Biomedical subjects

F Munschauer

Publications and source records attributed to F Munschauer.

10 recordsLinked to original sources

PubMed2006

Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis.

Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans, suggesting iron deposition, has been described in multiple sclerosis (MS) and is related to physical disability, disease course and brain atrophy. We tested the hypothesis that subcortical grey matter T2 hypointensity is related to cognitive impairment after adjusting for the effect of MRI lesion and atrophy measures. We studied 33 patients with MS and 14 healthy controls. Normalized T2 signal intensity in the caudate, putamen, globus pallidus and thalamus, total brain T1-hypointense lesion volume (T1LV), fluid-attenuated inversion-recovery-hyperintense lesion volume (FLLV) and brain parenchymal fraction (BPF) were obtained quantitatively. A neuropsychological composite score (NCS) encompassed new learning, attention, working memory, spatial processing and executive function. In each of the regions of interest, the normalized T2 intensity was lower in the MS versus control group (all P<0.001). Regression modelling tested the relative association between all MRI variables and NCS. Globus pallidus T2 hypointensity was the only variable selected in the final model (R2 = 0.301, P = 0.007). Pearson correlations between MRI and NCS were T1LV: r = -0.319; FLLV: r = -0.347; BPF: r = 0.374; T2 hypointensity of the caudate: r = 0.305; globus pallidus: r = 0.395; putamen: r = 0.321; and thalamus: r = 0.265. Basal ganglia T2 hypointensity and BPF demonstrated the strongest associations with cognitive impairment on individual cognitive subtests. Subcortical grey matter T2 hypointensity is related to cognitive impairment in MS, supporting the clinical relevance of T2 hypointensity as a biological marker of MS tissue damage. These data implicate a role for basal ganglia iron deposition in neuropsychological dysfunction.

Adult↗

PubMed2005

Significance of neutralizing antibodies to interferon beta during treatment of multiple sclerosis: expert opinions based on the Proceedings of an International Consensus Conference.

On August 30, 2002, an international panel of neurologists who specialize in the treatment of multiple sclerosis (MS) was convened in Paris (France) to discuss the issue of neutralizing antibodies (NAb) to interferon beta (IFN-beta) therapy in patients with MS. The goals of this meeting were to: (i) review the most recent clinical information on NAb, (ii) come to a consensus on the clinical relevance of NAb in the management of patients with MS receiving IFN-beta therapy, and (iii) establish a framework for the development of patient management guidelines based on scientific consensus. The meeting was chaired by Hans-Peter Hartung (Heinrich-Heine University, Düsseldorf, Germany) and Huub Schellekens (Utrecht University, Utrecht, the Netherlands). This article summarizes the opinions of the expert panel on a number of key issues raised at the meeting.

Animals↗

PubMed2003

Screening for multiple sclerosis cognitive impairment using a self-administered 15-item questionnaire.

Since there is a need for cost-effective screening techniques to identify neuropsychological impairment in multiple sclerosis (MS) patients, and because existing methods require cognitive testing with subsequent interpretation by a neuropsychologist, a brief self-report procedure was developed to screen for neuropsychological impairment in MS. In the first phase of the study, a pool of 80 items was generated based on a literature review and consultation with healthcare professionals. The set was reduced to 15 via Rasch analysis. Using these items, a brief (five minute) MS Neuropsychological Screening Questionnaire (MSNQ), including patient- and informant-report forms, was composed. In phase II, 50 MS patients and their caregivers completed the MSNQ. A comprehensive neuropsychological test battery was also administered. Analyses covered the reliability of the MSNQ and correlations between both patient- and informant-report scores and objective neuropsychological testing. Cronbach's alpha coefficients were 0.93 and 0.94 for the patient- and informant-report forms, respectively, and both forms of the test were strongly correlated with a more general cognitive complaints questionnaire. The patient MSNQ form correlated significantly with measures of depression but not with objective tests of cognitive function. In contrast, the informant form was correlated with patient cognitive performance but not depression. A cut-off score of 27 on the informant form of the MSNQ optimally separated patients based on a neuropsychological summary score encompassing measures of processing speed and memory. There were two false-negatives and one false-positive, giving the test a sensitivity of 0.83 and a specificity of 0.97. It is concluded, therefore, that this self-administered neuropsychological screening test is reliable and predicts neuropsychological impairment in MS patients with a reasonable degree of accuracy.

Adult↗

PubMed2003

Pattern reversal visual evoked potentials as a measure of visual pathway pathology in multiple sclerosis.

BACKGROUND: Pattern reversal visual evoked potentials (PRVEPs) have a well-documented role in diagnosis of multiple sclerosis (MS), but their value as a visual function surrogate remains controversial. METHODS: We evaluated PRVEP in 37 patients with MS who were participating in a long-term follow-up study following a phase III trial of interferon beta-1a (Avonex). Patients were examined to determine the Kurtzke Extended Disability Status Score (EDSS), multiple sclerosis functional composite (MSFC), contrast letter acuity (CLA), and had cranial MRI scans to determine whole brain atrophy (BPF). PRVEP was evaluated for P100 latency, amplitude, and waveform morphology. Two summary scores were created: for Score A, abnormal latencies, morphologies, and amplitudes of each individual eye were added; for Score B, abnormal latencies, morphologies, and amplitude ratio between eyes was determined. Sixteen patients in this group also had PRVEP at the time they enrolled in the clinical trial, eight years previously. RESULTS: At the follow-up exam, over 75% of patients had abnormal PVEP parameters while visual acuity (VA) was abnormal only in 59%. Increased PRVEP latency over the eight-year period correlated with deterioration assessed by EDSS (P = 0.006), BPF (P = 0.0001), and MSFC (P = 0.0041). Score A was significantly correlated with EDSS, BPF, CLA, cognitive function, and quality of life assessed with the Sickness Impact profile. No correlation was seen with the MSFC. CONCLUSIONS: The results indicate that PRVEP measures MS-related pathology, and can provide not only diagnostic but also prognostic information during evaluation of MS patients.

Evoked Potentials, Visual↗

PubMed2001

Personality disorder in multiple sclerosis correlates with cognitive impairment.

Previous studies of personality change in multiple sclerosis (MS) relied on brief, nonstandardized assessments or tests that are confounded with symptoms of acute psychiatric disorder. Objectives of the present study were to evaluate character change in MS by using comprehensive trait measures of personality and to determine if there is an association between personality change and cognitive dysfunction. Thirty-four MS patients and 14 healthy volunteers were studied. All underwent comprehensive neurologic and neuropsychologic evaluation. Personality assessments included both self and informant reports on the Hogan Empathy Scale and the NEO Personality Inventory. Abnormalities were found among MS patients indicating elevated neuroticism and reduction in empathy, agreeableness, and conscientiousness. Large patient/informant discrepancies were observed in the MS but not the control group. Three neuropsychological tests emphasizing executive control predicted the presence of these abnormalities; this association suggests a neurogenic, frontal lobe syndrome.

Adult↗

PubMed2000

Neuropsychological counseling improves social behavior in cognitively-impaired multiple sclerosis patients.

We studied the effectiveness of a newly-developed cognitive-behavioral intervention in 15 patients with marked cognitive impairment and behavior disorder. The design was a single-blind test of a neuropsychological intervention, with pre- and post-treatment assessments of personality and social behavior. MS patients underwent neurological examination and neuropsychological testing at baseline. The patients were then randomly assigned to neuropsychological counseling or standard, non-specific supportive psychotherapy. The active 12-week treatment emphasized enhancement of insight through education, social skills training, and behavior modification. All patients were re-examined within 2 weeks of the termination of treatment. Neuropsychological technicians were blind to treatment condition. Both groups showed evidence of cognitive impairment and personality/behavior disorder prior to treatment and were well matched on demographic, disability, and cognitive measures. Patients who underwent neuropsychological counseling showed significant positive response on measures of social behavior (e.g. excessive ego-centric speech) compared to those who underwent standard counseling. We conclude that these data support the use of non-pharmacological, neuropsychological counseling in patients with acquired, MS-associated behavior disorder.

Adult↗

PubMed1999

Flow cytometric analysis of in vitro proinflammatory cytokine secretion in peripheral blood from multiple sclerosis patients.

The cytokines, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2) are important endogenous proinflammatory proteins and have been linked to disease activity in multiple sclerosis. In this study, we use flow cytometric methodology to compare the secretion of IFN-gamma, IL-2, and TNF-alpha from peripheral blood-derived T cells of multiple sclerosis patients to the secretion in healthy controls. The percentages of IFN-gamma, IL-2, and TNF-alpha secreting cells are not significantly different between multiple sclerosis patients and controls. However, the TNF-alpha secreting CD3 cell percentage is correlated with the IFN-gamma and IL-2 secreting CD3 cell percentages in multiple sclerosis patients. In the controls, only the TNF-alpha secreting CD3 cell percentage is correlated with IFN-gamma. These findings show that correlated secretion of cytokines occurs in multiple sclerosis and suggest that concerted intercytokine interactions may play an important role in the disease.

Adolescent↗

PubMed1996

Interrater agreement of computed tomography infarct measurement.

To determine the reliability of infarct measurements on hard-copy computed tomography (CT) images the in vivo (IV) infarct volumes of 20 CT-detected infarcts were estimated and divided into four size groups with 5 infarcts in each group: Group A, less than 0.5 ml; Group B, 0.5 to 5.0 ml; Group C, 5 to 50 ml; and Group D, more than 50 ml. Seventeen infarcts were measured once and 3 infarcts three times to the nearest 0.5 mm by each of two neurologists and two neuroradiologists using a ruler on hard-copy CT images. The longest diameter (designated AP), the greatest diameter at right angles to AP (designated LAT), and the number of slices showing the infarct were recorded and multiplied by the hard-copy minification factor to give IV dimensions. Volume (VOL) was calculated according to a previously published method. Interrater intraclass correlation coefficients for all infarcts combined were 0.98 (AP), 0.91 (LAT), and 0.97 (VOL). Using all raters' measurements for any single infarct, the difference between the largest and the smallest measurement of AP and LAT was smallest (< 6 mm IV) for Group A and largest (< 31 mm IV) for Group D. This difference was largest relative to the dimension being measured in Groups A and B, where it reached 101% of the mean of the four raters' measurements for the AP dimension being measured in Group B, and 70% of the dimension being measured in Group A. With all raters' measurements for any single infarct, the difference between the largest and smallest measurement of VOL was smallest (< 0.5 ml) for Group A and largest (< 260 ml) for Group D. This difference was largest relative to the mean volume of the infarct being measured in Group B, where it reached 153% of the mean of the four raters' measurements for VOL and reached 115% of the mean of the four raters' measurements for VOL in Group A. The authors conclude that infarcts can be measured on hard-copy images with good interrater agreement. When infarcts with a volume smaller than 5 ml are measured, differences between raters' measurements may exceed the size of the dimensions being measured.

Cerebral Infarction↗

PubMed1995

Pontine ischemic rarefaction.

To investigate apparently asymptomatic, bilateral symmetrical predominantly pontine hyperintensities (PHI) on magnetic resonance imaging (MRI) scans in elderly patients, we examined the pons histopathologically in two brains of elderly hypertensives with PHI, and in three without PHI, on postmortem MRI scans. We also reviewed 85 serial in vivo MRI scans of patients over 60 and compared scan findings, vascular risk factors, and clinical symptoms between patients with PHI and a control group. A subcortical arteriosclerotic encephalopathy (SAE)-like pathology was present in the pons in only the two autopsy brains with PHI and corresponded with the location of PHI on the postmortem MRI scans and with the most frequent sites of PHI on in vivo scans. SAE also involved the hemispheric white matter in one of the autopsy brains. Five of 16 (31%) patients with, and 4 of 69 (6%) without, PHI on in vivo MRI scans had marked periventricular hyperintensity (PVHI) compatible with SAE (p = 0.01). We conclude that an SAE-like pathology may be seen in the pons in elderly hypertensives and this pathology is probably the cause of PHI seen on MRI scans of patients over 60 years of age.

Aged↗

PubMed1994

Pentoxifylline and meclofenamic acid treatment reduces clinical manifestations in a murine model of AIDS.

C57/BL/6 mice infected with LP-BM5 MuLV virus developed an AIDS-like disease (MAIDS) with splenomegaly, leukopenia, thrombocytopenia, anemia, decreased numbers of helper/inducer and suppressor/cytotoxic T-cells and decreased production of interferon alpha. We have shown previously that HIV-associated Kaposi's sarcoma tissue contains high levels of prostaglandin E2 (PgE2), and this inhibits interferon synthesis through a cAMP-dependent second-messenger process. In this study we treated groups of MAIDS-infected mice with combinations of pentoxifylline, an agent which increases cAMP and inhibits phosphodiesterases, and sodium meclofenamic acid, a PgE2 inhibitor. Treated mice showed: 1) significantly higher total leukocyte and platelet counts, 2) higher total L3T4+ (helper/inducer) and Lyt-2+ (suppressor-cytotoxic) T-cell population. Pathologic examination also showed significantly less hepatosplenomegaly and lymphadenopathy in animals treated with pentoxifylline and meclofenamic acid. Partly, PgE2-induced suppression of interferon alpha production may mediate expression of retrovirus infection in this murine model of AIDS.

Acquired Immunodeficiency Syndrome↗