Henrik Kahr Mathiesen

Magnetic resonance imaging at 3.0 tesla detects more lesions in acute optic neuritis than at 1.5 tesla

Objective:We sought to assess whether magnetic resonance imaging (MRI) at 3.0 T detects more brain lesions in acute optic neuritis (ON) than MRI at 1.5 T. Materials and Methods:Twenty-eight patients with acute ON were scanned at both field-strengths using fast-fluid-attenuated inversion recovery (FLAIR), proton density and T2-weighted turbo spin echo, and T1-weighted spin echo after contrast. In addition, magnetization-prepared rapid acquisition gradient echo (MPRAGE) was obtained after contrast at 3.0 T. Lesion number and volumes were assessed by an observer blind to patient identity and field strength. Results:Scans at 3.0 T showed a significantly increase in number of lesions detected on FLAIR images (P = 0.002) relative to scanning at 1.5 T. MPRAGE proved to be suitable for detecting enhancing lesions in ON. Conclusion:The MRI protocol at 3.0 T was more sensitive to hyperintense brain lesions in ON than the standard MRI protocol at 1.5 T.

Multi-slice echo-planar spectroscopic MR imaging provides both global and local metabolite measures in multiple sclerosis

MR spectroscopy (MRS) provides information about neuronal loss or dysfunction by measuring decreases in N‐acetyl aspartate (NAA), a metabolite widely believed to be a marker of neuronal viability. In multiple sclerosis (MS), whole‐brain NAA (WBNAA) has been suggested as a marker of disease progression and treatment efficacy in treatment trials, and the ability to measure NAA loss in specific brain regions early in the evolution of this disease may have prognostic value. Most spectroscopic studies to date have been limited to single voxels or nonlocalized measurements of WBNAA only, and longitudinal studies have often been hampered by standardization and reproducibility problems. Multi‐slice echo‐planar spectroscopic imaging (EPSI) is presented as a promising alternative to single‐voxel or nonlocalized spectroscopy for obtaining global metabolite estimates in MS. In the same session, measurements of metabolites in specific brain areas chosen after image acquisition (e.g., normal‐appearing white matter (NAWM), gray matter (GM), and lesions) can be obtained. The identification and exclusion of regions that are inadequate for spectroscopic evaluation in global assessments can significantly improve quality and reproducibility, as demonstrated by a low within‐subject variance in healthy controls. The reproducibility of the technique makes it a promising tool for future longitudinal spectroscopic studies of MS. Magn Reson Med 53:750–759, 2005.

The relationship between MRI and PET changes and cognitive disturbances in MS

Cognitive dysfunction in multiple sclerosis (MS) is present in approximately 50% of the patients. Only moderate correlations have been found between cognitive dysfunction and T(2) lesion load, black holes or atrophy. Cognitive dysfunction in MS is probably related to the overall disease burden of the brain including abnormalities in normal appearing white matter (NAWM) and cortical grey matter, which is undetected with conventional magnetic resonance imaging (MRI). Hence, imaging techniques that embrace such abnormalities are needed to achieve better correlation with cognitive dysfunction. MR spectroscopy (MRS) performed with multi-slice echo planar spectroscopic imaging (EPSI) and PET measurements of brain metabolism as the cortical cerebral metabolic rate of glucose are imaging methods that are able to provide information on axonal loss or dysfunction in both MS lesions and in NAWM and cortical grey matter. Measurements of global NAA using multi-slice EPSI is a new promising method for measurement of the global neuron capacity and can be repeated with only little discomfort and without any risk for the patient.

Cerebral metabolism, magnetic resonance spectroscopy and cognitive dysfunction in early multiple sclerosis: an exploratory study

Abstract Objectives: Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal deterioration, and several studies have shown reductions in MS. Furthermore, both PET and MRS reductions correlate with cognitive dysfunction in MS. Our aim was to determine if changes in cortical CMRglc in early MS correlate with NAA/Cr measurements of neuronal deterioration, as well as cognitive dysfunction and neurological disability. Methods: We studied 20 recently diagnosed, clinically definite, relapsing–remitting MS patients. Global and cortical CMRglc was estimated using PET with 18-F-deoxyglucose and NAA/Cr ratio was measured using multislice echo-planar spectroscopic imaging. All subjects were neuro-psychologically tested and a cognitive dysfunction factor (CDF) was calculated. Results: Cortical CMRglc correlated with cortical NAA/Cr (r = 0·45; P<0·05), but there were no correlation between CMRglc and other NAA/Cr measurements, conventional magnetic resonance imaging measurements, or CDF. Stepwise regression analysis showed association between cortical NAA/Cr and CMRglc of the left ventrolateral prefrontal cortex (P<0·001), left putamen (P = 0·010), and left hippocampus (P = 0·011). Furthermore, CDF was related to CMRglc in the left cerebellum (P = 0·001) and the left caudate nucleus (P = 0·013). The results of the statistical analysis should be regarded as exploratory, since we did not correct for multiple comparisons. Conclusion: Our findings suggest that reductions in cortical CMRglc are associated with reductions in cortical NAA/Cr in early MS. These changes affect cortical and subcortical neural circuits of importance to cognitive function.

Prolonged-release fampridine improves walking in a proportion of patients with multiple sclerosis

Fampridine is indicated to improve walking in adult multiple sclerosis (MS) patients. Indications vary between countries and the prescribing neurologist should be aware of the labeling and indication in his own country. The prolonged-release formulation of 4-aminopyridine has reduced the risk of seizure to a level near the intrinsic MS risk, and the risk can be further minimized if it emphasized that patients should not exceed the recommended dose of 10 mg twice a day, should not catch up on missed doses and should not divide, crush or chew tablets. It is imperative to check the renal function before and during treatment and make sure the patient does not get concomitant medications affecting the renal elimination. The use of fampridine is considered safe, and the side effects are often mild and acceptable. Approximately one-third of MS patients treated with fampridine will experience an improvement of their walking speed above 20% on the timed 25-foot walk test (T25FW), which is considered to be clinically relevant.

Cortical N-acetyl aspartate is a predictor of long-term clinical disability in multiple sclerosis.

Abstract Objective: To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in early relapsing-remitting multiple sclerosis (RRMS). Methods: Sixteen patients with newly diagnosed RRMS were studied by serial MRI and MR spectroscopic imaging (MRSI) once every 6 months for 24 months. Clinical examinations, including the expanded disability status scale (EDSS), were performed at baseline, month 24, and at year 7. Results: Baseline cortical NAA/Cr correlated inversely with EDSS at month 24 (r  =  −0·61, P < 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P < 0·05). Baseline cortical NAA/Cr also correlated inversely with EDSS at the 7-year follow-up (r  =  −0·56, P < 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P < 0·05). Baseline brain parenchymal fraction (BPF) correlated inversely with EDSS at month 24 (r  =  −0·61, P < 0·05), but not with EDSS at year 7. Discussion: Cortical NAA/Cr in early RRMS correlated with clinical disability after 2 and 7 years and may be used as a predictor of long-term disease outcome.