M Maschke

University of Duisburg-Essen, Essen, North Rhine-Westphalia, Germany

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Publications (148)485.8 Total impact

  • Mycoses 05/2014; 57:7-8. · 1.81 Impact Factor
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    ABSTRACT: Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals Abstract Dysfunction of dopaminergic neurotransmis-sion has been implicated in HIV infection. We showed previously increased dopamine (DA) levels in CSF of therapy-nave HIV patients and an inverse correlation between CSF DA and CD4 counts in the periphery, sug-gesting adverse effects of high levels of DA on HIV infection. In the current study including a total of 167 HIV-positive and negative donors from Germany and South Africa (SA), we investigated the mechanistic background for the increase of CSF DA in HIV individuals. Interest-ingly, we found that the DAT 10/10-repeat allele is present more frequently within HIV individuals than in uninfected subjects. Logistic regression analysis adjusted for gender and ethnicity showed an odds ratio for HIV infection in DAT 10/10 allele carriers of 3.93 (95 % CI 1.72–8.96; p = 0.001, Fishers exact test). 42.6 % HIV-infected patients harbored the DAT 10/10 allele compared to only 10.5 % uninfected DAT 10/10 carriers in SA (odds ratio 6.31), whereas 68.1 versus 40.9 %, respectively, in Ger-many (odds ratio 3.08). Subjects homozygous for the 10-repeat allele had higher amounts of CSF DA and reduced DAT mRNA expression but similar disease severity compared with those carrying other DAT geno-types. These intriguing and novel findings show the mutual interaction between DA and HIV, suggesting caution in the interpretation of CNS DA alterations in HIV infection solely as a secondary phenomenon to the virus and open the door for larger studies investigating consequences of the DAT functional polymorphism on HIV epidemiology and progression of disease.
    Journal of Neural Transmission 10/2013; 120:1411-1419. DOI:10.1007/s00702-013-1086-x · 2.87 Impact Factor
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    ABSTRACT: Studies about recovery from cerebellar stroke are rare. The present study assessed motor deficits in the acute phase after isolated cerebellar stroke focusing on postural impairment and gait ataxia and outlines the role of lesion site on motor outcome, the course of recovery and the effect of treadmill training. 23 patients with acute and isolated cerebellar infarction participated. Deficits were quantified by ataxia scores and dynamic posturography in the acute phase and in a follow up after 2 weeks and 3 months. MRI data were obtained to correlate lesion site with motor performance. Half of the patients that gave informed consent and walked independently underwent a 2-week treadmill training with increasing velocity. In the acute phase patients showed a mild to severe ataxia with a worse performance in patients with infarction of the superior in comparison to the posterior inferior cerebellar artery. However, after 3 months differences between vascular territories were no longer significant. MRI data showed that patients with larger infarct volumes had a significantly more severe ataxia. In patients with ataxia of stance, gait and lower limbs lesions were more common in cerebellar lobules IV to VI. After 3 months a mild ataxia in lower limbs and gait, especially in gait speed persisted. Because postural impairment had fully recovered, remaining gait ataxia was likely related to incoordination of lower limbs. Treadmill training did not show significant effects. Future studies are needed to investigate whether intensive coordinative training is of benefit in patients with cerebellar stroke.
    Gait & posture 09/2013; 39(1). DOI:10.1016/j.gaitpost.2013.09.011 · 2.30 Impact Factor
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    ABSTRACT: OBJECTIVE: In Assessment of OraL Laquinimod in PrEventing ProGRession in Multiple SclerOsis (ALLEGRO), a phase III study in relapsing-remitting multiple sclerosis (RRMS), oral laquinimod slowed disability and brain atrophy progression, suggesting laquinimod may reduce tissue damage in MS. MRI techniques sensitive to the most destructive aspects of the disease were used to further investigate laquinimod's potential effects on inflammation and neurodegeneration. METHODS: 1106 RRMS patients were randomised 1:1 to receive once-daily oral laquinimod (0.6 mg) or placebo for 24 months. White matter (WM), grey matter (GM) and thalamic fractions were derived at months 0, 12 and 24. Also assessed were evolution of gadolinium-enhancing and/or new T2 lesions into permanent black holes (PBH); magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT), WM, GM and T2 lesions; and N-acetylaspartate/creatine (NAA/Cr) levels in WM. RESULTS: Compared with placebo, laquinimod-treated patients showed lower rates of WM at months 12 and 24 (p=0.004 and p=0.035) and GM (p=0.004) atrophy at month 12 and a trend for less GM atrophy at month 24 (p=0.078). Laquinimod also slowed thalamic atrophy at month 12 (p=0.005) and month 24 (p=0.003) and reduced the number of PBH at 12 and 24 months evolving from active lesions (all p<0.05). By month 24, MTR decreased significantly in NABT (p=0.015), WM (p=0.011) and GM (p=0.034) in placebo-treated patients, but not in laquinimod-treated patients. WM NAA/Cr tended to increase with laquinimod and decrease with placebo at 24 months (p=0.179). CONCLUSIONS: Oral laquinimod may reduce (at least in the initial phase of treatment) some of the more destructive pathological processes in RRMS patients. TRIAL REGISTRATION: The ALLEGRO trial identifier number with clinicaltrials.gov is NCT00509145. KEYWORDS: MRI, Multiple Sclerosis
    Journal of neurology, neurosurgery, and psychiatry 09/2013; DOI:10.1136/jnnp-2013-306132 · 5.58 Impact Factor
  • Handbook of the Cerebellum and Cerebellar Disorders, 01/2013: pages 2055-2078; , ISBN: 978-94-007-1332-1
  • Aktuelle Neurologie 09/2012; 39(07):358-373. DOI:10.1055/s-0032-1305273 · 0.32 Impact Factor
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    ABSTRACT: HIV-associated dementia and its precursors are frequently observed complications of HIV infection, even in the presence of combination antiretroviral treatment (cART). The development, surveillance and treatment of this condition are still not completely understood. Cytokines, as immunological transmitters, may be one key to gaining a deeper understanding of the disease. A total of 33 HIV-positive male patients were evaluated by neuropsychological testing, lumbar and venous puncture, neuroimaging and neurological examination. The cytokine content in the CSF (cerebrospinal fluid) was examined by a solid-phase protein array. The Digit-Symbol Test, contraction time analysis, Rey-Osterrieth Figure and Grooved-Pegboard Test showed inferior results in the presence of an inflammatory CSF environment, whereas neuroprotective or anti-inflammatory conditions were correlated to better results in contraction time analysis. Higher CSF levels of cytokines were independently correlated with the duration of HIV infection. The study showed a correlation of cytokine levels in the CSF of HIV patients with test results of their neuropsychological functioning. The effect was pronounced with regard to the more complex executive tasks. Determining CSF cytokine levels may be a useful supplement to the assessment of HIV patients and contribute helpful information to predict neurocognitive performance. Therapeutic strategies to ameliorate a negative impact of an altered cytokine milieu may aid in slowing the evolution of neurocognitive dysfunction.
    Journal of NeuroVirology 04/2012; 18(3):157-61. DOI:10.1007/s13365-012-0091-4 · 3.32 Impact Factor
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    ABSTRACT: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.).
    New England Journal of Medicine 03/2012; 366(15):1404-13. DOI:10.1056/NEJMoa1200933 · 54.42 Impact Factor
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    ABSTRACT: BACKGROUND: Two proof-of-concept clinical trials have provided evidence that laquinimod reduces disease activity in patients with relapsing-remitting multiple sclerosis. METHODS: We conducted a randomized, double-blind, phase 3 study at 139 sites in 24 countries. A total of 1106 patients with relapsing-remitting multiple sclerosis were randomly assigned in a 1:1 ratio to receive oral laquinimod at a dose of 0.6 mg once daily or placebo for 24 months. The primary end point was the annualized relapse rate during the 24-month period. Secondary end points included confirmed disability progression (defined as an increase in the score on the Expanded Disability Status Scale that was sustained for at least 3 months) and the cumulative number of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted magnetic resonance imaging. RESULTS: Treatment with laquinimod as compared with placebo was associated with a modest reduction in the mean (±SE) annualized relapse rate (0.30±0.02 vs. 0.39±0.03, P=0.002) and with a reduction in the risk of confirmed disability progression (11.1% vs. 15.7%; hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; P=0.01). The mean cumulative numbers of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted images were lower for patients receiving laquinimod than for those receiving placebo (1.33±0.14 vs. 2.12±0.22 and 5.03±0.08 vs. 7.14±0.07, respectively; P<0.001 for both comparisons). Transient elevations in alanine aminotransferase levels to greater than three times the upper limit of the normal range were observed in 24 patients receiving laquinimod (5%) and 8 receiving placebo (2%). CONCLUSIONS: In this phase 3 study, oral laquinimod administered once daily slowed the progression of disability and reduced the rate of relapse in patients with relapsing-remitting multiple sclerosis. (Funded by Teva Pharmaceutical Industries; ClinicalTrials.gov number, NCT00509145.). Comment in Oral laquinimod for multiple sclerosis. [N Engl J Med. 2012] New and old: notable drug developments for clinical practice. [J Neurol. 2012]
    New England Journal of Medicine 01/2012; 366(11):1000-1009. DOI:10.1056/NEJMoa1104318. · 54.42 Impact Factor
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    ABSTRACT: In this cross-sectional study we used magnetic resonance imaging (MRI)-based voxel based morphometry (VBM) in a sample of HIV positive patients to detect structural gray and white matter changes. Forty-eight HIV positive subjects with (n = 28) or without (n = 20) cognitive deficits (mean age 48.5 ± 9.6 years) and 48 age- and sex-matched HIV negative controls underwent MRI for VBM analyses. Clinical testing in HIV patients included the HIV dementia scale (HDS), Unified Parkinson's Disease Rating Scale (UPDRS) and the grooved pegboard test. Comparing controls with HIV positive patients with cognitive dysfunction (n = 28) VBM showed gray matter decrease in the anterior cingulate and temporal cortices along with white matter reduction in the midbrain region. These changes were more prominent with increasing cognitive decline, when assigning HIV patients to three cognitive groups (not impaired, mildly impaired, overtly impaired) based on performance in the HIV dementia scale. Regression analysis including all HIV positive patients with available data revealed that prefrontal gray matter atrophy in HIV was associated with longer disease duration (n = 48), while motor dysfunction (n = 48) was associated with basal ganglia gray matter atrophy. Lower CD4 cell count (n = 47) correlated with decrease of occipital gray matter. Our results provide evidence for atrophy of nigro-striatal and fronto-striatal circuits in HIV. This pattern of atrophy is consistent with motor dysfunction and dysexecutive syndrome found in HIV patients with HIV-associated neurocognitive disorder.
    Journal of Neurology 06/2011; 258(6):1066-75. DOI:10.1007/s00415-010-5883-y · 3.84 Impact Factor
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    Mark Obermann, Michael Küper, Matthias Maschke
    MMW Fortschritte der Medizin 05/2011; 153(18):52-5.
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    ABSTRACT: The aim of the present study was to examine if the most frequent cognitive disorders after cortical damage with a well-known cerebral lateralization, namely aphasia, neglect and extinction, are present in an unselected series of continuously admitted patients with acute cerebellar stroke. Twenty-two adults with acute cerebellar stroke were compared with 22 age- and education-matched healthy control subjects. High-resolution magnetic resonance images showed infarctions of the left cerebellar hemisphere in 12 and of the right hemisphere in ten patients. Standard aphasia tests revealed no statistically significant difference comparing patients with right- and left-sided ischemia and controls, whereas patients with left-sided ischemia showed mild deficits in a verb generation task. Neglect and extinction tasks revealed no significant differences between groups. Our findings support previous observations in the literature that cerebellar patients frequently perform within the normal range in standard neuropsychological tests. This does not exclude, however, that abnormalities may be present in more sophisticated testing of language and visuospatial functions.
    The Cerebellum 12/2010; 9(4):556-66. DOI:10.1007/s12311-010-0197-2 · 2.86 Impact Factor
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    ABSTRACT: The relevance of the sensory system in the pathophysiology of cervical dystonia (CD) has been discussed since the description of sensory tricks associated with this disorder. Our objective was to locate changes in somatosensory processing of patients with CD responding in a passive sensory task of body regions that are not affected by dystonic symptoms. We used functional magnetic resonance imaging (fMRI) in 17 patients with CD and 17 healthy controls performing a strictly passive 30-degree forearm movement task with the left arm. TSUI and TWSTRS rating scales were used for clinical assessment. All patients were treated with botulinum neurotoxin type A (BoNT-A; Dysport®). Patients with CD showed BOLD-signal increase in the contralateral primary and secondary sensory cortex, the cingulate cortex and cerebellum bilaterally compared to healthy controls. We found a strong positive correlation of this activation with BoNT-A dosage in the supplementary motor area (SMA) and a negative correlation with the TWSTRS in that same region. The observed sensory overactivation suggests a general disinhibition of the somatosensory system in CD as it was not limited to the motor-system or the direct neuronal representation of the affected dystonic musculature alone.
    Movement Disorders 11/2010; 25(15):2627-33. DOI:10.1002/mds.23321 · 5.63 Impact Factor
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    ABSTRACT: Loss of movement coordination is the main postacute symptom after cerebellar infarction. Although the course of motor recovery has been described previously, detailed kinematic descriptions of acute stage ataxia are rare and no attempt has been made to link improvements in motor function to measures of neural recovery and lesion location. This study provides a comprehensive assessment of how lesion site and arm dysfunction are associated in the acute stage and outlines the course of upper limb motor recovery for the first 4 months after the infarction. Sixteen adult patients with cerebellar stroke and 11 age-matched healthy controls participated. Kinematics of goal-directed and unconstrained finger-pointing movements were measured at the acute stage and in 2-week and 3-month follow-ups. MRI data were obtained for the acute and 3-month follow-up sessions. A voxel-based lesion map subtraction analysis was performed to examine the effect of ischemic lesion sites on kinematic performance. In the acute stage, nearly 70% of patients exhibited motor slowing with hand velocity and acceleration maxima below the range of the control group. MRI analysis revealed that in patients with impaired motor performance, lesions were more common in paravermal lobules IV/V and affected the deep cerebellar nuclei. Stroke affecting the superior cerebellar artery led to lower motor performance than infractions of the posterior cerebellar artery. By the 2-week-follow-up, hand kinematics had improved dramatically (gains in acceleration up to 86%). Improvements between the 2-week and the 3-month-follow-ups were less pronounced. In the acute stage, arm movements were mainly characterized by abnormal slowness (bradykinesia) and not dyscoordination (ataxia). The motor signs were associated with lesions in paravermal regions of lobules IV/V and the deep cerebellar nuclei. Motor recovery was fast, with the majority of gains in upper limb function occurring in the first 2 weeks after the acute phase.
    Stroke 10/2010; 41(10):2191-200. DOI:10.1161/STROKEAHA.110.583641 · 6.02 Impact Factor
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    ABSTRACT: Central dopaminergic (DA) systems are affected during human immunodeficiency virus (HIV) infection. So far, it is believed that they degenerate with progression of HIV disease because deterioration of DA systems is evident in advanced stages of infection. In this manuscript we found that (a) DA levels are increased and DA turnover is decreased in CSF of therapy-naïve HIV patients in asymptomatic infection, (b) DA increase does not modulate the availability of DA transporters and D2-receptors, (c) DA correlates inversely with CD4+ numbers in blood. These findings show activation of central DA systems without development of adaptive responses at DA synapses in asymptomatic HIV infection. It is probable that DA deterioration in advanced stages of HIV infection may derive from increased DA availability in early infection, resulting in DA neurotoxicity. Our findings provide a clue to the synergism between DA medication or drugs of abuse and HIV infection to exacerbate and accelerate HIV neuropsychiatric disease, a central issue in the neurobiology of HIV.
    Journal of Neural Transmission 06/2010; 117(6):699-705. DOI:10.1007/s00702-010-0415-6 · 2.87 Impact Factor
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    ABSTRACT: The objective of this study was to evaluate immune cytokine expression in cerebrospinal fluid (CSF) of patients with human immunodeficiency virus-1 (HIV-1)-associated dementia (HAD) using a novel cytokine array assay. HIV-1 induces a condition resembling classical subcortical dementia, known as HAD. The immune mechanisms contributing to HAD have not been elucidated. Cytokine expression in CSF was determined by solid-phase protein array in 33 neurologically asymptomatic HIV-positive male patients and were compared to levels in non-HIV controls and patients with HAD. Neurological examinations and lumbar and venous punctures were conducted in all patients and controls. Interleukin (IL)-1, IL-4, and IL-10, were up-regulated in all treated acquired immunodeficiency syndrome (AIDS) patients independent of neurological status compared to controls. In contrast, interferon gamma (IFN-gamma), IL-1alpha, IL-15, and tumor necrosis factor alpha (TNF-alpha) were highly expressed in patients with HAD compared to undemented HIV-positive patients. These results show that solid-phase protein array can detect immunological changes in patients infected with HIV. Cytokine expression levels differ in different disease stages and in patients on different treatment paradigms. Pending further validation on a larger number of patients, this method may be a useful tool in CSF diagnostics and the longitudinal evaluation of patient with HAD.
    Journal of NeuroVirology 12/2009; 15(5-6):390-400. DOI:10.3109/13550280903350192 · 3.32 Impact Factor
  • Aktuelle Neurologie 09/2009; 36(S 02). DOI:10.1055/s-0029-1238627 · 0.32 Impact Factor
  • Aktuelle Neurologie 09/2009; 36(S 02). DOI:10.1055/s-0029-1238324 · 0.32 Impact Factor
  • Aktuelle Neurologie 09/2009; 36(S 02). DOI:10.1055/s-0029-1238521 · 0.32 Impact Factor
  • T Jacobs, M Maschke, C Klawe
    Aktuelle Neurologie 09/2009; 36(S 02). DOI:10.1055/s-0029-1238576 · 0.32 Impact Factor

Publication Stats

3k Citations
485.80 Total Impact Points

Institutions

  • 2000–2013
    • University of Duisburg-Essen
      • Erwin L. Hahn Institute for Magnetic Resonance Imaging
      Essen, North Rhine-Westphalia, Germany
  • 1999–2011
    • University Hospital Essen
      • • Klinik für Neurologie
      • • Institute of Diagnostic and Interventional Radiology and Neuroradiology
      Essen, North Rhine-Westphalia, Germany
  • 2009
    • Krankenhaus Barmherzige Brüder München
      München, Bavaria, Germany
  • 2006–2007
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2002
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany