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T Kümpfel

Publications and source records attributed to T Kümpfel.

16 recordsLinked to original sources
PubMed2006

[Pregnancy and immunomodulatory therapy in multiple sclerosis patients].

Pregnancy and family planning issues are prominent concerns in the medical care of multiple sclerosis patients, since the disease onset often coincides with a period of life that is decisive in this regard. Multiple sclerosis is a chronic disorder with an unpredictable course and is widely treated with long-term immunomodulatory agents, raising questions regarding the complications and effects of these therapies on pregnancy. This paper gives an overview of the relevant literature and provides a basis for individual counselling of this group of multiple sclerosis patients.

Female↗
PubMed2005

[Multiple sclerosis: between wish and reality].

The guidelines for the therapy of multiple sclerosis (MS) are unchanged. An acute episode is treated intravenously with high-dosed glucocorticoid. This is usually followed by an immunomodulating basic therapy, although the currently approved preparations for this purpose are only partially effective. During the last ten years, a series of new therapeutic approaches have been developed. The monoclonal antibody natalizumab (Tysabri) was approved for use in the U.S.A. in 2004 and showed good success, but had to be removed from the market in February 2005 because of grave side effects. Up until now, the chemokine receptor antagonist CCR1 has been tested in a pilot study. A clinical phase III study is being planned with MS patients for the interleukin-2 receptor antagonist daclizumab.

Antibodies, Monoclonal↗
PubMed2002

[Antegren (natalizumab). A promising new approach to therapy of multiple sclerosis].

Antegren (Natalizumab) is a humanized monoclonal antibody directed against alpha 4-integrin. This antibody binds to the alpha 4 subunit of alpha 4 beta 1-integrin (VLA-4) and alpha 4 beta 7-integrin on leukocytes and blocks the interaction of these integrins with their ligands (VCAM and MadCAM). Disruption of these cell adhesion molecule interactions inhibits the migration of leukocytes through the blood-brain barrier and the trafficking of leukocytes through the extracellular matrix. In clinical studies, short-term treatment of patients with multiple sclerosis (MS) with antegren resulted in a clear reduction of the number of new active brain lesions on magnetic resonance imaging (MRI). Antegren was safe and well tolerated. Two large phase III studies will help to determine the long-term effect of antegren on MRI and clinical outcome in relapsing-remitting MS patients.

Animals↗
PubMed2002

Treatment with glatiramer acetate induces specific IgG4 antibodies in multiple sclerosis patients.

We analysed the humoral immune response to glatiramer acetate (GA, Copaxone) in 20 multiple sclerosis patients treated with GA, 20 patients not treated with GA and 20 normal control subjects. Using an ELISA for detection of total GA-reactive immunoglobulins (all isotypes), all treated patients but also 3/20 untreated and 8/20 healthy subjects scored positive at 1:20 plasma dilutions. At higher dilutions, 5/20 treated patients and two healthy donors had relatively high levels of anti-GA antibodies. Isotype and IgG subclass analysis revealed that the two antibody-positive normal subjects had IgM and small titers of IgG1 or IgG2 antibodies. In contrast, 18 of 20 GA-treated patients, had low but significant titers of GA-reactive IgG4 antibodies. This finding is consistent with the previously described GA-mediated induction of T-helper 2 (TH2)-like regulatory T cells.

Adult↗
PubMed2002

Fatigue in multiple sclerosis: a comparison of different rating scales and correlation to clinical parameters.

OBJECTIVES: Fatigue is one of the most common, yet poorly defined, disabling symptoms in patients with multiple sclerosis (MS). To delineate more clearly the frequency and type of fatigue, we first compared four widely used fatigue scales in consecutive MS patients. Secondly, to further clarify the nature of fatigue, we investigated its relation to physical disability, course of the disease, immunotherapy, and depression. PATIENTS AND METHODS: Between February and September 2000, 151 consecutive MS patients entering our outpatient clinic (94 relapsing-remitting, 50 secondary progressive, and 7 primary progressive patients; mean age 29.0 +/- 7.3 years, mean disease duration 9.9 +/- 6.7 years, median EDSS 3.5) filled in a standardized questionnaire induding four fatigue scales--Fatigue Severity Scale (FSS), MS-specific FSS (MFSS), Modified Fatigue Impact Scale (MFIS), and Visual Analogue Scale (VAS). Patients were included in the 'MS-related fatigue group' (MS-F) when they stated in the questionnaire that fatigue: 1) is one of their three most disabling symptoms; 2) occurs daily or on most of the days; and 3) limits their activities at home or at work Patients fulfilling none of these criteria were classified as 'MS-related nonfatigue group' (MS-NF). Depression was measured by Beck's Depression Inventory (BDI). RESULTS: Although all scales showed significant differences between MS-F and MS-NF, correlation between these scales was, at best moderate (correlation coeffcients ranging from 0.06 to 0.56). The most discriminative scales were FSS and MFIS, showing no overlap of the 10th and 90th percentiles for the MS-F and MS-NF groups, with cut-off values of 4.6 and 38, respectively. Depression (BDI > or = 18) was present in 24 of 148 patients who filled in the BDI (16%). FSS was significantly correlated with physical disability (r=0.33, p<0.0001) and BDI (r=0.41, p<0.0001), but not with age, disease duration, clinical activity, and treatment with interferon-beta. In multivariate analysis, however, only BDI independently predicted fatigue. CONCLUSIONS: The association of fatigue and depression suggests that there might be either common underlying mechanisms or interdependence by a cause-and-effect relationship that requires further investigation. The weak correlation within various fatigue scales is best explained by the fact that fatigue is a multidimensional symptom and, therefore, the available tests measure and weight different aspects of fatigue. Our findings underline the necessity for a more exact definition of fatigue and the development of more valid tools if these are to be used to evaluate treatments.

Adult↗
PubMed2001

[Familial myoclonus-renal failure syndrome].

In 1986 Andermann et al. described a syndrome presenting with renal failure, myoclonus, cerebellar symptoms, and epilepsy. They presumed a hereditary cause. We describe the first appearance of this syndrome in Europe, affecting three family members with comparable symptoms. Two of these patients were treated by us, and the third, already decreased, is described according to the available reports. The first clinical symptoms were manifested between the ages of 14 and 20. A female patient suffered from compensated kidney insufficiency and her two brothers aged 18 and 26 required dialysis. Biopsy of kidney tissue revealed nonspecific nephritis. All cases showed a cerebellar syndrome and action myoclonus. Two of them were diagnosed with epilepsy and grand mal seizures, and all suffered from demyelinizing or mixed polyneuropathy. Anamnesis of the family seems to indicate autosomal recessive inheritance.

Adolescent↗
PubMed2001

Combined treatment with corticosteroids and moclobemide favors normalization of hypothalamo-pituitary-adrenal axis dysregulation in relapsing-remitting multiple sclerosis: a randomized, double blind trial.

Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system, is presumably due to diminished corticosteroid receptor function. It probably influences the immune response, but its clinical significance is not clear. Similar HPA dysregulation occurs in depression and is reversible with successful antidepressant treatment. We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded Disability Status Scale score of neurological impairment, 2.0--6.5) in acute relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary units in the moclobemide group vs. 225.8 +/- 65.1 in the steroid alone group; mean +/- SEM]. In a group of healthy controls with comparable demographic characteristics, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment resulted in normalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/- 22.8 vs.177.1 +/- 68.5; on day 75, 111.0 +/- 46.0 vs. 199.2 +/- 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticosteroids favors normalization of the HPA response in relapsing-remitting MS.

Adrenal Cortex Hormones↗
PubMed2000

Acute effects of interferon beta-1a on plasma cytokine levels in patients with MS.

The acute effects of a i.m. injection of interferon beta-1a on the secretion of the cytokines interleukin-6, tumor necrosis factor-alpha, soluble tumor necrosis factor receptor I, and interleukin-1 receptor antagonist and its relation to peripheral concentrations of adrenocorticotropic hormone (ACTH) and cortisol in patients with MS were investigated, as well as the influence of cotreatment with indomethacin on these parameters. After interferon beta injection we found an acute rise in plasma cytokine levels and an increase in plasma hormone concentrations, both of which were modulated by indomethacin comedication.

Adult↗
PubMed2000

Non-convulsive status epilepticus with marked neuropsychiatric manifestations and MRI changes after treatment of hypercalcaemia.

We describe a 77-year-old woman who developed a confusional state, cognitive impairment, behavioural abnormalities and dysphasia after treatment of hypercalcaemia. Repeated EEG recording revealed rhythmic sharp-wave activity over the right parietal-occipital lobe. Magnetic resonance imaging (MRI) showed marked hyperintense signal changes bilaterally. The diagnosis of a non-convulsive status epilepticus (NCSE) was made. With antiepileptic treatment the patient improved and MRI as well as EEG changes were almost all reversible. NCSE is an important differential diagnosis of patients with neuropsychiatric symptoms and can develop after rapid lowering of serum calcium levels in hypercalcaemia.

Aged↗
PubMed1999

Dysregulation of the hypothalamo-pituitary-adrenal axis is related to the clinical course of MS.

OBJECTIVE: To investigate whether dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis is related to clinical characteristics in MS. METHODS: The authors performed the combined dexamethasone-corticotropin-releasing hormone test (Dex-CRH test) in 60 MS patients and 29 healthy control subjects. In addition, the short adrenocorticotropic hormone (ACTH) test was performed in 39 consecutive patients. All patients had active disease and none were treated with glucocorticoids, immunosuppressants, or immunomodulators. RESULTS: The patients had an exaggerated rise in plasma cortisol concentrations in the Dex-CRH test (p < 0.05), indicating hyperactivity of the HPA system. The degree of hyperactivity was moderate in relapsing-remitting MS patients (n = 38; area under the time-course curve for cortisol [AUC-Cort] 226.2+/-38.9 arbitrary units [AU], mean +/- SEM), intermediate in secondary progressive MS patients (n = 16; AUC-Cort, 286.8+/-60.2 AU), and marked in primary progressive MS patients (n = 6; AUC-Cort, 670.6+/-148.6 AU). Differences were significant between the three patient groups (p < 0.005), and between control subjects (n = 29; AUC-Cort, 150.8+/-34.1 AU) and each patient group. Indicators of HPA axis activation correlated with neurologic disability (Kurtzke's Expanded Disability Status Scale), but not with the duration of the disease, number of previous relapses, previous corticosteroid treatments, or depressed mood (Hamilton Depression Scale). The ACTH test was normal in 31 of the 33 patients studied. CONCLUSION: HPA axis hyperactivity in MS is related to the clinical type of disease, with a suggestion of increasing HPA axis dysregulation with disease progression.

Adrenocorticotropic Hormone↗
PubMed1999

Dehydroepiandrosterone response to the adrenocorticotropin test and the combined dexamethasone and corticotropin-releasing hormone test in patients with multiple sclerosis.

Basic and clinical research suggest that disturbed neuroendocrine function may be involved in the pathogenesis and course of autoimmune diseases including multiple sclerosis (MS). Dehydroepiandrosterone (DHEA) in this connection is of particular interest as it appears to have effects on the immune system. Moreover, DHEA levels are decreased in chronic inflammatory diseases. To further investigate the role of DHEA in MS, we administered the adrenocorticotropin (ACTH) stimulation test and the combined dexamethasone and corticotropin-releasing hormone (DEX-CRH) test to 24 patients with active MS (13 women, 11 men; age 39 +/- 2 years, mean +/- SEM; Expanded Disability Status Scale, EDSS score 4.4 +/- 0. 4, mean +/- SEM; 12 with acute relapse, 12 with chronic progression) and to 18 healthy controls matched for age and sex (8 women, 10 men; age 37 +/- 3 years). There were no statistically significant differences in the plasma cortisol response to ACTH between any groups. In the DEX-CRH test, plasma cortisol concentrations showed higher values before (DEX-pretreated) and after CRH stimulation in the MS patients than in the controls (AUC(cortisol) 738.3 +/- 154.5 vs. 295.7 +/- 55.8; p < 0.05), this finding was more pronounced in chronic progressive patients. DHEA concentrations were decreased in MS patients (AUC (DHEA) 14.4 +/- 1.6 vs. 23 +/- 2.4; p < 0.05) and cortisol/DHEA ratios were increased in the patients compared to the controls (p < 0.05). There was a positive correlation between the EDSS score and maximum cortisol/DHEA ratio (r = 0.45; p = 0.031). As with the hypothalamic-pituitary-adrenal axis system, our results suggest a dysfunction in the DHEA secretion in patients with MS.

Adrenocorticotropic Hormone↗
PubMed1998

[Exacerbation of tics by prednisolone].

Tics-disorders are hyperkinetic movement disorders which manifest in childhood or early adolescence and ameliorate in later adulthood. We report on two patients with a basically subclinical tic-disorder (age of 53 and 68 years). During the therapy of polymyalgia rheumatica and endocrine orbitopathy in Graves disease with prednisolone the tics exacerbated and were therefore diagnosed and treated for the first time. Possible causes for the exacerbation of the tics during the therapy with glucocorticosteroids are discussed in the context of the dopamine hypothesis of tics.

Aged↗
PubMed1998

[Prolonged non-convulsive status epilepticus as an early clinical manifestation of epilepsy in connection with HIV infection--case report with EEG and MRI follow-up].

The non-convulsive status epilepticus (NCSE) is a complication of petit mal epilepsy or epilepsy with temporal lobe seizures. Very rarely it is the primary manifestation of a symptomatic epilepsy. This report is on a 30-year old female inpatient with NCSE as the primary manifestation of symptomatic epilepsy, occurring four years after HIV infection (stage B3 according to the CDC classification) through heterosexual contact. After an initial tonic-clonic seizure, the patient suffered from NCSE for four weeks with diminished consciousness and major cognitive deficits. During this whole time period the EEG showed bilateral synchrone 1-2 Hz spike-wave complexes. After several failed treatment attempts, the NCSE was successfully and permanently treated with a combination of valproic acid and ethosuximide. The cerebrospinal fluid, cranial CT and cranial MRI were completely uneventful with regard to a CNS infection by the HI-virus or other infectious agents. 20 days after the initial symptoms, MRI showed bilateral cortical-subcortical and bilateral hippocampal lesions which stood out as focal edema zones, gradually disappeared completely and occurred in combination with the development of a discrete brain and right sided hippocampal atrophy. The EEG continued to show signs of right-temporal epileptic discharges with tendencies to generalise after 3 months but normalised after 6 months. Epileptic seizures are rarely an initial clinical sign of an infection with the HI-Virus even if no signs of encephalitis is detectable in the cerebrospinal fluid or in the cerebral MRI.

Adult↗
PubMed1995

Involvement of substance P in pial arteriolar vasodilatation during pneumococcal meningitis in the rat.

The present study investigated whether the endogenous vasodilating neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) contribute to pial arteriolar vasodilatation in the early phase of pneumococcal meningitis in the rat. Using a closed cranial window preparation we measured the diameters of pial arterioles during 4 h after pneumococcal infection. Arteriolar vasodilatation in infected rats was significantly attenuated by pretreatment with the SP-antagonist spantide up to 3 h after infection. Neither post-treatment with spantide (administered 2 h after infection) nor pretreatment with the CGRP antagonist CGRP(8-37) affected the pneumococci-induced pial arteriolar dilatation. These data suggest that SP is involved as a mediator in early pneumococci-induced dilatation of pial arterioles.

Animals↗