Faculty Bibliography

A genetic basis for clustering of multiple sclerosis (MS) cases, based on studies of MS families, has been proposed for decades. Few reports provide detailed neurological as well as neuroradiological findings on these patients. We report total T2-weighted intracranial lesion volumes on members of three familial MS cohorts: a mother and father with conjugal MS with one affected son and a neurologically normal son and daughter, one pair of monozygotic twin sisters with MS, and a female sibling pair with MS. We hypothesized that asymptomatic siblings in a family with two affected parents and another affected child might demonstrate clinically silent T2-weighted lesions; and that monozygotic twins with MS are more likely to express similar T2-weighted lesion volumes than non-twin sibling pairs. We found clinically silent lesions in unaffected children of the symptomatic parent couple, with a significant difference in total T2 lesion volume between these unaffected siblings and their parents, as well as their affected brother. In our other sibling pairs, T2 lesion volumes were similar between the twins and significantly different in the non-twin pair, despite similar levels of clinical functioning as determined by EDSS scoring. These results suggest that foci of demyelination might be expected in clinically normal offspring of parents with MS, possibly reflecting a genetic predisposition to subsequent development of MS

This study was designed to evaluate with magnetization transfer imaging (MTI) and conventional magnetic resonance (MR) imaging the manifestation of diffuse axonal injury (DAI) in an animal model of injury via nonimpact coronal plane rotational acceleration. A second objective was to investigate the diagnostic use of quantitative MTR imaging based on statistical parameters in a single subject, as opposed to grouped analysis. Seven mini-swine were subjected to brain trauma known to produce isolated DAI and to MR imaging at two time points. Following sacrifice, the brains were harvested for histopathologic examination. Magnetization transfer ratio (MTR) maps were generated for double-blinded comparison of regions with abnormal MTR values and regions with documented DAI. Positive and negative predictive values for MTR detection of DAI were 67 and 56%, respectively, and in acute studies alone, 89 and 61%. Gains in sensitivity over conventional imaging for detection of DAI were demonstrated

PURPOSE: To investigate the cross-sectional relationships among multiple quantitative brain magnetic resonance (MR) imaging measurements in patients with relapsing-remitting versus chronic progressive multiple sclerosis (MS). MATERIALS AND METHODS: Thirty-eight patients with MS (relapsing-remitting, 26, chronic progressive, 12) were examined. Lesion volume on T2-weighted MR images, contrast material-enhancing lesion volume, percentage of brain parenchymal volume (brain volume/[brain volume + cerebrospinal fluid volume), and magnetization transfer ratio histogram peak height for the whole brain were calculated. RESULTS: Significant negative correlation was noted between volume on T2-weighted images and magnetization transfer ratio histogram peak height for both the relapsing-remitting and chronic progressive groups (P < .001 for both). A positive correlation was demonstrated for lesion volume on T2-weighted images and enhancing lesion volume in the relapsing-remitting group (P < .01) but not in the chronic progressive group. Negative correlations were demonstrated for enhancing lesion volume and magnetization transfer ratio histogram peak height (P = .02), for Expanded Disability Status Scale score and magnetization transfer histogram peak height (P = .02), and for Expanded Disability Status Scale score and percentage of brain parenchymal volume in the relapsing-remitting group (P = .004) but not in the chronic progressive group. CONCLUSION: The cross-sectional relationships among multiple quantitative brain MR imaging measurements are different between relapsing-remitting and chronic progressive MS

Extracorporeal photopheresis is a safe therapy for cutaneous T-cell lymphoma and may have efficacy in certain autoimmune disorders. We performed a randomized, double-blinded, placebo-controlled trial of monthly photopheresis therapy in 16 patients with clinically definite multiple sclerosis (MS). All patients had progressed during the preceding year with entry Expanded Disability Status Scale (EDSS) scores between 3.0 and 7.0. Patients received photopheresis or sham therapy for 1 year and were followed for an additional 6 to 12 months. Patients were clinically evaluated by three disability scales: (1) EDSS; (2) Ambulation index and (3) Scripp's quantitative neurologic assessment. No serious side effects occurred in either group. There were no differences between the photopheresis and sham therapy groups by the disability measures. Additionally, there were no differences in progression of MRI plaque burden or evoked potential latencies. In this limited study, photopheresis was found to be safe but did not significantly alter the course of chronic progressive MS

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a demyelinating disease most often associated with progressive physical impairment; however, its effects are noted to extend beyond physical disability. Our purpose was to determine the relationship between T2 lesion volume and neurocognitive and physical disability in relapsing-remitting multiple sclerosis. METHODS: We studied a cohort of 19 patients with relapsing-remitting MS. Of this group, there were 15 women and four men from varying socioeconomic backgrounds. This volunteer sample was selected from a larger group of 53 patients with MS in our longitudinal MS study because they had been untreated with any beta-interferon medications, had been followed for at least 12 months, and had a clinical status of relapsing-remitting MS. RESULTS: Of 12 neurocognitive parameters tested, two correlated significantly with lesion loads. The correlation of the Symbol-Digit Modalities test, which analyzes information-processing speed, was significant (P = .0204). The correlation of the fifth trial of the Rey Auditory Verbal Learning test, which tests verbal long-term memory, was also significant (P = .0348). None of the other 10 neurocognitive examinations, however, showed a significant correlation with total lesion volume (Paced Auditory Serial Addition test-1.6, P = .7381; Paced Auditory Serial Addition test-2.0, P = .4180; Controlled Oral Word Association test, P = .8906; Category Fluency test, P = .4423; Bells test, P = .9097; Rey Auditory Verbal Learning test-delay, P = .9843, Rey Auditory Verbal Learning test-recognition, P = .7467; Word Span test, P = .4939; Road Map test, P = 0.4939). The lesion load also did not correlate with the physical disability scales as rated according to the Expanded Disability Status Scale (P = .68) or Ambulation Index (P = .95). CONCLUSION: Our results indicate that T2 lesion volume does not seem to be a robust surrogate marker of neuropsychological impairment in patients with MS. We think that global measurements of parameters that are more specific to the disease process may offer more precise correlation with cognitive dysfunction and other disability parameters

BACKGROUND AND PURPOSE: Magnetization transfer imaging provides information about the structural integrity of macromolecular substances, such as myelin. Our objective was to use this imaging technique and contour plotting to characterize and to define the extent of white matter lesions in multiple sclerosis and traumatic brain injury. METHODS: Magnetization transfer imaging was performed of 30 multiple sclerosis plaques and 10 traumatic white matter lesions. Magnetization transfer ratios (MTRs) were calculated for the lesions, for the normal- or abnormal-appearing surrounding white matter, and for remote normal-appearing white matter. MTR contour plots were constructed about these lesions. RESULTS: The contour plot appearance of MS plaques differed from that of traumatic white matter lesions. There was a gradual increase in MTR values at points at increasing distances from the center of the MS plaques; this was true for those lesions with and without surrounding T2 signal abnormality (halos). In contrast, there was an abrupt transition in MTR values between traumatic lesions and normal-appearing surrounding white matter. Additionally, the size of the MTR abnormality exceeded the size of the T2 signal abnormality for the MS plaques. CONCLUSION: MTR contour plots permit characterization and border definition of white matter lesions. Analysis of the contour plots suggests that MS is a centrifugal process with the lowest MTR within the center of the lesion. In contrast, traumatic white matter injuries are discrete lesions with abrupt transitions between the abnormal lesion and normal brain

MRI is very sensitive in showing MS lesions throughout the CNS. Using MRI for diagnostic purposes, however useful, is a complex issue because of limited specificity of findings and a variety of options as to when, how, and which patients to examine. Comparability of data and a common view regarding the impact of MRI are needed. Following a review of the typical appearance and pattern of MS lesions including differential diagnostic considerations, we suggest economic MRI examination protocols for the brain and spine. Recommendations for referral to MRI consider the need to avoid misdiagnosis and the probability of detecting findings of diagnostic relevance. We also suggest MRI classes of evidence for MS to determine the diagnostic weight of findings and their incorporation into the clinical evaluation. These proposals should help to optimize and standardize the use of MRI in the diagnosis of MS

The evolution of our understanding of multiple sclerosis (MS) has been facilitated by the technique of magnetization transfer, which has the ability to detect and categorize lesions that are both visible and occult by conventional magnetic resonance (MR) imaging. The methodology can be applied to individual MS lesions as well as to the global brain disease. The results of studies performed in centers throughout the world reveal multiple correlations with clinical parameters as well as greater specificity and sensitivity to lesion than other presently available MR measures

OBJECTIVE: To review studies on the assessment of correlations between magnetization transfer ratio (MTR) histogram analysis and measures of clinical and neuropsychological function. BACKGROUND: Since its recent introduction, MTR histogram analysis has attracted attention in the field of multiple sclerosis (MS). METHODS: In this paper, studies are discussed that deal with MTR histogram analysis. The principles of MTR, application of MTR methodology as regional and volumetric MTR analysis, clinical and neuropsychological correlates, and potential use of MTR histogram analysis as an estimate of cerebral lesion load in MS are discussed respectively. RESULTS: In several preliminary studies, it has been shown that in MS patients, measures derived from MTR histograms correlate with measures of clinical and particularly neuropsychological function. CONCLUSION: MTR histogram analysis is a promising method to estimate cerebral lesion load in MS patients. Before it can be routinely used as an outcome measure in clinical trials, a number of questions about this technique have to be addressed