrase histochemistry of the nervous system.

We present a modification of Hansson's method for the demonstration of carbonic anhydrase activity. Using a semipermeable membrane together with a fluid incubation medium, frozen sections of aldehyde-fixed tissue were incubated without floating or dipping. Thin sections (thickness, 20-40 microns) were mounted on the outer surface of a tubular-shaped, semipermeable cellophane dialysis membrane containing the incubation fluid. After incubation for 25-30 min at room temperature, the sections were rinsed in buffer and treated with 0.5% (NH4)2S solution. The histochemical reaction was fully inhibited by 10(-4) M acetazolamide.