Biomedical subjects

Frederik Barkhof

Publications and source records attributed to Frederik Barkhof.

At least 19 recordsLinked to original sources

PubMed2007

CSF and MRI markers independently contribute to the diagnosis of Alzheimer's disease.

BACKGROUND: Decreased amyloid beta (1-42) (Abeta42) and increased (phosphorylated) tau in cerebrospinal fluid (CSF) are considered to be a reflection of plaques, tangles, and neuronal degeneration in Alzheimer's disease (AD). Atrophy of the medial temporal lobe (MTA) on magnetic resonance imaging (MRI) reflects neuronal loss in this area. OBJECTIVE: To compare diagnostic accuracy of CSF biomarkers and MTA in AD versus controls. METHODS: Abeta42, tau and tau phosphorylated at threonine 181 (Ptau-181) were measured in CSF from 61 AD patients and 32 controls by sandwich enzyme-linked immunosorbent assay. A CSF biomarker profile for AD was constructed. MTA was rated visually on MRI. RESULTS: When AD patients and controls were evaluated separately, no correlations were present between the CSF markers and MTA score. Both MTA and CSF biomarker profile were independently associated with the diagnosis AD (MTA: OR (95% CI)=28 (3-239); CSF biomarker profile: OR (95% CI)=57 (13-262)). Among individuals younger than 65 years old and without MTA 60% suffered AD, and the finding of an abnormal CSF biomarker profile was limited to AD patients only. CONCLUSIONS: MTA and CSF biomarkers seem to be of incremental value for the diagnosis AD. CSF analysis is most sensitive in the absence of MTA, and especially among early-onset AD patients.

Aged↗

PubMed2007

Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study.

BACKGROUND: Age-related white matter changes (ARWMCs), frequently detected on neuroimaging, are associated with motor, cognitive, urinary, and mood disorders. The LADIS (LeukoAraiosis and DISability) Study primarily aims to assess ARWMCs as a determinant of global functional decline in the elderly population. METHODS: We enrolled 639 patients (mean age, 74.1 +/- 5.0 years; 45.1% male) referred for nondisabling complaints, who had ARWMCs detected on brain magnetic resonance imaging (MRI) of mild, moderate, or severe grade according to the Fazekas scale. At the 1-year follow-up, 619 were reassessed using the Instrumental Activities of Daily Living (IADL) scale. Of these, 506 were totally independent at baseline, and 113 were impaired in only 1 item of the IADL scale. We studied the 1-year transition to 2 or more activities limited and selective functional impairments as cofactors of functional decline. RESULTS: The rate of transition was 9%, 15%, and 26%, in the mild, moderate, and severe ARWMC group, respectively. Comparing the severe with the mild ARWMC groups and adjusting for age and for other predictors of decline, the risk was more than 2-fold higher (odds ratio; 2.38; 95% confidence interval, 1.29-4.38) in patients with 0 or 1 activity limited, and 3-fold higher (odds ratio, 3.02; 95% confidence interval, 1.34-6.78) among patients fully independent at baseline. Both motor and cognitive deterioration predominantly explained the effect of ARWMCs on global functional decline. CONCLUSION: Elderly patients who are functionally independent and who have severe ARWMCs are at considerable risk of becoming more dependent in a short period, mostly owing to motor and cognitive deterioration.

Aged↗

PubMed2007

Delineation of brain AVMs on MR-Angiography for the purpose of stereotactic radiosurgery.

PURPOSE: To assess the dosimetric consequences of brain arteriovenous malformation (bAVM) delineation on magnetic resonance angiography (MRA) for the purpose of stereotactic radiosurgery. METHODS AND MATERIALS: Three observers contoured a bAVM in 20 patients, using digital subtraction angiography (V(DSA)) and three-dimensional time-of-flight MRA (V(MRA)). Displacement between contours was calculated. Agreement and differences between observers and imaging modalities were assessed. A standardized treatment plan with dynamic conformal arcs was generated and dosimetric coverage of all contours and the volume of normal brain tissue within the high dose region was determined. RESULTS: The generalized reliability coefficient was "fair" for target volume (0.79), but "poor" for displacement (0.35). V(MRA) was larger than V(DSA) (5.0 vs. 4.0 mL, p = 0.001). No difference in displacement was found (2.8 vs. 2.5 mm, p = 0.156). Dosimetric coverage of V(MRA) was 62.9% (95% CI, 56.9-68.8) when V(DSA) was used as planning target volume, and coverage of V(DSA) was 83.5% (95% CI, 78.1-88.8) when V(MRA) was used for planning (p < 0.001). The mean volume of normal brain within the 80% isodose was larger when the bAVM was delineated on MRA (0.7 vs. 1.0 mL (p = 0.02) for targets < or =3 mL and 3.7 vs. 7.0 mL (p = 0.01) for targets >3 mL). CONCLUSIONS: Brain arteriovenous malformations delineated on MRA are larger and more randomly displaced. However, for bAVMs < or =3 mL, the difference in volume of normal brain tissue within the high-dose region does not seem to be clinically relevant. Therefore, MRA-images might be used as the sole imaging modality for the radiosurgical treatment of bAVMs < or =3 mL when the bAVM is located in a noneloquent position.

Humans↗

PubMed2007

Lack of correlation between cortical demyelination and white matter pathologic changes in multiple sclerosis.

BACKGROUND: Histopathologic studies have shown that subpial cortical demyelination is extensive in chronic multiple sclerosis (MS). OBJECTIVE: To study whether subpial cortical demyelination in MS is associated with focal or diffuse white matter (WM) pathologic features on magnetic resonance imaging (MR imaging). DESIGN: Comparison of postmortem MR imaging findings with histopathologic findings. SETTING: Brain donations from a general community. PATIENTS: Three patients with MS with extensive cortical demyelination and 3 patients with minor cortical demyelination were selected from an MS autopsy data set. The postmortem MR imaging and histopathologic data of the patients were compared. MAIN OUTCOME MEASURES: Two observers blinded to the results of each other assessed the presence, extent, and distribution of focal and diffuse pathologic changes in WM by MR imaging and by histopathology. RESULTS: Extensive subpial demyelination was not associated with a significant increase in the area of focal and diffuse WM pathologic changes as assessed by Luxol fast blue histochemistry or by MR imaging or with the presence or extent of juxtacortical abnormalities on MR imaging. CONCLUSIONS: The lack of association of MS gray matter demyelination with diffuse or focal WM changes indicates that gray matter demyelination in MS occurs largely independent of WM pathologic changes. The extent or distribution of WM abnormalities cannot be used to identify extensive cortical demyelination in the clinical setting.

Aged↗

PubMed2006

Human gray matter: feasibility of single-slab 3D double inversion-recovery high-spatial-resolution MR imaging.

The purpose of this study was to develop and prospectively evaluate the feasibility of a single-slab three-dimensional (3D) double inversion-recovery, or DIR, sequence for magnetic resonance imaging at 1.5 T. The study was approved by the local ethics committee, and informed consent was obtained from six healthy control subjects (one woman, five men; age range, 26-47 years) and two patients with multiple sclerosis (one woman, aged 39; one man, aged 56). Gray matter (GM)-only images were obtained by selectively suppressing cerebrospinal fluid (CSF) and white matter (WM) signals. Whole-brain high-spatial-resolution 3D images (1.2 x 1.2 x 1.3 mm) were acquired within 10 minutes. Cortical and deep GM structures were clearly delineated from WM and CSF, and there were regional differences in GM signal intensity. No flow artifacts from blood or CSF were observed. These GM images with high spatial resolution are suitable to identify cortical pathologic conditions and can potentially be used for segmentation purposes to determine cortical thickness or volume.

Adult↗

PubMed2006

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study.

BACKGROUND: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. OBJECTIVE: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). METHODS: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. RESULTS: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing--namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. CONCLUSIONS: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.

Aged↗

PubMed2006

White matter lesions are associated with progression of medial temporal lobe atrophy in Alzheimer disease.

BACKGROUND AND PURPOSE: Medial temporal lobe atrophy (MTA) is a hallmark of Alzheimer disease (AD). Its progression is often seen during the course of AD, but its frequency and risk factors remain unclear. METHODS: We investigated MTA in 35 patients with AD from whom sequential magnetic resonance imaging scans were available. White matter lesions (WML; for the periventricular [PV] and subcortical [SC] regions separately) and MTA were rated semiquantitatively. RESULTS: In approximately two thirds of all patients, progression of MTA was found. The mean MTA progression was 0.8 (standard deviation: 0.5) and 0.3 (standard deviation: 0.4) for patients with or without PVWML at baseline (P=0.01). Patients who showed progression of PVWML over the course of their disease had a significantly higher mean progression of MTA than those without PVWML progression (0.9 [SD: 0.4]) and 0.4 [SD: 0.5]; P=0.01). Patients with PVWML at baseline had a 40-fold increased risk for progression of MTA compared with those without baseline PVWML (odds ratio=40.0, 95% CI=1.3 to 1.2x10(3), P=0.03). Patients with progression of PVWML during the course of the disease had an increased risk for MTA progression (odds ratio=3.7 per unit increase of progression of PVWML, 95% CI=1.1 to 12.9, P=0.04). There was higher risk for progression of MTA for those with progression of PVWML than those without (odds ratio=10.9, 95% CI=1.0 to 122.5, P=0.05). This was not found for SCWML. CONCLUSIONS: Our findings suggest that the presence and the progression of WML are associated with progression of MTA in AD. WML may be a predictor of the course of the disease and a potential treatment target in AD.

Aged↗

PubMed2006

Endogenous cortisol level interacts with noradrenergic activation in the human amygdala.

Animal studies show that high cortisol levels exert their effect on stressful task performance via modulation of the amygdala. Availability of noradrenaline in this brain region appears to be a critical prerequisite for this effect. This relationship between noradrenaline and cortisol is explained by an animal model where the amygdala constitutes a crucial region for this interaction. In humans this model has not been extensively tested so far. In a previously reported study human subjects (aged 20.93+/-2.38) were scanned using fMRI when watching sets of emotional and neutral pictures after taking the beta-adrenergic antagonist propranolol or placebo. Stimulus sets consisted of 92 pictures, divided in four emotional categories that ranged from neutral scenes of domestic objects (CAT1) to extremely negative scenes of mutilation or accidents (CAT4). Confrontation with arousing emotional pictures, accompanied by increased noradrenaline levels, evoked increased amygdala activation under placebo but not under betablocker condition. This new and additional analysis of this data set was carried out to determine the effect of differential endogenous cortisol levels on amygdala activation. Cortisol levels during scanning were determined using salivary samples and subjects were post hoc divided in a High (n=14) and Low cortisol group (n=14). When subjects were watching emotional stimuli, presumably associated with enhanced noradrenaline (NA) levels, amygdala activation was contrasted between the two cortisol groups. We hypothesized that emotional stimuli would elicit more amygdala activation in the High than in the Low cortisol group. Here we demonstrate indeed a significant interaction effect of the endogenous cortisol level with increasing activation in the amygdala under placebo but not under betablocker condition, thereby extending the rodent based model of a synergistic effect of the two stress hormones to the human.

Adolescent↗

PubMed2006

Whole-brain T1 mapping in multiple sclerosis: global changes of normal-appearing gray and white matter.

PURPOSE: To prospectively investigate whether T1 changes in normal-appearing white matter (WM) and normal-appearing gray matter (GM) in multiple sclerosis (MS) are global or regional and their relationship to disease type. MATERIALS AND METHODS: The institutional ethics review board approved study; written informed consent was obtained. Whole-brain T1 maps were obtained in 67 patients with MS and 24 healthy control subjects with three-dimensional fast low-angle shot flip angle-array method, with correction for B(1) imperfections. Analysis of variance was performed on T1 histogram parameters of global normal-appearing WM and GM. Regional mean T1 values were analyzed with a multilevel approach. Multiple linear regression analysis was performed to investigate associations with clinical disability and overall atrophy. For patients, T2 lesion load was determined. RESULTS: T1 histograms of normal-appearing WM had significantly higher peak positions for patients with MS (792 msec +/- 36 in secondary progressive [SP] MS) than for control subjects (746 msec +/- 23) and were significantly broader and lower (all P < .001). Histograms for cortical normal-appearing GM were significantly shifted (peak positions, 1263 msec +/- 44 in control subjects and 1355 msec +/- 62 in patients with SP MS) (P < .001). Histogram peak positions were significantly higher in SP MS than in relapsing-remitting (RR) and primary progressive MS (P < .05). In SP disease, at least 31% of normal-appearing WM and 20% of cortical normal-appearing GM were affected. In MS, T1 was significantly elevated in all normal-appearing WM and cortical normal-appearing GM regions (all P < .01) but was elevated only in the thalamus in deep GM (P < .05). Cortical T1 histogram peak position was associated with clinical disability; T2 lesion load was not. CONCLUSION: Results suggest that a global disease process affects large parts of both normal-appearing WM and GM in MS and effects are worse for SP MS than for RR MS.

Adult↗

PubMed2006

Automated segmentation of multiple sclerosis lesion subtypes with multichannel MRI.

PURPOSE: To automatically segment multiple sclerosis (MS) lesions into three subtypes (i.e., enhancing lesions, T1 "black holes", T2 hyperintense lesions). MATERIALS AND METHODS: Proton density-, T2- and contrast-enhanced T1-weighted brain images of 12 MR scans were pre-processed through intracranial cavity (IC) extraction, inhomogeneity correction and intensity normalization. Intensity-based statistical k-nearest neighbor (k-NN) classification was combined with template-driven segmentation and partial volume artifact correction (TDS+) for segmentation of MS lesions subtypes and brain tissue compartments. Operator-supervised tissue sampling and parameter calibration were performed on 2 randomly selected scans and were applied automatically to the remaining 10 scans. Results from this three-channel TDS+ (3ch-TDS+) were compared to those from a previously validated two-channel TDS+ (2ch-TDS+) method. The results of both the 3ch-TDS+ and 2ch-TDS+ were also compared to manual segmentation performed by experts. RESULTS: Intra-class correlation coefficients (ICC) of 3ch-TDS+ for all three subtypes of lesions were higher (ICC between 0.95 and 0.96) than that of 2ch-TDS+ for T2 lesions (ICC = 0.82). The 3ch-TDS+ also identified the three lesion subtypes with high specificity (98.7-99.9%) and accuracy (98.5-99.9%). Sensitivity of 3ch-TDS+ for T2 lesions was 16% higher than with 2ch-TDS+. Enhancing lesions were segmented with the best sensitivity (81.9%). "Black holes" were segmented with the least sensitivity (62.3%). CONCLUSION: 3ch-TDS+ is a promising method for automated segmentation of MS lesion subtypes.

Adult↗

PubMed2006

Interobserver agreement on the radiological criteria of the International Panel on the diagnosis of multiple sclerosis.

We assessed the interobserver agreement on the radiological part of the International Panel (IP) criteria for the diagnosis of multiple sclerosis (MS), comprising the assessment of dissemination in space (DIS) and time (DIT) based exclusively on MRI. Four radiologists trained and four radiologists naive in the application of the IP criteria scored the fulfillment for DIS (i.e., > or =3 periventricular, > or =1 infratentorial, > or =1 juxtacortical, > or = 1 enhancing lesion or a total of > or =9 T2-weighted lesions) and DIT (presence of new or enhancing lesions at follow-up) in baseline and two follow-up scans from 20 patients suspected for having MS. The IP-trained radiologists agreed at least moderately on all assessments (kappa>0.40), whereas the IP-naive radiologists showed fair agreement (kappa<0.40) on five of 16 assessments. In the final conclusion on DIS and DIT, the IP-trained radiologists agreed substantially on both items (kappa=0.62 and kappa=0.60, respectively) compared with a fair agreement on DIS (kappa=0.29) and moderate agreement on DIT (kappa=0.52) among the IP-naive radiologists. Given the poor interobserver agreement among IP-naive observers, the new IP criteria for MS require additional training and should perhaps be simplified.

Adolescent↗

PubMed2006

Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) was reported to have developed in three patients treated with natalizumab. We conducted an evaluation to determine whether PML had developed in any other treated patients. METHODS: We invited patients who had participated in clinical trials in which they received recent or long-term treatment with natalizumab for multiple sclerosis, Crohn's disease, or rheumatoid arthritis to participate. The clinical history, physical examination, brain magnetic resonance imaging (MRI), and testing of cerebrospinal fluid for JC virus DNA were used by an expert panel to evaluate patients for PML. We estimated the risk of PML in patients who completed at least a clinical examination for PML or had an MRI. RESULTS: Of 3417 patients who had recently received natalizumab while participating in clinical trials, 3116 (91 percent) who were exposed to a mean of 17.9 monthly doses underwent evaluation for PML. Of these, 44 patients were referred to the expert panel because of clinical findings of possible PML, abnormalities on MRI, or a high plasma viral load of JC virus. No patient had detectable JC virus DNA in the cerebrospinal fluid. PML was ruled out in 43 of the 44 patients, but it could not be ruled out in one patient who had multiple sclerosis and progression of neurologic disease because data on cerebrospinal fluid testing and follow-up MRI were not available. Only the three previously reported cases of PML were confirmed (1.0 per 1000 treated patients; 95 percent confidence interval, 0.2 to 2.8 per 1000). CONCLUSIONS: A detailed review of possible cases of PML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalizumab for a mean of 17.9 months. The risk associated with longer treatment is not known.

Antibodies, Monoclonal↗

PubMed2006

Impact of white matter hyperintensities scoring method on correlations with clinical data: the LADIS study.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are associated with decline in cognition, gait, mood, and urinary continence. Associations may depend on the method used for measuring WMH. We investigated the ability of different WMH scoring methods to detect differences in WMH load between groups with and without symptoms. METHODS: We used data of 618 independently living elderly with WMH collected in the Leukoaraiosis And DISability (LADIS) study. Subjects with and without symptoms of depression, gait disturbances, urinary incontinence, and memory decline were compared with respect to WMH load measured qualitatively using 3 widely used visual rating scales (Fazekas, Scheltens, and Age-Related White Matter Changes scales) and quantitatively with a semiautomated volumetric technique and an automatic lesion count. Statistical significance between groups was assessed with the chi2 and Mann-Whitney tests. In addition, the punctate and confluent lesion type with comparable WMH volume were compared with respect to the clinical data using Student t test and chi2 test. Direct comparison of visual ratings with volumetry was done using curve fitting. RESULTS: Visual and volumetric assessment detected differences in WMH between groups with respect to gait disturbances and age. WMH volume measurement was more sensitive than visual scores with respect to memory symptoms. Number of lesions nor lesion type correlated with any of the clinical data. For all rating scales, a clear but nonlinear relationship was established with WMH volume. CONCLUSIONS: Visual rating scales display ceiling effects and poor discrimination of absolute lesion volumes. Consequently, they may be less sensitive in differentiating clinical groups.

Aged↗

PubMed2006

Neonatal porencephaly and adult stroke related to mutations in collagen IV A1.

OBJECTIVE: The objective of this study was to describe leukoencephalopathy, lacunar infarcts, microbleeds and macrobleeds in the context of a collagen IV A1 mutation. METHODS: We examined a family with autosomal dominant porencephaly, in whom a defect in collagen IV A1 was detected recently. The patients underwent neurological, ophthalmological, and cardiological examinations and magnetic resonance imaging of the brain. Electron microscopy of a skin biopsy was performed. Extensive laboratory screening was performed for thrombophilia and increased bleeding tendency. RESULTS: The porencephaly was symptomatic in the infantile period in two patients, whereas it led to only minor neurological dysfunction in their affected mother. However, she experienced development of recurrent strokes in her 40s. In addition to the porencephaly, all patients had a leukoencephalopathy, which was most severe in the mother. Her magnetic resonance imaging results also showed lacunar infarcts, macrobleeds and a multitude of microbleeds. No other risk factors for recurrent stroke were found. Electron microscopy showed interruptions of the basement membrane of skin capillaries and inhomogeneous thickening of the basement membrane with pools of basement membrane fragments. INTERPRETATION: Leukoencephalopathy, ischemic infarcts, microbleeds, and macrobleeds are indicative of an underlying microangiopathy, of which the best-known causes are hypertension, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and cerebral amyloid angiopathy. Mutations in collagen IV A1, a major component of the vascular basement membrane, appear to be another risk factor.

Adult↗

PubMed2006

Altered diffusion tensor in multiple sclerosis normal-appearing brain tissue: cortical diffusion changes seem related to clinical deterioration.

PURPOSE: To investigate normal-appearing white (NAWM) and cortical gray (NAGM) matter separately in multiple sclerosis (MS) in vivo using diffusion tensor imaging (DTI). MATERIALS AND METHODS: In 64 MS patients (12 primary progressive [PP], 38 relapsing remitting [RR], 14 secondary progressive [SP]) and 20 healthy controls, whole-brain apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were acquired. A stimulated echo acquisition mode (STEAM) DTI sequence was used with minimal geometrical distortion in comparison to echo-planar imaging (EPI). NAWM and NAGM were identified using conventional magnetic resonance (MR) images, allowing a cautious assessment of FA in cortex. RESULTS: Histogram analyses showed significant global FA decreases and ADC increases in MS NAWM compared to control WM. MS cortical NAGM had no significant global ADC increase, but FA was decreased significantly. In regional analyses, nearly all NAWM regions-of-interest (ROIs) had significantly increased ADC compared to controls, but FA was not changed. In nearly all cortical NAGM ROIs, ADC was significantly increased and FA significantly reduced. In multiple linear regression analyses in RR/SPMS patients, NAGM-ADC histogram peak height was associated more strongly with clinical disability than T2 lesion load. CONCLUSION: Tissue damage occurs in both NAWM and cortical NAGM. The cortical damage appears to have more clinical impact than T2 lesions.

Adult↗

PubMed2006

MR spectroscopic evidence for thalamic and hippocampal, but not cortical, damage in multiple sclerosis.

Gray matter (GM) damage is an important pathophysiological feature in Multiple Sclerosis (MS), and may be related to clinical, including cognitive, deficits. Quantitative single-voxel (1)H-Magnetic Resonance Spectroscopy (TR/TE 6000/20 ms) was performed in 33 MS patients (11 per disease subtype; mean age 48 years, 16 females) and 10 healthy controls (mean age 43 years, 7 females). No overall spectroscopic changes were found in MS cortex. In MS thalamus, a 9% decrease of N-acetyl aspartate (NAA; P=0.005) and a 31% increase of myo-inositol (Ins; P=0.002) were found. A 21% Ins increase was observed (P=0.02) in MS hippocampus. Reduced NAA and increased Ins concentrations are thought to reflect neuro-axonal damage or loss and gliosis, respectively. Significant correlations between Ins concentrations and total-brain T(2) lesion load were found for MS thalamus (r=0.65, P<0.001) and hippocampus (r=0.57, P=0.001). MS thalamic and hippocampal Ins concentrations also correlated with each other (r=0.68; P<0.001). Cortical Gln correlated with thalamic NAA (r=-0.38; P=0.03) in MS. Thalamic and hippocampal Ins increases were most prominent in secondary-progressive (SP) patients (37% and 34%, respectively), whereas the largest thalamic NAA decrease (14%) was found in primary-progressive (PP) patients. In conclusion, thalamic and hippocampal GM pathology are important features of (progressive) MS.

Adult↗

PubMed2006

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

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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.

Adolescent↗

PubMed2006

MRI and the diagnosis of multiple sclerosis: expanding the concept of "no better explanation".

Although the diagnosis of multiple sclerosis relies on the demonstration of disease dissemination in space and time, the exclusion of other neurological disorders is also essential. The limited specificity of abnormalities disclosed by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients affected by other disorders. The available criteria for diagnosis of multiple sclerosis have not taken advantage of the potential of MRI to detect features "not suggestive" of multiple sclerosis. Recognition of such features in the work-up of patients suspected of having multiple sclerosis may reduce the likelihood of a false positive diagnosis of the disorder in some, while suggesting the correct alternative diagnosis in other patients. On the basis of this, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held to define a series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses. The presence of such red flags should alert clinicians to reconsider the differential diagnosis more extensively. In this review we will report on the conclusions of this international consensus, which should represent a first step beyond the concept of "no better explanation", and inform future diagnostic criteria for multiple sclerosis.

Brain Diseases↗