Dissemination In Space Criteria Research Articles

Application of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Spanish cohort of patients with clinically isolated syndromes

Background: Recently the International Panel on Diagnosis of Multiple Sclerosis (MS) has proposed new magnetic resonance imaging (MRI) criteria for the diagnosis of MS in patients with clinically isolated syndromes (CIS). We aimed to evaluate the accuracy of these new criteria for lesions dissemination in space (DIS) and time (DIT), from a single MRI scan, to predict conversion from CIS to clinically definite MS. Methods: We studied 67 CIS patients with baseline MRI performed within the first 3 months after onset. The follow-up was of at least 24 months. The sensitivity, specificity and accuracy of Barkhof–Tintoré criteria and the new proposed MRI criteria for DIS and DIT were calculated with SPSS v.15.0. Results: The mean age for clinical onset was 30 years and 64% of patients were female. The overall conversion rate was 74%. In our cohort, Barkhof–Tintoré criteria showed a sensitivity of 71.43%, a specificity of 66.67%, with an accuracy of 73.1%. New DIS criteria showed a sensitivity of 85.71%, a specificity of 64.71% and an accuracy of 80.30%. We also evaluated the new DIT criteria with a single MRI scan in 54 patients with baseline scans that included gadolinium-enhanced images. The sensitivity of the test was 52.63% with a specificity of 75.00% and an accuracy of 59.26%. Conclusion: New DIS criteria are simpler and more sensitive than previous criteria. The sensitivity of DIT criterion using a single MRI scan was rather low, as other previous studies showed, reflecting its stringency, but it could improve the accuracy of early MS diagnosis in that group of patients with typical CIS and gadolinium-enhancing and non-enhancing lesions on their baseline scans. These results reinforce their use in MS diagnosis.

Clinical isolated syndrome: A 3-year follow-up study in China

Objective To summarize the characteristics of Chinese clinically isolated syndrome (CIS) patients and their 3-year follow-up results. Investigate the relationship between CIS features and clinical outcomes. Methods Forty-nine CIS patients were recruited and 42 of them were able to be followed up for a mean of 38 months (range 26–48 months). We recorded baseline features including patient demographics, site of CIS, presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OCB) and MRI lesions in brain and spinal cord. The incidence of conversion to clinically definite MS (CDMS) or neuromyelitis optica (NMO) after CIS was calculated, and the relationship between baseline features and CDMS was explored. All data were statistically processed with SPSS for Windows Version 11.5. Results After a mean follow-up of 38 months, 10/42 patients had converted to CDMS (24%), and one patient had developed definite NMO. The other 31 patients remained in CIS status. A spinal cord syndrome was the initial CIS manifestation in 57% of patients. The conversion rates to MS were 22% (5/23) for patients presenting with a spinal cord syndrome and 27% (3/11) for multi-focal manifestations. The three-year CDMS conversion rates were 70% (7/10) for patients who fulfilled the MRI dissemination in space criteria (2005 revised McDonald) at onset of CIS, while only 9% (3/32) of patients who did not fulfill these criteria converted to CDMS. Females had significantly higher conversion rate than males. Conclusion A spinal cord syndrome was the most common initial presentation of our Chinese CIS group. After a mean follow-up of 38 months, the conversion rate to MS was approximately 25%. The 2005 revised McDonald MRI criteria for dissemination in space is a key prognostic factor for conversion to MS in CIS in Chinese patients.

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

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. 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. 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). 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.

Predictive factors for multiple sclerosis in patients with clinically isolated spinal cord syndrome

Objectives: To identify predictors of conversion to definite multiple sclerosis (MS) in patients with a cord clinically isolated syndrome. Methods: The predictive values for conversion to MS of clinical, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) variables in 114 patients with acute partial myelitis confirmed by a spinal cord lesion on MRI were studied. Other causes of cord syndromes were excluded. Results: MS was diagnosed in 78 patients (86%) during 4.0 ± 1.9 years of follow-up. Some 67 of these patients had a second clinical episode. The diagnosis of isolated myelitis was maintained for 36 patients, 78% of whom (28 cases) were followed for at least 2 years, comparable to the MS patients. Age, bladder involvement, ≥2 cord lesions on MRI, ≥9 brain lesions, ≥3 periventricular lesions and intrathecal IgG synthesis predicted conversion to clinically definite MS. Multivariate logistic analysis identified three predictors of MS diagnosis: age ≤40 years, inflammatory CSF and ≥3 periventricular lesions on brain MRI. Conclusion: Two out of three baseline factors (age, periventricular lesions and inflammatory CSF) predicted conversion to MS with better accuracy than the revised McDonald criteria for dissemination in space.

Relapsing demyelinating CNS disease in a Korean pediatric population: Multiple sclerosis versus neuromyelitis optica

Background and Objective:Our objective was to characterize the clinical and radiologic features of Korean pediatric patients with relapsing central nervous system (CNS) demyelination disease. Methods:Twenty-one patients with relapsing CNS demyelinating events were classified as having multiple sclerosis (MS, 18 patients) or neuromyelitis optica (NMO, three patients) according to the international consensus definitions. Retrospective analysis of clinical and radiologic features was conducted. Anti-aquaporin-4 antibody (AQP4 Ab) test was performed in six patients (including three NMO patients) who showed selective involvement of optic nerve and spinal cord. Results: Median age at the initial episode in patients with MS was 7.0 years (range, 4.4–13.6 years). Three of 18 MS patients (3/18, 17%) showed selective involvement of the optic nerve and spinal cord during the clinical course. Five patients (31%) at the initial episode and nine patients (50%) at relapse met the McDonald magnetic resonance imaging criteria for dissemination in space. Oligoclonal bands detected with a silver staining method were positive in only one patient of 16 patients tested. Two NMO patients positive for AQP4 Ab showed frequent relapses and early disabilities that were unresponsive to interferon treatment. Conclusions:We conclude that Korean pediatric patients with relapsing CNS demyelination disease were characterized by preferential involvement of the optic nerve or spinal cord. The AQP4 Ab test seems to be useful for predicting clinical courses in the setting of heterogeneous opticospinal presentations.

The radiologically isolated syndrome: take action when the unexpected is uncovered?

The increasing diagnostic application of magnetic resonance imaging (MRI) in neurology has resulted in an increase in accidental disclosure of asymptomatic brain pathologies with potential clinical significance. Here, we discuss the incidental detection of multiple sclerosis (MS) typical central nervous system (CNS) lesions fulfilling MRI criteria for dissemination in space (radiologically isolated syndrome, RIS) and its diagnostic, prognostic and therapeutic implications. Three recent studies, including a total of 136 RIS cases which were followed for up to 10 years, indicate that a subgroup of such patients will develop MS. MRI-based dissemination in time (DIT) was determined in more than two-thirds and clinically isolated syndrome (CIS) occurred in almost one-third of the patients. Presence of Gadolinium (Gd)-enhancing lesions was identified as potential predictor for MRI-based DIT in one study, and pathological visual evoked potential (VEP) examinations at baseline and Gd-enhancement at the second MRI scan for CIS (clinical DIT) in another study. In the lack of established management guidelines, we propose a pragmatic diagnostic and therapeutic approach for patients with RIS. Individual concepts are required and both "wait" as well as "follow" strategies are justifiable. Further prospective studies are required to elucidate potential biomarkers for narrowing down the high-risk cohort and exploring further characteristics of this disease stage.

Evaluation of the 2005 McDonald MRI criteria for dissemination in space in Afro‐Caribbean patients with clinically isolated syndromes

In 2005, the McDonald MRI criteria for dissemination in space were revised to improve diagnosis of multiple sclerosis (MS) in non-Caucasians. We included patients with a first clinically isolated syndrome (CIS) to assess their performance in the Afro-Caribbean population. Baseline brain and spine MRI examinations were available within 3 months after onset of CIS. The development of a second clinical event was used as the main outcome indicating clinically definite MS. A total of 66 patients (52F/14M) were included between January 1998 and January 2008 (mean age: 34.7; median follow-up: 34 months). CIS was classified as spinal cord (30.3%), optic neuritis (28.8%), brainstem (24.2%), multiregional (10.6%), hemispheric (4.5%), or undetermined (1.5%). Overall conversion rate was 42.4% (median: 11 months). The McDonald criteria revised for dissemination in space were fulfilled in 33.3% (sensitivity: 0.39 (+/-0.18); specificity: 0.66 (+/-0.15), positive predictive value: 0.46 (+/-0.20), negative predictive value: 0.60 (+/-0.15). The Afro-Caribbean population is characterized by a strong proportion of CIS in the spinal cord and a lower burden of disease on the baseline brain MRI. This may explain the low sensitivity of the 2005 McDonald criteria for dissemination in space. Further prospective studies emphasizing MRI spinal cord features are needed to improve diagnostic criteria in a population of African descent.

Magnetic resonance imaging at first episode in pediatric multiple sclerosis retrospective evaluation according to KIDMUS and lesion dissemination in space criteria

Background: Several diagnostic imaging criteria are being described and examined in pediatric multiple sclerosis (MS). Compared to adults, children are more likely to experience acute or relapsing demyelinating episodes of various etiologies which show similar clinical and magnetic resonance imaging (MRI) findings. Aim: To investigate the fulfillment of MRI diagnostic criteria at initial episode in pediatric MS. Methods: We reviewed our series of children and adolescents with the final diagnosis of clinically definite MS and applied the McDonald dissemination in space (DIS) and KIDMUS criteria to their initial MRI scans. Results: Thirty patients (17 girls, 13 boys), most with brainstem dysfunction and polysymptomatic presentation, were included in the study. Twenty-five (83.3%) patients fulfilled both McDonald and KIDMUS criteria. Patients who did not meet any McDonald DIS criteria did not meet KIDMUS criteria either. Only one patient met the McDonald criteria but not the KIDMUS criteria because of the absence of lesions perpendicular to corpus callosum. Conclusions: Our results show 5/30 (16.6%) of MS patients may not present the diagnostic MRI features initially. The variable sensitivity observed for the current MRI criteria in different series can be due to referral biases, differences between populations and length of follow-up, and the definition of MS patients by two attacks only.

A search for new MRI criteria for dissemination in space in subjects with a clinically isolated syndrome

The International Panel on the Diagnosis of Multiple Sclerosis (MS) incorporated the Barkhof/Tintoré (B/T) magnetic resonance criteria into their diagnostic scheme to provide evidence of dissemination in space of central nervous system lesions, a prerequisite for diagnosing MS in patients who present with clinically isolated syndromes (CIS). Although specific for MS, the B/T criteria were criticised for their low sensitivity and relative complexity in clinical use. We used lesion characteristics at onset from 349 CIS patients in logistic regression and recursive partitioning modelling in a search for simpler and more sensitive criteria, while maintaining current specificity. The resulting models, all based on the presence of periventricular and deep white matter lesions, performed roughly in agreement with the B/T criteria, but were unable to provide higher diagnostic accuracy based on information from a single scan. Apparently, findings from contrast-enhanced and follow-up magnetic resonance scans are needed to improve the diagnostic algorithm.

A Single, Early Magnetic Resonance Imaging Study in the Diagnosis of Multiple Sclerosis

A diagnosis of multiple sclerosis in patients who present for the first time with a clinically isolated syndrome (CIS) can be established with brain magnetic resonance imaging (MRI) if the MRI demonstrates demyelinating lesions with dissemination in space (DIS) and dissemination in time (DIT). To investigate the diagnostic performance of a single MRI study obtained within the first 3 months after symptom onset in a cohort of patients with a CIS suggestive of multiple sclerosis at presentation. Multicenter inception cohort with a follow-up of at least 24 months. Referral hospitals. Patients Patients with CIS onset between April 1, 1995, and September 30, 2004, who fulfilled the following criteria were included: (1) age of 14 to 50 years and (2) clinical follow-up for at least 24 months after CIS onset or until development of clinically definite multiple sclerosis (CDMS), if this occurred within 2 years. Main Outcome Measure All patients underwent 2 comparable brain MRI examinations, the first within 3 months (early) and the second between 3 and 12 months (delayed) after CIS onset. We defined DIS using several existing MRI criteria, and DIT was inferred when there were simultaneous gadolinium-enhancing and nonenhancing lesions on a single MRI. Two hundred fifty patients were included in the study. The comparison of the diagnostic performance of various MRI criteria for identifying early converters to CDMS showed similar sensitivity and specificity between early and delayed MRIs. In addition, the use of less stringent criteria for DIS yielded better sensitivity and similar specificity, particularly when assessed in the first weeks after CIS onset. A single brain MRI study that demonstrates DIS and shows both gadolinium-enhancing and nonenhancing lesions that suggest DIT is highly specific for predicting the early development of CDMS, even when the MRI is performed within the first 3 months after the onset of a CIS.

The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28-May 5, 2007

The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28-May 5, 2007

Accuracy of CSF and MRI criteria for dissemination in space in the diagnosis of multiple sclerosis

Demonstration of lesion dissemination in space (DIS) and time (DIT) is necessary for the diagnosis of multiple sclerosis (MS) in clinically isolated syndromes (CIS). The McDonald criteria accepted two methods to demonstrate DIS. The fulfillment of at least three of four MRI Barkhof criteria (MRI-BC) or, alternatively, the finding of at least two MRI lesions on T2-weighted images (T2 lesions) plus the presence of oligoclonal IgG bands (OCGB) in cerebrospinal fluid (CSF). We aimed to evaluate the accuracy of both methods for DIS demonstration to predict conversion of CIS to MS using a new OCGB test. We studied fifty-eight CIS patients with OCGB detection and brain MRI, and followed them up during 6 years. Twenty-eight patients fulfilled MRI-BC. Twenty-five of them converted to MS during follow-up (sensitivity 73.53%, specificity 87.50%, accuracy 79.31%). Thirty-four patients had at least two T2 lesions plus oligoclonal bands. Thirty-three converted to MS during follow-up (sensitivity 94.29%, specificity 95.65%, accuracy 94.82%). The presence of oligoclonal IgG bands plus two T2 lesions accurately predicts CIS conversion to MS. MRI-BC criteria have a high specificity but less sensitivity and accuracy. These results reinforce the role of CSF study in MS diagnosis.

MRI criteria for dissemination in space in patients with clinically isolated syndromes: a multicentre follow-up study

The McDonald International Panel accepted the Barkhof/Tintoré criteria for providing MRI evidence of dissemination in space to allow a diagnosis of multiple sclerosis in patients with clinically isolated syndromes (CIS). We applied these criteria in a large cohort of patients with CIS, representative of those seen in a general diagnostic setting, to assess their accuracy in predicting conversion to definite multiple sclerosis and to identify factors that affect this risk. In a collaborative study of seven centres, baseline MRI and clinical follow-up data for 532 patients with CIS were studied, with the development of a second clinical event used as the main outcome. All scans were scored for lesion counts and spatial lesion distribution to assess the fulfilment--ie, at least three out of four--of the Barkhof/Tintoré criteria. We used survival analysis and 2x2 tables to assess the test characteristics of the criteria at baseline. Overall conversion rate was 32.5% with a median survival time of 85.3 months. Fulfilment of the criteria at baseline showed, after a survival time of 2 years, a conversion rate of about 45% (95% CI 37-53) versus about 10% (6-16) in those with no asymptomatic lesions at baseline (p<0.0001). For patients with a follow-up of at least 2 years, the fulfilment of the MRI criteria showed an accuracy of 68% (sensitivity 49%, specificity 79%) for predicting conversion and an increase in risk of nearly four times for conversion compared with those not fulfilling the criteria (odds ratio 3.7, 95% CI 2.3-5.9; p<0.0001). Cox proportional hazards regression analysis accorded with this increased risk. No effects were recorded on the performance of the criteria by sex, presenting symptoms, or centre. Age at baseline did have a small but significant effect as predictor (hazard ratio 0.97, 0.95-0.99; p=0.002), but did not affect the prognostic value of the MRI criteria. MRI abnormalities have important prognostic value. The cut-off, based on the Barkhof/Tintoré criteria, as incorporated in the McDonald diagnostic scheme yields acceptable specificity, but could have lower sensitivity than previously reported.

MULTIPLE SCLEROSIS IN THE TROPICS

Objectives: Multiple sclerosis (MS) is not commonly seen in children, more so amongst Asian children living in the tropics. We report four cases of definite relapsing-remitting multiple sclerosis, and a fifth child with a florid first demyelinating episode and a high risk towards developing subsequent MS, occurring in Malaysian children. Methods: Five children were seen over the last three years (January 2003 till October 2005). The children with definite MS fulfilled MacDonald's criteria for dissemination in time and space, whilst the child with high risk for MS fulfilled criteria for dissemination in space. Results: Age of onset ranged from 4 to 10 years. All four children (two girls, two boys) with definite MS had an initial optic neuritis of insidious onset, followed by subsequent symptomatic and silent demyelinating syndromes involving the brain and spinal cord. Long segment contiguous lesions were seen when the spinal cord was involved. Clinical symptoms included deterioration in vision, aphasia, cerebellar dysfunction, hemiparesis, monoparesis or quadriparesis, paraparesis and sphincteric involvement. All clinical episodes improved with intravenous methylprednisolone and oral prednisolone. The first child we saw had five relapses before receiving prophylactic interferon beta-1a, experiencing a further single relapse after a year on treatment. Two other children have recently been started on interferon beta-1a after the second episode. The boy with high risk for MS had a first demyelinating episode with bilateral optic neuritis and multiple gadolinium enhancing perpendicular periventricular and callosal lesions, with complete resolution after treatment with steroids. Conclusion: Multiple sclerosis is seen in Asian children. The disease in these children may have a preponderance towards optic neuritis and spinal cord syndromes.

Overdiagnosis of multiple sclerosis and magnetic resonance imaging criteria

Retrospectively, we assessed the specificity of two proposed magnetic resonance imaging (MRI) criteria for multiple sclerosis (MS) in patients suspected to have MS but who ultimately receive another diagnosis. Brain MRIs of 28 patients mixed with 28 MRIs of MS patients from the same cohort of 377 consecutively referred patients were scored by a neuroradiologist masked to the final diagnosis. The criteria for dissemination in space incorporated in the McDonald International Panel showed good specificity (89%). However, the more sensitive criteria proposed by a Subcommittee of the American Academy of Neurology resulted in a lower specificity (29%), indicating an increased risk of a false-positive diagnosis.

Modification of MRI criteria for multiple sclerosis in patients with clinically isolated syndromes

Background: The McDonald criteria include MRI evidence for dissemination in space and dissemination in time for the diagnosis of multiple sclerosis in young adult patients who present with clinically isolated...

MRI criteria for multiple sclerosis

This study assessed the validity of established MRI criteria for multiple sclerosis (MS) in a cohort of 20 children with clinically definite MS. The authors found that many pediatric MS patients did not meet the MRI criteria established for adult-onset MS, particularly the McDonald MRI criteria for dissemination in space. The authors thus suggest that MRI criteria for adult MS be applied cautiously to pediatric MS patients.

Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination.

The most recent diagnostic criteria for multiple sclerosis (MS) ascertain that findings from spinal cord MRI can be used to demonstrate dissemination in space. Because little is known about the prevalence and characteristics of cord lesions early in the disease, the authors studied the prevalence of spinal cord abnormalities in patients with early-stage MS and assessed their impact on diagnostic classification. The brains and spinal cords of 104 recently diagnosed patients with MS were examined. Median interval between first symptom and diagnosis was 18.4 months. The brain MRI protocol included before and after gadolinium axial T1-weighted conventional spin-echo sequences and dual-echo spin-echo images. For spinal cord MRI, sagittal cardiac-triggered dual-echo T2-weighted and sagittal T1-weighted spin-echo images were included. Clinical assessment for each patient included age, sex, clinical signs for spinal cord involvement, and Expanded Disability Status Scale. Abnormal cord MRIs were found in 83% of patients, usually with only focal lesions. Diffuse cord abnormalities were found in 13% of patients, although in isolation they were found in only three patients. Focal cord lesions were often multiple (median number, 3.0), small (median, 0.8 vertebral segments), and primarily (56.4%) situated in the cervical spinal cord. In 68 of 104 patients (65.4%), two or more focal lesions were visible on spinal cord images. The criteria for dissemination in space, as defined in the McDonald criteria for the brain, were met in only 66.3% of the patients. This percentage increased to 84.6% when spinal cord MRI abnormalities were also included. Spinal cord abnormalities are prevalent in patients with early-stage MS, have distinct morphologic characteristics, and help to determine dissemination in space at time of diagnosis.

MRI/MRS of corpus callosum in patients with clinically isolated syndrome suggestive of multiple sclerosis.

Atrophy of corpus callosum (CC) related to axonal loss has previously been observed in patients at the early stage of clinically definite multiple sclerosis (CDMS). Atrophy increases with the progression of the disease. Nevertheless, no data concerning the onset of atrophy of CC are currently available. The purpose of this study is to determine if damage in callosal tissue was present at the earliest stage of MS, in a subgroup of patients presenting with a clinically isolated syndrome suggestive of MS (CISSMS), fulfilling the dissemination in space criteria according to McDonald. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) techniques were applied to measure CC volume, magnetization transfer ratio (MTR), mean diffusivity (MD), N-acetyl aspartate/choline-containing compounds (NAA/Cho) ratio, N-acetyl aspartate/total creatine (NAA/Cr) ratio and Cho/Cr ratio inside the CC of 46 CISSMS patients and 24 sex- and age-matched controls. No atrophy of CC was observed in the CISSMS group. CC of patients was characterized by decreased MTR and increased MD. No change in the NAA/Cr ratio was observed while the NAA/Cho ratio decreased and Cho/Cr ratio increased in the splenium and the central anterior part of CC. These abnormalities were present in patients with, but also without, macroscopic lesions inside the CC. Our results indicate that diffuse structural and metabolic changes, which may be interpreted as representing predominantly myelin pathology, occur in the CC at the earliest stage of MS before any atrophy is detected.