M Gottschalk

Max Planck Institute of Psychiatry, München, Bavaria, Germany

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Publications (6)18.46 Total impact

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    ABSTRACT: 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. To investigate the relationship between fatigue and the hypothalamo-pituitary-adrenal (HPA) axis in patients with MS. A prospective survey. Outpatient and inpatient study at the Max Planck Institute of Psychiatry, Munich, Germany. Thirty-one patients with clinically definite MS, a relapsing-remitting disease course, and without MS-specific treatment. 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. 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. 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.
    JAMA Neurology 03/2005; 62(2):277-80. DOI:10.1001/archneur.62.2.277 · 7.01 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Multiple Sclerosis 05/2004; 10(2):165-9. DOI:10.1191/1352458504ms991oa · 4.86 Impact Factor
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    ABSTRACT: 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. 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). 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. 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.
    Multiple Sclerosis 12/2002; 8(6):523-6. DOI:10.1191/1352458502ms839oa · 4.86 Impact Factor
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    ABSTRACT: 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.
    Der Nervenarzt 09/2001; 72(8):636-40. · 0.86 Impact Factor
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    ABSTRACT: Im Jahre 1986 beschrieben Andermann et al. [1] ein Syndrom bestehend aus Niereninsuffizienz, Myoklonien, einer zerebellären Symptomatik und Epilepsie. Eine hereditäre Ursache wurde vermutet. Wir beschreiben erstmalig in Europa drei betroffene Mitglieder einer Familie mit einer vergleichbaren Symptomatik. Zwei dieser Patienten waren in unserer Behandlung, bei einem dritten bereits verstorben Patienten stützt sich der Bericht auf die verfügbaren Befunde. Das Manifestationsalter der ersten klinischen Symptome lag zwischen dem 14. und 20. Lebensjahr. Eine Patientin litt unter einer kompensierten Niereninsuffizienz, ihre zwei Brüder waren im Alter von 18 und 26 Jahren dialysepflichtig. Die Nierenbiopsie zeigte jeweils eine unspezifische Nephritis. Bei allen drei Patienten bestanden ein zerebelläres Syndrom und Aktionsmyoklonien. Bei zwei Patienten wurde eine Epilepsie mit Grand-mal-Anfällen diagnostiziert, alle litten unter einer demyelinisierenden oder gemischten Polyneuropathie. Die Familienanamnese spricht für einen autosomal-rezessiven Erbgang. 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 deceased, 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.
    Der Nervenarzt 01/2001; 72(8):636-640. DOI:10.1007/s001150170065 · 0.86 Impact Factor
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    ABSTRACT: Synopsis Diffusion tensor studies are known to be sensitive to the pathobiology of MS. To evaluate possible surrogate markers, we studied global histogram-derived metrics from mean diffusivity (D) and FA maps in MS patients and controls and tested for correlations with the Expanded Disability Status Scale and the MS Functional Composite score. We confirmed abnormal DT characteristics in MS and found interrelations with both scores, the strongest correlations were between variance and asymmetry of D and MSFC global and PASAT z-scores. Thus, global diffusivity histograms reflect the burden of disease and global CNS functioning may provide useful MS surrogate markers. Introduction In recent years, numerous studies attempted to use quantitative MRI and MRS to establish surrogate markers in CNS diseases. This was particularly successful in MS, with widely accepted surrogate markers of the inflammatory disease activity and the final brain atrophy. Diffusion tensor studies may, however, be better suited to depict and quantify the demyelinating and inflammatory pathology in MS. 1-3 To evaluate global histogram-derived potential surrogate markers from DT studies, we studied how abnormal these measures are in patients with clinical definite MS and correlated the variables with symptom severity assessed by the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC). 4-5 We hypothesized that the MSFC would better correlate with a global measure of disease since it is posited to better reflect overall mental and motor functions. Material and Methods Thirty-one patients (20 women, 11 men, mean age=39.2 yrs, SD=11.8 yrs) with clinically definite multiple sclerosis of the relapsing remitting (RR, n=22), secondary progressive (n=7) and primary progressive (n=2) course and 22 controls (13 women, 9 men, mean age=37.5 yrs, SD=14.3 yrs) were included in this study. At the time of MRI patients were clinically stable and were scored using the Extended Disability Status Scale (EDSS) and the MS Functional Composite (MSFC) within one month. For diffusion measurements, a spin echo echoplanar diffusion tensor sequence (TR=2500, TE=80, with six non collinear gradient directions and b = 880 s/mm2 [3 averages] was used (24 slices, 1.9x1.9x3mm 3 , gap=1mm). Postprocessing was done with inhouse software to calculate the diffusion tensor, mean diffusivity (D) and fractional anisotropy (FA). To extract brain tissue, a region-growing algorithm was used and manually corrected where needed. We then calculated histograms for global brain tissue including CSF and derived peak positions, mean values, variance (VAR) and asymmetry. These measures were subjected to multivariate analysis comparing patients and controls and correlation analysis was performed with EDSS and z-transformed total and subtests (Timed 25-Foot Walk, Nine-Hole Peg Test and Paced Auditory Serial Addition Test (PASAT)) of the MSFC.