Whole-brain diffusion MR histograms differ between MS subtypes

OBJECTIVE: To determine whether quantitative whole-brain MR diffusion histograms in patients with MS differ from those of normal control subjects. BACKGROUND: MRI detects macroscopic cerebral lesions in MS, but the white matter lesion burden on MRI correlates imperfectly to clinical disability. Previous reports have further suggested abnormalities in white matter of MS patients with no visible lesions on conventional MRI. METHODS: A total of 25 subjects (13 with MS [9 relapsing-remitting, 4 secondary progressive] and 12 healthy control subjects) underwent diffusion-weighted echoplanar MRI encompassing the entire brain. The average apparent diffusion coefficient (ADCave, or diffusion trace) was calculated on a pixel-by-pixel basis after segmentation of intracranial space from calvarium and extracranial soft tissues. Whole-brain ADCave histograms were calculated and plotted for statistical comparison. RESULTS: Mean whole-brain MR ADCave in MS patients was elevated and histograms were shifted to higher values compared with normal control subjects. Mean whole-brain ADCave of secondary progressive patients was shifted to higher values compared with relapsing-remitting patients. Whole-brain ADCave histograms of relapsing-remitting patients showed no significant difference from normal control subjects. CONCLUSION: Whole-brain MR diffusion histograms may quantitate overall cerebral lesion load in patients with MS and may be able to discern differences between clinical subgroups.     

Motor evoked potential: A reliable and objective measure to document the functional consequences of multiple sclerosis? Relation to disability and MRI

OBJECTIVE: In an attempt to analyze whether MEP can serve as a valid measure for evaluating neurological dysfunction in multiple sclerosis (MS), we related MEP to clinical and MRI measures. METHODS: Transcranial magnetic stimulation was applied in 52 MS patients to determine the central motor conduction time (CMCT) to the extremities. We calculated Z-scores for each CMCT (Zcmct) corrected for height. All patients underwent two clinical measurements and a MRI scan, of which T1 and T2 brain lesion volumes, brain volume, spinal cord volume and the number of T2 spinal cord lesions were derived. RESULTS: The clinical measurements correlated significantly with various Zcmct (Spearman correlation coefficients ranged from 0.29 to 0.53; p<0.05). The number of spinal cord lesions, brain T1 and T2 lesion volume and spinal cord volume correlated with various Zcmct (r=0.31-0.53; p<0.05). Linear regression analysis revealed that the clinical measurements were explained by Zcmct left leg and T1 lesion volume (adjusted R(2)=0.38). For one clinical measurement the number of spinal cord lesions was also included (adjusted R(2)=0.43). CONCLUSION: We found a relation between MEP, brain and spinal cord MRI measures, and two clinical measures. Moreover, a model for explaining disability in MS revealed that MEP measures provide information in addition to MRI measures. SIGNIFICANCE: This study suggests that MEP is a measure that might adequately reflect pathology and neurological dysfunction in MS.     

Quality of life and its relationship to brain lesions and atrophy on magnetic resonance images in 60 patients with multiple sclerosis

CONTEXT: Disease-modifying multiple sclerosis (MS) therapeutic trials continue to rely on physical disability as the main clinical outcome measure, while the impact of treatment on quality of life (QOL) is poorly understood. Weak correlations exist between physical disability and the disease burden as shown using conventional brain magnetic resonance imaging (MRI), indicating poor sensitivities of these measures alone in defining the clinical course of MS. OBJECTIVES: To investigate the impact of MS on QOL; to determine whether impaired QOL in patients with MS was related to any regional brain abnormalities assessed using conventional MRI sequences; and to determine if the severity of MS as assessed by the Expanded Disability Status Scale (EDSS) and clinical course was associated with worsening QOL. DESIGN, SETTING, AND PATIENTS: Prospective, cross-sectional study of 60 consecutive patients with MS treated in a community-based, university-affiliated MS clinic. MAIN OUTCOME MEASURES: Assessments of QOL using the Multiple Sclerosis Quality of Life-54 Instrument were correlated with the scores of the EDSS, clinical course, and findings on brain MRI. RESULTS: Quality of life was significantly impaired in patients with MS and was worse in patients with secondary-progressive MS compared with those with relapsing-remitting MS. Brain MRI lesions and atrophy were associated with impaired QOL with respect to sexual dysfunction, overall mental health, and limitations due to physical and emotional dysfunction. Correlations between MRI results and QOL assessments were much stronger for hypointense lesions and atrophy on T1-weighted images than for hyperintense lesions on T2-weighted images and were insignificant for lesions on contrast-enhanced images. Higher EDSS scores were associated with impairments in most physical and mental health QOL scales but were weakly correlated with cognitive and sexual dysfunction. CONCLUSIONS: In patients with MS, QOL is impaired and is associated with increasing neurologic disability. Quality of life assessments are related in part to brain lesions and atrophy shown on MRI. Assessments of QOL provide unique information not readily evaluated by EDSS and may be useful as secondary clinical outcome measures. Arch Neurol. 2000;57:1485-1491     

Classification of patients with a clinically isolated syndrome based on signs and symptoms is supported by magnetic resonance imaging results

BACKGROUND: Recently, a clinical classification system was described to determine whether symptoms and signs of patients presenting with a first episode suggestive of multiple sclerosis (MS) indicate the presence of monofocal or multifocal disease. OBJECTIVES: To evaluate the value of this new classification system by comparing the results with those of simultaneously obtained magnetic resonance imaging (MRI) scans. METHODS: The 487 patients, randomised in the BENEFIT study, were centrally assessed using the new system and classified as monofocal or multifocal, based on clinical information by two neurologists masked for the MRI results. MRI analyses were performed by expert readers masked for the clinical classification. RESULTS: Patients classified as multifocal had more T2 hyperintense (median: 21 versus 15.5) and more T1 hypo-intense lesions (median: 2 versus 1) than those classified as monofocal. Patients classified at the local site as having evidence of a single clinical lesion, but reclassified centrally as having a clinical multifocal central nervous system presentation, had more T2 lesions than monofocal patients. In addition, patients with a multifocal presentation more often fulfilled the MRI criteria for dissemination in space, as incorporated in the International Panel (IP) diagnostic criteria for MS. CONCLUSION: These data provide justification for the recently proposed clinical classification system to be used in patients who present with a first episode suggestive of MS, in that ;multifocal', based on symptoms and signs, is associated with more lesions on MRI.     

Clinical and magnetic resonance imaging in optic neuritis

We found 23 of 48 patients (48%) with isolated monosymptomatic optic neuritis (ON) to have 1 to several brain lesions by MRI. All the brain lesions were clinically silent and had characteristics consistent with multiple sclerosis (MS). During 4 years of follow-up, 9 patients (19%) developed definite MS on clinical grounds. Six of the converting patients had abnormal MRIs; the other 3 had MRIs that were normal both initially (when they had ON only) and when repeated after they had developed MS. The other 17 patients with abnormal MRIs have not developed symptoms or signs of MS during follow-up. Thus, an abnormal MRI does not auger development of clinical MS within a mean of 4 years, nor does a normal MRI protect against development of disseminated disease. It is not prudent to give a patient with isolated monosymptomatic ON the diagnosis of MS (probable or definite) because of an abnormal MRI (with or without other laboratory abnormalities).     

Multisequence MRI in clinically isolated syndromes and the early development of MS.

OBJECTIVE: To apply multisequence MRI techniques to patients with clinically isolated syndromes, to document the pattern and frequency of abnormalities at baseline and early follow-up, and to determine their predictive values for the early development of clinical MS. BACKGROUND: Disseminated lesions on T2-weighted brain MRI confer an increased risk of progression to clinically definite MS. Newer MRI techniques increase detection of lesions in both brain and spinal cord, and clarify further their pathology. The predictive value of such techniques for the development of clinical MS needs to be defined. METHODS: Brain and spinal MRI were performed on 60 patients after their first demyelinating event. A total of 50 patients were followed for 1 year, and 49 underwent repeat brain MRI 3 months after the initial scan. RESULTS: At baseline, 73% of patients had lesions on T2-weighted fast spin-echo (FSE) brain images and 42% had asymptomatic spinal cord lesions. Fast fluid-attenuated inversion-recovery brain did not improve detection of brain lesions. Repeat brain MRI demonstrated new FSE lesions in 43% of patients. After 1 year, 26% of patients developed MS. The MRI features that provided the best combination of sensitivity and specificity for the development of MS were the presence of new FSE lesions at follow-up and enhancing lesions at baseline. The frequency of developing clinical MS was higher for those with both brain and spinal cord lesions at baseline (48%) than brain lesions alone (18%). CONCLUSIONS: The combination of baseline MRI abnormalities and new lesions at follow-up, indicating dissemination in space and time, was associated with a high sensitivity and specificity for the early development of clinical MS. These data suggest a potential role for new diagnostic criteria for MS based on early MRI activity. Such criteria may be useful in selecting patients for therapeutic trials at this early clinical stage.     

Defining interferon beta response status in multiple sclerosis patients

IFN-beta is effective in reducing relapses and magnetic resonance imaging (MRI) lesions in multiple sclerosis (MS). It is assumed that individual therapeutic responses vary, but methods to identify IFN-beta responsiveness have not been validated. Our objective was to evaluate methods to classify IFN-beta responder status using relapses and MRI lesions. Data was analyzed from 172 patients who were followed up in a placebo-controlled clinical trial of IFN-beta1a for 2 years. Patients were classified as responders or nonresponders using (1) the number of relapses during the 2-year trial; (2) the number of new T2 lesions after 2 years; and (3) the number of gadolinium-enhancing lesions at year 1 and year 2 on study. Outcomes included 2-year change in the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, and brain parenchymal fraction. We found that subgroups with high on-study relapse numbers had more disease progression, differences between responder subgroups were similar in the IFN-beta1a and placebo arms. In contrast, subgroups with high numbers of new MRI lesions had significantly more disease progression only in the IFN-beta1a arm. Baseline characteristics failed to account for differential outcome. New MRI lesion activity during IFN-beta1a treatment correlates with poor response to IFN-beta1a. MRI classification may facilitate rational therapeutic decisions, better clinical trial designs, and studies correlating biomarkers with therapeutic response.     

Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis

BACKGROUND: In patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS), the extent of brain magnetic resonance imaging (MRI) lesion load influences the probability and time to development of clinically definite MS. Cerebral atrophy is recognised in established MS, but its time of onset and whether, in early disease, it is related to MRI lesion load or clinical outcome is less certain. OBJECTIVES: This study investigated ventricular enlargement over one year in CIS patients and explored its relation with lesion load and clinical outcome. METHODS: A semi-automated thresholding technique for measuring ventricular volume (MIDAS) was applied to MRI scans in a cohort of 55 patients with CIS, recruited consecutively and imaged within three months of the onset of symptoms and again after one year. RESULTS: Clinical MS had developed after one year in 16 of 40 patients with an abnormal baseline T2 scan and 2 of 15 with a normal scan. Significant ventricular enlargement was seen in 27 of 55 patients who fulfilled the new McDonald MRI criteria for MS using all available MRI at clinical follow up (median increase 0.3 cm(3), p=0.005) Significant increase in ventricular volume was also seen in the 18 of 55 patients who developed clinical MS over the follow up period (median increase 0.5 cm(3), p=0.006). There were significant but modest correlations between baseline lesion measures and subsequent ventricular enlargement. CONCLUSIONS: (1) Lesions and atrophy are both associated with early relapse leading to a diagnosis of clinical MS; (2) while lesions contribute to the development of atrophy, atrophy may also develop by other mechanisms. This suggests that MR measures have a complementary role in monitoring the course of MS, even from the earliest clinical stage.     

Clinical, magnetic resonance imaging, cerebrospinal fluid and electrophysiological characteristics of the earliest multiple sclerosis

OBJECTIVES: The vast majority of clinically isolated syndrome (CIS) patients with at least two silent brain MRI lesions progress to multiple sclerosis (MS) as early as after 2 years meaning that they actually have MS, the earliest MS. Effective therapy with interferon beta preparations in patients with the earliest MS demands early and accurate diagnosis of the disease. PATIENTS AND METHODS: In order to find the differentiating clinical and paraclinical characteristics of patients with the earliest MS we compared clinical, MRI, CSF and evoked potential findings in patients with the earliest MS and patients with relapsing-remitting (RR) MS. Retrospective analysis included 149 patients (103 women), among them 40 patients with the earliest MS and 95 patients with RR MS. RESULTS: Patients with the earliest MS had more often predominant afferent symptoms (p=0.023) but less often predominant cerebellar (p=0.033) and efferent symptoms (p=0.012) than patients with RR MS. They were less likely to fulfill the Barkhof brain MRI criteria (p=0.050) and had less often prolonged latencies of visual evoked potentials (VEP) (p=0.006) than patients with RR MS. On the other hand they were more likely to have elevated CSF cells (p=0.010) than patients with RR MS and had as often present CSF oligoclonal bands (p=0.112). CONCLUSION: The differentiating characteristics of patients with the earliest MS are predominance of afferent symptoms, less brain MRI dissemination and more frequently normal VEP, but on the other hand abnormal CSF findings with elevated CSF cells and positive oligoclonal bands.     

Depression in the early phase of MS: influence of functional disability, cognitive impairment and brain abnormalities

This study investigated the relationship between depression, physical disability, cognitive deficit and brain abnormalities on magnetic resonance imaging (MRI) in patients with early MS. Eighteen relapsing-remitting MS patients were evaluated: depression was diagnosed according to DSM-III R and measured by the MMPI depression subscale, physical disability was assessed by using the Kurtzke Expanded Disability Status Scale (EDSS) and cognitive functions by means of an extensive neuropsychological test battery. A neuroradiologist blinded to clinical findings quantified cerebral lesion on MRI. Weighted brain area lesion score were developed according to number and size of cerebral lesions. On the basis of DSM-III criteria, six patients were classified as having major depression, seven patients had minor depression and five patients were without depressive symptoms. No significant differences were found among the three groups on both neuropsychological performances and weighted MRI lesion scores. However patients with major depression exhibit greater physical disability than the other MS subgroups. A significant correlation was found between MMPI depression subscale and physical disability. This study suggests that at least in the early phase of MS, depression appears more related to the physical disability than to the severity of pathological brain involvement.     

Linear pontine trigeminal root lesions in multiple sclerosis: clinical and magnetic resonance imaging studies in 5 cases

BACKGROUND: Magnetic resonance imaging (MRI) is useful for demonstrating demyelinating lesions in patients with multiple sclerosis (MS). Magnetic resonance imaging studies show that MS lesions are generally not uniform in shape, size, or distribution. Linearly shaped lesions at the trigeminal root entry zone have been occasionally reported in single cases of MS, but, to our knowlege, the frequency and the clinical features of such patients have not been comprehensively characterized. OBJECTIVE: To describe the frequency and the clinical and laboratory features of patients with MS who had linearly shaped lesions at the trigeminal root as seen on MRI. DESIGN AND SETTING: A retrospective review of medical records and MRI films of Japanese patients with MS admitted to a university hospital and its affiliated hospital in Sendai, Japan. PATIENTS AND METHODS: Brain MRI films of 74 consecutive Japanese patients with MS (51 females and 23 males) were studied retrospectively and the clinical and laboratory features of the patients with linearly shaped lesions at the trigeminal root were also investigated retrospectively. RESULTS: Five patients (6.8%) were shown to have T1-weighted-hypointense, T2-weighted-hyperintense, nonenhanced linear lesions in the pons on MRI, and these were uniformly localized in the intramedullary portion of the trigeminal root. All of these patients had clinically definite MS and had various types of facial sensory disturbances, such as neuralgia (1 patient), hypesthesia (2 patients), or paresthesia (3 patients). No other clinical or laboratory feature was characteristic in these 5 patients. CONCLUSIONS: Linear pontine trigeminal root lesions were common in our patients with MS. They were associated with various facial sensory symptoms. Since similar lesions are formed in animal models of herpes simplex virus infection, further study is needed to clarify whether these MS lesions are virally induced.     

Linomide in relapsing and secondary progressive MS: part II: MRI results. MRI Analysis Center of the University of Texas-Houston, Health Science Center, and the North American Linomide Investigators

OBJECTIVE: To determine the safety and efficacy of roquinimex (linomide) in the management of relapsing-remitting and secondary progressive MS as monitored by MRI. BACKGROUND: Preclinical studies and several short term randomized trials of linomide suggested clinical and MRI-measured benefits with acceptable risk for closely followed MS patients. METHODS: The North American Linomide Trial formally screened 853 individuals for relapsing or secondary progressive, clinically definite MS; recent disease activity or progression; and an Expanded Disability Status Scale score at entry of 3.0 to 6.5 inclusive. MRI was obtained on 811 subjects at pre-enrollment, 718 cases at enrollment, and then at three monthly intervals until the trial was prematurely terminated for unacceptable toxicity. RESULTS: Enhancement was found on 40.2% of 718 entry scans. Statistically robust correlations were found between clinical demographic data and several entry MRI measures including CSF volume, a reflection of brain atrophy. Assessment of the effect of treatment on MRI-measured disease was limited by early trial termination. However, active treatment for 3 months reduced the proportion of patients with one or more enhancements. An exploratory analysis suggested that 2.5 mg was the most active of three doses tested in limiting the total volume of enhanced tissue, the proportion of MRI-defined lesions designated as "black holes," and by a novel MRI composite disease measure. CONCLUSIONS: The short term signature of the effect of linomide on MRI-measured aspects of the disease suggests that safer drugs of this class might be useful in the management of MS. The use of a composite index of the heterogeneous nature of the pathology of MS as captured by MRI may have merit as an outcome measure in clinical trials.     

Overcoming barriers to mental health care: multimodal trauma-focused treatment approach for unaccompanied refugee minors

Juvenile delinquents constitute a heterogeneous group, which complicates decision-making based on risk assessment. Various psychosocial factors have been used to define clinically relevant subgroups of juvenile offenders, while neurobiological variables have not yet been integrated in this context. Moreover, translation of neurobiological group differences to individual risk assessment has proven difficult. We aimed to identify clinically relevant subgroups associated with differential youth offending outcomes, based on psychosocial and neurobiological characteristics, and to test whether the resulting model can be used for risk assessment of individual cases. A group of 223 detained juveniles from juvenile justice institutions was studied. Latent class regression analysis was used to detect subgroups associated with differential offending outcome (recidivism at 12 month follow-up). As a proof of principle, it was tested in a separate group of 76 participants whether individual cases could be assigned to the identified subgroups, using a prototype ‘tool’ for calculating class membership. Three subgroups were identified: a ‘high risk—externalizing’ subgroup, a ‘medium risk—adverse environment’ subgroup, and a ‘low risk—psychopathic traits’ subgroup. Within these subgroups, both autonomic nervous system and neuroendocrinological measures added differentially to the prediction of subtypes of reoffending (no, non-violent, violent). The ‘tool’ for calculating class membership correctly assigned 92.1% of participants to a class and reoffending risk. The LCRA approach appears to be a useful approach to integrate neurobiological and psychosocial risk factors to identify subgroups with different re-offending risk within juvenile justice institutions. This approach may be useful in the development of a biopsychosocial assessment tool and may eventually help clinicians to assign individuals to those subgroups and subsequently tailor intervention based on their re-offending risk.     

The use of magnetic resonance imaging in multiple sclerosis: lessons learned from clinical trials

Magnetic resonance imaging (MRI) is an important paraclinical tool for the diagnosis of multiple sclerosis (MS) and for monitoring its disease course. The efficacy of most of the available MS disease-modifying treatments has been tested in clinical trials where MRI-derived quantities served as primary or secondary outcome measures. However, conventional MRI measures (i.e., the number and volume of contrast-enhancing, the volumes of T2-hyperintense and T1-hypointense lesions and the assessment of brain volume changes) are limited in terms of pathological specificity and, as a consequence, are modestly correlated with clinical measures of disease activity and have a modest prognostic value as predictors of MS evolution. In the present review, we discuss the main factors potentially responsible for the so-called 'clinical MRI paradox' and how modern quantitative MR-based techniques might contribute to, at least partially, overcome it. The lessons learned from MS trials suggest that future applications of MRI to assess MS evolution should rely upon the use of composite measures thought to reflect the various components of the disease, as well as on study protocols specifically designed on the individual trial characteristics.     

Brain atrophy and magnetization transfer ratio following methylprednisolone in multiple sclerosis: short-term changes and long-term implications

BACKGROUND: The short-term effect of corticosteroids on MRI measures of multiple sclerosis (MS) is not well understood and may have a significant impact when using these quantitative measures to evaluate disease activity and changes following other therapeutic interventions. OBJECTIVE: To determine the impact of a course of intravenous methylprednisolone (IVMP) on quantitative measures of disease activity and tissue injury in MS patients. METHODS: We prospectively measured brain parenchymal fraction (BPF), magnetization transfer ratio (MTR, lesional and whole brain), and lesion volumes on nine weekly brain MRI studies in ten MS patients receiving a course of IVMP. A group of nine MS patients not receiving IVMP served as controls. RESULTS: In comparison to untreated controls, BPF declined over the eight weeks following IVMP treatment (P <0.02). BPF decline was most prominent in patients with secondary progressive MS (SPMS, P <0.03), and was not seen in relapsing-remitting (RR) MS patients. Short-term change in BPF correlated with baseline BPF (r =0.62, P =0.05) and short-term change in lesional MTR (r = -0.55, P =0.03), but not with change in enhancing lesion volume. Short-term change in lesional MTR inversely correlated with baseline lesional and whole brain MTR (r = -0.79, P =0.04 for both). There was no significant difference between treated and control patients in measures of MTR or T2, T1 or enhancing lesion volumes. CONCLUSIONS: Patients with SPMS showed a greater decline in BPF following IVMP than RRMS patients. A correlation between changes in BPF and MTR suggest that these changes are secondary to altered water content within MS lesions. Differential response to a standardized therapeutic intervention in RRMS and SPMS suggests that responses to therapy may differ due to a fundamental pathologic difference between early and late stage MS.     

Magnetic resonance imaging predictors of disability in primary progressive multiple sclerosis: a 5-year study

Magnetic resonance imaging (MRI) has become an accepted tool for monitoring therapeutic trials in relapsing-remitting and secondary progressive multiple sclerosis (MS); it is however unclear whether such MRI markers are equally applicable to primary progressive MS (PPMS). Forty-two patients with PPMS were reviewed five years after commencing a two-year MRI and clinical study. Clinical measures recorded at baseline and five years included both the Expanded Disability Status Scale and the MS functional composite. MRI data collected at baseline and two years included T1 and T2 lesion loads, the number of new brain and cord lesions, and measures of both brain and cord atrophy. The study demonstrated that both the number of new T2 lesions and rate of increase in ventricular volume over two years were modestly predictive of subsequent disease progression and therefore may be useful tools in the testing of new therapeutic agents in PPMS.     

Contribution of cervical cord MRI and brain magnetization transfer imaging to the assessment of individual patients with multiple sclerosis: a preliminary study

This study was performed to assess how established diagnostic criteria for brain magnetic resonance imaging (MRI) interpretation in cases of suspected multiple sclerosis (MS) (Barkhofs criteria) would perform in the distinction of MS from other diseases and whether other MR techniques (cervical cord imaging and brain magnetization transfer imaging [MTI]), might help in the diagnostic work-up of these patients. We retrospectively identified 64 MS and 59 non-MS patients. The latter group included patients with systemic immune-mediated disorders (SID; n=44) and migraine (n=15). All patients had undergone MRI scans of the brain (dual echo and MTI) and of the cervical cord (fast short-tau inversion recovery). The number and location of brain T2-hyperintense lesions and the number and size of cervical cord lesions were assessed. Brain images were also postprocessed to quantify the total lesion volumes (TLV) and to create histograms of magnetization transfer ratio (MTR) values from the whole of the brain tissue. Barkhofs criteria correctly classified 108/123 patients, thus showing an accuracy of 87.8%. "False negative" MS patients were 13, while 2 patients with systemic lupus erythematosus (SLE) were considered as "false positives". Using brain T2 TLV, nine of the "false negative" patients were correctly classified. Correct classification of 10 MS patients and both the SLE patients was possible based upon the presence or absence of one cervical cord lesion. Two MS patients with negative Barkhofs criteria and no cervical cord lesions were correctly classified based on their brain MTR values. Overall, only one MS patient could not be correctly classified by any of the assessed MR quantities. These preliminary data support a more extensive use of cervical cord MRI and brain MTI to differentiate between MS and other disorders in case of incondusive findings on T2-weighted MRI scans of the brain.     

Brain atrophy in relapsing-remitting multiple sclerosis: relationship with 'black holes', disease duration and clinical disability

Recent MRI studies in multiple sclerosis have highlighted the potential role of brain atrophy evaluation as a putative marker of disease progression. In the present study, we evaluated the supratentorial and infratentorial brain volume in patients with relapsing remitting multiple sclerosis (RR MS) and in healthy subjects. Moreover, we determined whether brain volumes of MS patients are associated with different aspects of brain MRI abnormalities and clinical findings. Two-dimensional acquired MRI was performed on 52 relapsing-remitting multiple sclerosis and 30 healthy subjects. The volume of supratentorial and infratentorial structures was measured in selected representative slices. Gd-enhancement, T2 hyperintense, T1 hypointense (i.e. 'black holes') total lesion load, as well as the area of corpus callosum was calculated in the MS group and related to brain volume measures. Correlations between MRI parameters and clinical features were also considered. MS patients had significantly lower supratentorial, infratentorial brain volume and corpus callosum area than healthy subjects (P<0.01). Supratentorial brain volume was significantly related to corpus callosum area (r=0.58; P<0.01) and T1 hypointense lesion load (r=0.48; P<0.01), but not with T2 hyperintense lesion load. Infratentorial/supratentorial ratio was significantly associated with disease duration and EDSS score (r=-0.34; P=0.02 and r=-0.49; P<0.01, respectively). This study documents that brain atrophy is an early MRI finding in RR MS and it is closely related to 'black holes' burden. The use of relative values (infratentorial/supratentorial ratio) may increase the conspicuity of correlation between clinical and MRI findings.     

No major association of ApoE genotype with disease characteristics and MRI findings in multiple sclerosis

BACKGROUND: Whereas a number of studies suggest that the ApoE polymorphism is not associated with disease susceptibility in multiple sclerosis (MS), results with regard to disease severity, however, are conflicting. Some studies suggest an unfavourable role of the epsilon4 allele. This study was performed to assess the association of the ApoE polymorphism with both disease susceptibility and disease course in a large group of MS patients using clinical and MRI measures. In addition the data were combined with available data from the literature. METHODS: In a group of 408 patients with clinically definite MS, genotype distribution was compared with that of 144 healthy controls. Combined analysis of published data on the association of ApoE polymorphism with MS was performed. Demographic and clinical findings were recorded and related to the ApoE genotype. In a subgroup, longitudinal MRI findings were available and related to the ApoE genotype. RESULTS: No significant differences were found in the distribution of genotypes between MS patients and controls. Combined analysis of published data showed a slightly increased susceptibility for MS in epsilon2-carriers. Disease characteristics (including age at onset and onset type), disease severity (progression index, time to reach EDSS 6) and MRI findings (lesion volumes and atrophy measures) were not associated with carriership o epsilon2 or epsilon4. CONCLUSIONS: In this cohort no association of the ApoE genotype with disease susceptibility nor clinical and MRI measures could be identified. However, combined analysis of published data could not definitely exclude the possibility of a minor role for epsilon2-carriership in MS.