Patient-reported quality of life in multiple sclerosis differs between cultures and countries: a cross-sectional Austrian-German-Polish study.

BACKGROUND: Patient-reported quality of life (QOL) is an outcome measure in clinical trials in multiple sclerosis (MS), but translated QOL instruments may affect the actual comparability of data. OBJECTIVES: We aimed to investigate possible differences in QOL in MS between cultures and countries. We employed the Functional Assessment of Multiple Sclerosis (FAMS) Version 4 questionnaire, which is a state-of-the-art QOL instrument. METHODS: Some 484 MS patients from Austria (145), Germany (144), and Poland (195) aged 20-60 years, and stratified for sex and disease severity as measured by the Expanded Disability Status Scale (EDSS) score completed the respective FAMS translation and a socio-demographic questionnaire. RESULTS: Analysis of variance and post-hoc Scheffé-test showed that 64% of the FAMS items were answered significantly differently (p < 0.001) between the three countries. A multivariate regression analysis including all the available disease-related and socio-demographic variables revealed the factors age, EDSS score, employment, social contacts, MS course, and country to be significant predictors of both the total FAMS score and the score for items answered differently between the three countries. CONCLUSIONS: Differences exist in the QOL of MS patients from Austria, Germany, and Poland which seem to lie beyond the impact of disease severity. They appear to be related to culture or other country-specific factors, as country was an independent predictor of differently answered items of the FAMS and thus also of the whole FAMS. QOL instruments should consider this aspect to faithfully reflect subjective information such as patient-reported benefit of treatment in multinational clinical trials.

Altered Cerebrospinal Fluid Concentrations of Hydrophobic and Hydrophilic Compounds in Early Stages of Multiple Sclerosis-Metabolic Profile Analyses.

The lack of a single predictive or diagnostic test in multiple sclerosis (MS) remains a major obstacle in the patient's care. The aim of this study was to investigate metabolic profiles, especially lipids in cerebrospinal fluid (CSF) using 1H-NMR spectroscopy and metabolomics analysis to discriminate MS patient group from the control ones. In this study, 19 MS patients and 19 controls, without neurological problems, patients were enrolled. To obtain the CSF metabolic profiles, NMR spectroscopy was used. Hydrophilic and hydrophobic compounds were analyzed using univariate and multivariate supervised analysis orthogonal partial least square discriminant analysis (OPLS-DA). Targeted OPLS-DA analysis of 32 hydrophilic and 17 hydrophobic compounds obtained 9 hydrophilic metabolites and 8 lipid functional groups which had the highest contribution to patient's group separation. Lower concentrations of CSF hydrophilic and hydrophobic compounds were observed in MS patients as compared to control group. Acetone, choline, urea, 1,3-dimethylurate, creatinine, isoleucine, myo-inositol, leucine, and 3-OH butyrate; saturated and monounsaturated acyl groups of ω-9, ω-7, ω-6, ω-3, and fatty acid, triglycerides, 1,3-DG, 1-MG, and unassigned component signal at 3.33 ppm were the most important signal compounds in group separation. Analysis of metabolic profile of raw CSF and their lipid extract shows decreased levels of many compounds and led to the conclusion that MS patients could have a disturbance in many metabolic pathways perhaps leading to the decreased level of acetyl-CoA and/or inflammation. CSF metabolic profile analyses could be used as a fingerprint for early MS diagnosis.

Extensive mixed vascular malformation clinically imitating multiple sclerosis--case report.

Vascular malformations usually develop as a result of influence of teratogenic factor(s) acting in the defined embryonic/fetal period. However, in the case examined by us, various types of vascular malformations formed in different periods of the ontogenic development were found. They were seen in all parts of the central nervous system and clinically mimicked multiple sclerosis. On the background of generalized ischemic lesions of the CNS, certain kinds of vascular malformations were seen: cavernous or fetallike vessels within meninges, superficially located capillary angioma penetrating into the brain and spinal cord white matter, and arterio-venous pathological conglomerates forming meningeal angiomatosis. In pathological vessels, immunocytochemical assessment of vascular endothelium with antibodies against antigens CD31, CD34, von Willebrand factor and lectin Ulex europaeus was normal but examination of the vascular basal membrane compounds revealed poor immunoreactivity to laminin and fibronectin. There were no disturbances in expression of angiopoietin, platelet-derived growth factor, transforming growth factor beta and vascular endothelial growth factor receptors Tie-1/2, PDGFR-alpha/beta, endoglin and Flk-1, respectively. The presence of various types of pathological vessels originating from different ontogenic periods indicates remittent or prolonged influence of teratogenic factor(s) in all periods of fetal vessel development.

Is pruritus in chronic uremic patients related to peripheral somatic and autonomic neuropathy? Study by R-R interval variation test (RRIV) and by sympathetic skin response (SSR).

The problem of pruritus in uremic dialysed patients remains unsolved. The etiology of pruritus has not been precisely explained, and sometimes no efficient treatment is available. The aim of this study was to analyse the relationship between somatic neuropathy and pruritus as well as the relationship between pruritus and dysautonomia. Fifty-one patients with end-stage renal failure underwent basic neurological examination, nerve conduction velocity studies, and pruritus assessment by means of a questionnaire. Two tests were used to assess the autonomic nervous system, namely the R-R interval variation test in basal and profound breath conditions (RRIV) and the sympathetic skin response (SSR). Pruritus was found in 63% patients of the sample. Most of them had clinical symptoms and signs of peripheral sensorimotor neuropathy and dysautonomia. About 59% of uremic patients revealed abnormally reduced RRIV. About 45% of patients had abnormal (delayed or absent) SSR. The pruritus in uremic patients occurred significantly more frequently (P < 0.01) in patients with paresthesia. A nonsignificant but sizeable trend towards a relationship of pruritus with hypohidrosis and pathological SSR results was also observed. There was no relationship between the pruritus presence and RRIV results. According to our results the activity of the nervous system might play an important role in the mechanism of uremic pruritus, but paradoxically this latter appeared more tightly related to somatic neuropathy than to autonomic dysfunction. Our results also suggest that SSR may become a useful technique for the assessment of autonomic dysfunction in uremic patients.

Obstructive sleep apnea syndrome in patient with Creutzfeldt-Jakob disease. Clinical and morphological report.

We report a case of Creutzfeldt-Jakob disease (CJD) which at the beginning of the disease presented clinical syndrome of progressive supranuclear palsy. Rapid intellectual deterioration, supranuclear palsy, postural instability and myoclonic jerks suggested clinical diagnosis of CJD. After five months suffering from the disease patient developed obstructive sleep apnea syndrome (OSAS) confirmed by serial polysomnograms. OSAS is discussed in the context of the localization of histopathological findings and possible involvement of central autonomic structures. The main structures affected by spongiosis and astrogliosis were cortex, thalamus, basal ganglia and midbrain. OSAS was found as another sleep disturbance in CJD apart from insomnia and sleep-wake cycle abnormalities.

Sympathetic skin response in scleroderma, scleroderma overlap syndromes and inflammatory myopathies.

Sympathetic skin response (SSR), a non-invasive method for evaluation of the autonomic nervous system, was studied in 57 patients with various connective tissue disorders: scleroderma, dermatomyositis, polymyositis, scleromyositis and unclassified collagenoses. The patients were divided into three main groups: scleroderma (SSc), myositis or other inflammatory myopathy (M) and scleromyositis (ScM). The aim of the study was to detect abnormalities of the SSR in the connective tissue diseases, to define the pattern for each group and to evaluate the usefulness of SSR in detection of subclinical impairment of sympathetic cholinergic function. In the myositis group, an abnormal SSR was found in 88% of patients; the main abnormality was absence of the response from the lower limbs (in 50% of patients). In scleroderma, the SSR was abnormal in 77% of patients, consisting mainly of absence of the response from the lower limbs, whereas responses from the upper limbs were normal. In scleromyositis, the SSR was abnormal in 80% of patients, the most frequent finding was an increase in latency in one limb. The SSR changes were most pronounced in connective tissue disorders with myositis or inflammatory myopathy. The SSR, although non-disease-specific, because of its sensitivity, seems to be useful in the assessment of the abnormalities of the autonomic nervous system in scleroderma and inflammatory myopathies. The study showed a very high prevalence of autonomic nervous system dysfunction in connective tissue diseases associated with myopathy or myositis, displaying no clinical symptoms of autonomic system involvement.

Reconsiderations about the abnormalities of somatosensory evoked potentials in motor neuron disease.

The frequency of involvement of sensory pathways in motor neuron disease (MND) remains the matter of controversy. For this reason the purpose of the present work was to test how often sensory system involvement might be detected by somatosensory evoked potentials (SEP) studies and then to verify the presence of alteration of the sensory conduction and to detect the frequency of abnormalities of somatosensory peripheral, spinal, subcortical and cortical potentials in MND. SEP were tested after median nerve stimulation at the wrist, recorded from Erb's point, Ce2, Ce7 and scalp. Pearson's correlation coefficients test and Wilcoxon rank-sum test were used for statistical analysis. 74 patients (22 women and 52 men) were examined. Mean age of patients was 54.07 +/- 11.24 years; mean duration of the disease -19.25 +/- 15.87 months. SEP were abnormal in 39 of 74 patients (about 53%) whereas the sensory NCV in median nerve was abnormal in 14 of 74 patients (19%). The most frequent pattern of abnormalities consisted of the absence or delay of cortical responses. The mean values of SEP latencies (N9, N11, N13, N20 and P25) were significantly increased in MND patients (p < 0.05) as compared with controls. The N9 and N11 latencies correlated with the duration of the disease. The results of our study (concerning a large group of MND patients) suggest that the involvement of sensory pathways is not rare in MND.

[High dose methylprednisolone therapy in patients with multiple sclerosis]. / Wysokie dawki methylprednisolonu w leczeniu stwardnienia rozsianego.

A trial of high-dose pulsed intravenous methylprednisolone was carried out in 20 patients with multiple sclerosis (MS). Multimodal evoked potentials examination (visual, brainstem auditory and somatosensory evoked potentials) were evaluated before and after treatment with methylprednisolone (a single daily dose of 1000 mg was administrated for five consecutive days). Clinical improvement did not correlate well with evoked potential changes.

Sympathetic skin response (SSR) in multiple sclerosis.

The function of the autonomic system in multiple sclerosis (MS) is often afflicted. In order to reveal the presence of autonomic disturbances examination of sympathetic skin response (SSR), as a simple non-invasive method of the evaluation of conduction in autonomic nervous system, was performed in 25 patients with clinically defined MS. The diagnosis was confirmed by MRI and evoked potentials studies. Bimodal type of stimulation was used: the median nerve was stimulated, then the auditory stimulus (burst) was presented to the patient. Responses were recorded simultaneously from the palms and soles. SSR was abnormal in 19 patients (76%). Absence of the response from lower limbs and normal response from upper limbs were found in 6 patients (24%), increase in latency and decrease in amplitude from upper and lower limbs were found in 8 patients (32%) and increase in latency, decrease in amplitude of the response from upper limbs with absence of the response from lower limbs were found in 5 patients (20%). SSR appears to be a simple and effective method of assessing sympathetic disturbances in multiple sclerosis.

[A case of neurogenic dysphagia responding to nitrates]. / Przypadek neurogennej dysfagii z dobra odpowiedzia na leczenie azotanami.

We described a 47-year-old man with ischemic stroke who developed a brainstem syndrome with persistent dysphagia. He was fed by the nasogastric tube placed intermittently by himself for almost 7 months after the stroke. Elective feeding via percutaneous endoscopic gastrostomy (PEG) was not accepted by the patient. All treatment attempts with benzodiazepines, antidepressants and spasmolytic agents were unsuccessful. Videofluoroscopic investigation revealed excessive and long-lasting spasm of the upper esophageal sphincter which was associated with the massive aspiration of the contrast. The patient dramatically improved after treatment with nitroglycerin and long-acting nitrates with almost complete recovery of normal swallowing. A strikingly good effect of nitrates in the treatment of oropharyngeal dysphagia is emphasized by the authors.

[Diagnostic yield of electrophysiological and immunological studies in inflammatory myopathies]. / Zastosowanie badan elektrofizjologicznych i immunologicznych do diagnostyki miopatii w chorobach tkanki lacznej.

The aim of the study was to estimate the value of the immune markers in defining distinct subsets of inflammatory myopathies. The series of 76 patients was divided, on the basis of the clinical data, into 5 groups (polymyositis (PM), dermatomyositis (DM), scleromyositis (Scm), mixed connective tissue disease (MCTD), unclassified). In all cases detailed clinical, electrophysiological (concentric needle electromyography (CNEMG) and skin sympathetic response (SSR)) were performed as well as immunologic studies: the anti Mi-2, anti RNP, PM-Scl, Jo-1. The findings indicate that immune markers have a diagnostic value in differentiating the defined subsets of patients different in respect of course, prognosis and therapeutic indications. The authors stressed the value of the Jo-1 antibody in detecting the subset of polymyositis with coexisting interstitial lung disease. Electrophysiological data do not differentiate the groups of patients with different clinical syndrome and different immune markers. EMG results seem however to be useful in monitoring the course of the disease and response to the therapy.

APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.

BACKGROUND: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. METHODS: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. RESULTS: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of epsilon2 or epsilon4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. CONCLUSION: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

[Uremic neuropathy--I. Is uremic neuropathy related to patient age, duration of nephropathy and dialysis treatment?]. / Neuropatia mocznicowa--czesc I. Czy neuropatia mocznicowa wykazuje zwiazek z wiekiem pacjentów oraz czasem trwania nefropatii i dializoterapii?

The aim of the study was to analyse the relationship between clinical and electrophysiological features of uremic neuropathy and age of patients, duration of kidney disease, renal failure and dialysis treatment. 51 patients with end-stage renal failure without diabetes were examined. Apart from a basic neurological examination, conduction velocities in the sural and tibial nerves were determined, and in order to assess the function of the autonomic nervous system, R-R interval variation and sympathetic skin response were tested. In majority of patients, symptoms and signs of sensorimotor neuropathy were found, and about 50% of them had dysautonomia. A negative correlation between age and R-R interval variation was observed. No relationship was found between neuropathy and the duration of nephropathy, duration of renal nor dialysis treatment.

[Uremic neuropathy--II. Is pruritus in dialyzed patients related to neuropathy?]. / Neuropatia mocznicowa--czesc II. Czy swiad u pacjentów dializowanych ma zwiazek z neuropatia?

The problem of pruritus in dialyzed patients remains unsolved. The aim of this study was to analyse the relationship between pruritus and clinical symptoms and signs, and electrophysiological aspects of peripheral neuropathy, both somatic and autonomic. 51 patients with end-stage renal failure undergoing hemodialysis were examined. Diabetics were excluded. Apart from taking history and physical examination, conduction velocities in peripheral nerves were determined, and R-R interval variation (RRIV: assessment of vagal function) and sympathetic skin response (SSR) tests were performed. Pruritus was present in about 63% of patients. In majority of them, symptoms and sings of neuropathy were also found. A significant relationship between pruritus and paresthesia was noted. This indicates a possible relationship between pruritus and secondary neuropathy.

[Uremic neuropathy is more frequent in male patients]. / Neuropatia mocznicowa jest czestsza u mezczyzn.

The aim of this study was to analyse the relationship between clinical and electrophysiological features of somatic and autonomic neuropathy and gender of 51 patients on chronic hemodialysis. Apart from basic neurological examination, conduction velocities in peripheral nerves were determined, and the function of the autonomic nervous system was assessed with the help of two tests: R-R interval variation (RRIV) and sympathetic skin response (SSR). The incidence and intensity of clinical and electrophysiological signs of sensomotor neuropathy were statistically significantly more prevalent among male patients, whereas the symptoms suggesting autonomic involvement were more frequent in women. Results of parasympathetic electrophysiological tests were similar in both groups, but abnormal SSR results prevailed in male patients.

Association of apolipoprotein E and myeloperoxidase genotypes to clinical course of familial and sporadic multiple sclerosis.

The importance of apolipoprotein E (ApoE) and myeloperoxidase (MPO) genotypes in the clinical characteristics of multiple sclerosis (MS) has been recently emphasized. In a large group of Polish patients we have tested the hypothesis that polymorphism in ApoE and MPO genes may influence the course of the disease. Genotypes were determined in 117 MS patients (74 females and 43 males; 99 sporadic and 18 familial cases) with mean EDSS of 3.6, mean age of 44. 1 years, mean duration of the disease 12.8 years and mean onset of MS at 31.2 years, and in 100 healthy controls. The relationship between ApoE and MPO genes' polymorphism and the MS activity as well as the defect of remyelination (diffuse demyelination) and brain atrophy on MRI were analysed. The ApoE epsilon4 allele was not related to the disease course or the ApoE epsilon2 to the intensity of demyelination on MRI. The genotype MPO G/G was found in all familial MS and in 57% (56/99) of sporadic cases. This genotype was also related to more pronounced brain atrophy on MRI. The MPO G/G subpopulation was characterized by a significantly higher proportion of patients with secondary progressive MS (P < 0.05) and by a higher value of EDSS. According to our results the MPO G allele is frequently found (in 96% of cases) among Polish patients with MS. More severe nervous tissue damage in the MPO G/G form can be explained by the mechanism of accelerated oxidative stress. It seems that MPO G/G genotype may be one of the genetic factors influencing the progression rate of disability in MS patients.