[Anterior Cruciate Ligament Tears - Influence on Terminal Extension]. / Ruptury predního zkrízeného vazu ­ vliv na terminální extenzi.

PURPOSE OF THE STUDY The aim of this paper was to compare terminal extension in normal and anterior cruciate ligament (ACL) deficient knees, and therefore to determine the role of the ACL during this motion. MATERIAL AND METHODS Ten knees with ACL tears (7 knees with recent ACL tears, 3 knees with long-standing tears) and 10 normal contralateral knees have been examined using MRI in passive hyperextension, 20° flexion and 20° flexion with a 9 kg posteriorly directed load on the femur. Movements of the femoral condyles on the tibia were calculated using previously described methods. RESULTS 1. Under the load at 20° flexion, knees with ACL tear showed posterior femoral subluxation (equivalent to a Lachman test), chronic tears being more unstable. Contralateral normal knees were antero-posteriorly stable. In hyperextension, both femoral condyles subluxed posteriorly in ACL tears but not in normal knees. 2. In all knees with ACL tear, the lateral femoral condyle moved posteriorly from hyperextension to 20°, equating to femoral external rotation. 3. The longitudinal rotation axis during terminal extension in normal knees was medial but in ACL tears it was central causing the medial femoral condyle to move forward from hyperextension to 20°. In normal knees, the medial femoral condyle did not move antero-posteriorly from hyperextension to 20° flexion. DISCUSSION Internal rotation of the femur during terminal extension has been recognized for 150 years. The question remains: what causes the usual combination of longitudinal rotation and extension? In the current literature ACL is considered to be responsible for internal rotation of the femur during terminal extension of the knee. So far, as we are aware, the kinematics of terminal extension, including hyperextension, have not been reported after ACL tear in the living knee. CONCLUSIONS Results of this study imply that: 1. The ACL prevents anterior tibial subluxation in hyperextension. 2. The ACL does not cause rotation in terminal extension. 3. The ACL locates the axis of longitudinal rotation in terminal extension. We hope that by studying living knees with and without ACL tear we may not only clarify the nature and mechanism of rotation in terminal extension, and hence the role of the ACL, but do so in a context of direct clinical relevance. Key words: knee, terminal extension, ACL tear, axis of longitudinal rotation, antero-posterior instability, MRI.

Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach.

BACKGROUND AND PURPOSE: While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients. METHODS: Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24). RESULTS: The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds ratio (OR) of 6.5 (95% CI 4.4-9.5). Low BPF together with high T2-LV identified in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7). CONCLUSIONS: The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment.

Early magnetic resonance imaging predictors of clinical progression after 48 months in clinically isolated syndrome patients treated with intramuscular interferon ß-1a.

BACKGROUND AND PURPOSE: Our aim was to identify early imaging surrogate markers of clinical progression in patients after the first demyelinating event suggestive of multiple sclerosis treated with weekly intramuscular interferon ß-1a. In a prospective observational study, the predictive role of baseline and 6-month changes in magnetic resonance imaging outcomes was investigated with respect to relapse activity and development of confirmed disability progression in patients after 48 months. METHODS: This study examined 210 patients. Multivariate Cox proportional hazard models were used to analyse predictors of relapse activity and confirmed disability progression after 48 months. RESULTS: Greater T2 lesion volume [hazard ratio (HR) 1.81; P = 0.005] and the presence of contrast-enhancing lesions (HR 2.13; P < 0.001) at baseline were significantly associated with increased cumulative risk of a second clinical attack over 48 months. A greater decrease of the corpus callosum volume (HR 2.74; P = 0.001) and greater lateral ventricle volume enlargement (HR 2.43; P = 0.002) at 6 months relative to baseline were associated with increased cumulative risk of a second clinical attack between months 6 and 48. In addition, increased risk of confirmed disability progression over 48 months in patients with greater lateral ventricle volume enlargement between baseline and 6 months (HR 4.70; P = 0.001) was detected. CONCLUSIONS: A greater T2 lesion volume, the presence of contrast-enhancing lesions at baseline, decrease of corpus callosum volume and lateral ventricle volume enlargement over the first 6 months in patients after the first demyelinating event treated with weekly intramuscular interferon ß-1a may assist in identification of patients with the highest risk of a second clinical attack and progression of disability.

Multiple sclerosis susceptibility loci do not alter clinical and MRI outcomes in clinically isolated syndrome.

It has not yet been established whether genetic predictors of multiple sclerosis (MS) susceptibility also influence disease severity and accumulation of disability. Our aim was to evaluate associations between 16 previously validated genetic susceptibility markers and MS phenotype. Patients with clinically isolated syndrome verified by positive magnetic resonance imaging (MRI) and cerebrospinal fluid findings (n=179) were treated with interferon-ß. Disability and volumetric MRI parameters were evaluated regularly for 2 years. Sixteen single-nucleotide polymorphisms (SNPs) previously validated as predictors of MS susceptibility in our cohort and their combined weighted genetic risk score (wGRS) were tested for associations with clinical (conversion to MS, relapses and disability) and MRI disease outcomes (whole brain, grey matter and white matter volumes, corpus callosum cross-sectional area, brain parenchymal fraction, T2 and T1 lesion volumes) 2 years from disease onset using mixed-effect models. We have found no associations between the tested SNPs and the clinical or MRI outcomes. Neither the combined wGRS predicted MS activity and progression over 2-year follow-up period. Power analyses confirmed 90% power to identify clinically relevant changes in all outcome variables. We conclude that the most important MS susceptibility loci do not determine MS phenotype and disease outcomes.

Early predictors of non-response to interferon in multiple sclerosis.

OBJECTIVE: To identify early clinical and MRI predictors of non-response to interferon (IFN) treatment in multiple sclerosis (MS). METHODS: In 172 patients with relapsing-remitting MS treated with IFNß, we evaluated prediction of future treatment non-response. Candidate predictors comprised disability and its sustained progression, relapse score (combining frequency and severity of relapses), brain volume change, brain parenchymal fraction, number of new T2 lesions, and T2 and T1 lesion volume within the initial year of treatment. Treatment non-response was evaluated as confirmed disability progression or overall average annual relapse score exceeding 1 over the following 5 years. Logistic regression model was adjusted for patient age, gender, disease duration and changes in treatment. RESULTS: Ninety patients (52%) reached the status of IFN non-responders in years 2-6. Patients with ≥1 new T2 lesion and relapse score ≥2 (odds ratio ≥5.7) or those with ≥3 new T2 lesions regardless of the relapse score (odds ratio = 3) were in a significantly higher risk of future treatment non-response. CONCLUSIONS: In patients with MS treated with IFNß for 1 year, number of new T2 lesions and annualized relapse score predict individual risk of treatment non-response over the following 5 years.

Corpus callosum atrophy--a simple predictor of multiple sclerosis progression: a longitudinal 9-year study.

AIM: To determine whether corpus callosum atrophy predicts future clinical deterioration in multiple sclerosis. METHODS: In 39 multiple sclerosis patients the area of corpus callosum in the sagittal plane, T2 and T1 lesion volumes, brain parenchymal fraction and brain atrophy were determined at baseline and 1 year after treatment initiation. Non-parametric and multiple regression models were built to identify the most reliable predictors of disability and of its changes over 9 years. RESULTS: Corpus callosum atrophy during the first year of treatment was the best predictor of disability (r = -0.56) and of its increase at 9 years (r = 0.65). Corpus callosum atrophy of at least 2% predicted increase in disability with 93% sensitivity and 73% specificity (odds ratio = 35). CONCLUSION: Corpus callosum atrophy is a simple and accurate predictor of future disability accumulation and is feasible for routine clinical practice.

Two patients with clinically distinct manifestation of pyruvate dehydrogenase deficiency due to mutations in PDHA1 gene.

The most common cause of pyruvate dehydrogenase complex (PDHc) deficiency is the deficit of the E1α-subunit. The aim of this study was to describe distinct course of the disease in two boys with mutations in PDHA1 gene and illustrate the possible obstacles in measurement of PDHc activity. Clinical data and metabolic profiles were collected and evaluated. PDHc and E1α-subunit activities were measured using radiometric assay. Subunits of PDHc were detected by Western blot. PDHA1 gene was analysed by direct sequencing. In patient 1, the initial hypotonia with psychomotor retardation was observed since early infancy. The child gradually showed symptoms of spasticity and arrest of psychomotor development. In patient 2, the disease manifested by seizures and hyporeflexia in the toddler age. The diagnosis was confirmed at the age of seven years after attacks of dystonia and clinical manifestation of myopathy with normal mental development. Brain MRI of both patients revealed lesions typical of Leigh syndrome. Enzymatic analyses revealed PDHc deficiency in isolated lymphocytes in the first but not in the second patient. The direct measurement of PDH E1-subunit revealed deficiency in this individual. In patient 1, a novel hemizigous mutation c.857C>T (Pro250Leu) was detected in the X-linked PDHA1 gene. Mutation c.367C>T (Arg88Cys) was found in patient 2. We present first two patients with PDHc deficit due to mutations in PDHA1 gene in the Czech Republic. We document the broad variability of clinical symptoms of this disease. We proved that normal PDHc activity may not exclude the disease.

Multiple sclerosis and the accumulation of iron in the Basal Ganglia: quantitative assessment of brain iron using MRI t(2) relaxometry.

The aim of this work was to quantify the accumulation of iron in the basal ganglia in multiple sclerosis (MS) patients and in a control group, and to investigate the relationship between iron accumulation and other parameters assessed in MS, i.e. lesion load (LL) and brain parenchymal fraction (BPF). Magnetic resonance imaging T(2) relaxometry was used for the measurement. 970 patients with clinically definite MS and 117 controls were examined. Patients were divided into three subgroups according to LL and BPF. This work provides quantitative evidence of increased iron accumulation in the basal ganglia in MS patients in comparison to healthy controls. We also found that in the subgroup with small LL value, iron accumulation is higher than in the subgroup with large LL value. The hypothesis of a neurodegenerative component of MS is supported by the changes in iron content in the brain.

Apolipoprotein E ε4-positive multiple sclerosis patients develop more gray-matter and whole-brain atrophy: a 15-year disease history model based on a 4-year longitudinal study.

Multiple sclerosis is a disease with considerable individual variation, and genetic background plays a key role in disease susceptibility and severity. The objective of the study was to evaluate the relationship between apolipoprotein E (APOE) genotype and the evolution of different clinical and MRI parameters. We investigated a group of 150 relapsingremitting patients that completed 4-year follow-up. The mean age was 30.2 years, disease duration 56.8 months, and baseline Expanded Disability Status Scale (EDSS) 1.8. The changes in brain parenchymal volume (BPV), gray matter (GMV), white matter (WMV) and peripheral gray volume (PGMV) were measured by SIENA/X. T2-lesion volume was assessed by semi-automated methods. The mixed-effect model analysis was used to investigate evolution of clinical and MRI parameters in relation to the APOE ε4 genotype considering two different time models: 4-year follow-up and 15-year period from disease onset. We identified 36 APOE ε4-positive patients. Decline of GMV (P = 0.017), and BPV (P = 0.029) were significantly faster in APOE ε4-positive than in APOE ε4-negative patients in the 15-year model. In the 4- year model, a trend for faster decrease of GMV was found in APOE ε4-positive patients (P = 0.067). No differences in other MRI parameters or EDSS were found between the APOE groups. The results of the study suggest that APOE ε4-positive patients experience faster rate of gray matter atrophy.

[Comparison of prenatal ultrasound examination, post-mortem magnetic resonance imaging and autopsy (a case report--schizencephaly)]. / Komparace prenatáního ultrazvukového vysetrení, post mortem magnetické rezonance a patologicko-anatomické pitvy (kazuistika--schizencefalie).

OBJECTIVE: To improve prenatal diagnostic with a feedback of autopsy, complemented by post mortem magnetic resonance imaging (MRI). MRI is important for malformations of CNS, where autopsy can be insufficient. SUBJECT: Case report. SETTING: MR unit of the Department of radiology, Department of obstetrics and gynaecology and Department of pathology, 1st medical school, Charles University in Prague, General Teaching Hospital. SUBJECT AND METHOD: To compare prenatal ultrasound, post mortem MRI and autopsy. CONCLUSION: Case report documented complementarity of all three method; full agreement in brain malformation type was found.

A Serial 10-Year Follow-Up Study of Atrophied Brain Lesion Volume and Disability Progression in Patients with Relapsing-Remitting MS.

BACKGROUND AND PURPOSE: Disappearance of T2 lesions into CSF spaces is frequently observed in patients with MS. Our aim was to investigate temporal changes of cumulative atrophied brain T2 lesion volume and 10-year confirmed disability progression. MATERIALS AND METHODS: We studied 176 patients with relapsing-remitting MS who underwent MR imaging at baseline, 6 months, and then yearly for 10 years. Occurrence of new/enlarging T2 lesions, changes in T2 lesion volume, and whole-brain, cortical and ventricle volumes were assessed yearly between baseline and 10 years. Atrophied T2 lesion volume was calculated by combining baseline lesion masks with follow-up CSF partial volume maps. Ten-year confirmed disability progression was confirmed after 48 weeks. ANCOVA detected MR imaging outcome differences in stable (n = 76) and confirmed disability progression (n = 100) groups at different time points; hierarchic regression determined the unique additive variance explained by atrophied T2 lesion volume regarding the association with confirmed disability progression, in addition to other MR imaging metrics. Cox regression investigated the association of early MR imaging outcome changes and time to development of confirmed disability progression. RESULTS: The separation of stable-versus-confirmed disability progression groups became significant even in the first 6 months for atrophied T2 lesion volume (140% difference, Cohen d = 0.54, P = .004) and remained significant across all time points (P ≤ .007). The hierarchic model, including all other MR imaging outcomes during 10 years predicting confirmed disability progression, improved significantly after adding atrophied T2 lesion volume (R 2 = 0.27, R 2 change 0.11, P = .009). In Cox regression, atrophied T2 lesion volume in 0-6 months (hazard ratio = 4.23, P = .04) and 0-12 months (hazard ratio = 2.41, P = .022) was the only significant MR imaging predictor of time to confirmed disability progression. CONCLUSIONS: Atrophied T2 lesion volume is a robust and early marker of disability progression in relapsing-remitting MS.

Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years: a case-control study.

BACKGROUND: There is growing evidence for the concept of multiple sclerosis (MS) as an inflammatory neurodegenerative disease, with a different pattern of atrophy evolution in grey matter (GM) and white matter (WM) tissue compartments. OBJECTIVE: We aimed to investigate the evolution of different MRI measures in early relapsing-remitting patients with MS and in normal controls (NCs) over 2 years. We also evaluated the progression of these MRI measures in a subset of patients who were followed for up to 5 years. METHODS: Included in this study were 147 patients who participated in the combination ASA (Avonex Steroids Azathioprine) study and completed full treatment, clinical and MRI assessment at 0, 12 and 24 months. A subgroup of 66 patients was followed for 36 months, 51 patients for 48 months and 43 patients for 60 months. Mean age at baseline was 30.7 years, mean disease duration was 5.5 years, mean EDSS was 1.8 and mean annualised relapse rate before study entry was 1.7. MRI scans were performed on a 1.5T scanner every 2 months for the first 2 years and thereafter once yearly for up to 5 years. In addition to the MS group, 27 NCs were examined at months 0, 12 and 24 using the same MRI protocol. Percentage brain volume change (PBVC), GM volume (GMV), WM volume (WMV) and peripheral grey volume (PGV) were measured annually using SIENA/X software. T2-hyperintense lesion volume (LV), lateral ventricle volume (LVV) and third ventricle width (3VW) were also assessed annually. RESULTS: Over the period of 0-24 months, patients with MS lost significantly more GMV (-2.6% vs -0.72%, p<0.001), PGV (-2.4% vs -1.03%, p<0.001) and PBVC (-1.2% vs -0.22%, p<0.001), and increased in LVV (+16.6% vs +0.55%, p<0.003) and 3VW (+9.3% vs 0%, p = 0.003), when compared with NCs. Within-person change in MRI measures for patients with MS over 5 years was -4.2% for PBVC, -6.2% for GMV, -5.8% for PGV, -0.5% for WMV (all p<0.001), +68.7 for LVV (p<0.001), +4% for 3VW (p<0.001) and +42% for T2-LV (p<0.001). CONCLUSIONS: Our study confirmed a different pattern of GM, WM and central atrophy progression over 2 years between patients with MS and NCs. The study showed a different evolution of tissue compartment atrophy measures in patients with MS, with faster decline in cortical and deep GM regions, as well as periventricular WM regions, over a 5-year period.

Asymmetry of basal ganglia in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatry disorder with several key symptoms, such as inattentiveness, impulsivity and hyperactivity. Neuropsychiatry studies have implicated the frontostriatal circuit in the pathological physiology of the disorder. Using magnetic resonance imaging (MRI), we examined the basal ganglia in 13 ADHD patients and eight unaffected comparison children. The volume of caudate, putamen and globus pallidus was measured. In the ADHD patients, we detected an increased left > right asymmetry of the basal ganglia. This reversal of asymmetry in the globus pallidus and caudate nucleus were statistically significant. These finding provide further evidence of morphological brain abnormalities in ADHD.

[Randomly discovered enlargement in the region of sella turcica]. / Náhodne zjistené expanze v selární oblasti.

Computer tomography (CT) and magnetic resonance imaging (MRI) quite often detect unexpected cases of enlargement in the hypothalamus-hypophysial region, without the above methods being indicated for clinical manifested symptomatology provoked by the tumour. This is not surprising if we consider that autopsies show the presence of hypophysial adenomas of 10-15% of population on an average. X ray, CT or MRI are indicated in the case of head traumas, lateral nasal cavity inflammations, headaches, strokes, neurological diseases and other disorders. A number of tumours of diverse etiology occur in the hypothalamus-hypophysial region, but hypophysial adenomas are by far the most frequent among all (above 90 %). Among other primary enlargements, the most frequent are craniopharyngeomas and meningeomas, while other enlargements are by fare less common. Such randomly detected tumours are mostly asymptomatic, but targeted anamnesis may show some of the symptoms quite clearly. The symptomatology can be linked with possible slight hormonal overproduction of hypophysial adenomas, a deficit of hypophysial hormones or local manifestations of expansion. Exact assessment of MRI results, of hormonal activity of the enlargement, of the relation to surrounding structures, especially the optic nerves, and the assessment of hypophysial functions are important for the therapeutic decision. Depending on the type and extension of the tumour the options considered are pharmacotherapy (the treatment of choice in the case of prolactinomas), surgery, radiotherapy (today prevailingly using the gamma knife), and if no intervention is necessary, follow up with regular MRI examinations. Tumorous growth is more often observed in "macroadenomas" than in "microadenomas" (up to 10 mm).

Thalamic Iron Differentiates Primary-Progressive and Relapsing-Remitting Multiple Sclerosis.

BACKGROUND AND PURPOSE: Potential differences between primary progressive and relapsing remitting multiple sclerosis are the subject of ongoing controversial discussions. The aim of this work was to determine whether and how primary-progressive and relapsing-remitting multiple sclerosis subtypes differ regarding conventional MR imaging parameters, cerebral iron deposits, and their association with clinical status. MATERIALS AND METHODS: We analyzed 24 patients with primary-progressive MS, 80 with relapsing-remitting MS, and 20 healthy controls with 1.5T MR imaging for assessment of the conventional quantitative parameters: T2 lesion load, T1 lesion load, brain parenchymal fraction, and corpus callosum volume. Quantitative susceptibility mapping was performed to estimate iron concentration in the deep gray matter. RESULTS: Decreased susceptibility within the thalamus in relapsing-remitting MS compared with primary-progressive MS was the only significant MR imaging difference between these MS subtypes. In the relapsing-remitting MS subgroup, the Expanded Disability Status Scale score was positively associated with conventional parameters reflecting white matter lesions and brain atrophy and with iron in the putamen and caudate nucleus. A positive association with putaminal iron and the Expanded Disability Status Scale score was found in primary-progressive MS. CONCLUSIONS: Susceptibility in the thalamus might provide additional support for the differentiation between primary-progressive and relapsing-remitting MS. That the Expanded Disability Status Scale score was associated with conventional MR imaging parameters and iron concentrations in several deep gray matter regions in relapsing-remitting MS, while only a weak association with putaminal iron was observed in primary-progressive MS suggests different driving forces of disability in these MS subtypes.

Cognitive sequelae of methanol poisoning involve executive dysfunction and memory impairment in cross-sectional and long-term perspective.

Methanol poisoning leads to lesions in the basal ganglia and subcortical white matter, as well as to demyelination and atrophy of the optic nerve. However, information regarding cognitive deficits in a large methanol sample is lacking. The principal aim of the present study was to identify the cognitive sequelae of methanol poisoning and their morphological correlates. A sample of 50 patients (METH; age 48 ± 13 years), 3-8 months after methanol poisoning, and 57 control subjects (CS; age 49 ± 13 years) were administered a neuropsychological battery. Forty-six patients were followed in 2 years' perspective. Patients additionally underwent 1.5T magnetic resonance imaging (MRI). Three biochemical and toxicological metabolic markers and a questionnaire regarding alcohol abuse facilitated the classification of 24 patients with methanol poisoning without alcohol abuse (METHna) and 22 patients with methanol poisoning and alcohol abuse (METHa). All groups were compared to a control group of similar size, and matched for age, education, premorbid intelligence level, global cognitive performance, and level of depressive symptoms. Using hierarchical multiple regression we found significant differences between METH and CS, especially in executive and memory domains. METHa showed a similar pattern of cognitive impairment with generally more severe executive dysfunction. Moreover, all METH patients with extensive involvement on brain MRI (lesions in ≥2 anatomical regions) had a more severe cognitive impairment. From a longitudinal perspective, we did not find any changes in their cognitive functioning after 2 years' follow-up. Our findings suggest that methanol poisoning is associated with executive dysfunction and explicit memory impairment, supposedly due to basal ganglia dysfunction and disruption of frontostriatal circuitry proportional to the number of brain lesions, and that these changes are persistent after 2 years' follow-up.

Reduced hypothalamic gray matter in narcolepsy with cataplexy.

OBJECTIVES: Narcolepsy with cataplexy is associated with a loss of hypocretin. The question is, if there is an autoimmune or neurodegenerative process selectively killing the hypothalamic hypocretin-containing neurons or if these cells survive but fail to produce hypocretin. To support one of these hypothesis we aimed to detect structural changes in the hypothalamus of narcoletic patients. MATERIALS AND METHODS: Nineteen narcoleptic patients were compared to 16 healthy controls. We used voxel-based morphometry (VBM), an unbiased MRI morphometric method with a high sensitivity for subtle changes in gray and white matter volumes to investigate hypothalamic region in this condition. RESULTS: Classical MRI protocol revealed no structural abnormalities, but using VBM we found significant reduction in hypothalamic gray matter volumes between patients and controls. CONCLUSIONS: VBM showed hypothalamic gray matter loss in narcolepsy with cataplexy. This suggest that functional abnormalities of hypocretin neurons in narcolepsy are associated with structural changes of hypothalamus.

Longitudinal Mixed-Effect Model Analysis of the Association between Global and Tissue-Specific Brain Atrophy and Lesion Accumulation in Patients with Clinically Isolated Syndrome.

BACKGROUND AND PURPOSE: The relationship between lesion formation and brain atrophy development in the early phase of multiple sclerosis is unclear. We investigated the association between new lesion accumulation and brain atrophy progression in patients with clinically isolated syndrome over 48 months. MATERIALS AND METHODS: Patients with clinically isolated syndrome (n = 210) were evaluated with 1.5T MR imaging at baseline and at 6, 12, 24, 36, and 48 months as part of a multicenter observational study of early administration of intramuscular interferon ß-1a. Mixed-effect model analyses, adjusted for age, sex, and treatment status, investigated the association between accumulation of contrast-enhancing and T2 lesions and brain-volume percent changes in a 48-month period. RESULTS: In patients with clinically isolated syndrome, the average whole-brain volume decreased 2.5%, the mean lateral ventricle volume increased 16.9%, and a mean of 7.7 new/enlarging T2 lesions accumulated over the follow-up period. Patients with clinically isolated syndrome who showed greater percentages of change in whole-brain, white and gray matter, cortical, and lateral ventricle volumes over the follow-up period had more severe lesion outcomes at baseline (all P < .007). There were significant associations between decreased individual brain-volume measures at baseline and greater percentages of change during follow-up (P < .05). We found a significant association between the total cumulative number of new/enlarging T2 lesions and the evolution of whole-brain (P < .001), lateral ventricle (P = .007), gray matter and thalamic (P = .013), subcortical deep gray matter (P = .015), and cortical (P = .036) volumes over the follow-up period. CONCLUSIONS: Lesion accumulation and brain-volume changes occur simultaneously in the early phase of clinically isolated syndrome. More severe lesion and brain-volume outcomes at baseline were associated with greater development of brain atrophy over the follow-up period in patients with clinically isolated syndrome.

Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study).

BACKGROUND AND PURPOSE: Gadobutrol (Gadavist) and gadoteridol (ProHance) have similar macrocyclic molecular structures, but gadobutrol is formulated at a 2-fold higher (1 mol/L versus 0.5 mol/L) concentration. We sought to determine whether this difference impacts morphologic contrast-enhanced MR imaging. MATERIALS AND METHODS: Two hundred twenty-nine adult patients with suspected or known brain tumors underwent two 1.5T MR imaging examinations with gadoteridol or gadobutrol administered in randomized order at a dose of 0.1 mmol/kg of body weight. Imaging sequences and T1 postinjection timing were identical for both examinations. Three blinded readers evaluated images qualitatively and quantitatively for lesion detection and for accuracy in characterization of histologically confirmed brain tumors. Data were analyzed by using the Wilcoxon signed rank test, the McNemar test, and a mixed model. RESULTS: Two hundred nine patients successfully completed both examinations. No reader noted a significant qualitative or quantitative difference in lesion enhancement, extent, delineation, or internal morphology (P values = .69-1.00). One hundred thirty-nine patients had at least 1 histologically confirmed brain lesion. Two readers found no difference in the detection of patients with lesions (133/139 versus 135/139, P = .317; 137/139 versus 136/139, P = .564), while 1 reader found minimal differences in favor of gadoteridol (136/139 versus 132/139, P = .046). Similar findings were noted for the number of lesions detected and characterization of tumors (malignant/benign). Three-reader agreement for characterization was similar for gadobutrol (66.4% [κ = 0.43]) versus gadoteridol (70.3% [κ = 0.45]). There were no significant differences in the incidence of adverse events (P = .199). CONCLUSIONS: Gadoteridol and gadobutrol at 0.1 mmol/kg of body weight provide similar information for visualization and diagnosis of brain lesions. The 2-fold higher gadolinium concentration of gadobutrol provides no benefit for routine morphologic imaging.

The Benefits of High Relaxivity for Brain Tumor Imaging: Results of a Multicenter Intraindividual Crossover Comparison of Gadobenate Dimeglumine with Gadoterate Meglumine (The BENEFIT Study).

BACKGROUND AND PURPOSE: Gadobenate dimeglumine (MultiHance) has higher r1 relaxivity than gadoterate meglumine (Dotarem) which may permit the use of lower doses for MR imaging applications. Our aim was to compare 0.1- and 0.05-mmol/kg body weight gadobenate with 0.1-mmol/kg body weight gadoterate for MR imaging assessment of brain tumors. MATERIALS AND METHODS: We performed crossover, intraindividual comparison of 0.1-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 1) and 0.05-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 2). Adult patients with suspected or known brain tumors were randomized to Arm 1 (70 patients) or Arm 2 (107 patients) and underwent 2 identical examinations at 1.5 T. The agents were injected in randomized-sequence order, and the 2 examinations were separated by 2-14 days. MR imaging scanners, imaging sequences (T1-weighted spin-echo and T1-weighted high-resolution gradient-echo), and acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images for diagnostic information (degree of definition of lesion extent, lesion border delineation, visualization of lesion internal morphology, contrast enhancement) and quantitatively for percentage lesion enhancement and lesion-to-background ratio. Safety assessments were performed. RESULTS: In Arm 1, a highly significant superiority (P < .002) of 0.1-mmol/kg gadobenate was demonstrated by all readers for all end points. In Arm 2, no significant differences (P > .1) were observed for any reader and any end point, with the exception of percentage enhancement for reader 2 (P < .05) in favor of 0.05-mmol/kg gadobenate. Study agent-related adverse events were reported by 2/169 (1.2%) patients after gadobenate and by 5/175 (2.9%) patients after gadoterate. CONCLUSIONS: Significantly superior morphologic information and contrast enhancement are demonstrated on brain MR imaging with 0.1-mmol/kg gadobenate compared with 0.1-mmol/kg gadoterate. No meaningful differences were recorded between 0.05-mmol/kg gadobenate and 0.1-mmol/kg gadoterate.