Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SCLEROSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources
PubMed1994

Genetic disorders that masquerade as multiple sclerosis.

There are many genetic disorders that have signs and symptoms suggestive of multiple sclerosis and that may easily be overlooked in the evaluation of both adult and pediatric multiple sclerosis patients. The recognition of a genetic disorder as the cause of a patient's "multiple sclerosis" phenotype has important implications not only for the patient, but often also for others in the patient's family who may be at risk for the same disease. We present here a review of single gene disorders that can masquerade as multiple sclerosis. For each disorder, the major clinical and biochemical characteristics are discussed, together with the appropriate testing to screen for and confirm the diagnosis. In addition, guidelines are presented for when to suspect an underlying genetic condition in a patient with a diagnosis of definite or probable multiple sclerosis. The great variety of genetic disorders that can masquerade as multiple sclerosis and the many implications of a genetic diagnosis underscore the importance of recognizing genocopies of multiple sclerosis.

Diagnosis, Differential↗
PubMed2002

Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage.

In multiple sclerosis, the mechanisms underlying the accumulation of disability are poorly understood. Recently, it has been suggested that adaptive cortical changes may limit the clinical impact of multiple sclerosis injury. In this study, functional magnetic resonance imaging and a general search method were used to assess patterns of brain activation associated with a simple motor task in 14 right-handed, nondisabled relapsing-remitting multiple sclerosis patients that were compared to those from 15 right-handed, sex- and age-matched healthy volunteers. Also investigated were the extent to which the functional magnetic resonance imaging changes correlated with T2 lesion volume and severity of multiple sclerosis pathology in lesions and normal-appearing brain tissue, measured using magnetisation transfer and diffusion tensor magnetic resonance imaging. Compared to controls, multiple sclerosis patients showed increased activation in the contralateral primary sensorimotor cortex, bilaterally in the supplementary motor area, bilaterally in the cingulate motor area, in the contralateral ascending bank of the sylvian fissure, and in the contralateral intraparietal sulcus. T2 lesion volume was correlated with relative activation in the ipsilateral supplementary motor area, and in the ipsilateral and contralateral cingulate motor area. Average lesion magnetisaiton transfer ratio and average lesion water diffusivity were correlated with relative activation in the contralateral sensorimotor cortex. Average lesion magnetisation transfer ratio was also correlated with relative activation in the ipsilateral cingulate motor area. Average water diffusivity and peak height of the normal-appearing brain tissue diffusivity histogram were both correlated with relative activation in the contralateral intraparietal sulcus. This study shows that cortical activation occurs over a rather distributed sensorimotor network in nondisabled relapsing-remitting multiple sclerosis patients. It also suggests that increased recruitment of this cortical network contributes to the limitation of the functional impact of white matter multiple sclerosis injury.

Adaptation, Physiological↗
PubMed1985

Increased prevalence and titer of Epstein-Barr virus antibodies in patients with multiple sclerosis.

The prevalence and titer of serum antibodies to several Epstein-Barr virus (EBV) antigens were compared among patients with multiple sclerosis, healthy siblings of multiple sclerosis patients, patients with other neurological diseases, and healthy non-blood-related subjects. Serum-cerebrospinal fluid (serum-CSF) pairs were available on a selected number of multiple sclerosis and control subjects. An increased antibody response to EBV antigens was noted rather consistently in the sera of the multiple sclerosis group in comparison with the control groups. A greater number of reduced ratios of serum:CSF IgG antibody to EBV-capsid antigen and antibody to EBV-early antigen components than to adenovirus, a reference or control virus, were found in the multiple sclerosis group. Reduced ratios of these EBV antibodies were detected more frequently or showed a trend in this direction in multiple sclerosis patients compared with the group with other neurological diseases. Our findings extend the results of an earlier report and strengthen the association between EBV and multiple sclerosis.

Adenoviruses, Human↗
PubMed1996

Ultrastructural evidence for altered calcium in motor nerve terminals in amyotropic lateral sclerosis.

Numerous studies of amyotrophic lateral sclerosis have suggested that increased intracellular calcium is a common denominator in motoneuron injury. In experimental models, IgG from patients with amyotrophic lateral sclerosis enhanced calcium entry and induced apoptotic cell death in vitro as well as increased intracellular calcium and induced ultrastructural alterations of the motor nerve terminals in mice in vivo. To determine whether similar increases in intracellular calcium and altered morphology are present in motor nerve terminals of amyotrophic lateral sclerosis patients in vivo, muscle biopsy specimens from 7 patients with amyotrophic lateral sclerosis, 10 nondenervating disease control subjects, and 5 patients with denervating neuropathies were analyzed with ultrastructural techniques, employing oxalate-pyroantimonate fixation to preserve in situ calcium distribution. Motor nerve terminals from amyotrophic lateral sclerosis specimens contained significantly increased calcium, increased mitochondrial volume, and increased numbers of synaptic vesicles compared to any of the disease control groups, without exhibiting excess Schwann envelopment specific to denervating terminals. These results parallel the effect of amyotrophic lateral sclerosis IgG passively transferred to mice, and provide the first demonstration that neuronal calcium is, in fact, increased in amyotrophic lateral sclerosis in vivo.

Adult↗
PubMed1996

Immunoassays fail to detect antibodies against neuronal calcium channels in amyotrophic lateral sclerosis serum.

Recent studies suggested that autoantibodies that bind to voltage-dependent calcium channels and activate calcium entry may play a role in the progressive degeneration of motoneurons in sporadic amyotrophic lateral sclerosis. Immunoassays were performed to assess autoantibody titer in patients with amyotrophic lateral sclerosis or Lambert-Eaton myasthenic syndrome, a disease in which the presence of anti-calcium channel antibodies is well documented. Based on immunoprecipitation assays for antibodies against N-type calcium channels, only 8% (2/25) of amyotrophic lateral sclerosis patients had marginally positive titers, whereas 58% (18/31) of patients with Lambert-Eaton myasthenic syndrome had positive titers. Enzyme-linked immunosorbent assays with purified neuronal N-type calcium channels revealed immunoreactivity in 2 of 25 amyotrophic lateral sclerosis sera and 12 of 31 Lambert-Eaton myasthenic syndrome sera, which is not compatible with suggestions that enzyme-linked immunosorbent assay is a more sensitive technique for the detection of autoantibodies in amyotrophic lateral sclerosis. Furthermore, based on immunoprecipitation assays, amyotrophic lateral sclerosis sera were totally negative for antibodies against L-type calcium channels from skeletal muscle or brain. These data do not support the hypothesis that an autoimmune response against calcium channels plays a primary role in amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis↗
PubMed2003

Association of aortic valve sclerosis and coronary artery disease in patients with severe nonischemic mitral regurgitation.

BACKGROUND: The presence of aortic valve sclerosis accounts for a higher rate of ischemic events and increased cardiovascular mortality. It may reflect coronary artery disease (CAD) because of a shared pathologic background. HYPOTHESIS: We aimed to analyze whether the presence of aortic valve sclerosis might help in identifying patients with coronary atherosclerosis among those with severe nonischemic mitral regurgitation (MR), who undergo coronary angiography before surgery for screening, and not because of suspected ischemic heart disease. METHODS: In all, 84 patients (mean age 64 +/- 9 years; 71% men) with mitral valve prolapse and severe regurgitation underwent echocardiography and coronary angiography. Aortic valve sclerosis was defined as focal areas of increased echogenicity and thickening of the leaflets without restriction of leaflet motion on echocardiography. Coronary artery disease was defined by the presence/absence of atherosclerotic plaques, independent of the degree of stenosis. RESULTS: Coronary artery disease was diagnosed in 47.6% of patients with and 15.8% of those without aortic valve sclerosis (p = 0.008). On logistic regression analysis, the presence of aortic valve sclerosis predicted CAD (odds ratio 3.3, 95% confidence interval 1.03-10.5; p = 0.04) independent of age. In female patients, the risk ratio for CAD in the presence of aortic valve sclerosis was 9. CONCLUSIONS: Coronary artery atherosclerosis and aortic valve sclerosis are closely associated in patients with severe nonischemic MR.

Adult↗
PubMed2002

Genetic analysis of multiple sclerosis.

The increased recurrence risk within families indicates a role for genetic factors in the etiology of multiple sclerosis. Genes may influence susceptibility to the development of multiple sclerosis and the subsequent course of the disease. To date, associations have only been demonstrated consistently with class II major histocompatibility complex (MHC) alleles. The relatively low yield from additional candidate gene studies is only modestly advanced by several whole-genome linkage analyses, and by the first in a series of planned whole-genome linkage disequilibrium screens for allelic associations. The aims of linkage and association are to narrow the search for chromosomal regions encoding genes for multiple sclerosis and, with information from the human gene project, suggest new positional candidates. In time, it is expected that these genes will include some that confer susceptibility to the general process of autoimmunity, others that are specific for multiple sclerosis in all populations, some that act only in defined ethic groups, and those that determine particular phenotypes or shape the clinical course. These genetic analyses are predicated on the assumption that multiple sclerosis is one disease; a major part of future studies will be to resolve the question of disease heterogeneity in multiple sclerosis. When eventually in place, the potential of this genetic knowledge for improved understanding of the pathogenesis of multiple sclerosis and designing novel treatments is considerable.

DNA Mutational Analysis↗
PubMed1989

Absence of linkage of ABO blood group locus to familial tuberous sclerosis.

A mutation leading to tuberous sclerosis was linked to the ABO blood group locus (9q34) on the long arm of chromosome 9. In an effort to confirm this assignment, nine multigenerational families with tuberous sclerosis, comprising 126 sampled individuals, were assessed for linkage of the ABO locus to tuberous sclerosis. Two-point linkage analysis and multilocus linkage analysis were used to evaluate linkage between tuberous sclerosis and the markers ABO, MCT136, and AblK2. Linkage of ABO to tuberous sclerosis was excluded for a distance of 20 centimorgans (cM) encompassing the region of the ABO locus. There was no evidence for genetic heterogeneity within this data set. Using 23 polymorphic markers, exclusion mapping demonstrated only a 1% probability that the tuberous sclerosis locus was on the distal short arm of chromosome 9 and provided no evidence in support of a tuberous sclerosis locus on the remainder of chromosome 9 including the area of the ABO locus.

ABO Blood-Group System↗
PubMed1995

The imbalance of brain large-chain aminoacid availability in amyotrophic lateral sclerosis patients treated with high doses of branched-chain aminoacids.

Following the report of an increased mortality among patients with amyotrophic lateral sclerosis given high daily doses of branched-chain aminoacids, we assessed the plasma concentrations of large neutral aminoacids and glutamic acid and the large neutral aminoacid brain influx in 24 amyotrophic lateral sclerosis patients receiving placebo or branched-chain aminoacids (L-leucine 12 g, L-isoleucine 6 g, L-valine 6 g daily), in 15 untreated amyotrophic lateral sclerosis patients and in 15 healthy volunteers. The branched-chain aminoacid plasma concentrations increased three- to six-fold in the treated group compared to the patients receiving placebo or no treatment and to the healthy controls. Plasma glutamic acid concentrations in healthy volunteers were 51.59 +/- 7.53 nmol/ml while in the amyotrophic lateral sclerosis patients receiving no treatment, placebo or branched-chain aminoacids were 92.33 +/- 12.15 nmol/ml, 91.21 +/- 15.86 nmol/ml and 95.08 +/- 17.96 nmol/ml respectively. The glutamic acid concentration was significantly higher (P < 0.01) in amyotrophic lateral sclerosis patients than in healthy individuals. Plasma phenylalanine and tyrosine were lower in the amyotrophic lateral sclerosis patients than in healthy controls, regardless of treatment, whereas tryptophan levels were not significantly different. The branched-chain aminoacid brain influx of the treated group was 110-140% of that measured in the patients receiving placebo and in the healthy controls. The aromatic aminoacid brain influx was lower in the treated group than in the placebo group or healthy controls. An impairment of brain large neutral aminoacid availability might possible contribute to enhancing the progression of symptoms in patients with amyotrophic lateral sclerosis.

Adult↗
PubMed1995

Febrile seizures and hippocampal sclerosis: frequent and related findings in intractable temporal lobe epilepsy of childhood.

The relationship between hippocampal sclerosis, febrile seizures, and complex partial seizures in temporal lobe epilepsy continues to be the subject of great debate in the literature. Hippocampal sclerosis is reported infrequently in young children with temporal lobe epilepsy, a factor that has supported the theory that hippocampal sclerosis develops in later life during the course of recurrent complex partial seizures. In a blinded review of magnetic resonance imaging in 53 children, aged 2-17 years (mean: 10 years) with temporal lobe epilepsy, hippocampal sclerosis was diagnosed in 30 children (57%), concordant with ictal electroencephalographic lateralization in 93% and pathologic diagnosis in all children who had undergone surgery and had hippocampal tissue available for histologic examination. Fourteen of the children (47%) with hippocampal sclerosis were younger than 10 years of age, the youngest being 2 years. Thirty-four children (64%) had histories of neurologic insults prior to the onset of complex partial seizures, including idiopathic febrile seizures in 22. Hippocampal sclerosis was associated with a history of a neurologic insult prior to the onset of complex partial seizures (P < .001) and was not associated with age at onset of temporal lobe epilepsy, age at magnetic resonance imaging, duration of epilepsy, or presence of secondarily generalized seizures. These findings suggest that hippocampal sclerosis is underdiagnosed in children and is the cause and not the consequence of temporal lobe epilepsy.

Adolescent↗
PubMed2006

Evaluation of the myocardial performance index for early detection of mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis.

AIMS: Multiple sclerosis is the most common cause of neurological disability in young adults. Mitoxantrone is a synthetic anthracenedione, recently approved for the treatment of worsening multiple sclerosis, which is known to induce cardiotoxicity. This study was designed to evaluate the early alterations in left ventricular function in patients with multiple sclerosis receiving mitoxantrone, by the use of the myocardial performance index, a new parameter of global (systolic and diastolic) ventricular function. METHODS AND RESULTS: The study included 29 Caucasian patients with multiple sclerosis (mean age 41.8+/-9.3 years, 12 males and 17 females) treated with mitoxantrone (mean cumulative dose 30.8+/-18.2 mg/m(2)) who were compared with 28 healthy subjects (mean age 37.8+/-11.8 years, 13 males and 15 females). Both groups underwent a complete two-dimensional and Doppler echocardiography including assessment of the mitral inflow and left ventricular outflow patterns for estimation of the Doppler-derived myocardial performance index. This parameter is defined as the sum of isovolumic contraction time and isovolumic relaxation time, divided by ventricular ejection time. No differences were observed in blood pressure, heart rate, left ventricular diameters, mass and ejection fraction in multiple sclerosis patients compared to the controls. The mitral flow pattern showed a significant decrease of E wave calculated as peak velocity (E(pv)) (63.3+/-13.4 vs. 77.2+/-17.2, P<0.002) and time velocity integral (E(tvi)) (8.8+/-1.9 vs. 10.3+/-2.4, P<0.02), with a significant decrease of E(pv)/A(pv) ratio and a non-significant decrease of E(tvi)/A(tvi) ratio in the patients. In addition, E-wave deceleration time was significantly increased in multiple sclerosis patients compared to controls (178.2+/-30.2 vs. 137.9+/-14.7, P<0.0001). The mean value of myocardial performance index was 0.55+/-0.1 in patients compared to 0.37+/-0.06 in the controls (P<0.0001). A significant correlation between the given cumulative dose of mitoxantrone and myocardial performance index (r=0.67, P<0.001) and E-wave deceleration time (r=0.45, P<0.001) respectively were demonstrated. CONCLUSION: The myocardial performance index represents a parameter of combined systolic and diastolic myocardial performance strongly correlated with the given cumulative dose of mitoxantrone. The myocardial performance index may be an adjunctive parameter to conventional echocardiography for detecting sub-clinical cardiotoxicity of mitoxantrone in the clinical management of the multiple sclerosis patients.

Adult↗
PubMed2003

Multiple sclerosis vs acute disseminated encephalomyelitis in childhood.

The initial presenting clinical and laboratory findings of either acute disseminated encephalomyelitis or the first attack of multiple sclerosis in the pediatric population were compared and contrasted. A retrospective review of the medical records was conducted of all children younger than 17 years who presented with either the diagnosis of acute disseminated encephalomyelitis or multiple sclerosis between 1987 and 2001. Seventeen cases of clinically definite multiple sclerosis (seven female, mean age 12.4 +/- 4.5 years) and seven cases of acute disseminated encephalomyelitis (three female; mean age 8.7 +/- 3.8 years) were reviewed. Systemic and nonfocal neurologic symptoms were more commonly evident in acute disseminated encephalomyelitis than in multiple sclerosis: fever (43% vs 6%), headache (57% vs 24%), fatigue (71% vs 29%), vomiting (57% vs 0%), and encephalopathy (71% vs 6%). In multiple sclerosis patients, T(2)-weighted white matter magnetic resonance imaging lesions were more commonly located in the corpus callosum (64% vs 17%) and the periventricular area (91% vs 50%) compared with those in patients with acute disseminated encephalomyelitis. These results suggest that acute disseminated encephalomyelitis and multiple sclerosis can be differentiated to some degree according to clinical and radiologic data at initial presentation, which is important because the long-term prognosis for childhood multiple sclerosis appears to be less favorable.

Adolescent↗
PubMed2001

Prevalence of multiple sclerosis in Belgrade, Yugoslavia.

OBJECTIVES: To estimate the distribution of multiple sclerosis in the Belgrade population. METHODS: All persons who were affected and/or died from multiple sclerosis (Poser's criteria), with residence in the Belgrade region had been collected from January 1, 1985 to December 31, 1996. Prevalence was adjusted by direct method, using world population. RESULTS: From 1985 to 1996, 823 patients were suffering from multiple sclerosis. Sex ratio was 1:1.9. The mean age at onset was 32.2 +/- 9.8 years. A relapsing-remitting course of multiple sclerosis was reported in 50.7% patients, secondary progressive in 36.4%, patients, and primary progressive in 12.9% patients. On December 31, 1996, age-adjusted prevalence of multiple sclerosis in Belgrade was 41.5/100,000, 28.2/100,000 for males, and 54.1/100,000 for females. During the period studied, statistically highly significant increasing trend of multiple sclerosis prevalence was observed (P = 0.0001). CONCLUSIONS: According to findings presented in this study, Belgrade is an area with high prevalence of multiple sclerosis.

Adult↗
PubMed1990

T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis.

Multiple sclerosis is thought to be an autoimmune disease of the central nervous system mediated by T cells specific for a myelin antigen. Myelin basic protein has been studied as a potential autoantigen in the disease because of its role as an encephalitogen in experimental autoimmune encephalomyelitis and post-viral encephalomyelitis and because of the presence in the blood of multiple sclerosis patients of in vivo-activated T cells reactive to myelin basic protein. Immune involvement in multiple sclerosis has been further suggested by the association with the major histocompatibility complex class II phenotype DR2, DQw1. To define the T-cell specificity toward myelin basic protein, 15,824 short-term T-cell lines were established from multiple sclerosis subjects, subjects with other neurological diseases, and normal controls. Here we report a higher frequency of T-cell lines reactive with a DR2-associated region of myelin basic protein between residues 84-102 in patients with multiple sclerosis compared with controls. A second region, identified between residues 143-168, was recognized equally in multiple sclerosis patients and controls and was associated with the DRw11 phenotype. These DR2 and DRw11 associations were also observed among T-cell lines generated from family members of a multiple sclerosis patient. The immunodominant 84-102 peptide from myelin basic protein was both DR2- and DQw1-restricted among different T-cell lines. These results raise the possibility that this immunodominant region may be encephalitogenic in some DR2+ individuals.

Amino Acid Sequence↗
PubMed2002

Tuberous sclerosis: clinicopathologic features and review of the literature.

INTRODUCTION: Tuberous sclerosis is a hamartoneoplastic syndrome, which may involve multiple organ systems. Oral hard tissue manifestations of the syndrome have been described in the literature only as recently as 1955. Patients who presented with clinical manifestations of tuberous sclerosis did not routinely undergo oral surveys to rule out 'lesions', and consequently data on 'lesions' in the maxillofacial complex is scant. Ten cases have been found in the English language literature, which describe maxillofacial 'lesions', which may be tumours, new growths, neoplasms or overgrowths occurring in patients diagnosed with tuberous sclerosis. PURPOSE: To review the literature for all maxillofacial lesions associated with tuberous sclerosis and to present an eleventh case of a patient with a maxillofacial lesion diagnosed as having tuberous sclerosis. RESULTS: Eleven cases were found with maxillofacial fibroblastic lesions associated with tuberous sclerosis. These lesions were all fibrous benign neoplasms found in the maxillofacial bony complex. CONCLUSIONS: Maxillofacial fibroblastic lesions in tuberous sclerosis have various histopathological presentations, some of which may be difficult to differentiate. Consequently, close microscopic examination of these lesions is necessary so that adequate surgical treatment is provided.

Child, Preschool↗
PubMed1986

A population-based study of multiple sclerosis in twins.

Results from studies of twin concordance in multiple sclerosis have not conclusively differentiated between environmental and genetic factors that determine susceptibility to the disease. Published studies that have been based on case finding by public appeal have been characterized by difficulties in ascertainment. The data reported here are from a large population-based study of multiple sclerosis in twins, in which ascertainment has been relatively unbiased and the cooperation of patients nearly complete. A total of 5463 patients attending 10 multiple sclerosis clinics across Canada were surveyed. Twenty-seven monozygotic and 43 dizygotic twin pairs were identified, and the diagnosis of multiple sclerosis was verified by examination and laboratory investigation. Seven of 27 monozygotic pairs (25.9 percent) and 1 of 43 dizygotic pairs (2.3 percent) were concordant for multiple sclerosis. The concordance rate for 4582 nontwin siblings of patients at two multiple sclerosis clinics was 1.9 percent, closely paralleling the concordance rate in dizygotic twins. To the extent that the difference in concordance rates between monozygotic and dizygotic twins indicates genetic susceptibility, the results of this study show a major genetic component in susceptibility to multiple sclerosis.

Canada↗
PubMed1993

The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis. The Optic Neuritis Study Group.

BACKGROUND: Optic neuritis is often the first clinical manifestation of multiple sclerosis, but little is known about the effect of corticosteroid treatment for optic neuritis on the subsequent risk of multiple sclerosis. METHODS: We conducted a multicenter study in which 389 patients with acute optic neuritis (and without known multiple sclerosis) were randomly assigned to receive intravenous methylprednisolone (250 mg every six hours) for 3 days followed by oral prednisone (1 mg per kilogram of body weight) for 11 days, oral prednisone (1 mg per kilogram) alone for 14 days, or placebo for 14 days. Neurologic status was assessed over a period of two to four years. The patients in the first group were hospitalized for three days; the others were treated as outpatients. RESULTS: Definite multiple sclerosis developed within the first two years in 7.5 percent of the intravenous-methyl-prednisolone group (134 patients), 14.7 percent of the oral-prednisone group (129 patients), and 16.7 percent of the placebo group (126 patients). The adjusted rate ratio for the development of definite multiple sclerosis within two years in the intravenous-methylprednisolone group was 0.34 (95 percent confidence interval, 0.16 to 0.74) as compared with the placebo group and 0.38 (95 percent confidence interval, 0.17 to 0.83) as compared with the oral-prednisone group. The beneficial effect of the intravenous-steroid regimen appeared to lessen after the first two years of follow-up. Signal abnormalities on magnetic resonance imaging (MRI) of the brain were a strong indication of risk for the development of definite multiple sclerosis (adjusted rate ratio in patients with three or more lesions, 5.53; 95 percent confidence interval, 2.41 to 12.66). The beneficial effect of treatment was most apparent in patients with abnormal MRI scans at entry. CONCLUSIONS: In patients with acute optic neuritis, treatment with a three-day course of high-dose intravenous methylprednisolone (followed by a short course of prednisone) reduces the rate of development of multiple sclerosis over a two-year period.

Acute Disease↗
PubMed2002

A longitudinal study of abnormalities on MRI and disability from multiple sclerosis.

BACKGROUND: In patients with isolated syndromes that are clinically suggestive of multiple sclerosis, such as optic neuritis or brain-stem or spinal cord syndromes, the presence of lesions as determined by T2-weighted magnetic resonance imaging (MRI) of the brain increases the likelihood that multiple sclerosis will develop. We sought to determine the relation between early lesion volume, changes in volume, and long-term disability. METHODS: Seventy-one patients in a serial MRI study of patients with isolated syndromes were reassessed after a mean of 14.1 years. Disability was measured with the use of Kurtzke's Expanded Disability Status Scale (EDSS; possible range, 0 to 10, with a higher score indicating a greater degree of disability). RESULTS: Clinically definite multiple sclerosis developed in 44 of the 50 patients (88 percent) with abnormal results on MRI at presentation and in 4 of 21 patients (19 percent) with normal results on MRI. The median EDSS score at follow-up for those with multiple sclerosis was 3.25 (range, 0 to 10); 31 percent had an EDSS score of 6 or more (including three patients whose deaths were due to multiple sclerosis). The EDSS score at 14 years correlated moderately with lesion volume on MRI at 5 years (r=0.60) and with the increase in lesion volume over the first 5 years (r=0.61). CONCLUSIONS: In patients who first present with isolated syndromes suggestive of multiple sclerosis, the increases in the volume of the lesions seen on magnetic resonance imaging of the brain in the first five years correlate with the degree of long-term disability from multiple sclerosis. This relation is only moderate, so the volume of the lesions alone may not be an adequate basis for decisions about the use of disease-modifying treatment.

Adolescent↗