Assessment of posterior fossa damage in MS using MRI

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

Specificity of Barkhof criteria in predicting conversion to multiple sclerosis when applied to clinically isolated brainstem syndromes

BACKGROUND: Barkhof criteria have been adopted to demonstrate dissemination in space in the new multiple sclerosis diagnostic criteria because of their high specificity for predicting conversion to multiple sclerosis. One of the 4 Barkhof criteria is the presence of an infratentorial lesion. In clinically isolated syndromes (CIS) of the brainstem (CISB), the infratentorial criterion does not demonstrate dissemination in space, raising the possibility that the criteria may be less specific in CISB, as compared with specificity in other CIS, in which all 4 criteria demonstrate dissemination in space. OBJECTIVE: To compare the validity indices of Barkhof criteria in CISB with those in other CIS. DESIGN: Inception cohort with median follow-up of 34 months for CISB and 40 months for other CIS. SETTING: Institutional ambulatory referral center. PATIENTS: A sample of 51 patients with CISB and 102 patients with other CIS (46 with myelitis and 56 with optic neuritis) was analyzed. Barkhof criteria, with a cutoff of 3 of 4, were applied to magnetic resonance imaging performed at baseline. Four combinations each containing 3 parameters were also applied, with a cutoff of 2 of 3. MAIN OUTCOME MEASURE: Specificity of unmodified Barkhof criteria and of the 4 combinations to predict conversion to clinically definite multiple sclerosis. RESULTS: The specificity of the criteria in CISB was 61% against 73% in other CIS. The combinations that retained the infratentorial lesion parameter had lower specificities in the CISB group; in analysis of the group with other CIS, no such differences were found. CONCLUSION: The infratentorial lesion criterion is responsible for the lower specificity of Barkhof criteria in CISB.     

Benign versus chronic progressive multiple sclerosis: magnetic resonance imaging features

The extent of disease as detected by magnetic resonance imaging was compared between 32 patients with benign multiple sclerosis (MS) and 32 patients with the chronic progressive form matched for age, sex, and disease duration. Computer-assisted quantitation of magnetic resonance images revealed a higher mean lesion load in chronic progressive multiple sclerosis (CPMS); however, in approximately 20% of benign MS patients the lesion load was higher than that in the CPMS patients. CPMS patients had a higher number of infratentorial lesions, yet similar numbers of supratentorial lesions, when compared with benign MS patients. The degree of confluency of lesions and the clinical expression of infratentorial lesions were typically higher in the CPMS patients. Benign MS was characterized by a lower degree of confluency and a higher number of asymptomatic infratentorial lesions. Thus, magnetic resonance imaging shows characteristic differences in magnetic resonance-detected changes between MS patients with different clinical courses.     

Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI

OBJECTIVE: To identify differences in pathology between the principal clinical phenotypes of MS using conventional and magnetization transfer (MT) MRI. METHODS: T1-weighted and T2-weighted images as well as MT scans were obtained from 20 controls, 21 patients presenting with clinically isolated syndromes suggestive of MS, and 93 MS patients with relapsing-remitting, secondary progressive, benign, or primary progressive course. Metrics considered: hypointense T1 and T2 lesion volumes, average lesion MT ratio, average brain MT ratio, peak height and position from MT histograms. RESULTS: MS patients had lower MT metrics than controls. Patients with clinically isolated syndromes had MT measures similar to controls, whereas primary progressive MS patients had lower histogram peak height with normal peak position. Relapsing-remitting MS patients had lower MT measures, higher T2 lesion load and ratio of hypointense T1 to T2 lesion volumes than patients with clinically isolated syndromes, and lower MT ratio and peak height than benign MS patients. Benign MS patients were similar to controls and patients with clinically isolated syndromes. Secondary progressive MS patients had the lowest MT measures and highest lesion loads. CONCLUSIONS: Pathology in patients with clinically isolated syndromes is confined to modest tissue damage in the lesions seen on T2-weighted scans. Severe damage is important for the later development of disability. However, microscopic damage in normal-appearing white matter may be a major contributor to disability in primary progressive MS.     

New T2 lesions enable an earlier diagnosis of multiple sclerosis in clinically isolated syndromes

In clinically isolated syndromes, the new McDonald criteria for multiple sclerosis diagnosis require new gadolinium-enhancing lesions for dissemination in time at a 3-month follow-up magnetic resonance imaging scan. In a cohort of 56 patients, these criteria were specific (95%) but less sensitive (58%) for clinically definite multiple sclerosis at 3 years. If new T2 lesions were allowed as an alternative for dissemination in time, sensitivity increased (74%) with maintained specificity (92%), enabling an accurate diagnosis of multiple sclerosis in more patients.     

Symptomatic unruptured capillary telangiectasia of the brain stem: report of three cases and review of the literature

OBJECTIVES: With increasing evidence that permanent tissue damage occurs early in the course of multiple sclerosis, it is important that treatment trials include patients in the earliest stages of the disease. For many patients with multiple sclerosis the first presentation is a clinically isolated syndrome. Not all patients with a clinically isolated syndrome develop multiple sclerosis, however, and treatment of all such patients would be unwarranted. A single abnormal brain MRI identifies patients at a higher risk for the early development of multiple sclerosis, but current criteria are limited by either poor specificity (T2 lesions) or sensitivity (contrast enhancing lesions). The aim of the study was to assess the positive predictive value, sensitivity, and specificity of MRI indices for the development of multiple sclerosis after 1 year from two MRI examinations obtained 3 months apart. METHODS: MRI examinations were performed in 68 patients with a clinically isolated syndrome, with a clinical assessment after 1 year. RESULTS: Contrast enhancing lesions at both time points were the most predictive indices for developing multiple sclerosis (positive predictive value 70%) but had low sensitivity (39%). The combination of T2 lesions at baseline with new T2 lesions at follow up had the best overall positive predictive value (53%), sensitivity (83%), and specificity (76%). In patients with T2 lesions at baseline, the presence or absence of new T2 lesions at follow up significantly altered the risk of multiple sclerosis within 1 year (55% and 5% respectively, p<0.001). Multiple sclerosis also developed in 10% of patients with a normal baseline MRI. CONCLUSIONS: Serial imaging in patients with clinically isolated syndromes improved the positive predictive value, sensitivity, and specificity of MRI for the development of early multiple sclerosis and also identified patients at a lower risk of early multiple sclerosis than would have been expected from their abnormal baseline MRI. Selection of patients with clinically isolated syndromes for therapeutic intervention or clinical trials may benefit from serial MRI, to target those at greatest risk of early development of multiple sclerosis.     

Clinical and MRI study of brain stem and cerebellar involvement in Japanese patients with multiple sclerosis

OBJECTIVES: To investigate the clinical and MRI features of brain stem and cerebellar lesions in Japanese patients with multiple sclerosis. METHODS: A retrospective study of 66 consecutive Japanese patients with multiple sclerosis (42 women and 24 men) was done by reviewing the medical records and MRI films. Forty nine patients were diagnosed as having clinically definite multiple sclerosis and 17 patients as having clinically probable multiple sclerosis according to Poser's criteria. Prevalence rates of each brain stem and cerebellar manifestation and frequency and distribution of MRI lesions in these patients were studied. RESULTS: Forty three patients (65%) had one or more infratentorial manifestations. Cranial nerves were clinically involved in 28 patients (42%), and most of the lesions were identified by MRI. Among them, manifestations of facial, trigeminal, and abducens nerves were relatively common. Cerebellar ataxia was found in 20 patients (30%). The MRI study showed that the lesions responsible for ataxia in these patients were mainly found in the cerebellar peduncles, but cerebellar hemispheric lesions were detected in only four patients (6.4%). CONCLUSION: The low frequency (6.4%) of the cerebellar MRI lesions in these patients is in sharp contrast with the figures reported for white patients with multiple sclerosis (50%-90%). Racial and genetic differences may have an influence on the susceptibility of each part of the CNS to demyelination in multiple sclerosis.     

Brain magnetic resonance imaging and multimodal evoked potentials in benign and secondary progressive multiple sclerosis.

Brain MRI and multimodal evoked potentials (EPs) were obtained for 13 patients with benign multiple sclerosis and 13 patients with secondary progressive multiple sclerosis, matched for age and duration of the disease, to investigate the nature of the disability in multiple sclerosis. Patients with secondary progressive multiple sclerosis had significantly greater lesion loads for five of seven periventricular regions and for three of nine regions separate from the ventricles. Patients with secondary progressive multiple sclerosis also had more severe infratentorial atrophy scores (p = 0.04), whereas there were no differences between the two groups in number and extent of enhancing lesions. The frequencies were significantly higher and severities greater for multimodal EP abnormalities of all the modalities in patients with secondary progressive multiple sclerosis. At least one EP component was absent in 12 (92%) patients with secondary progressive multiple sclerosis but in only one patient (8%) with benign multiple sclerosis (p < 0.001). There was neurophysiological evidence for cervical cord involvement in eight (61%) patients with secondary progressive multiple sclerosis and in one with benign multiple sclerosis (p < 0.01). These data indicate that the total amount of lesions, the distribution, and the nature of the pathological process might all account for the development of disability in multiple sclerosis.     

Relationship between multiple sclerosis intention tremor severity and lesion load in the brainstem

Intention tremor due to multiple sclerosis is clinically similar to cerebellar tremor. This study investigated, in 14 multiple sclerosis patients, the relationship between intention tremor severity and the lesion load in different infratentorial regions. Tremor amplitude was quantified during step-tracking tasks. The lesion load was measured on magnetic resonance images using an automated segmentation method. Intention tremor amplitude was significantly related to lesion load in the brainstem but not in the cerebellum. Specifically, tremor amplitude correlated with the lesion load in the contralateral pons, and patients with more severe tremor in both arms had a greater lesion load bilaterally in the pons. These results support the view that multiple sclerosis intention tremor is related to dysfunction of cerebellar inflow and/or outflow pathways.     

The initial diagnosis of multiple sclerosis: clinical impact of magnetic resonance imaging

Thirty patients in whom the initial diagnosis of multiple sclerosis was clinically entertained underwent cranial magnetic resonance imaging (MRI) in close temporal relationship to cranial x-ray computed tomography (CT), electrodiagnostic studies (visual evoked responses, brainstem auditory evoked responses, and somatosensory evoked responses), and cerebrospinal fluid analyses (oligoclonal bands, myelin basic protein, and IgG/albumin ratio). In 26 of the 30 patients, MRI demonstrated lesions consistent with multiple sclerosis that corresponded, at least in part, with the clinically expected neuroanatomical lesion distribution. Two of the 4 patients with normal MRI had normal electrodiagnostic studies and cerebrospinal fluid analyses, and the other 2 had a single abnormal or equivocal electrodiagnostic study. All 26 patients with abnormal MRI had at least one other abnormal laboratory test. CT revealed only the largest lesions, and in the patients with abnormal CT, MRI demonstrated even more lesions. MRI, in this limited series, proved to be a strong tool in the initial diagnosis of multiple sclerosis; it may prove to be the single best test, with a sensitivity exceeding that of electrodiagnostic studies and cerebrospinal fluid analysis.     

Cranial MRI in idiopathic retinal vasculitis

Ten patients with clinically isolated idiopathic retinal vasculitis who had a positive family history for multiple sclerosis (MS) or positive typing for HLA B7 underwent magnetic resonance imaging (MRI) of brain and optic nerves in order to establish the frequency of clinically silent lesions. Brain MRI was normal in seven and abnormal in three: one had a single small white matter lesion, two had extensive white matter abnormalities resembling those seen in MS. In two patients a lesion was shown in the optic nerve. These findings suggest that a minority of patients with idiopathic retinal vasculitis have disseminated central nervous system lesions characteristic of MS, the frequency of such changes being less than in patients with isolated optic neuritis.     

Seizures due to multiple sclerosis: seven patients with MRI correlations.

The MRI data of seven patients with clinically definite multiple sclerosis who developed epileptic seizures are presented. Six of these cases demonstrated new or enhancing lesions. Cerebral biopsy in one of these lesions confirmed inflammation with myelin breakdown products. Lesions implicated in the causation of seizures involved the cortex or subcortical area. In one patient, a new lesion was associated with EEG abnormalities which resolved as the lesion reduced in size. In three patients epileptic activity was the only clinical manifestation of disease. Large, unresolving lesions tended to be associated with continuing seizures.     

Disease-modifying drugs for the early treatment of multiple sclerosis

The introduction of new immunomodulatory therapies such as, interferon-beta, glatiramer acetate (Copaxone, Teva Pharmaceutical Industries) and mitoxantrone (Ralenova, Wyeth Pharma; Novantrone, Immunex Corp.) has considerably improved the therapeutic options for patients with multiple sclerosis. These agents have been shown to reduce relapse rate, slow down progression of disability and prevent the accumulation of magnetic resonance imaging lesion load in clinically definite multiple sclerosis. Moreover, two formulations of interferon-beta delayed conversion into clinically definite multiple sclerosis in patients with clinically isolated syndromes suggestive of multiple sclerosis. Since axonal damage leading to irreversible neurological disability is already present early at the onset of the disease, immunomodulatory therapy should start as soon as possible. This article reviews the arguments for the early initiation of therapy and provides an overview of clinical studies dealing with the early treatment of multiple sclerosis.     

Rationale for early intervention with immunomodulatory treatments

The McDonald diagnostic criteria have allowed the formal diagnosis of multiple sclerosis in patients presenting with clinically isolated syndromes to be brought forward. Evidence from research suggests that many patients with clinically isolated syndromes or early multiple sclerosis should be treated with disease-modifying drugs at an early stage, since disease experience during the first few years are likely to have significant impact on the long-term evolution of the disease. Histopathological studies have demonstrated the presence of axonal transection in patients with less than five years of disease duration, and especially during the first twelve months. Natural history studies have shown that the number of relapses occurring during the first few years of the disease is related to the time to accrued disability. Moreover, longitudinal studies on patients with clinically isolated syndromes have shown that the presence of even a very small number of baseline MRI lesions is associated with an increased risk of developing clinically definite multiple sclerosis and, more importantly, that the increase in volume of the lesions seen in the first five years correlates with the degree of disability in the longer term. For example, long-term follow-up of a large cohort of patients presenting with a clinically isolated syndrome in Barcelona has shown that the number of Barkhof criteria fulfilled at baseline was correlated with the risk of relapse, EDSS disability scores at five years and the risk of reaching given EDSS disability thresholds. Three randomised clinical trials in patients with a clinically isolated syndrome and abnormal brain MRI have shown significant benefit of initiating early therapy with beta-interferons, and a similar study is underway with glatiramer acetate. It is concluded that choosing the right time to introduce treatment is critically important for outcome and the earlier treatment is initiated, the better the outcome.     

Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study

BACKGROUND: Gray matter (GM) atrophy has been reported in multiple sclerosis (MS). However, little is known about its regional distribution. OBJECTIVE: To investigate the regional distribution of GM atrophy in clinically early primary progressive MS (PPMS). DESIGN AND PATIENTS: Thirty-one patients with PPMS within 5 years of symptom onset (mean age, 43.2 years; median Expanded Disability Status Scale score, 4.5) and 15 healthy control subjects (mean age, 43.7 years) were studied. All subjects underwent a 3-dimensional inversion-recovery fast spoiled gradient-recalled echo sequence that was repeated after 1 year in patients only. Magnetic resonance images underwent an optimized voxel-based morphometric analysis that segments magnetic resonance data volumes in a normalized space and quantifies tissue atrophy on a voxel-by-voxel basis. A lesion mask was created for each patient and used in normalization and segmentation steps to minimize bias from lesions. A multisubject design was used in the cross-sectional study to compare patients with PPMS and controls. A 1-way analysis of variance (within-subjects) design was used in the longitudinal study. RESULTS: At baseline, patients with PPMS displayed bilateral thalamic atrophy compared with controls. In addition, a significant association between lesion load and decreased GM volume was found for the thalami. Loss of GM in the putamen, caudate, thalami, and cortical and infratentorial areas was observed in patients after 1 year of follow-up. CONCLUSIONS: Atrophy is most obvious in deep GM in clinically early PPMS. This may reflect increased sensitivity of these regions to neurodegeneration. Cortical and infratentorial atrophy developed as the disease evolved.     

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 isolated noncompressive spinal cord syndromes

The frequency with which patients presenting with acute or chronic noncompressive cord syndromes subsequently develop multiple sclerosis is uncertain. Magnetic resonance imaging (MRI) was performed on 121 patients with such syndromes to determine the frequency of asymptomatic brain lesions and to assess the sensitivity of MRI in detecting the local cord lesion. MRI findings were compared with those from visual, brainstem, and somatosensory evoked potentials (VEPs, BAEPs, SEPs), and cerebrospinal fluid electrophoresis. Lesions were seen in the appropriate cord region in 47 of 73 patients (64%) with a cervical syndrome, and in 7 of 25 patients (28%) with a thoracic or lumbar syndrome. MRI demonstrated more cervical lesions than did SEPs, but fewer thoracic or lumbar lesions. Cord swelling was seen in 6 patients and atrophy in 10. Of those with acute syndromes, abnormalities were seen with brain MRI in 18 of 32 patients (56%), with VEPs in 2 of 30 patients (7%), and with BAEPs in 2 of 24 patients (8%). In patients with chronic syndromes, abnormalities were seen with brain MRI in 73 of 89 patients (82%), with VEPs in 22 of 80 patients (28%), and with BAEPs in 12 of 62 patients (19%). Brain MRI was thus more sensitive than evoked potentials were in establishing multiplicity of lesions. However, in acute syndromes, it was not possible to diagnose multiple sclerosis from a single abnormal brain scan in chronic syndromes, a diagnosis of clinically probable multiple sclerosis could be made from one scan, provided there was no better explanation for the abnormalities: the added presence of oligoclonal bands allows a diagnosis of laboratory-supported, definite multiple sclerosis as was the case in 28 patients in this series.     

Inflammation and atrophy in multiple sclerosis: MRI associations with disease course

Brain atrophy may be a useful surrogate marker of axonal loss and disease progression in multiple sclerosis (MS). Several studies have suggested that inflammatory disease activity is a risk factor for atrophy in the early stages of the disease, but may become less important later in the disease course. We aimed to investigate the relationships between atrophy and active inflammation at different stages of the disease course using brain volume measurements from magnetic resonance imaging (MRI) in patients with both relapsing-remitting (RR) (n=95) and secondary progressive (SP) (n=76) MS. Conventional dual echo and three-dimensional magnetization-prepared rapid-acquisition gradient echo imaging were performed in all patients and in 31 healthy controls. Supratentorial and infratentorial brain, and lateral ventricular volumes were determined using modern design stereology.Patients with SP MS had smaller supratentorial (p=0.003) and infratentorial brain volumes (p=0.0003), and larger lateral ventricles (p=0.02) than patients with RR MS. RR MS patients with T(1)-enhancing lesions had smaller supratentorial (p=0.02) and infratentorial (p=0.002) brain volumes and larger ventricles (p=0.002) than those without enhancing lesions. SP MS patients with enhancing lesions also had significantly larger lateral ventricles (p=0.03). Categorical analysis showed that more RR MS patients with enhancing lesions had smaller supratentorial brain (p=0.005), or larger lateral ventricular (p=0.028) volumes, and more SP MS patients with enhancing lesions had increased lateral ventricle volumes (p=0.013), than patients without enhancements. The number of enhancing lesions was significantly correlated with lateral ventricular volumes in both RR MS (r=0.39, p=0.0001) and SP MS (r=0.46, p<0.0001). Our data shows that the presence of active inflammation on a single MRI in the course of RR and SP MS, is associated with a higher risk and higher level of brain atrophy. These findings emphasise the important long-term relationship between inflammation and atrophy in MS and provide additional support for the strategy of early anti-inflammatory treatment to protect tissue integrity.     

MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study

BACKGROUND: The 2001 and 2005 McDonald criteria allow MRI evidence for dissemination in space (DIS) and dissemination in time (DIT) to be used to diagnose multiple sclerosis in patients who present with clinically isolated syndromes (CIS). In 2006, new criteria were proposed in which DIS requires at least one T2 lesion in at least two of four locations (juxtacortical, periventricular, infratentorial, and spinal-cord) and DIT requires a new T2 lesion on a follow-up scan. We applied all three criteria in a large cohort of CIS patients to assess their performance by use of conversion to clinically definite multiple sclerosis (CDMS) as the outcome. METHODS: Patients who had two MRI scans within 12 months of CIS onset were identified in four centres in the Magnims European research network. The specificity and sensitivity of MRI criteria for CDMS after 3 years was assessed in 208 patients. A Cox proportional hazards model was applied in a larger cohort of 282 patients that included all patients irrespective of length of follow-up. FINDINGS: The specificity of all criteria for CDMS was high (2001 McDonald, 91%; 2005 McDonald, 88%; new, 87%). Sensitivity of the new (72%) and 2005 McDonald (60%) criteria were higher than the 2001 McDonald criteria (47%). The Cox proportional hazards model showed a higher conversion risk for all three criteria in those with both DIS and DIT than those with either DIS or DIT alone. When all three criteria were included in the model, only the new criteria had an independent significant effect on conversion risk. INTERPRETATION: The new criteria are simpler than the McDonald criteria without compromising specificity and accuracy. The presence of both DIS and DIT from two MRI scans has a higher specificity and risk for CDMS than either DIS or DIT alone.     

Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis

BACKGROUND: The number and volume of abnormalities on baseline brain magnetic resonance images in patients with initial findings suggestive of multiple sclerosis are known to predict outcome in terms of disability. However, no long-term data exist on specific locations or types of lesions. OBJECTIVE: To assess the long-term predictive value of baseline magnetic resonance imaging parameters, including location of lesions and gadolinium-enhancing and hypointense lesions in patients with initial findings suggestive of multiple sclerosis for the occurrence of clinically relevant disability as defined by an Expanded Disability Status Scale score of 3. PATIENTS: After a median follow-up period of 8.7 years, the medical records of 42 patients were reviewed and assessed for time until patients received an Expanded Disability Status Scale score of 3. Magnetic resonance imaging parameters were dichotomized according to maximum accuracy and then used to calculate hazard ratios using the Cox model for proportional hazard ratios. RESULTS: Conversion to clinically definite multiple sclerosis was observed in 26 patients (62%), of whom 14 (54%) progressed to an Expanded Disability Status Scale score of 3. Two or more infratentorial lesions best predicted long-term disability (hazard ratio, 6.3). Gadolinium-enhancing and hypointense T1-weighted lesions did not show prognostic value. CONCLUSION: Infratentorial lesions are related to long-term prognosis for patients with initial findings suggestive of multiple sclerosis and thus may help to identify patients at high risk for earlier occurrence of clinically relevant disability.