RESUMO
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.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Atrofia/diagnóstico por imagem , Atrofia/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
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.
Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/fisiopatologia , Instabilidade Articular , Articulação do Joelho , Adulto , Lesões do Ligamento Cruzado Anterior/diagnóstico , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Fenômenos Biomecânicos , Feminino , Humanos , Instabilidade Articular/diagnóstico , Instabilidade Articular/fisiopatologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Masculino , Amplitude de Movimento Articular , RotaçãoRESUMO
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.
Assuntos
Ferro/análise , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Tálamo/química , Tálamo/patologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/diagnóstico por imagem , Função Executiva , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/diagnóstico por imagem , Metanol/intoxicação , Adulto , Idoso , Transtornos Cognitivos/psicologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de TempoRESUMO
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.
Assuntos
Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Adulto , Atrofia/diagnóstico por imagem , Atrofia/patologia , Encéfalo/patologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Esclerose Múltipla/psicologia , Testes NeuropsicológicosRESUMO
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.
Assuntos
Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Meios de Contraste , Estudos Cross-Over , Feminino , Humanos , Masculino , Meglumina/análogos & derivados , Pessoa de Meia-Idade , Compostos OrganometálicosRESUMO
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.
Assuntos
Encefalopatias/patologia , Doenças Desmielinizantes/patologia , Adjuvantes Imunológicos/uso terapêutico , Adulto , Atrofia/patologia , Encefalopatias/tratamento farmacológico , Doenças Desmielinizantes/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Interferon beta-1a/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Biomarcadores , Doenças Desmielinizantes/diagnóstico , Progressão da Doença , Adjuvantes Imunológicos/administração & dosagem , Adulto , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/fisiopatologia , Feminino , Seguimentos , Humanos , Injeções Intramusculares , Interferon beta-1a/administração & dosagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
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.
Assuntos
Neoplasias Encefálicas/diagnóstico , Meios de Contraste/administração & dosagem , Compostos Heterocíclicos/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Compostos Organometálicos/administração & dosagem , Adulto , Idoso , Estudos Cross-Over , Feminino , Gadolínio/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodosRESUMO
BACKGROUND AND PURPOSE: Pathologic changes in GM have an important role in MS. We investigated the association between SDGM and cortical volume changes and disability progression in early RRMS. MATERIALS AND METHODS: One hundred eighty patients with RRMS had clinical assessment during 5 years and were divided into those with or without SDP at 5 years by the usual definition in treatment trials. The number of available MR imaging scans at various time points was the following: at baseline, 178; and at 6 months, 172; at 12 months, 175; at 24 months, 155; at 36 months, 160; at 48 months, 158; and at 60 months, 162, respectively. Longitudinal changes in cortical, GM, and WM volume were calculated by using the direct method. RESULTS: At 5 years, 90 patients with RRMS experienced SDP and 90 had stable disease. At baseline, patients with SDP had longer disease duration, greater T2-lesion volume, and smaller whole-brain, WM, cortical, and SDGM volume (P < .01). At 5 years, patients with SDP had significantly greater percentage decreases from baseline compared with those without SDP in the volume of the whole brain (P < .0001), cortex (P = .001), GM (P = .003), and thalamus (P = .01). In patients who developed SDP at 5 years and those who did not, mixed-effect models, adjusted for age, disease duration, and change of the treatment status, showed significant interactions between SDP status at 5 years and changes with time in whole-brain, cortical, lateral ventricle (all P < .001), thalamus (P = .006), and total SDGM (P = .0095) volume. CONCLUSIONS: SDP is associated with progression of cortical, central, and thalamic atrophy in early RRMS during 5 years.
Assuntos
Córtex Cerebral/patologia , Avaliação da Deficiência , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/patologia , Tálamo/patologia , Adjuvantes Imunológicos/uso terapêutico , Adulto , Atrofia/patologia , Atrofia/fisiopatologia , Azatioprina/administração & dosagem , Córtex Cerebral/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Diagnóstico Precoce , Feminino , Humanos , Interferon beta-1a , Interferon beta/administração & dosagem , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Estudos Prospectivos , Esteroides/administração & dosagem , Tálamo/fisiopatologia , Adulto JovemRESUMO
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.
Assuntos
Loci Gênicos , Predisposição Genética para Doença , Esclerose Múltipla/genética , Adolescente , Adulto , Biomarcadores/líquido cefalorraquidiano , Encéfalo/patologia , Feminino , Estudos de Associação Genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
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.
Assuntos
Corpo Caloso/patologia , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Atrofia/patologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND PURPOSE: Recent studies have shown that selective regional, but not global, GM atrophy occurs from clinical onset to conversion to clinically definite MS. Our aim was to investigate the difference in the extent of SDGM and cortical atrophy in a large sample of patients with CIS and early RRMS and to explore the relationship between SDGM and cortical atrophy and other MR imaging and clinical outcomes. MATERIALS AND METHODS: Two hundred twelve patients with CIS recruited at the first clinical event (mean age, 29.3 years; median EDSS, 1.5; median disease duration, 3 months) and 177 patients with early RRMS (mean age, 30.7 years; median EDSS, 2.0; median disease duration, 47 months) were imaged on a 1.5T scanner by using a high-resolution 3D T1 spoiled gradient-recalled sequence. Volumetric data for SDGM structures were obtained by using FSL FIRST, while whole-brain, GM, white matter, cortical, and lateral ventricle volumes were estimated by using SIENAX software. Comparisons between the groups were adjusted for age and sex. RESULTS: Patients with early RRMS showed significantly lower SDGM but not cortical volumes compared with patients with CIS. The most apparent SDGM differences were evident in the caudate and thalamus (P < .0001), total SDGM (P = .0001), and globus pallidus (P = .01). Patients with CIS with a median T2 lesion volume >4.49 mL showed lower total SDGM, caudate, thalamus (P < .001), globus pallidus (P = .007), hippocampus (P = .004), and putamen (P = .01) volumes and higher lateral ventricle volume (P = .001) than those with a median T2 lesion volume <4.49 mL. Decreased thalamic volume showed the most consistent relationship with MR imaging outcomes (P < .0001) in patients with CIS. CONCLUSIONS: Significant SDGM, but not cortical, atrophy develops during the first 4 years of the RRMS. GM atrophy is relevant for disease progression from the earliest clinical stages.
Assuntos
Encéfalo/patologia , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Atrofia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do ÓrgãoRESUMO
OBJECTIVE: To evaluate long-term effects of 2-year treatment with interferon beta combined with low-dose azathioprine and prednisone in multiple sclerosis. METHODS: In the original 2-year ASA study, 181 patients with early relapsing-remitting multiple sclerosis were randomised into 3 treatment arms: those treated with interferon beta (n=60), with interferon beta and low-dose azathioprine (n=58), and interferon beta, azathioprine and low-dose prednisone (n=63). Of these, 172 were included in this 4-year non-study extension. Three monthly clinical controls and annual MRI scans were carried out. The primary endpoint was annual relapse activity. The secondary endpoints were disability and quantitative MRI parameters. RESULTS: Nine patients were lost to follow-up and 172 were included in the analyses. None of relapse activity, disability accumulation or MRI parameters differed significantly between the groups over 6 years. Only 5.5% and 0.6% of patients were free from disease activity at year 2 and year 6 of the treatment initiation. CONCLUSION: The tested combined therapeutic regimen does not improve long-term outcomes in patients with multiple sclerosis. Furthermore, interferon is not able to completely abolish disease activity.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Corticosteroides/uso terapêutico , Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Adulto , Encéfalo/patologia , Estudos de Coortes , Avaliação da Deficiência , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Injeções Intramusculares , Interferon beta-1a , Interferon beta/administração & dosagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Prednisona/uso terapêutico , Recidiva , Falha de Tratamento , Adulto JovemRESUMO
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.
Assuntos
Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Método Duplo-Cego , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Curva ROC , Sensibilidade e EspecificidadeRESUMO
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.
Assuntos
Mutação , Piruvato Desidrogenase (Lipoamida)/genética , Doença da Deficiência do Complexo de Piruvato Desidrogenase/genética , Adolescente , Western Blotting , Criança , Humanos , Masculino , Doença da Deficiência do Complexo de Piruvato Desidrogenase/diagnóstico , Análise de Sequência de DNARESUMO
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.
Assuntos
Gânglios da Base/química , Gânglios da Base/patologia , Ferro/análise , Esclerose Múltipla/patologia , Adolescente , Adulto , Idoso , Química Encefálica , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
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.
Assuntos
Apolipoproteína E4/genética , Encéfalo/patologia , Esclerose Múltipla Recidivante-Remitente/genética , Adjuvantes Imunológicos/uso terapêutico , Adulto , Anti-Inflamatórios/uso terapêutico , Apolipoproteína E4/imunologia , Atrofia/patologia , Azatioprina/uso terapêutico , Progressão da Doença , Quimioterapia Combinada , Feminino , Seguimentos , Genótipo , Humanos , Processamento de Imagem Assistida por Computador , Imunossupressores/uso terapêutico , Interferon beta-1a , Interferon beta/uso terapêutico , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/patologia , Fibras Nervosas Mielinizadas/patologia , Prednisona/uso terapêuticoRESUMO
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.
Assuntos
Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/patologia , Ultrassonografia Pré-Natal , Aborto Induzido , Adulto , Autopsia , Feminino , Humanos , Malformações do Desenvolvimento Cortical/diagnóstico , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , GravidezRESUMO
BACKGROUND: Studies evaluating interferon beta (IFNbeta) for multiple sclerosis (MS) showed only partial efficacy. In many patients, IFNbeta does not halt relapses or disability progression. One strategy to potentially enhance efficacy is to combine IFNbeta with classical immunosuppressive agents, such as azathioprine (AZA) or corticosteroids, commonly used for other autoimmune disorders. OBJECTIVE: The Avonex-Steroids-Azathioprine study was placebo-controlled trial and evaluated efficacy of IFNbeta-1a alone and combined with low-dose AZA alone or low-dose AZA and low-dose corticosteroids as initial therapy. METHODS: A total of 181 patients with relapsing-remitting MS (RRMS) were randomized to receive IFNbeta-1a 30 microg intramuscularly (IM) once weekly, IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily, or IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily plus prednisone 10 mg orally every other day. The primary end point was annualized relapse rate (ARR) at 2 years. Patients were eligible for enrollment in a 3-year extension. RESULTS: At 2 years, adjusted ARR was 1.05 for IFNbeta-1a, 0.91 for IFNbeta-1a plus AZA, and 0.73 for combination. The cumulative probability of sustained disability progression was 16.8% for IFNbeta-1a, 20.7% for IFNbeta-1a plus AZA, and 17.5% for combination. There were no statistically significant differences among groups for either measure at 2 and 5 years. Percent T2 lesion volume change at 2 years was significantly lower for combination (+14.5%) versus IFNbeta-1a alone (+30.3%, P < 0.05). Groups had similar safety profiles. CONCLUSION: In IFNbeta-naïve patients with early active RRMS, combination treatment did not show superiority over IFNbeta-1a monotherapy.