Faculty Bibliography

On October 9-11, 2003, the third meeting of the White Matter Study Group of the International Society for Magnetic Resonance in Medicine was held in Venice, Italy. This article is the report of the meeting on how to use MRI in the diagnostic workup of multiple sclerosis (MS) and allied white matter disorders, and to define the nature and the extent of MS pathology in vivo. Both of these steps are central to the design of future treatment strategies aimed at limiting the functional consequences of the most disabling aspects of this disease

BACKGROUND AND PURPOSE: Recent animal and human studies have shown an increased frequency of enlarged, high-convexity Virchow-Robin spaces (VRS) in several neurologic diseases, suggesting their role as neuroradiologic markers of inflammatory changes. The aim of this study was to determine the prevalence of high-convexity dilated VRS in mild traumatic brain injury (TBI). METHODS: T2-weighted, T1-weighted, fluid-attenuated inversion recovery, and T2*-weighted gradient-echo brain MR images were acquired in 24 patients with TBI (10 women, 14 men; mean age, 33.6; range, 18.1-50.8 years) and 17 age- and sex-matched healthy control subjects (nine women, eight men; mean age, 32.8; range, 18.4-47.8 years). The mean interval after TBI was 3.6 days (range, 1-9 days) in 15 patients and 3.7 years (range, 0.6-13.4 years) in nine patients. Axial T2-weighted images were used to identify dilated VRS and to measure CSF volume; T1-weighted images were used to measure brain volume. Dilated VRS were identified as punctuate areas with CSF-like signal intensity in the high-convexity white matter. RESULTS: Mean (+/- standard deviation) number of VRS was significantly higher in patients (7.1 +/- 4.6) than in controls (2.4 +/- 2.9, P < .0003). In controls, VRS were associated with age (R = 0.69, P < .001) whereas in patients, they neither correlated with brain and CSF volumes nor with age and the elapsed time from injury. CONCLUSION: Our results suggest that the increased number of dilated VRS is a radiologic marker of mild head injury that is readily detectable on T2-weighted images. Because their number does not vary with time from injury, VRS probably reflect early and permanent brain changes

PURPOSE: To quantify, with three-dimensional proton magnetic resonance (MR) spectroscopy, metabolic characteristics of normal-appearing white matter and nonenhancing lesions in patients with relapsing-remitting multiple sclerosis (MS). MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained. Nine patients with relapsing-remitting MS (six women, three men) and nine age-matched control subjects (seven women, two men) were studied with T1- and T2-weighted MR imaging and three-dimensional proton MR spectroscopy at spatial resolution less than a cubic centimeter. Absolute N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were obtained from 171 voxels: 66 from lesions on T2-weighted MR images (43 hypointense and 23 isointense on T1-weighted MR images), 31 from normal-appearing white matter, and 74 from analogous normal white matter regions on images in control subjects. RESULTS: Mean NAA level in hypointense lesions (5.30 mmol/L +/- 2.27 [standard deviation]) was significantly lower (P < or = .05) than that in isointense lesions (7.82 mmol/L +/- 2.28), normal-appearing white matter (7.37 mmol/L +/- 1.71), and normal white matter in control subjects (8.89 mmol/L +/- 1.54). Cho (1.79 mmol/L +/- 0.65) and Cr (5.64 mmol/L +/- 1.50) levels in isointense lesions were indistinguishable from those in normal-appearing white matter (1.74 mmol/L +/- 0.46 and 4.99 mmol/L +/- 0.97, respectively) but were significantly higher (Cho, 20%; Cr, 24%) than those in normal white matter in control subjects (1.44 mmol/L +/- 0.40 and 4.30 mmol/L +/- 1.32, respectively). NAA, Cho, and Cr levels in normal-appearing white matter were significantly different than those in normal white matter in control subjects (NAA, 20% lower; Cho, 14% higher; and Cr, 17% higher). CONCLUSION: Abnormal metabolic activity persists in all MS tissue types. Increased Cr and Cho levels suggest (a) ongoing gliosis and attempted remyelination in isointense lesions on T1-weighted MR images and (b) membrane turnover (de- and remyelination), in addition to increased cellularity (gliosis, inflammation) in normal-appearing white matter

The metabolic changes in the deep gray matter (GM) nuclei, thalamus, and basal ganglia of patients with relapsing-remitting multiple sclerosis were investigated with quantitative, multivoxel, three-dimensional proton MR spectroscopy. This technique facilitated the study of several bilateral structures in a single session at sub-cubic centimeter spatial resolution. Compared with 9 matched control subjects, the deep GM nuclei of 11 patients showed 7% lower N-acetylaspartate and 14% higher choline levels (p = 0.02 for both)

BACKGROUND: About a quarter of familial Mediterranean fever (FMF) patients are partially or totally resistant to colchicine. A previous observation reported that acute attacks may be shortened by administration of interferon alpha (IFN). OBJECTIVE: We designed a double-blind, placebo-controlled trial to test our initial observations of a beneficial response with IFN in FMF attacks. METHODS: We treated 34 acute abdominal attacks with IFN 5 million IU or placebo sc in the early phase of the attack. Leucocytes, thrombocytes, the erythrocyte sedimentation rate, fibrinogen, C-reactive protein (CRP), serum amyloid A protein (SAA), haptoglobin, transferrin, IL-1beta and TNF-alpha were measured at hours 0, 6, 12, 24 and 48. RESULTS: The median time to recovery in those treated with IFN and placebo was not significantly different, while the leucocytosis and high levels of fibrinogen were significantly more prolonged in placebo-treated patients. CRP and SAA were extremely elevated and peaked at 24h, remaining less marked in the IFN-treated patients but the difference was not statistically significant. Observations regarding the other parameters were unremarkable. CONCLUSIONS: Although there were some clues indicating a depressed inflammatory response with IFN, we could not demonstrate a definitive effect of this agent in this double-blind trial. The drug may suppress the acute inflammation of FMF only if administered at the earliest phase. CRP and SAA may be more sensitive indicators of an attack than ESR or fibrinogen.

Multiple sclerosis (MS) has traditionally been viewed as an inflammatory demyelinating white matter (WM) disease of the central nervous system. However, recent pathology and MRI studies have shown lesions in the gray matter (GM) as well. To ascertain the extent of GM involvement, we obtained with nonlocalizing proton MR spectroscopy the concentration of N-acetylaspartate (NAA), a metabolite found almost exclusively in neuronal cells, T2-lesion loads, and GM and WM fractions in the entire brain of 71 relapsing-remitting (RR) MS patients (51 women, 20 men, 25-55 years old) and 41 healthy controls (27 women, 14 men, 23-55 years old). The average whole-brain NAA (WBNAA) difference between the patients and the controls was -2.9 mM (-22%, P < 0.0001); range: +1.2 to -7.8 mM (+8% to -63%). The patients' median T2 lesion volume was 5.5 (range: 0.140-28) cm(3). GM and WM comprised 50.4 +/- 3.8% and 30.4 +/- 5.0% (mean +/- standard deviation), respectively, of the total brain volume in the patients; 53.8 +/- 3.7% and 35.4 +/- 4.7% in the controls. Because WM and GM constitute approximately 40% and 60% of the brain parenchyma, respectively, and the NAA concentration in the former is 2/3 of the latter, WBNAA loss greater than 40% x 2/3 = 27% cannot be explained in terms of WM (axonal) pathology alone and must include widespread GM (neuronal) deficits. Therefore, the concept of MS, even at its earlier stages, as a WM disease might need to be reexamined

Global brain atrophy estimated using MRI and whole brain N-acetylaspartate (WBNAA) concentration measured with proton MR spectroscopy were obtained in 42 patients with relapsing-remitting multiple sclerosis and 41 matched control subjects. Patients exhibited cross-sectional atrophy (0.5%; p = 0.033) and WBNAA decline (1.8%/y; p = 0.005) vs disease duration. The 3.6-fold rate disparity between the two processes suggests that neuronal/axonal dysfunction (N-acetylaspartate decline) precedes parenchyma loss, not its consequence (i.e., is an earlier, more sensitive specific metric of the ongoing disease activity)