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Biomedical subjects

W Kristoferitsch

Publications and source records attributed to W Kristoferitsch.

At least 19 recordsLinked to original sources

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗

Genetic variants in the tumor necrosis factor receptor II gene in patients with multiple sclerosis.

Common genetic variants have been shown to influence disease susceptibility, disease course, or both in multiple sclerosis (MS). Several studies have suggested a role for tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of MS. Recently, it has been reported that the TNF receptor (TNFR) II plays an essential role in the pathology and progression of experimental autoimmune encephalomyelitis, an animal model of MS. To investigate whether TNFR II polymorphisms influence susceptibility and/or clinical progression of MS, genomic DNA of 321 samples of the Austrian Genetics in MS study group and DNA of 174 platelet donors, who served as healthy controls, were genotyped for five polymorphic sites in the TNFR II gene: exon 6 nucleotide (nt) 676*T-->G, exon 6 nt 783*G-->A (both are associated with non-conserved amino acid substitution), exon 10 nt 1663*G-->A, exon 10 nt 1668*T-->G, and exon 10 nt 1690*T-->C (all of which are located in the 3' non-coding region of the gene). We found a significant association between exon 10 nt 1668*T-->G polymorphism and susceptibility to MS. The other investigated nucleotide substitutions were not associated with susceptibility to or clinical parameters in MS.

Adult↗

Factors influencing quality of life in multiple sclerosis patients: disability, depressive mood, fatigue and sleep quality.

OBJECTIVES: In a series of 504 patients with multiple sclerosis (MS), quality of life (QOL) and its main clinical and demographic determinants were assessed in comparison with healthy individuals. MATERIALS AND METHODS: A postal questionnaire with self-completed measures of disability (Expanded Disability Status Scale, EDSS), QOL (Quality of Life Index, QLI), depressive mood (Self-rating Depression Scale, SDS), fatigue severity (Fatigue Severity Scale, FSS) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) was sent to this sample of MS patients. RESULTS: Most patients were severely disabled; almost half were mildly to severely depressed, suffering from reduced sleep quality and/or fatigue. The multiple sclerosis patients had significantly lower QLI scores than healthy controls. EDSS and SDS scores were found to be predictors of global QLI score. Regarding the different QLI domains, mean SDS scores remained predictive for all QLI items, while mean EDSS, PSQI and FSS scores were only predictive for physical domains. CONCLUSION: Our study clearly demonstrates that depressive mood is the main factor influencing QOL. The disability status, fatigue and reduced sleep quality have an impact mainly on physical domains of life quality.

Adult↗

Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis.

OBJECTIVE: The apolipoprotein E (APOE) polymorphism is known to impact on various neurologic disorders and has differential effects on the immune system and on CNS repair. Previous findings concerning a possible modulation of the clinical course of MS have been inconsistent, however. METHODS: In a cross-sectional study, the authors investigated 374 patients with clinically definite MS and a disease duration of at least 3 years and related their clinical and demographic findings to the allelic polymorphism of the APOE gene. The genotype distribution of patients with MS was compared with a cohort of 389 asymptomatic, randomly selected elderly volunteers. RESULTS: The authors found no significant differences in the distribution of genotypes between patients with MS and controls. However, patients with MS with the epsilon4 allele (n = 85) had a significantly higher progression index of disability (0.46 +/- 0.4 versus 0.33 +/- 0.26; p < 0.004) and a worse ranked MS severity score (5.1 +/- 1.9 versus 5.7 +/- 1.7; p = 0.05) than their non-epsilon4 counterparts, despite significantly more frequent long-term immunotherapy in epsilon4 carriers (74% versus 58%; p < 0.007). The annual relapse rate in epsilon4 carriers (0.87 +/- 0.56) was significantly higher than in patients with MS without an epsilon4 allele (0.71 +/- 0.47; p = 0.03). CONCLUSIONS: These results suggest no effect of the APOE genotype on susceptibility to MS, but indicate an association of the APOE epsilon4 allele with a more severe course of the disease.

Adult↗

Ganglionitis in paraneoplastic subacute sensory neuronopathy: a morphologic study.

A 69-year-old woman presented with subacute sensory neuropathy and autonomic dysfunction of 9 months' duration, associated with high serum titers of anti-Hu antibodies. A small cell carcinoma of the lung was diagnosed by biopsy. She died after cardiorespiratory arrest. At autopsy, spinal and autonomic ganglia showed subacute inflammation with diffuse endoneurial T-cell, B-cell, and plasma cell infiltration. The cytoplasm and nuclei of some ganglion neurons displayed IgG immunocytochemical positivity. CD8+ T cells were tightly attached to, and indented the cell surface of, IgG-positive and IgG-negative neurons. This observation suggests that both cytotoxic T-cell-mediated attack against neurons and humoral mechanisms play a role in paraneoplastic subacute sensory neuronopathy.

Aged↗

European Union Concerted Action on Risk Assessment in Lyme Borreliosis: clinical case definitions for Lyme borreliosis.

The EU Concerted Action on Risk Assessment in Lyme Borreliosis (EUCALB) has consulted other clinicians and scientists in Europe to produce case definitions of the principal manifestations of European Lyme borreliosis. These case definitions will not only be helpful in supporting its own research interests, but are also intended to assist other clinicians in appropriate management and to support further studies aimed at determining the full clinical spectrum of the disease. The case definitions were achieved after a series of meetings organised by EUCALB with other expert clinicians and scientists from twelve European countries. The definitions and the diagnostic criteria presented thus represent the consensus reached at these meetings. The proposed case definitions consider skin, nervous system, cardiac and musculoskeletal presentations and the role of laboratory investigation in supporting diagnosis.

Acrodermatitis↗

T-cell-mediated ganglionitis associated with acute sensory neuronopathy.

A 67-year-old man presented with acute painful sensory loss, areflexia, ataxia, urinary retention, and severe constipation and became unable to walk within 2 weeks. He died suddenly 5 weeks after the onset of symptoms. Autopsy revealed widespread inflammation of sensory and autonomic ganglia with immunocytochemical evidence of a CD8+ T cell-mediated cytotoxic attack against ganglion neurons. This observation suggests a novel pathogenetic mechanism of immune-mediated human ganglion cell damage comparable to mechanisms operating in polymyositis.

Acute Disease↗

Neurological manifestations of Lyme borreliosis: clinical definition and differential diagnosis.

Neurological manifestations occur in early disseminated Lyme Borreliosis and in the chronic late stage. Two of them, Bannwarth's syndrome and acrodermatitis chronica atraphicans-associated neuropathy, were known as well defined clinical entities many years prior to the detection of their causative agent. Soon after B. burgdorferi was identified and serologic tests became available, many reports were published which attributed to a large variety of different neurological disorders to Lyme borreliosis. In many cases the diagnosis was primarily based on serodiagnostic results. Yet some scepticism is indicated since 10-30% of the population in endemic areas have been found to be seropositive. While prior to 1983 and before the availability of serodiagnostic tests neurological manifestations of Lyme borreliosis were recognized by a minority of neurologists, they now seem to be overdiagnosed. Therefore clear diagnostic criteria have to be set up. They include the clinical picture, other preceding or concomitant diseases of the Lyme borreliosis complex, serodiagnostic results, cerebrospinal fluid findings, demonstration of intrathecal specific antibody synthesis, results of nerve biopsies, response to adequate antibiotic therapy and exclusion of other diseases. The significance of each of these criteria depends on the clinical involvement and on the stage of Lyme borreliosis.

Diagnosis, Differential↗

Lyme borreliosis in Europe. Neurologic disorders.

In Europe the tick-transmitted neurologic disorders MPN-GBB or Bannwarth's syndrome and ACA-associated neuropathy have been identified as clinical entities long before their causative agent was discovered. When Lyme disease and its neurologic manifestations were recognized in the United States, differences in the clinical pattern between North American and European cases with Lyme borreliosis were described in the initial reports. In the same way with the availability of serodiagnostic tests as the clinical spectrum of Lyme borreliosis was enlarging in Europe and in North America, these clinical differences became less prominent.

Central Nervous System Diseases↗

Neuroborreliosis in morphea and lichen sclerosus et atrophicus.

Nine cases of different types of morphea and two of lichen sclerosus et atrophicus were investigated for the presence of neurologic symptoms. The Borrelia origin of morphea and lichen sclerosus et atrophicus was verified by the presence of antibodies against Borrelia burgdorferi and by the visualization of spirochetes on histologic sections by immunohistochemical methods. One patient had intrathecally synthesized IgG antibodies against B. burgdorferi that indicated intrathecal infection. A second patient had an elevated cell count and oligoclonal bands of unknown specificity in cerebrospinal fluid. In another patient a disturbance of the blood-brain barrier was detected. Seven patients had signs of peripheral neural involvement, mostly lesional dysesthesias. Our findings indicate frequent neural involvement in morphea and lichen sclerosus et atrophicus, suggesting the necessity of adequate antibiotic treatment in these diseases.

Adult↗

[A cerebral air embolism due to a central venous catheter in the computed tomogram].

A case of air embolism to the brain occurred via a disconnected central venous catheter. Computed tomography disclosed a number of small air bubbles in the right hemisphere. If the clinician suspects air embolism a CT scan should be obtained immediately to verify the presence of intracerebral air. On later CT scans only secondary effects like in any embolism will be seen.

Catheterization, Central Venous↗

Progressive cerebellar syndrome in adult coeliac disease.

A case of slowly progressing cerebellar syndrome and pathologically confirmed adult coeliac disease is presented. Neurological symptoms progressed although the patient had no enteric complaints. This case seems to be identical with 18 previously reported cases of encephalopathy and adult coeliac disease. However, the aetiology and pathogenesis of the encephalopathy are still not known.

Atrophy↗

Oligoclonal antibodies in CSF of patients with meningopolyneuritis Garin-Bujadoux-Bannwarth: Ig class, light chain type and specificity.

Detection of intrathecally produced antibodies in cerebrospinal fluid (CSF) of patients with meningopolyneuritis Garin-Bujadoux-Bannwarth (MPN-GBB) is well documented. Analysis of CSF has revealed the oligoclonal nature of these antibodies. We investigated oligoclonal antibodies (OA) in CSF and serum of MPN-GBB patients with regard to immunoglobulin class, light chain type and specificity and compared the findings with those in other neurological diseases (OND). For this purpose an immunofixation (IF) technique after agarosegel electrophoresis (AE) of concentrated CSF was used. 87% of patients with MPN-GBB demonstrated in the acute stage of their disease oligoclonal bands (OB) in their CSF which could not be detected in paired serum samples. IF revealed in most cases of MPN-GBB IgG banding. While IgM banding was a common finding in CSF of MPN-GBB patients, this was not the case in OND. Specificity of CSF OA against components of Borrelia burgdorferi could be demonstrated by agarose isoelectric focusing (AIEF), transfer to nitrocellulose paper and reaction with 125I labelled B. burgdorferi antigen.

Antibodies, Bacterial↗

Electrophysiologic findings in meningopolyneuritis of Garin-Bujadoux-Bannwarth.

Previous reports on neuropathy in Lyme disease and related disorders suggest predominant demyelination in most of the few cases investigated. We analysed retrospectively electrophysiologic data in 29 patients with MPN-GBB. In peripheral nerve involvement slowed NCV and/or prolonged DL was the prominent finding, concordant with primary demyelination. Distribution of pathology resembles mononeuritis. Facial nerve palsy was common and often bilateral.

Adolescent↗