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K Schmierer

Publications and source records attributed to K Schmierer.

12 recordsLinked to original sources

A review of structural magnetic resonance neuroimaging.

Magnetic resonance imaging (MRI) is often divided into structural MRI and functional MRI (fMRI). The former is a widely used imaging technique in research as well as in clinical practice. This review describes the more important developments in structural MRI in recent years, including high resolution imaging, T2 relaxation measurement, T2*-weighted imaging, T1 relaxation measurement, magnetisation transfer imaging, and diffusion imaging. The principles underlying these techniques, as well as their use in research and in clinical practice, will be discussed.

Brain↗

High field MRI correlates of myelin content and axonal density in multiple sclerosis--a post-mortem study of the spinal cord.

Different MRI techniques are used to investigate multiple sclerosis (MS) in vivo. The pathological specificity of these techniques is poorly understood, in particular their relationship to demyelination and axonal loss. The aim of this study was to evaluate the pathological substrate of high field MRI in post-mortem (PM) spinal cord (SC) of patients with MS. MRI was performed in PMSCs of four MS patients and a healthy subject on a 7 Tesla machine. Quantitative MRI maps (PD; T2; T1; magnetization transfer ratio, MTR; diffusion weighted imaging) were obtained. After scanning, the myelin content and the axonal density of the specimens were evaluated neuropathologically using quantitative techniques. Myelin content and axonal density correlated strongly with MTR, T1, PD, and diffusion anisotropy, but only moderately with T2 and weakly with the apparent diffusion coefficient. Quantitative MR measures provide a promising tool to evaluate components of MS pathology that are clinically meaningful. Further studies are warranted to investigate the potential of new quantitative MR measures to enable a distinction between axonal loss and demyelination and between demyelinated and remyelinated lesions.

Aged↗

Stereotactic co-registration of magnetic resonance imaging and histopathology in post-mortem multiple sclerosis brain.

A number of groups have examined the pathological substrate of signal changes on magnetic resonance imaging (MRI) in post-mortem (PM) brain of patients with multiple sclerosis (MS). Such studies will benefit from using a standardized method to reliably co-register regions of interest on MRI and tissue specimens. We investigated the usefulness of a stereotactic navigation system for this purpose. We also addressed the sensitivity of different standard MRI sequences with regard to lesion conspicuity in PM MS brain. Post-mortem brains of eight patients with MS were studied. Formalin-fixed coronal slices were placed in the head frame of a stereotactic system. Proton density-, T2-weighted and fast fluid-attenuated inversion recovery (FLAIR) scans were obtained and visually matched with scans that had been previously obtained on the same, but fresh, specimens. Guided by the stereotactic target points, the dissection of the fixed specimens was performed. After processing the blocks for embedding in paraffin, sections were stained with haematoxylin-eosin and Luxol fast blue. T2-weighted MRI of fixed brain revealed 24 areas suspected to be MS lesions, all of which were confirmed histologically. Three of these lesions were not visible on macroscopic inspection. There were 14 additional hyperintensities on T2-weighted or FLAIR MRI of the fresh specimens, five of which did not correlate to MS lesions histologically. Stereotactic navigation is a useful approach to co-register MRI and histopathology in PM brain of MS patients and may improve the precision of MRI-guided sampling of tissue specimens. Standard T2-weighted MRI appeared to be the single most useful approach for lesion detection in fresh and fixed specimens.

Brain↗

Correlates of disability in multiple sclerosis detected by transcranial magnetic stimulation.

OBJECTIVE: To study the usefulness of corticospinally mediated excitatory responses and transcallosal inhibition (TI) elicited by transcranial magnetic stimulation (TMS) as a surrogate marker of disability in patients with different courses of MS. METHODS: Focal TMS of the motor cortex was performed in 118 patients with MS (96 with relapsing-remitting, 19 with primary progressive, and three with secondary progressive disease) who had an Expanded Disability Status Scale (EDSS) score between 0 and 6.5 and in 35 normal subjects. Central motor latencies (CML) and TI (onset latency, duration) were investigated. The Spearman rank correlation was used for statistical analysis. RESULTS: TMS disclosed prolonged CML in 52.5% and abnormal TI in 61% of the patients. In all patients the EDSS correlated with the frequency of abnormal TI (r = 0.58, p < 0.01) and abnormal CML (r = 0.51, p < 0.01). In patients with primary progressive MS (EDSS 1.5 to 6.5) the frequency of TI abnormalities correlated with EDSS (r = 0.65, p < 0.01) whereas CML did not. Delayed corticospinal responses in hand muscles always led to abnormal TI. CONCLUSIONS: The combination of central motor latencies and transcallosal inhibition evoked by transcranial magnetic stimulation yields objective data to estimate disease progression in MS as assessed by the EDSS.

Adolescent↗

Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.

Chorea↗

Partial synergy of bisindolylmaleimide with apoptotic stimulus in antigen-specific T cells--implications for multiple sclerosis.

In multiple sclerosis (MS), induction of T cell apoptosis constitutes a promising therapeutic strategy. Recently, bisindolylmaleimide has been shown to be an effective treatment of experimental autoimmune encephalomyelitis, presumably due to enhancement of CD95-mediated T cell apoptosis. Therefore, we studied the effects of bisindolylmaleimide on human (auto)antigen-specific T cells. We observed a synergistic effect of bisindolylmaleimide with apoptotic stimulus assessed via caspase activity and annexin V-binding, but no potentiation of DNA fragmentation or cell death. Thus, bisindolylmaleimide might be useful for modulating T cell apoptosis, yet more potent substances have to be generated re-establishing immunological control over auto-reactive T cells.

Annexin A5↗

Conduction deficits of callosal fibres in early multiple sclerosis.

OBJECTIVE: To study the diagnostic usefulness of transcallosal inhibition (TI) elicited by transcranial magnetic stimulation (TMS) in detecting central conduction deficits in early multiple sclerosis. Corticospinally mediated excitatory responses evoked by TMS are accepted as a sensitive diagnostic tool in multiple sclerosis. Recently, TI evoked by TMS has been introduced as a new paradigm to test the function of callosal fibres interconnecting both hand associated motor cortices. METHODS: Focal TMS of the motor cortex was performed in 50 patients with early relapsing-remitting multiple sclerosis. Corticospinally mediated (central motor latencies, amplitudes) and transcallosally mediated (onset latency and duration of TI) stimulation effects were investigated. RESULTS: TMS disclosed abnormalities of corticospinally mediated responses in 62% and of TI in 80% of the patients. CONCLUSION: The assessment of TI allows the discovery of lesions within the periventricular white matter that were not accessible by neurophysiological techniques before. This new paradigm increases the sensitivity of TMS with which to detect central conduction deficits in early multiple sclerosis.

Adolescent↗

Atypical stiff-person syndrome with spinal MRI findings, amphiphysin autoantibodies, and immunosuppression.

In an atypical case of stiff-person syndrome (SPS), spinal T2-weighted MRI revealed a hyperintense lesion extending from C2 to C7 that corresponded with the clinical symptoms and signs. CSF showed lymphocytic pleocytosis and oligoclonal bands. Amphiphysin autoantibodies were detected in serum and CSF; however, unlike other reported cases, no malignancy occurred during a 3-year observation period. Methylprednisolone and cyclophosphamide pulse therapy led to a marked reduction of symptoms.

Anti-Inflammatory Agents↗

Assessment of normal flow velocity in basal cerebral veins. A transcranial doppler ultrasound study.

BACKGROUND AND PURPOSE: Transcranial Doppler ultrasound has not yet been applied systematically to the analysis of the venous system and cerebrovenous disorders. Assessment of the intracranial venous system, however, would contribute to the understanding of cerebral hemodynamics and thus allow new possibilities for clinical application of the Doppler technique. Therefore, we demonstrated the validity of the transcranial Doppler technique in analyzing the basal cerebral veins. METHODS: Venous transcranial Doppler ultrasound was performed with a range-gated 2-MHz transducer in 60 healthy volunteers in patients without central nervous disorders ranging in age from 10 to 71 years (mean +/- SD, 41.9 +/- 15 years). RESULTS: A venous signal away from the probe and adjacent to the posterior cerebral artery, considered to correspond to the basal vein of Rosenthal, was found in all subjects on at least one side. Mean blood flow velocity ranged from 4 to 17 cm/s (mean +/- SD, 10.1 +/- 2.3 cm/s). Analysis for age dependency revealed a trend of decreasing values with increasing age, exclusively caused by a significant reduction of velocity in men aged 40 years or older. No significant intraindividual side-to-side differences were found. A venous signal away from the probe and paralleling the middle cerebral artery, interpreted as corresponding to the deep middle cerebral vein, was found in 21.7% of the subjects with similar velocities. CONCLUSIONS: We have shown that transcranial Doppler methods can also be used for evaluation of the basal cerebral veins in both sexes, in differing age groups, and without major difficulty. The cerebral basal veins could be identified on the basis of their anatomic relation to specific arteries.

Adolescent↗