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Biomedical subjects

Peter Flachenecker

Publications and source records attributed to Peter Flachenecker.

12 recordsLinked to original sources
PubMed2006

Epidemiology of neuroimmunological diseases.

This review gives an overview of various neuroimmunological diseases in terms of incidence and prevalence rates, age and sex distribution, and the frequency of subtypes, if applicable. The disorders selected for review are inflammatory muscle disorders (polymyositis, dermatomyositis and inclusion body myositis), myasthenia gravis, immune-mediated polyneuropathies (Guillain-Barré syndrome, chronic polyneuritis and vasculitic neuropathies), and multiple sclerosis.

Autoimmune Diseases of the Nervous System↗
PubMed2005

The role of stress-response systems for the pathogenesis and progression of MS.

Disease progression in multiple sclerosis (MS)--an inflammatory demyelinating and neurodegenerative disease with a presumed T-cell driven autoimmune origin--has long been hypothesized to be associated with stress. However, this notion has only recently been supported by prospective clinical studies. Several clinical and molecular studies in MS and its animal models have recently shown disruptions in the communication between the immune system and the two major stress response systems, the hypothalamo-pituitary-adrenal (HPA) axis and the autonomic nervous system. Insensitivity to glucocorticoid and beta-adrenergic modulation might be involved in overshooting inflammation in MS, whereas hyperactivity of the HPA axis has been linked to neurodegeneration and increased disability. Here, we integrate findings from molecular, cellular, experimental, clinical and epidemiological research to describe the involvement of stress response systems in MS pathogenesis and progression.

Animals↗
PubMed2005

Fatigue and regulation of the hypothalamo-pituitary-adrenal axis in multiple sclerosis.

BACKGROUND: Fatigue is a common and disabling symptom in patients with multiple sclerosis (MS). Underlying mechanisms postulated so far have involved localization of brain lesions and abnormalities of the neuroendocrine system and cytokine regulation. OBJECTIVE: To investigate the relationship between fatigue and the hypothalamo-pituitary-adrenal (HPA) axis in patients with MS. DESIGN: A prospective survey. SETTING: Outpatient and inpatient study at the Max Planck Institute of Psychiatry, Munich, Germany. PATIENTS: Thirty-one patients with clinically definite MS, a relapsing-remitting disease course, and without MS-specific treatment. INTERVENTIONS: Assessment of fatigue with 3 questionnaires: the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale (MFIS), and the Visual Analog Scale. Assessment of HPA axis regulation with the combined dexamethasone-corticotropin releasing hormone (Dex-CRH) test. RESULTS: The FSS score was significantly correlated with the MFIS score. Patients with fatigue had significantly elevated adrenocorticotropin (ACTH) levels in the combined Dex-CRH test. CONCLUSIONS: In contrast to results for chronic fatigue syndrome, where a hyporeactivity of the HPA axis has been shown, MS patients with fatigue exhibited a higher activity of the HPA axis than those without fatigue, as evidenced by significantly increased ACTH concentrations. Proinflammatory cytokines, known to be elevated in patients with MS, may cause both HPA axis alterations and fatigue.

Adrenocorticotropic Hormone↗
PubMed2005

Autonomic dysfunction in ALS: a preliminary study on the effects of intrathecal BDNF.

This pilot study aimed at exploring the effects of intrathecally administered brain derived neurotrophic factor (BDNF) on autonomic functions in patients with ALS. A battery of autonomic sympathetic and parasympathetic tests was performed at baseline and after nine months of treatment in 10 ALS patients participating in a double-blind placebo-controlled phase II/III study of intrathecally administered BDNF. Results of patients treated with BDNF (25 or 150 microg/day) were compared to those receiving placebo. Sudomotor function and blood pressure response to handgrip significantly worsened during the treatment period (55.4+/-26.1 vs. 38.9+/-23.9 g/m(2)h, p<0.05; 20+/-6 vs. 13+/-4 microHg, p<0.05) whereas other sympathetic and all parasympathetic function tests only tended to be more abnormal at follow-up. Serum norepinephrine levels increased significantly during the nine-months observation period. The results of autonomic function tests were not different between patients treated with BDNF and placebo, but norepinephrine levels were higher in the BDNF group. We conclude that autonomic nervous system function deteriorates along with poorer motor performance independently from treatment with BDNF. The elevation of norepinephrine levels might reflect a non-specific up-regulation, and its association with BDNF an autocrine effect.

Adult↗
PubMed2004

Determination of ventricular diameters in multiple sclerosis patients with transcranial sonography (TCS)--a two year follow-up study.

CONTEXT: Brain atrophy is an indicator of diffuse brain pathology that appears even in the early stages of multiple sclerosis (MS). Magnetic resonance imaging (MRI) techniques used in clinical trials suggest a correlation between ventricular enlargement and axonal pathology and clinical disability in MS. OBJECTIVE: To evaluate by transcranial sonography (TCS) and MRI ventricular diameters in order to assess prospectively the development of brain atrophy in MS. SETTING: MS outpatient clinic of a university hospital. PATIENTS AND METHODS: 38 MS patients (27 females, 11 males) were followed up for 2 years. Ventricular diameters (third ventricle, right and left lateral ventricle) were determined by TCS at baseline, 12 and 24 months and correlated with clinical disability (Expanded Disability Status Scale, EDSS), and the Multiple Sclerosis Functional Composite Score (MSFC). MRI was performed at study entry and after two years. MAIN OUTCOME MEASURE: Correlation of ventricular diameters measured by TCS and MRI with assessment of clinical disability in MS patients at baseline and after two years. RESULTS: TCS and MRI measurements especially of third ventricle diameter matched closely at study entry and after two years (r = 0.9; p < 0.0001). At all time points the width of the third ventricle was significantly correlated with clinical disability (EDSS: r = 0.6, p < 0.01; MSFC: r = -0.6, p < 0.02). In the follow-up over 2 years there was an increase of the width of the third ventricle in comparison with study entry (p < 0.002). Increase of third ventricular width at study entry was associated with higher EDSS levels after 2 years (p = 0.01). CONCLUSION: Assessment of ventricular diameters by TCS is a reliable tool with which to monitor brain atrophy in the longitudinal follow-up of MS patients. Because TCS is a simple, inexpensive, non-invasive and generally available bedside-test it may be used in clinical practice as well as in therapeutic trials to assess brain atrophy.

Adolescent↗
PubMed2004

Health outcomes in multiple sclerosis.

PURPOSE OF REVIEW: Economic considerations are increasingly important in the evaluation of innovative medical technologies. In the past few years, evaluations of cost and cost-effectiveness analysis became a popular topic for multiple sclerosis research. Here, we review cost-of-illness and cost-utility studies in multiple sclerosis published during the past 2 years. RECENT FINDINGS: Despite differences in methodology, several cost-of-illness studies unequivocally demonstrated that indirect costs as a result of sick leave, premature retirement or loss of income made up almost half of the overall costs, and that total costs were higher in the more advanced stages of the disease. Cost-effectiveness studies of recombinant IFN-beta preparations demonstrated a marked variability in the incremental cost per quality-adjusted life-year, with amounts ranging from Euro 28 432 to US$338 738. For glatiramer acetate and mitoxantrone, only limited data are available, but even these few studies differed in their results. SUMMARY: Health outcome studies constitute a new and emerging field of multiple sclerosis research. All studies performed so far underscore the importance of indirect cost in multiple sclerosis. However, the marked differences in cost-effectiveness studies illustrate that the method of economic modeling has considerable impact on the results of these studies, which need standardization in order to evaluate properly the economic consequences of new and expensive therapies in multiple sclerosis.

Cost-Benefit Analysis↗
PubMed2004

Cytokine mRNA expression in patients with multiple sclerosis and fatigue.

BACKGROUND: Fatigue is one of the most common disabling symptoms in patients with multiple sclerosis (MS), but the putative role of proinflammatory cytokines remains to be elucidated. METHODS: Thirty-seven patients (27 women, 10 men) with relapsing remitting (n = 29) and secondary progressive (n = 8) MS, aged 41.0 +/- 10.2 years, were studied. Fatigue was assessed by Krupp's Fatigue Severity Scale (FSS). Cytokine mRNA expression for interferon (IFN)-gamma tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 were measured by real time RT PCR. Autonomic function was evaluated by standard tests for parasympathetic and sympathetic function, as well as by serum levels of norepinephrine and epinephrine. RESULTS: Median levels of TNF-alpha mRNA expression were significantly higher in MS patients with (FSS > or = 4.0 and > or = 5.0, n = 26 and n = 14, respectively) than in those without fatigue (FSS < 4.0, n = 11). No differences were seen for IFN-gamma and IL-10 mRNA expression. Cytokine levels were not correlated to autonomic tests or to serum catecholamine levels. CONCLUSIONS: These results suggest that TNF-alpha, as a principal proinflammatory mediator, is associated with MS-related fatigue. This is in support of a pathogenic role of the MS-related inflammatory process in the development of fatigue.

Adult↗
PubMed2004

Disease-modifying drugs for the early treatment of multiple sclerosis.

The introduction of new immunomodulatory therapies such as, interferon-beta, glatiramer acetate (Copaxone, Teva Pharmaceutical Industries) and mitoxantrone (Ralenova, Wyeth Pharma; Novantrone, Immunex Corp.) has considerably improved the therapeutic options for patients with multiple sclerosis. These agents have been shown to reduce relapse rate, slow down progression of disability and prevent the accumulation of magnetic resonance imaging lesion load in clinically definite multiple sclerosis. Moreover, two formulations of interferon-beta delayed conversion into clinically definite multiple sclerosis in patients with clinically isolated syndromes suggestive of multiple sclerosis. Since axonal damage leading to irreversible neurological disability is already present early at the onset of the disease, immunomodulatory therapy should start as soon as possible. This article reviews the arguments for the early initiation of therapy and provides an overview of clinical studies dealing with the early treatment of multiple sclerosis.

Adjuvants, Immunologic↗
PubMed2003

Assessment of cardiovascular autonomic function in myotonic dystrophy type 2 (DM2/PROMM).

BACKGROUND: Proximal myotonic myopathy is an autosomal dominant multisystem disorder with a recently defined CCTG expansion on chromosome 3 in the major subgroup (myotonic dystrophy type 2). Cardiac rhythm disturbances have been described in patients with this disease, but it is not known whether myotonic dystrophy type 2/proximal myotonic myopathy patients suffer from dysautonomia and whether cardiac arrhythmias relate to autonomic dysfunction. OBJECTIVES: To investigate cardiovascular autonomic function in myotonic dystrophy type 2/proximal myotonic myopathy patients with and without cardiac arrhythmias. PATIENTS AND METHODS: Standard autonomic function tests (heart rate responses to Valsalva manoeuvre, deep breathing and active change of posture, and blood pressure responses to active change of posture and sustained handgrip), resting heart rate variability in the time- and frequency-domain, and the corrected QT interval length were determined in 16 patients with genetically defined myotonic dystrophy type 2/proximal myotonic myopathy and compared to the results obtained in 16 age- and sex-matched healthy control subjects. RESULTS: Standard autonomic tests yielded similar results in both groups. Measures of heart rate variability tended to be lower in myotonic dystrophy type 2/proximal myotonic myopathy patients compared to healthy controls, but reached statistical significance only for the number of R-R intervals exceeding 50 ms (p50) and the power spectrum density in the low-frequency range (low-frequency power). Four patients (25%) suffered from mild cardiac rhythm disturbances encompassing paroxysmal tachycardia, sinoatrial block, right bundle branch block, ventricular premature beats and bradycardia. The autonomic responses of these patients were essentially similar compared to those without cardiac arrhythmias, apart from a decreased heart rate response to deep breathing in the patients with cardiac arrhythmias. CONCLUSIONS: We found no major abnormalities of cardiovascular autonomic function in patients with myotonic dystrophy type 2/proximal myotonic myopathy, neither in the whole study group nor in the subgroup of patients with cardiac rhythm abnormalities.

Adult↗
PubMed2003

Early intervention in multiple sclerosis : better outcomes for patients and society?

Multiple sclerosis (MS) is thought to be a chronic inflammatory disorder of the CNS. The past decade has seen the introduction of the new immunomodulatory drugs, interferon (IFN)-beta and glatiramer acetate, that have considerably improved the therapeutic options for this often disabling disease. The efficacy of these treatments in terms of reducing relapse rate and slowing progression has been proven in several large, multicentre, randomised, controlled trials. Similarly, early IFNbeta treatment of patients with clinically isolated syndromes suggestive of MS has been shown to lengthen time to conversion into definite MS. Cost-effectiveness has been questioned with the increasing use of these innovative and, therefore, costly therapies; however, modern studies with appropriate economic modelling suggest that treatment with IFNbeta may indeed be cost-effective. Since increasing disability is associated with increasing costs, stabilisation of the disease at low functional grades of disability should aim at not only improving quality of life for the individual patient, but provide for prospective cost-benefit analysis focussing on the socioeconomic aspects of MS.

Clinical Trials as Topic↗
PubMed2002

sICAM-1 is not a marker for disease activity in the relapse-free interval of multiple sclerosis--a cross-sectional pilot study.

In multiple sclerosis (MS), serum levels of ICAM-1 were elevated during acute exacerbations and were therefore proposed as a marker of disease activity, but the potential of this molecule as an indicator of long-term activity, i. e. the progression of the disease outside acute exacerbations, is not known. We therefore measured sICAM-1 levels by an enzyme-linked immunosorbent assay in 26 patients with active relapsing-remitting (RR) MS (at least two relapses in the preceding 2 years, but not within the last 30 days), in 10 patients with active secondary-progressive MS (progression of at least one point on the EDSS and/or two relapses in the preceding 2 years, but not within the last 30 days), in 8 patients with stable RR MS (no relapse and no progression during the last two years), and in 16 healthy controls. There was no significant difference between the different MS subtypes and healthy controls, nor within the different MS subtypes. Thus, while sICAM-1 may be useful to indicate short-term activity of MS in terms of relapses and MRI activity, this does not hold true for the long-term activity of MS outside acute exacerbations.

Adult↗