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R I Grossman

Publications and source records attributed to R I Grossman.

At least 19 recordsLinked to original sources

Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: quantitative MR assessment.

OBJECTIVE: To evaluate the efficacy of glatiramer acetate (GA, Copaxone; Teva Pharmaceutical Industries, Ltd., Petah Tiqva, Israel) by MRI-based measures in patients with relapsing-remitting (RR) MS. METHODS: Twenty-seven patients with clinically definite RR-MS were treated with either 20 mg of GA by daily subcutaneous self-injection (n = 14) or placebo (n = 13) for approximately 24 months. Axial dual-echo fast-spin-echo T2-weighted images and T1-weighted images before and after gadolinium (Gd) were acquired at 1.5 tesla and transferred into an image processing computer system. The main outcome measures were the number of Gd-enhanced T1 and T2 lesions and their volume as well as brain parenchyma volume. RESULTS: The values of age, disease duration, Expanded Disability Status Scale (EDSS) score, the number of T1- and T2-weighted lesions, and their volume were similar between GA- and placebo-receiving groups at the entry of this study. There was a decrease in the number of T1-enhanced lesions (p = 0.03) and a significant percent annual decrease of their volume in GA recipients compared with those of placebo recipients. There were no significant differences between changes in the two groups in the number of T2 lesions and their volume. The loss of brain tissue was significantly smaller in the GA group compared with that of the placebo group. CONCLUSIONS: These results show that GA treatment may decrease both lesion inflammation and the rate of brain atrophy in RR-MS.

Adult

Assessment of spinal cord damage in MS using MRI.

Spinal cord imaging is important in the evaluation of patients with MS. There are several techniques available which provide satisfactory images of lesions in the spinal cord. Conventional measures used in the assessment of damage to the spinal cord include quantification of: (1) high intensity on T2 weighted images; (2) spinal cord enhancement; and (3) spinal cord atrophy. Although not presently implemented, newer methods including magnetization transfer, diffusion, and proton spectroscopy offer the potential for more specific classification of spinal cord MS. Assessment of spinal cord damage using MR still remains behind the development of brain methodology and represents both a challenge and an opportunity.

Humans

The contribution of MRI in the differential diagnosis of posterior fossa damage.

In multiple sclerosis patients, magnetic resonance imaging (MRI) frequently detects lesions in the brain stem and cerebellum. However various pathologies that have a predelection to occur in posterior fossa parenchyma may share similar features with inflammatory-demyelinating lesions. In this paper, we review the contribution of MRI to the differential diagnosis of posterior fossa pathology. Vascular lesions due to chronic hypoperfusion and arteriolosclerosis or occlusion of the main supplying arteries of the posterior circulation leading to acute infarction frequently produce characteristic pontine or cerebellar lesions. Neoplastic disease, in particular pontine gliomas in younger patients may have similar MRI features and may be difficult to distinguish from inflammatory-demyelinating lesions. Central pontine myelinolysis usually occurs in severely ill patients but the pontine MRI changes have an overlapping profile with inflammatory demyelination. Diffuse axonal injury of the midbrain and brainstem after head trauma and atrophy of posterior fossa structures in degenerative diseases may appear similar on MRI to tissue changes also seen frequently in MS. Analysis of the MRI appearance and clinical information is most often useful to narrow the fairly long list of differential diagnoses of posterior fossa pathology.

Brain Diseases

Assessment of posterior fossa damage in MS using MRI.

In multiple sclerosis (MS), brain stem and cerebellum are frequent sites of damage in clinically isolated syndromes at presentation and it is likely that lesions located in such structures can have an important impact on the development of disability in the definite forms of the disease. In patients presented with isolated brain stem syndromes, the symptomatic lesion was often not detected by magnetic resonance (MR) imaging. But patients with asymptomatic infratentorial lesions progressed to clinically definite MS in 65% of cases. Infratentorial lesions are included in various MR criteria designed to assist in the differential diagnosis of MS lesions from incidental lesions, to differentiate MS from subcortical encephalopathic arteriopathy. The preferred MR sequence to visualize infratentorial lesions is the fast spin echo sequence. It is preferred to conventional spin echo and fast fluid attenuated inversion recovery sequences because of its relatively short acquisition time and good sensitivity. The correlation between disability and infratentorial lesion load on T2 weighted sequences is controversial. However, it was recently shown that the correlations between clinical measures and T1 lesion load, histogram magnetization transfer ratio and peak positions, and infratentorial volume measurements are strong. These findings suggest that one of the major factors in the development of disability in patients with MS is the pathological damage in clinically eloquent sites such as the brain stem and cerebellum.

Brain Diseases

The contribution of magnetic resonance imaging in the differential diagnosis of the damage of the cerebral hemispheres.

There are presently many magnetic resonance (MR) measures that can aid the assessment of damage to the brain. The conventional measures include T2 lesion volume, T1 enhanced lesion volume, and brain atrophy. Newer methodologies include magnetization transfer measures and proton spectroscopy. These methods have the potential for improving the specificity of MR with respect to the underlying pathology. MR spectroscopy offers the ability to quantitate the component of axonal loss in multiple sclerosis. MR techniques can be implemented to assess the effectiveness of treatment algorithms.

Blood-Brain Barrier

Total brain N-acetylaspartate: a new measure of disease load in MS.

OBJECTIVE: To quantitate the extent of neuronal cell loss in MS via the whole brain's N-acetylaspartate (NAA) concentration (WBNAA). METHODS: Because NAA is assumed to be present only in neuronal cell bodies and their axons, we measured WBNAA as a marker for viable neurons in 12 patients (9 women and 3 men, 26 to 53 years of age) suffering from relapsing-remitting (RR) MS for at least 5 years and compared them with 13 age- and sex-matched normal controls. Total brain NAA was determined with proton MR spectroscopy, and WBNAA was obtained by dividing it by the total brain volume, calculated from high resolution MRI. RESULTS: The WBNAA of the RR MS patients was lower than their matched controls (p<0.005). This difference was greater among older than younger subjects. The linear prediction equations of WBNAA with age indicate a faster, x10, decline in the patients, approximately 0.8% per year of age (p = 0.022). CONCLUSION: The age-dependent decrease of whole brain N-acetylaspartate (WBNAA) in the patients suggests that progressive neuronal cell loss is a cardinal feature of this disease. WBNAA offers a quick, highly reproducible measure of disease progression and may be an important marker of treatment efficacy in MS as well as other neurodegenerative diseases.

Adolescent

Magnetization transfer imaging of traumatic brain injury.

Magnetization transfer imaging (MTI) has been shown to be sensitive for the detection of white matter abnormalities in entities such as multiple sclerosis, progressive multifocal leukoencephalopathy, and wallerian degeneration. Our hypothesis was that MTI would detect traumatic white matter abnormalities (TWMA) and provide information additional to that obtainable with routine spin- and gradient-echo imaging. We hypothesized that the presence of TWMA defined by MTI would correlate with outcome following TBI. Twenty-eight victims of head trauma and 15 normal controls underwent magnetic resonance imaging including MTI. Magnetization transfer ratios (MTR) were calculated for areas of shearing injury and for normal-appearing white matter (NAWM) in locations frequently subject to diffuse axonal injury. Abnormal MTRs were detected in NAWM in eight patients. All eight had persistent neurologic deficits, including cognitive deficits, aphasia, and extremity weakness. Seven of the 28 patients had no abnormal findings on neurologic exam at discharge, transfer, or follow-up. None of these patients had an abnormal MTR in NAWM. In the remaining 13 patients, who had persistent neurologic deficits, no regions of abnormal MTR were detected in NAWM. MTI is a sensitive method for the detection of TWMA. Detection of abnormal MTR in NAWM that is prone to axonal injury may predict a poor patient outcome. The presence of normal MTR in NAWM in these areas does not necessarily confer a good outcome, however.

Adult

Brain atrophy in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis: longitudinal quantitative analysis.

PURPOSE: To determine annual rates of volumetric changes in the whole-brain parenchyma of patients with relapsing-remitting and secondary progressive multiple sclerosis (MS) and test the hypothesis that these changes correlate with clinical disability. MATERIALS AND METHODS: A computer-assisted segmentation technique with thin-section magnetic resonance (MR) imaging was used in 36 patients with MS (27 relapsing-remitting, nine secondary progressive) and in 20 control subjects to quantify brain and cerebrospinal fluid volumes. To determine the degree of brain atrophy, the percentage brain parenchyma volume (PBV) relative to that of intracranial contents was calculated. RESULTS: At the beginning of the study, the PBV was smaller in the MS group than in the control group (P = .007); brain parenchyma volumes were similar. The median rate of brain volume loss was 17.3 mL per year in patients with relapsing-remitting MS and 23.6 mL per year in those with secondary progressive MS. There was a negative correlation between brain atrophy and Expanded Disability Status Scale (EDSS) score in patients with secondary progressive MS (r = -0.69, P = .004) and no correlation in patients with relapsing-remitting MS. T2 lesion volume did not correlate with brain atrophy in either group. CONCLUSION: The correlation between brain atrophy and EDSS score was better in patients with secondary progressive MS than in those with relapsing-remitting MS.

Adult

Brain imaging.

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Brain Diseases

Evidence for preganglionic pupillary involvement in superficial siderosis.

A 36-year-old man presented with spinal myoclonus, ataxia, hearing loss, and unilateral pupillary dilation. MRI demonstrated hemosiderin deposition along the superficial surfaces of the brain, brainstem, cerebellum, and spine. The pupillary changes were localized to the preganglionic oculomotor nerve. In contrast to vasculopathic oculomotor nerve palsies, superficial siderosis may cause selective involvement of the superficially located pupillary fibers.

Adult

The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis.

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.

Brain

Diffuse axonal pathology detected with magnetization transfer imaging following brain injury in the pig.

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.

Animals

Differences between relapsing-remitting and chronic progressive multiple sclerosis as determined with quantitative MR imaging.

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.

Adult

Relapsing-remitting multiple sclerosis: longitudinal analysis of MR images--lack of correlation between changes in T2 lesion volume and clinical findings.

PURPOSE: To determine the relationship between T2 lesion volume and either disability measurements or change in T2 lesion volume over time in multiple sclerosis (MS). MATERIALS AND METHODS: Eighteen patients (age range, 26-53 years) with clinically proved relapsing-remitting MS were examined every 6 months for over 2 years. Three-millimeter-thick contiguous images of the whole brain were obtained. T2 lesion volume was calculated with a highly reproducible volumetric computer method. RESULTS: A substantial annual increase in T2 lesion volume, with a median annual increase of approximately 8%, was demonstrated. However, there was no significant correlation between absolute T2 lesion volume and either the absolute expanded disability status scale (EDSS) grade (P = .32) or the absolute ambulation index (AI) (P = .20). In addition, no significant correlation between change in T2 lesion volume and change in EDSS grade (P = .42) or AI (P = .37) was found. There was no significant correlation between T2 lesion volume and duration of disease (P = .08). CONCLUSION: There is no significant correlation between T2 lesion volume and standardized disability measurements despite a substantial increase in T2 lesion volume over time. Patients have an increase in total T2 lesion volume in the brain regardless of their clinical status or disability measurements. T2 lesion volumes as outcomes in therapeutic clinical trials on MS should be viewed as secondary outcomes rather than as surrogate markers of clinical responses.

Adult

Familial multiple sclerosis: volumetric assessment in clinically symptomatic and asymptomatic individuals.

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.

Adult

A double-blind, placebo-controlled trial of extracorporeal photopheresis in chronic progressive multiple sclerosis.

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.

Adult

Application of magnetization transfer imaging to multiple sclerosis.

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.

Animals