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.     

Incidental MRI lesions suggestive of multiple sclerosis in asymptomatic patients in Karachi, Pakistan

The objective of this study was to identify asymptomatic patients with brain MRI lesions suggestive of multiple sclerosis (MS) in a low-prevalence area of Pakistan. Brain MRIs for 864 patients were reviewed at the Aga Khan University (Karachi, Pakistan) during an 8-month period of 2006 and 2007 to identify patients with lesions suggestive of MS. The lesions were characterised based on modified Barkhof criteria. Six (two females) (0.7%) of 864 patients fulfilled brain MRI criteria suggestive of MS. The mean number of MRI lesions (total lesions on T2) were 9 (range 5-14). Although Pakistan is considered a low-prevalence area for MS, 0.7% of brain MRI scans in patients without clinical MS symptoms showed lesions fulfilling brain MRI criteria of MS.     

Acute transverse myelitis with normal brain MRI

Objective To investigate the long-term risk of developing MS in patients presenting with acute transverse myelitis (ATM) and normal brain MRI scans at onset. Methods We studied 58 ATM patients with normal brain MRI at presentation for up to 5 years with serial neurologic and imaging studies. All patients underwent CSF analysis at onset which was defined positive if two or more IgG oligoclonal bands and/or elevated IgG index were present. Brain and spinal cord MRI scans were obtained every 6 months for the first 2 years, and annually thereafter unless the patient experienced a second neurologic attack different from the initial episode to confirm CDMS or there was demonstration of MRI lesions confirming dissemination in time and space to fulfill McDonald imaging criteria to diagnose MS. Results Seventeen of 58 (29%) patients developed MS of which 7 (41%) patients developed CDMS and 10 (59%) developed MS using McDonald Imaging Criteria. Mean time to CDMS by a second clinical attack was 11. 1 months compared to 19. 2 months by MRI lesions (P = 0. 03). None of the patients developed MS after 24 months of onset. All 17 patients who developed MS had positive CSF although 15 patients who had positive CSF did not develop MS during the 5 years of follow-up. Conclusions The majority of patients with ATM and normal brain MRI do not develop MS after 5 years of follow-up confirming the relatively low risk compared to patients with abnormal brain MRI scans. CSF is helpful in distinguishing patients more likely to develop MS. Compared to clinical attacks, serial imaging may not lead to an earlier diagnosis in ATM patients with normal brain MRI.     

Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group

BACKGROUND: Episodic inflammation in the CNS during the early stages of MS results in progressive disability years later, presumably due to myelin and axonal injury. MRI demonstrates ongoing disease activity during the early disease stage, even in some patients who are stable clinically. The optimal MRI measure for the destructive pathologic process is uncertain, however. METHODS: In this post-hoc study, MRI scans were analyzed from patients with relapsing MS participating in a placebo-controlled trial of interferon beta-1a. The brain parenchymal fraction, defined as the ratio of brain parenchymal volume to the total volume within the brain surface contour, was used to measure whole brain atrophy. The relationship between disease features and brain atrophy and effect of interferon beta-1a were determined. RESULTS: MS patients had significant brain atrophy that worsened during each of 2 years of observation. In many patients, brain atrophy worsened without clinical disease activity. Baseline clinical and MRI abnormalities were not strongly related to the rate of brain atrophy during the subsequent 2 years. Treatment with interferon beta-1a resulted in a reduction in brain atrophy progression during the second year of the clinical trial. CONCLUSIONS: Patients with relapsing-remitting MS have measurable amounts of whole brain atrophy that worsens yearly, in most cases without clinical manifestations. The brain parenchymal fraction is a marker for destructive pathologic processes ongoing in relapsing MS patients, and appears useful in demonstrating treatment effects in controlled clinical trials.     

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 multiple sclerosis patients by latent class analysis of magnetic resonance imaging characteristics

BACKGROUND: Disease heterogeneity is a major issue in multiple sclerosis (MS). Classification of MS patients is usually based on clinical characteristics. More recently, a pathological classification has been presented. While clinical subtypes differ by magnetic resonance imaging (MRI) signature on a group level, a classification of individual MS patients based purely on MRI characteristics has not been presented so far. OBJECTIVES: To investigate whether a restricted classification of MS patients can be made based on a combination of quantitative and qualitative MRI characteristics and to test whether the resulting subgroups are associated with clinical and laboratory characteristics. METHODS: MRI examinations of the brain and spinal cord of 50 patients were scored for 21 quantitative and qualitative characteristics. Using latent class analysis, subgroups were identified, for whom disease characteristics and laboratory measures were compared. RESULTS: Latent class analysis revealed two subgroups that mainly differed in the extent of lesion confluency and MRI correlates of neuronal loss in the brain. Demographics and disease characteristics were comparable except for cognitive deficits. No correlations with laboratory measures were found. CONCLUSIONS: Latent class analysis offers a feasible approach for classifying subgroups of MS patients based on the presence of MRI characteristics. The reproducibility, longitudinal evolution and further clinical or prognostic relevance of the observed classification will have to be explored in a larger and independent sample of patients.     

Benign course of tumour-like multiple sclerosis. Report of five cases and literature review

BackgroundMultiple sclerosis (MS) with initial neuroradiological features suggestive of brain tumour (tumour-like MS) may represent a challenging diagnosis.MethodsAmong the patients seen at the MS centre of our Institution between 2000 and 2010, we identified cases presenting with a large (diameter > 2 cm), well-defined lesion, suggestive of brain tumour on initial brain magnetic resonance imaging (MRI). Only patients with at least 10 years follow-up were included.ResultsFive young women with MS who presented with a tumour-like lesion on initial brain MRI are described. All cases presented with sudden-onset neurological deficits due to a single large brain lesion compatible with neoplasm at MRI. Two cases underwent brain stereotactic biopsy, both misdiagnosed as astrocytoma. However, the subsequent clinical and MRI follow-up was consistent with MS in all cases. Unnecessary surgery and radiotherapy were responsible for disability in two cases. In three cases, the course of the disease remains benign after more than 13 years from symptoms onset.ConclusionsOur report of clinical, radiological and pathological features of five tumour-like MS cases confirms that it is mandatory to consider a demyelinating process in the differential diagnosis of tumour-like brain lesions. Many tumour-like MS cases may have a favourable long term prognosis.     

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).     

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.     

Magnetic resonance imaging in patients with multiple sclerosis and spinal cord involvement: 28 cases

In patients with clinically isolated spinal disease, magnetic resonance imaging (MRI) provides a non-invasive method of detecting surgically treatable causes and is also useful in detecting asymptomatic brain lesions where the cord syndrome is due to multiple sclerosis (MS). We report the findings of spinal and brain MRI in 28 patients with spinal cord disorder due to MS. It was possible to detect intrinsic plaques reliably in the majority of patients (60.7%) with clinical findings of spinal cord MS. The results of MRI are compared with the clinical status and with cerebrospinal fluid findings and evoked potentials.     

Cognition in multiple sclerosis: relevance of lesions,brain atrophy and proton MR spectroscopy

The overall burden of brain MRI-visible lesions does not fully account for cognitive impairment in multiple sclerosis (MS). Several MRI studies have highlighted the importance of brain damage in the normal-appearing brain tissue. Brain atrophy (global, cortical, white and deep grey matter) is related to cognitive deficits in MS patients and this holds true since the earliest disease stages. Non-conventional MRI techniques such as proton MR spectroscopy have related metabolic changes in specific brain areas to specific cognitive deficits. Overall, data provided by MRI support the notion that cognitive disturbances need to be considered for a more complete clinical characterisation of patients with MS, including those with “benign” MS.     

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.     

Prognostic value of spinal cord MRI in multiple sclerosis patients

Multiple sclerosis [MS] is a common inflammatory, demyelinating and neurodegenerative disease of the central nervous system that affects both the brain and the spinal cord. In clinical practice, spinal cord MRI is performed far less frequently than brain MRI, mainly owing to technical limitations and time constraints. However, improvements of acquisition techniques, combined with a strong diagnosis and prognostic value, suggest an increasing use of spinal cord MRI in the near future. This review summarizes the current data from the literature on the prognostic value of spinal cord MRI in MS patients in the early and later stages of their disease. Both conventional and quantitative MRI techniques are discussed. The prognostic value of spinal cord lesions is clearly established at the onset of disease, underlining the interest of spinal cord conventional MRI at this stage. However, studies are currently lacking to affirm the prognostic role of spinal cord lesions later in the disease, and therefore the added value of regular follow-up with spinal cord MRI in addition to brain MRI. Besides, spinal cord atrophy, as measured by the loss of cervical spinal cord area, is also associated with disability progression, independently of other clinical and MRI factors including spinal cord lesions. Although potentially interesting, this measurement is not currently performed as a routine clinical procedure. Finally, other measures extracted from quantitative MRI have been established as valuable for a better understanding of the physiopathology of MS, but still remain a field of research.     

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.     

Magnetic resonance imaging of Asians with multiple sclerosis was similar to that of the West

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.     

A brain MRI study of different types of chronic-progressive multiple sclerosis

Introduction –This study was performed to define the pattern of brain magnetic resonance imaging (MRI) abnormalities in chronic-progressive MS (MS). Material and methods — Brain MRIs were obtained for 17 patients with secondary progressive MS (SPMS), 14 with primary progressive MS (PPMS) and 5 with "transitional" progressive MS (TPMS). Results — Total lesion loads were different for the three groups of patients (p<0.01). At post-hoc analysis, there was no difference between patients with TPMS and those with PPMS, while both these groups had lesion loads lower than those of patients with SPMS. Patients with PPMS with clinical signs indicating involvement of both brain and spinal cord had greater total lesion loads than those with clinical isolated spinal cord involvement (p<0.05). Conclusion — These data indicate that brain MRI patterns of abnormalities are related to the clinical manifestations in patients with chronic-progressive MS.     

Acute disseminated encephalomyelitis that meets modified McDonald criteria for dissemination in space is associated with a high probability of conversion to multiple sclerosis in Taiwanese patients

Background: Patients with acute disseminated encephalomyelitis (ADEM) may relapse and some may ultimately convert to multiple sclerosis (MS); however, no criteria that can predict MS conversion are available to date. Our aim was to describe the clinical and magnetic resonance imaging (MRI) features of patients with an initial ADEM attack and evaluate which MRI criteria can predict conversion to MS. Methods: We retrospectively reviewed the records of 36 patients diagnosed with ADEM. We determined clinical signs/symptoms, examined the cerebrospinal fluid (CSF), and performed brain MRI scans and compared the findings between patients who did and did not convert to MS. Results: Clinical signs/symptoms, and CSF analysis show no significant difference between the two groups. The rate of conversion to MS from ADEM in Taiwanese patients is low (11%) after a mean follow‐up period of 28.36 months. Modified McDonald criteria were fulfilled in 19/36 patients: 21% (4/19) of those patients developed MS according to Poser criteria subsequently. Of the other patients (17/36) who did not fulfill these criteria, none converted to MS. (log rank test; P = 0.027). Conclusions: It is difficult to predict from initial clinical presentations to address which patients with ADEM will convert to MS. Patients with ADEM whose brain MRI findings met the modified McDonald criteria may have clinically isolated syndrome because they have a significantly higher probability of conversion to MS. In contrast, patients whose brain MRI findings did not meeting these criteria may be considered as having classic ADEM because they have a lower probability of conversion to MS.     

Multiple sclerosis diagnosis: magnetic resonance imaging compared with other paraclinical examinations

Examination by magnetic resonance imaging (MRI), evoked potentials (EP) and cerebrospinal fluid (CSF) analyses was carried out on 97 definite, 20 probable and 40 possible multiple sclerosis (MS) patients (McAlpine's clinical criteria). MRI of only 4 transverse brain sections at the level of the ventricles and the analysis of the first 4 echoes showed periventricular or parenchymal lesions, or both, in 114 of the 117 definite and probable MS patients and in 25 of the possible MS patients. MRI was more sensitive than the CSF analyses or EP. The MRI abnormalities were not, however, MS-specific.     

Vaccinations and steroids in MS: effects on disease progression and mood

OBJECTIVE: To investigate the effects of vaccinations and steroids on disease progression and mood in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Twenty-three patients with clinically definite MS were questioned with respect to vaccination history and the cumulative dose of steroids given during their life-time. EDSS scores and MRI scans of the brain were obtained and used to quantify clinical and MRI disease progression. Mood was assessed by using a self-estimated adjective mood scale. RESULTS: The number of vaccinations showed no effect on disease progression or mood. High cumulative steroid doses were associated with rapid MRI disease progression and the number of supratentorial MRI lesions. The absence of band-like MRI lesions was correlated with rapid clinical and MRI disease progression. Self-estimated mood tended to be worse in patients with chronic-progressive MS compared to those with relapsing-remitting MS. CONCLUSION: Neither clinical nor MRI-documented disease progression nor mood are influenced by the total number of vaccinations whereas high cumulative steroid doses and the absence of band-like MRI lesions indicate rapidly progressive MS. Self-estimated mood tends to be worse in patients with chronic-progressive MS compared to patients with relapsing-remitting MS.     

A comparative study of Japanese multiple sclerosis patients with and without oligoclonal IgG bands

The cerebrospinal fluid oligodonal IgG bands (OB) are less frequently observed in Japanese multiple sclerosis (MS) patients compared with Caucasian patients. We studied 40 consecutive Japanese MS patients to investigate the differences in the clinical and magnetic resonance imaging (MRI) features of MS between OB-positive patients and OB-negative ones. Among the 40 patients, 22 (55%) patients were OB-positive by either agarose gel electrophoresis (AGE) or isoelectric focusing (IEF), and 18 (45%) patients were OB-negative by both AGE and IEF. There were differences between the two groups only in the clincal forms of MS, but not in terms of gender, onset age, disease duration, or disease severity. In the OB-negative group, nine (50%) of the patients had the optic-spinal form of MS (OS-MS), but only one patient (4.5%) in the OB-positive group had OS-MS. Although most OB-positive patients showed brain MRI lesions typical of MS, 13 (72%) of the OB-negative patients showed no or few brain MRI lesions and the rest of the OB-negative patients showed atypical MS lesions, such as diffuse white matter lesions or large ring-enhanced lesions. Our results suggest that the majority of OB-negative Japanese MS patents show either no or few brain MRI lesions or atypical brain MRI lesions.