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Relapsing-remitting multiple sclerosis and whole-brain N-acetylaspartate measurement: evidence for different clinical cohorts initial observations

Gonen, Oded; Moriarty, David M; Li, Belinda S Y; Babb, James S; He, Juan; Listerud, John; Jacobs, Dina; Markowitz, Clyde E; Grossman, Robert I
PURPOSE: To quantify the rate of concentration decline of neuronal marker N-acetylaspartate (NAA) in the entire brain of patients with relapsing-remitting multiple sclerosis (MS) in relation to healthy age-matched control subjects. MATERIALS AND METHODS: Whole-brain NAA (WBNAA) concentration was quantified in 49 patients with relapsing-remitting MS by using magnetic resonance (MR) imaging and proton MR spectroscopy. It was statistically analyzed by using Spearman rank correlation coefficients to test the intragroup relationship between WBNAA and Expanded Disability Status Scale (EDSS) score and Mann-Whitney analyses to test for differences between subgroups' EDSS scores versus previously published WBNAA values for healthy subjects, disease duration, and age. RESULTS: Analyses indicated three subgroups of WBNAA dynamics: Ten patients' conditions were 'stable,' exhibiting an insignificant change of about 0% (0.02/14.37) per year of clinically definite disease duration (P =.54); 27 patients showed 'moderate' decline, -2.8% (-0.34/12.18) per year (P <.01); and 12 patients experienced 'rapid' decline, -27.9% (-3.39/12.14) per year (P <.01). No correlation was found between WBNAA deficit, EDSS score, and age. CONCLUSION: Ascertaining an individual's NAA concentration dynamics might enable early forecast of disease course, reflect disease severity and thus influence treatment decisions, and improve clinical trial efficiency by allowing selection of candidates on the basis of WBNAA dynamics in addition to clinical status
PMID: 12355014
ISSN: 0033-8419
CID: 33784

Magnetization transfer ratio histogram analysis of normal-appearing gray matter and normal-appearing white matter in multiple sclerosis

Ge, Yulin; Grossman, Robert I; Udupa, Jayaram K; Babb, James S; Mannon, Lois J; McGowan, Joseph C
PURPOSE: The purpose of this work was to determine the extent of disease and disease severity in the conventional MR normal-appearing gray matter (NAGM) and white matter (NAWM) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) utilizing quantitative magnetization transfer ratio (MTR) histogram analysis. METHOD: Twenty-seven patients with MS (16 RR, 11 SP) and 16 healthy control subjects were studied. MTR was calculated in the totally segmented GM and WM without T2 lesions in each group. RESULTS: Each of the RR and SP MS patient groups had significantly smaller MTR histogram mean values in NAGM and NAWM than the healthy subjects (p </= 0.0015). SP MS patients had a significantly lower first quartile and MTR histogram peak height for NAGM only (p </= 0.004) when compared with both RR MS patients and healthy subjects. The T2 lesion load had a modest negative correlation with MTR values in both RR and SP MS, but only in NAGM. CONCLUSION: Separate analysis of GM and WM MTR histograms may allow better detection of subtle damage and better understanding of the natural history of MS disease and ultimately the response to therapeutics
PMID: 11801905
ISSN: 0363-8715
CID: 39727

Development of a posterior cerebral artery aneurysm subsequent to occlusion of the contralateral internal carotid artery for giant cavernous aneurysm [Case Report]

Wolf, R L; Imbesi, S G; Galetta, S L; Hurst, R W; Sinson, G P; Grossman, R I
We report a case of a patient who developed a left posterior cerebral artery aneurysm 5 years after balloon occlusion of the right internal carotid artery for a giant cavernous aneurysm. The location of the new aneurysm was outside of the primary collateral pathways to the contralateral, proximally occluded, anterior circulation, illustrating the complexity of hemodynamic factors contributing to the development of intracranial saccular aneurysms. The appearance of an aneurysm in this setting supports the hypothesis that degenerative factors and hemodynamic stresses are important in the etiology of intracranial aneurysms
PMID: 12012132
ISSN: 0028-3940
CID: 43949

Age-related total gray matter and white matter changes in normal adult brain. Part II: quantitative magnetization transfer ratio histogram analysis

Ge, Yulin; Grossman, Robert I; Babb, James S; Rabin, Marcie L; Mannon, Lois J; Kolson, Dennis L
BACKGROUND AND PURPOSE: The magnetization transfer ratio (MTR) is a sensitive and quantitative identifier of underlying structural changes in the brain. We quantitatively evaluated age- and sex-related MTR changes in global gray matter (GM) and global white matter (WM) in healthy adults. METHODS: Fifty-two healthy volunteers (21 men, 31 women) aged 20-86 years underwent dual-echo fast spin-echo and magnetization transfer imaging performed with and then without a saturation pulse. GM and WM were distinguished by using a computer-assisted semiautomated segmentation technique. MTR histograms were generated for each segmented tissue in each subject and compared among age and sex groups. RESULTS: The mean, median, first quartile, and peak height of the MTR histogram were significantly lower in the older group (> or =50 years) than those in the younger group (<50 years) for both GM and WM. The age dependency of these values can be expressed in a quadratic fashion over the entire span of adulthood. The MTRs started to decline only after the age of approximately 40 years in both tissues. No statistically significant differences in MTR histogram measurements between the sexes were observed. CONCLUSION: The different MTR values for both GM and WM in the two age groups suggest that notable microscopic changes occur in GM and WM with advancing age, yet no significant sex-related variations in MTR measurements were found in these neurologically healthy adults. Such normative data based on the inherent contrast in MTRs are essential in studies of specific disorders of aging, and they may have implications for our understanding of the gross structural changes in both GM and WM in the aging brain
PMID: 12223374
ISSN: 0195-6108
CID: 43787

Correlation between percentage of brain parenchymal volume and neurocognitive performance in HIV-infected patients

Patel, Sohil H; Kolson, Dennis L; Glosser, Guila; Matozzo, Isabel; Ge, Yulin; Babb, James S; Mannon, Lois J; Grossman, Robert I
BACKGROUND AND PURPOSE: This study was designed to determine whether neuropsychological function in HIV-infected persons is correlated with loss of brain volume (as measured by percentage of brain parenchymal volume [PBV]). We hypothesized that whole-brain parenchymal volume might correlate with neuropsychologic performance, even before overt clinical dysfunction is apparent. METHODS: A computer-assisted segmentation technique with thin section MR imaging was used for 15 patients with HIV infection (seven symptomatic, eight asymptomatic) and for five HIV-negative control participants to quantify whole brain and CSF volumes. To determine the degree of brain atrophy, the PBV relative to that of intracranial content was calculated. Neuropsychological performance was assessed by using a standard battery of eight tests (NPZ-8 test battery). RESULTS: HIV-infected patients had significantly lower NPZ-8 scores (t[18] = 2.26, P <.05) and lower PBV (t[18] = 1.79, P <.01) than those of healthy control participants. With the Spearman rank order correlation coefficients, data analyzed for all 20 study participants (15 HIV-infected patients and five noninfected control participants) showed a significant (r = -0.50, P <.05) negative correlation between PBV and NPZ-8 test battery score. In addition, there was a significant negative correlation between subtest score of motor impairment and PBV (r = -0.69, P <.01) and between AIDS dementia complex score (r = -0.64) and PBV (P <.01). CONCLUSION: These correlations suggest that quantitation of PBV may offer an objective, easily acquired surrogate predictor of neuropsychological impairment and clinically apparent cognitive/motor dysfunction among HIV-infected persons
PMID: 11950642
ISSN: 0195-6108
CID: 43789

Whole brain N-acetylaspartate concentrations are reduced in patients at presentation with clinically isolated syndromes suggestive of MS [Meeting Abstract]

Filippi, M; Bozzali, M; Gambini, A; Rovaris, M; Falini, A; Ghezzi, A; Martinelli, V; Scotti, G; Gonen, O; Grossman, RI; Comi, G
ISI:000174875900386
ISSN: 0028-3878
CID: 105109

Evidence for early widespread gray matter involvement in relapsing remitting multiple sclerosis [Meeting Abstract]

Inglese, M; Ge, YL; Filippi, M; Falini, A; Grossman, RI; Gonen, O
ISI:000177900500099
ISSN: 0364-5134
CID: 105107

Whole-brain N-acetylaspartate in relapsing-remitting multiple sclerosis? Evidence for different clinical cohorts [Meeting Abstract]

Gonen, O; Li, BSY; Babb, JS; He, J; Jacobs, D; Markowitz, CE; Grossman, RI
ISI:000177900500105
ISSN: 0364-5134
CID: 105108

Proton magnetic resonance spectroscopic characteristics of hypo- and iso-intense T1 lesions versus normal-appearing white matter in relapsing-remitting multiple sclerosis patients [Meeting Abstract]

He, J; Li, BS; Regal, J; Babb, JS; Grossman, RI; Gonen, O
ISI:000178825102169
ISSN: 0033-8419
CID: 105106

Proton magnetic resonance spectroscopy evidence for early gray matter involvement in relapsing remitting MS [Meeting Abstract]

Inglese, M; Ge, Y; Filippi, M; Falini, A; Grossman, RI; Gonen, O
ISI:000178825101247
ISSN: 0033-8419
CID: 105103