Biomedical subjects

Jop P Mostert

Publications and source records attributed to Jop P Mostert.

7 recordsLinked to original sources

PubMed2006

Fluoxetine increases cerebral white matter NAA/Cr ratio in patients with multiple sclerosis.

Axonal degeneration in multiple sclerosis (MS) may be caused by mitochondrial dysfunction and is associated with decreased levels of N-acetylaspartate (NAA) as measured with 1H-magnetic resonance spectroscopy (MRS). Fluoxetine stimulates astrocytic glycogenolysis, which serves as an energy source for axons. Eleven patients with MS received fluoxetine orally 20 mg a day during the first week, and 40 mg a day during the second week. The mean NAA/Creatine ratio in cerebral white matter of the MS patients increased from 1.77 at baseline to 1.84 at the end of the second week (p=0.007). These findings show evidence for a reversible axonal dysfunction in patients with MS and provide a rationale for investigating whether fluoxetine has neuroprotective effects in MS.

Administration, Oral↗

PubMed2005

Relationships between brain water content and diffusion tensor imaging parameters (apparent diffusion coefficient and fractional anisotropy) in multiple sclerosis.

Fifteen multiple sclerosis patients were examined by diffusion tensor imaging (DTI) to determine fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in a superventricular volume of interest of 8 x 8 x 2 cm(3) containing gray matter (GM) and white matter (WM) tissue. Point resolved spectroscopy 2D-chemical shift imaging of the same volume was performed without water suppression. The water contents and DTI parameters in 64 voxels of 2 cm(3) were compared. The water content was increased in patients compared with controls (GM: 244+/-21 vs. 194+/-10 a.u.; WM: 245+/-32 vs. 190+/-11 a.u.), FA decreased (GM: 0.226+/-0.038 vs. 0.270+/-0.020; WM: 0.337+/-0.044 vs. 0.402+/-0.011) and ADC increased [GM: 1134+/-203 vs. 899+/-28 (x10(-6) mm(2)/s); WM: 901+/-138 vs. 751+/-17 (x10(-6) mm(2)/s)]. Correlations of water content with FA and ADC in WM were strong (r=-0.68, P<0.02; r=0.75; P<0.01, respectively); those in GM were weaker (r=-0.50, P<0.05; r=0.45, P<0.1, respectively). Likewise, FA and ADC were more strongly correlated in WM (r=-0.88; P<0.00001) than in GM (r=-0.69, P<0.01). The demonstrated relationship between DTI parameters and water content in multiple sclerosis patients suggests a potential for therapy monitoring in normal-appearing brain tissue.

Anisotropy↗

PubMed2005

(1)H MR spectroscopy of the brain in multiple sclerosis subtypes with analysis of the metabolite concentrations in gray and white matter: initial findings.

Many MR spectroscopy (MRS) studies of multiple sclerosis (MS) have focussed on metabolism in normal-appearing white matter (NAWM) and in white matter lesions (WML). In this study, eight patients suffering from primary or secondary progressive MS (PPMS/SPMS) and seven patients with relapsing/remitting MS (RRMS) were examined by (1)H-MRS to assess metabolite levels in gray matter (GM) as well. (1)H-MRS chemical-shift imaging of a cerebral volume of interest of 8x8x2 cm(3) above the lateral ventricles revealed differences between the metabolite concentrations in the three groups varying from almost significant [NAWM, choline (cho); P=0.0547] to highly significant [GM, N-acetylaspartate (NAA); P=0.0003]. In PPMS/SPMS patients, the decreases in choline, creatine (Cr) and N-acetylaspartate compared with six healthy controls were significant in GM and to a lesser extent, in NAWM. No significant differences in metabolite concentrations were found between RRMS and controls. In WML, all metabolites were reduced compared with white matter in controls (Cho: P=0.0020; Cr and NAA: P<0.0001, both). In conclusion, the concentrations of Cho, Cr and NAA are reduced in PPMS/SPMS patients, especially in GM and in WML. Despite contrary observations in previous studies, increases in the concentrations of Cr and/or Cho were not observed.

Adult↗

PubMed2005

Analysis of the human brain in primary progressive multiple sclerosis with mapping of the spatial distributions using 1H MR spectroscopy and diffusion tensor imaging.

Primary progressive multiple sclerosis (ppMS; n=4) patients and controls (n=4) were examined by 1H magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in order to map choline (Cho), creatine and N-acetylaspartate (NAA), the fractional anisotropy (FA) and the apparent diffusion constant (ADC). After chemical shift imaging (point-resolved spectroscopy, repetition time/echo time 1,500 ms/135 ms) of a supraventricular volume of interest of 8x8x2 cm3 (64 voxels) MRS peak areas were matched to the results of DTI for the corresponding volume elements. Mean FA and NAA values were reduced in the ppMS patients (P<0.01, both) and the ADC increased (P<0.02). The spatial distribution of NAA showed strong correlation to ADC in both ppMS patients and controls (r =-0.74 and r= -0.70; P<0.00001, both), and weaker correlations to FA (r=0.49 and r=0.41; P<0.00001, all). FA and ADC also correlated significantly with Cho in patients and controls (P<0.00001, all). The relationship of Cho and NAA to the ADC and the FA and thus to the content of neuronal structures suggests that these metabolite signals essentially originate from axons (NAA) and the myelin sheath (Cho). This is of interest in view of previous reports in which Cho increases were associated with demyelination and the subsequent breakdown of neurons.

Adult↗

PubMed2005

Serum uric acid levels and leukocyte nitric oxide production in multiple sclerosis patients outside relapses.

BACKGROUND: A number of studies found that patients with multiple sclerosis (MS) have low serum levels of uric acid. It is unclear whether this represents a primary deficit or secondary effect. Uric acid is a scavenger of peroxynitrite, which is the product of nitric oxide (NO) and superoxide. Because peripheral blood leukocyte NO production and NO metabolites in serum are raised in MS patients, associations might be expected between serum uric acid levels and peripheral NO production. METHODS: Serum levels of uric acid and NO production by peripheral blood leukocytes were measured in 60 patients with MS without a relapse in the past 3 months, and 30 age- and sex-matched healthy controls. Uric acid was determined with the uricase PAP method, and NO production was assayed by measuring nitrite concentration in supernatants of lysed leukocytes. RESULTS: Serum uric acid levels were not different between MS patients and controls. Compared to controls, patients with MS had significantly higher peripheral blood leukocytes nitrite concentrations (p<0.001). There was no correlation between leukocyte nitrite concentration and serum uric acid levels. CONCLUSIONS: Our findings suggest that in MS patients there is no primary deficit in serum uric acid. NO production by peripheral blood leukocytes is increased, but there is no association with serum uric acid levels.

Adult↗

PubMed2004

1H Magnetic resonance spectroscopy of the internal capsule in human brain: a feasibility study to detect lactate following contralateral motor activity.

Animal experiments suggest that astrocytic glycogen may act as an energy source for axons especially during heightened activity. In this model astrocytic glycogen breaks down to lactate that is shuttled to axons where it is metabolized oxidatively to generate ATP. The aim of this study was to investigate whether (1)H-magnetic resonance spectroscopy could be used to detect a rise in lactate levels in human white matter during enhanced axonal activation. Six healthy volunteers (four women and two men; age range 21-38 years) participated in the study. We were unable to detect any significant MR spectral change, i.e. neither in the peak areas of inositol, choline, creatine, glutamate and N-acetylaspartate nor in the lactate level, in the contralateral posterior limb of the internal capsule during intense motor activation of the hand (four successive episodes of squeezing a soft ball for 7 min followed by 7 min rest). Possible explanations are that the technique is not sensitive enough to detect a small rise in lactate, or lactate turnover is too fast to be detected, or that another monocarboxylate different from lactate may be involved in axonal energy metabolism.

Adenosine Triphosphate↗

PubMed2004

Visual stimulation, 1H MR spectroscopy and fMRI of the human visual pathways.

The purpose was to assess changes in lactate content and other brain metabolites under visual stimulation in optical chiasm, optic radiations and occipital cortex using multiple voxel MR spectroscopy (MRS). 1H chemical shift imaging (CSI) examinations of transverse planes centered to include the above structures were performed in four subjects at an echo time of 135 ms. Functional MRI (fMRI) was used to confirm the presence of activity in the visual cortex during the visual stimulation. Spectral maps of optical chiasm were of poor quality due to field disturbances caused by nearby large blood vessels and/or eye movements. The optic radiations and the occipital lobe did not show any significant MR spectral change upon visual stimulation, i.e., the peak areas of inositol, choline, creatine, glutamate and N-acetylaspartate were not affected. Reproducible lactate signals were not observed. fMRI confirmed the presence of strong activations in stimulated visual cortex. Prolonged visual stimulation did not cause significant changes in MR spectra. Any signal observed near the 1.33 ppm resonance frequency of the lactate methyl-group was artifactual, originating from lipid signals from outside the volume of interest (VOI). Previous claims about changes in lactate levels in the visual cortex upon visual stimulation may have been based on such erroneous observations.

Adult↗