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AIM: To assess how atypical language organization after early left-hemispheric brain lesions affects grey matter in the contralesional hemisphere. METHOD: This was a cross-sectional study with between-group comparisons of 14 patients (six female, 8-26 years) with perinatal left-hemispheric brain lesions (two arterial ischemic strokes, 11 periventricular haemorrhagic infarctions, one without classification) and 14 typically developing age-matched controls (TDC) with functional magnetic resonance imaging (fMRI) documented left-hemispheric language organization (six female, 8-28 years). MRI data were analysed with SPM12, CAT12, and custom scripts. Language lateralization indices were determined by fMRI within a prefrontal mask and right-hemispheric grey matter group differences by voxel-based morphometry (VBM). RESULTS: FMRI revealed left-dominance in seven patients with typical language organization (TYP) and right-dominance in seven patients with atypical language organization (ATYP) of 14 patients. VBM analysis of all patients versus controls showed grey matter reductions in the middle temporal gyrus of patients. A comparison between the two patient subgroups revealed an increase of grey matter in the middle frontal gyrus in the ATYP group. Voxel-based regression analysis confirmed that grey matter increases in the middle frontal gyrus were correlated with atypical language organization. INTERPRETATION: Compatible with a non-specific lesion effect, we found areas of grey matter reduction in patients as compared to TDC. The grey matter increase in the middle frontal gyrus seems to reflect a specific compensatory effect in patients with atypical language organization. WHAT THIS PAPER ADDS: Perinatal stroke leads to decreased grey matter in the contralesional hemisphere. Atypical language organization is associated with grey matter increases in contralesional language areas.
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Encéfalo , Substância Cinzenta , Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Mapeamento Encefálico/métodos , Estudos Transversais , Idioma , Imageamento por Ressonância Magnética/métodos , Infarto , Lateralidade FuncionalRESUMO
BACKGROUND: Expert committees of the German medical associations provide a free and out-of-court evaluation of putative cases of medical malpractice. They prepare reports that contain valuable information on process steps that precede the actual treatment error. The aim of the present study was to identify and systematically categorize individual process steps in the expert reports and thus to lay the foundations for the understanding of malpractice evaluation processes. METHODS: In this study, ten randomly selected and anonymized expert reports of the Expert Committee for Questions of Medical Liability of the District Medical Association of South Württemberg with identified GP treatment errors were evaluated, using the method of qualitative content analysis. In an iterative process, central elements of expert reports were classified into a deductively and inductively built category system. RESULTS: Six main categories with associated subcategories were identified: 1) structural aspects of the report, 2) doctor-patient communication, 3) medical course, 4) patient's experience, 5) action by the GP team, and 6) coordinative role in the health care system. The category system showed sufficient reliability with repeated use. CONCLUSION: This study offers an opportunity to learn from errors. The proposed system allows to structure the complexity of expert reports on GP malpractice and may thus serve as a tool in various contexts. In particular, it facilitates the preparation and comparative analysis of reports in a structured way. It could also be used in health care research as well as in education and training.
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Medicina de Família e Comunidade , Imperícia , Humanos , Reprodutibilidade dos Testes , Alemanha , Relações Médico-Paciente , Erros Médicos , Prova PericialRESUMO
BACKGROUND: Metachromatic leukodystrophy (MLD) is a lysosomal enzyme deficiency disorder leading to progressive demyelination and, consecutively, to cognitive and motor decline. Brain magnetic resonance imaging (MRI) can detect affected white matter as T2 hyperintense areas but cannot quantify the gradual microstructural process of demyelination more accurately. Our study aimed to investigate the value of routine MR diffusion tensor imaging in assessing disease progression. METHODS: MR diffusion parameters (apparent diffusion coefficient [ADC] and fractional anisotropy [FA]) were in the frontal white matter, central region (CR), and posterior limb of the internal capsule in 111 MR datasets from a natural history study of 83 patients (age: 0.5-39.9 years; 35 late-infantile, 45 juvenile, 3 adult, with clinical diffusion sequences of different scanner manufacturers) as well as 120 controls. Results were correlated with clinical parameters reflecting motor and cognitive function. RESULTS: ADC values increase and FA values decrease depending on disease stage/severity. They show region-specific correlations with clinical parameters of motor and cognitive symptoms, respectively. Higher ADC levels in CR at diagnosis predicted a disease course with more rapid motor deterioration in juvenile MLD patients. In highly organized tissues such as the corticospinal tract, in particular, diffusion MR parameters were highly sensitive to MLD-associated changes and did not correlate with the visual quantification of T2 hyperintensities. CONCLUSION: Our results show that diffusion MRI can deliver valuable, robust, clinically meaningful, and easily obtainable/accessible/available parameters in the assessment of prognosis and progression of MLD. Therefore, it provides additional quantifiable information to established methods such as T2 hyperintensity.
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Imagem de Tensor de Difusão , Leucodistrofia Metacromática , Adulto , Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Imagem de Tensor de Difusão/métodos , Leucodistrofia Metacromática/diagnóstico por imagem , Relevância Clínica , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imagem de Difusão por Ressonância MagnéticaRESUMO
PURPOSE: Presurgical functional MRI (fMRI) and diffusion MRI tractography (dMRI tractography) are widely employed to delineate eloquent brain regions and their connections prior to brain tumor resection in adults. However, such studies are harder to perform in children, resulting in suboptimal neurosurgical care in pediatric brain tumor surgery as compared to adults. Thus, our objective was to assess the feasibility and the influence of presurgical advanced MR imaging on neurosurgical care in pediatric brain tumor surgery. METHODS: Retrospective analyses of 31 presurgical fMRI/dMRI tractography studies were performed in children with low-grade tumors near eloquent brain regions at our site between 2005 and 2017. RESULTS: In only 3/31 cases, imaging results were not interpretable (10%). All 28 successful imaging sessions were used for neurosurgical risk assessment. Based on this, surgery was canceled in 2/28 patients, and intention to treat was changed in 5/28 patients. In 4/28 cases, the surgical approach was changed and in 10/28, electrode placement for intraoperative neurophysiological monitoring was guided by imaging results. Gross total resection (GTR) was planned in 21/28 cases and could be achieved in 15/21 (71%). Despite highly eloquent tumor location, only four children suffered from a mild permanent neurological deficit after the operation. CONCLUSIONS: We demonstrate that presurgical fMRI/dMRI tractography can have a profound impact on pediatric brain tumor management, optimizing preoperative risk-assessment and pre- as well as intraoperative decision-making. We believe that these tools should be offered to children suffering from eloquent brain tumors as part of a comprehensive operative work-up.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neuroimagem/métodos , Cirurgia Assistida por Computador/métodos , Adolescente , Criança , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos RetrospectivosRESUMO
Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building.
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Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Modelos Neurológicos , Plasticidade Neuronal/fisiologia , Animais , Encéfalo/fisiopatologia , Lesões Encefálicas/fisiopatologia , HumanosRESUMO
OBJECTIVE: Functional magnetic resonance imaging (fMRI) activation of the mesial temporal lobe (MTL) may be important for epilepsy surgical planning. We examined MTL activation and lateralization during language fMRI in children and adults with focal epilepsy. METHODS: One hundred forty-two controls and patients with left hemisphere focal epilepsy (pediatric: epilepsy, n = 17, mean age = 9.9 ± 2.0; controls, n = 48; mean age = 9.1 ± 2.6; adult: epilepsy, n = 20, mean age = 26.7 ± 5.8; controls, n = 57, mean age = 26.2 ± 7.5) underwent 3T fMRI using a language task (auditory description decision task). Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8); regions of interest (ROIs) included MTL, Broca's area, and Wernicke's area. We assessed group and individual MTL activation, and examined degree of lateralization. RESULTS: Patients and controls (pediatric and adult) demonstrated group and individual MTL activation during language fMRI. MTL activation was left lateralized for adults, but less so in children (p's < 0.005). Patients did not differ from controls in either age group. Stronger left-lateralized MTL activation was related to older age (p = 0.02). Language lateralization (Broca's and Wernicke's) predicted 19% of the variance in MTL lateralization for adults (p = 0.001), but for not children. SIGNIFICANCE: Language fMRI may be used to elicit group and individual MTL activation. The developmental difference in MTL lateralization and its association with language lateralization suggests a developmental shift in lateralization of MTL function, with increased left lateralization across the age span. This shift may help explain why children have better memory outcomes following resection compared to adults.
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Envelhecimento/patologia , Epilepsia/patologia , Lateralidade Funcional/fisiologia , Idioma , Imageamento por Ressonância Magnética , Lobo Temporal/irrigação sanguínea , Adolescente , Adulto , Criança , Tomada de Decisões/fisiologia , Eletroencefalografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Oxigênio/sangue , Estudos Retrospectivos , Adulto JovemRESUMO
We have previously established an fMRI task battery suitable for mapping the language processing network in children. Among the tasks used, the synonyms and the vowel identification task induced robust task-related activations in children with average language abilities; however, the fixed presentation time seems to be a drawback in participants with above- or below-average language abilities. This feasibility study in healthy adults (n = 20) was aimed at adapting these tasks to the individual level of each patient by implementing a self-paced stimulus presentation. The impact of using a block- versus an event-related statistical approach was also evaluated. The self-paced modification allowed our participants with above-average language abilities to process stimuli much faster than originally implemented, likely increasing task adherence. A higher specificity of the event-related analysis was confirmed by stronger left inferior frontal and crossed cerebellar activations. We suggest that self-paced paradigms and event-related analyses may both increase specificity and applicability.
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Mapeamento Encefálico/normas , Encéfalo/fisiologia , Idioma , Imageamento por Ressonância Magnética/normas , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Estimulação Luminosa/métodosRESUMO
We report on a girl with progressive left frontal tissue destruction starting at the age of almost 8 years. She manifested acutely with epileptic seizures accompanied by Broca aphasia as well as transient right hemiparesis. Due to refractory epilepsy developing over the next years, which originated from the left frontal lobe, the decision was made to proceed to epilepsy surgery. By then, her language functions had recovered despite progressive left frontal tissue-destruction, raising the possibility of a hemispheric shift of language. Clinical functional magnetic resonance imaging (fMRI) was conducted to localize brain regions involved in language production. A complex pattern of clear right-hemispheric dominance, but with some left-sided contribution was found. However, a Wada test suggested the left hemisphere to be critical, seemingly contradicting fMRI. Invasive electroencephalogram recordings could reconcile these results by identifying the fMRI-detected, residual left-sided activation as being relevant for speech production. Only by combining the localizing information from fMRI with the information obtained by two invasive procedures could the unusual pattern of late-onset language reorganization be uncovered. This allowed for extensive left frontal resection, with histology confirming meningocerebral angiodysplasia. Postoperatively, language functions were preserved and seizure outcome was excellent. The implications of our findings for presurgical assessments in children are discussed.
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Angiodisplasia/cirurgia , Afasia de Broca/fisiopatologia , Encefalopatias/cirurgia , Epilepsia do Lobo Frontal/cirurgia , Idioma , Angiodisplasia/complicações , Angiodisplasia/patologia , Angiodisplasia/fisiopatologia , Afasia de Broca/etiologia , Encefalopatias/complicações , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Mapeamento Encefálico , Criança , Eletroencefalografia , Epilepsia do Lobo Frontal/etiologia , Epilepsia do Lobo Frontal/fisiopatologia , Feminino , Lateralidade Funcional , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Plasticidade Neuronal , Paresia/etiologiaRESUMO
OBJECTIVE: To evaluate whether an early postnatal infection poses a long-term risk for neuropsychological impairment to neonates born very prematurely. STUDY DESIGN: Adolescents born very preterm (n = 42, 11.6-16.2 years, mean = 13.9; 15 girls; 19 with and 23 without an early postnatal human cytomegalovirus [CMV] infection) and typically developing, term born controls (n = 24, 11.3-16.6 years, mean = 13.6; 12 girls) were neuropsychologically assessed with the German version of the Wechsler Intelligence Scale and the Developmental Test for Visual Perception. RESULTS: As expected, the full cohort of adolescents born preterm had significantly lower scores than term born controls on IQ (preterm: mean [SD] = 98.43 [14.83], control: 110.00 [8.10], P = .015) and on visuoperceptive abilities (95.64 [12.87] vs 106.24 [9.95], P = .016). Furthermore, adolescents born preterm with early postnatal CMV infection scored significantly lower than those without this infection regarding overall cognitive abilities (92.67 [14.71] vs 102.75 [13.67], P = .030), but not visuoperceptive abilities (91.22 [10.88] vs 98.96 [13.45], P > .05). CONCLUSIONS: In our small but well-characterized group, our results provide evidence for adverse effects of early postnatal CMV infection on overall cognitive functions in adolescents born preterm. If confirmed, these results support the implementation of preventive measures.
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Cognição/fisiologia , Infecções por Citomegalovirus/diagnóstico , Doenças do Prematuro/diagnóstico , Recém-Nascido Prematuro/psicologia , Testes Neuropsicológicos , Percepção Visual/fisiologia , Adolescente , Criança , Pré-Escolar , Citomegalovirus/genética , Infecções por Citomegalovirus/psicologia , DNA Viral/análise , Feminino , Seguimentos , Humanos , Doenças do Prematuro/psicologia , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Advanced modalities such as functional magnetic resonance imaging (MRI) and diffusion MR tractography offer in vivo information about brain networks and are therefore increasingly used for neurosurgical planning in children also. AIM: This study aims to study the application of routine and advanced tractography algorithms and its comparison with intraoperative subcortical electrical stimulation. METHOD: Presurgical functional MRI and MR diffusion tractography were performed on a 6-year-old patient presenting with seizures, but no motor symptoms, due to a neuroectodermal tumor in the left central region. Three different tractography algorithms were compared: deterministic diffusion tensor imaging (DTI)-tracking, probabilistic DTI-tracking, and probabilistic constrained spherical deconvolution tracking (pCSD). RESULTS: All three tractography algorithms could localize the core of the corticospinal tract with good agreement. The pCSD-tracking algorithm was more sensitive in revealing the anatomically most realistic fiber distribution and a proportion of fibers traversing a solid part of the tumor. Intraoperative stimulation confirmed these fibers close to the tumor. As a result, only a subtotal resection was performed, preventing postoperative sensorimotor deficits. CONCLUSION: Although, all tractography algorithms successfully identified the core of the corticospinal pathway, deterministic DTI-tractography, as widely used in clinical neuronavigation software, only insufficiently visualized critical fibers here. We believe these results argue for a stronger consideration of advanced tractography approaches in neurosurgical planning.
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Algoritmos , Neoplasias Encefálicas/cirurgia , Processamento de Imagem Assistida por Computador/métodos , Neurocirurgia/métodos , Tratos Piramidais/patologia , Neoplasias Encefálicas/complicações , Criança , Epilepsia/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Tratos Piramidais/irrigação sanguínea , Reprodutibilidade dos TestesRESUMO
Very preterm (PT) birth (≤32 weeks of gestation) carries a high risk for an adverse neurodevelopmental outcome. In recent years, the importance of neurocognitive deficits in the language domain has been increasingly recognized, which can be well-characterized using neuropsychological testing and noninvasive imaging approaches. We compared former early PT born children and adolescents (PT, n = 29, 20M) and typically developing children (TD, n = 19, 7M), using conventional fMRI group analyses as well as functional connectivity analyses. We found only small regions with significantly different group activation (PT > TD) but significantly stronger connectivity between superior temporal lobe (STL) language regions in TD participants. There were also significant differences in local and global network efficiency (TD > PT). Surprisingly, there was a stronger connectivity of STL regions with non-STL regions both intrahemispherically and interhemispherically in PT participants, suggesting the coexistence of reduced and increased connectivity in the language network of former PTs. Very similar results were obtained when using task-based versus resting state functional connectivity approaches. Finally, lateralization of functional connectivity correlated with verbal comprehension abilities, suggesting that a more bilateral language comprehension representation is associated with better performance. Our results underline the importance of interhemispheric crosstalk for language comprehension.
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Mapeamento Encefálico , Encéfalo/fisiopatologia , Transtornos do Desenvolvimento da Linguagem/etiologia , Vias Neurais/fisiopatologia , Nascimento Prematuro/patologia , Nascimento Prematuro/fisiopatologia , Adolescente , Análise de Variância , Encéfalo/irrigação sanguínea , Criança , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Transtornos do Desenvolvimento da Linguagem/patologia , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/irrigação sanguínea , Oxigênio/sangueRESUMO
Automated morphometric approaches are used to detect epileptogenic structural abnormalities in 3D MR images in adults, using the variance of a control population to obtain z-score maps in an individual patient. Due to the substantial changes the developing human brain undergoes, performing such analyses in children is challenging. This study investigated six features derived from high-resolution T1 datasets in four groups: normal children (1.5T or 3T data), normal clinical scans (3T data), and patients with structural brain lesions (3T data), with each n = 10. Normative control data were obtained from the NIH study on normal brain development (n = 401). We show that control group size substantially influences the captured variance, directly impacting the patient's z-scores. Interestingly, matching on gender does not seem to be beneficial, which was unexpected. Using data obtained at higher field scanners produces slightly different base rates of suprathreshold voxels, as does using clinically derived normal studies, suggesting a subtle but systematic effect of both factors. Two approaches for controlling suprathreshold voxels in a multidimensional approach (combining features and requiring a minimum cluster size) were shown to be substantial and effective in reducing this number. Finally, specific strengths and limitations of such an approach could be demonstrated in individual cases.
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Lesões Encefálicas/patologia , Encéfalo/fisiopatologia , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Adolescente , Distribuição por Idade , Fatores Etários , Algoritmos , Encéfalo/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Distribuição por Sexo , Estatísticas não Paramétricas , Adulto JovemRESUMO
Early postnatal infection with human cytomegalovirus (hCMV) may contribute to an adverse cognitive outcome in early preterm-born children (PT). We here set out to explore whether long-term neurobiological consequences of such an infection are detectable using fMRI in children and adolescents who were born very preterm and who either did (PThCMV+ ) or did not (PT(hCMV-)) suffer from an early postnatal hCMV-infection, when compared with typically developing healthy control (HC) subjects. Overall, data from 71 children and adolescents could be included, 34 PT (of which 15 were PT(hCMV+) and 19 were PT(hCMV-)) and 37 HC. Using a recently established "dual use" fMRI task, we investigated language and visuospatial functions. There were significant activation differences in the left hippocampus (PT > HC and PT(hCMV+) > HC), and in the right anterior cingulate cortex (PT(hCMV-) > PT(hCMV+)) when performing the language task. Surprisingly, only a small region in the occipital cortex showed a significant activation difference (HC > PT(HCMV-)) when performing the visuospatial task. Targeted analyses revealed differences in gray matter volume, but not density, in several brain regions. Our results suggest that long-term neurobiological consequences of an early postnatal hCMV infection are detectable even in older children and adolescents formerly born very preterm, compatible with a higher effort when performing a cognitive task. This suggests that measures to prevent such an infection are warranted. Furthermore, an interrelation of brain structure and function was detected that may constitute a severe confound when using fMRI to compare structurally differing groups.
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Encéfalo/fisiologia , Infecções por Citomegalovirus , Doenças do Prematuro , Idioma , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Adolescente , Encéfalo/patologia , Mapeamento Encefálico , Criança , Feminino , Giro do Cíngulo/patologia , Giro do Cíngulo/fisiologia , Hipocampo/patologia , Hipocampo/fisiologia , Humanos , Recém-Nascido Prematuro , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Lobo Occipital/patologia , Lobo Occipital/fisiologia , Tamanho do ÓrgãoRESUMO
BACKGROUND: Congenital grouped skin lesions are alarming signs of a variety of threatening diagnoses of quite different origin. The present case report shows an impressive clinical pattern of a neonate and illustrates the difficulty in differential diagnosis of mixed connective tissue disease and neonatal lupus erythematosus in newborns. This reported case is to our knowledge the first description of an unrecognized mixed connective tissue disease in the mother with an unusual clinical manifestation in the newborn, comprising skin lesions, neurological damage and non-typical antibody constellation. CASE PRESENTATION: We report on a Caucasian female neonate from a perinatally asymptomatic mother, who presented with grouped facial pustular-like skin lesions, followed by focal clonic seizures caused by multiple ischemic brain lesions. Herpes simplex virus infection was excluded and both the mother and her infant had the antibody pattern of systemic lupus erythematosus and neonatal lupus erythematosus, respectively. However, clinical signs in the mother showed overlapping features of mixed connective tissue disease. CONCLUSION: This case report emphasizes congenital Lupus erythematosus and mixed connective tissue disease as important differential diagnoses of grouped skin lesions in addition to Herpes simplex virus-infection. The coexistence of different criteria for mixed connective tissue disease makes it difficult to allocate precisely maternal and congenital infantile disease.
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Isquemia Encefálica/patologia , Epilepsia Motora Parcial/etiologia , Dermatoses Faciais/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Doença Mista do Tecido Conjuntivo/diagnóstico , Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Diagnóstico Diferencial , Feminino , Herpes Simples/diagnóstico , Humanos , Recém-Nascido , Lúpus Eritematoso Sistêmico/congênito , Lúpus Eritematoso Sistêmico/imunologia , Imageamento por Ressonância Magnética , Deficiência de Proteína C/complicações , Ribonucleoproteínas Nucleares Pequenas/imunologia , Proteínas Centrais de snRNP/imunologiaRESUMO
The first step in spatial normalization of magnetic resonance (MR) images commonly is an affine transformation, which may be vulnerable to image imperfections (such as inhomogeneities or "unusual" heads). Additionally, common software solutions use internal starting estimates to allow for a more efficient computation, which may pose a problem in datasets not conforming to these assumptions (such as those from children). In this technical note, three main questions were addressed: one, does the affine spatial normalization step implemented in SPM12 benefit from an initial inhomogeneity correction. Two, does using a complexity-reduced image version improve robustness when matching "unusual" images. And three, can a blind "brute-force" application of a wide range of parameter combinations improve the affine fit for unusual datasets in particular. A large database of 2081 image datasets was used, covering the full age range from birth to old age. All analyses were performed in Matlab. Results demonstrate that an initial removal of image inhomogeneities improved the affine fit particularly when more inhomogeneity was present. Further, using a complexity-reduced input image also improved the affine fit and was beneficial in younger children in particular. Finally, blindly exploring a very wide parameter space resulted in a better fit for the vast majority of subjects, but again particularly so in infants and young children. In summary, the suggested modifications were shown to improve the affine transformation in the large majority of datasets in general, and in children in particular. The changes can easily be implemented into SPM12.
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Objectives: This study aims to investigate the long-term language outcome in children with unilateral childhood stroke in comparison to those with perinatal strokes and typically developing individuals and to explore the impact of lesion-specific modifiers. Methods: We examined nine patients with childhood stroke, acquired between 0;2 and 16;1 years (CHILD; 3 female, median = 13.5 years, 6 left-sided), 23 patients with perinatal strokes (PERI; 11 female, median = 12.5 years, 16 left-sided), and 33 age-matched typically developing individuals (CONTROL; 15 female, median = 12.33 years). The language outcome was assessed using age-appropriate tasks of the Potsdam Illinois Test of Psycholinguistic Abilities (P-ITPA) or the Peabody Picture Vocabulary Test (PPVT). For group comparisons, study-specific language z-scores were calculated. Non-verbal intelligence was assessed using the Test of Non-verbal Intelligence (TONI-4), language lateralization with functional MRI, and lesion size with MRI-based volumetry. Results: All four patients with childhood stroke who initially presented with aphasic symptoms recovered from aphasia. Patients with childhood stroke showed significantly lower language scores than those in the control group, but their scores were similar to those of the patients with perinatal stroke, after adjusting for general intelligence (ANCOVA, language z-score CHILD = -0.30, PERI = -0.38, CONTROL = 0.42). Among the patients with childhood stroke, none of the possible modifying factors, including lesion side, correlated significantly with the language outcome. Conclusion: Childhood stroke, regardless of the affected hemisphere, can lead to chronic language deficits, even though affected children show a "full recovery." The rehabilitation of children and adolescents with childhood stroke should address language abilities, even after the usually quick resolution of clear aphasic symptoms.
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AIM: Early unilateral brain lesions can lead to a persistence of ipsilateral corticospinal projections from the contralesional hemisphere, which can enable the contralesional hemisphere to exert motor control over the paretic hand. In contrast to the primary motor representation (M1), the primary somatosensory representation (S1) of the paretic hand always remains in the lesioned hemisphere. Here, we report on differences in exercise-induced neuroplasticity between individuals with such ipsilateral motor projections (ipsi) and individuals with early unilateral lesions but 'healthy' contralateral motor projections (contra). METHOD: Sixteen children and young adults with congenital hemiparesis participated in the study (contralateral [Contra] group: n=7, four females, three males; age range 10-30y, median age 16y; ipsilateral [Ipsi] group: n=9, four females, five males; age range 11-31y, median age 12y; Manual Ability Classification System levels I to II in all individuals in both groups). The participants underwent a 12-day intervention of constraint-induced movement therapy (CIMT), consisting of individual training (2h/d) and group training (8h/d). Before and after CIMT, hand function was tested using the Wolf Motor Function Test (WMFT) and diverging neuroplastic effects were observed by transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG). Statistical analysis of TMS data was performed using the non-parametric Wilcoxon signed-rank test for pair-wise comparison; for fMRI standard statistical parametric and non-parametric mapping (SPM5, SnPM3) procedures (first level/second level) were carried out. Statistical analyses of MEG data involved analyses of variance (ANOVA) and t-tests. RESULTS: While MEG demonstrated a significant increase in S1 activation in both groups (p=0.012), TMS showed a decrease in M1 excitability in the Ipsi group (p=0.036), but an increase in M1 excitability in the Contra group (p=0.043). Similarly, fMRI showed a decrease in M1 activation in the Ipsi group, but an increase in activation in the M1-S1 region in the Contra group (for both groups p<0.001 [SnPM3] within the search volume). INTERPRETATION: Different patterns of sensorimotor (re)organization in individuals with early unilateral lesions show, on a cortical level, different patterns of exercise-induced neuroplasticity. The findings help to improve the understanding of the general principles of sensorimotor learning and will help to develop more specific therapies for different pathologies in congenital hemiparesis.
Assuntos
Encéfalo/patologia , Técnicas de Exercício e de Movimento/métodos , Plasticidade Neuronal/fisiologia , Paresia/etiologia , Paresia/terapia , Adolescente , Adulto , Análise de Variância , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Criança , Feminino , Lateralidade Funcional/fisiologia , Mãos/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Paresia/classificação , Paresia/congênito , Tempo de Reação , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
Introduction: Preterm birth is increasingly recognized to cause lifelong functional deficits, which often show no correlate in conventional MRI. In addition, early postnatal infection with human cytomegalovirus (hCMV) is being discussed as a possible cause for further impairments. In the present work, we used fixel-based analysis of diffusion-weighted MRI to assess long-term white matter alterations associated with preterm birth and/or early postnatal hCMV infection. Materials and methods: 36 former preterms (PT, median age 14.8 years, median gestational age 28 weeks) and 18 healthy term-born controls (HC, median age 11.1 years) underwent high angular resolution DWI scans (1.5 T, b = 2 000 s/mm2, 60 directions) as well as clinical assessment. All subjects showed normal conventional MRI and normal motor function. Early postnatal hCMV infection status (CMV+ and CMV-) had been determined from repeated screening, ruling out congenital infections. Whole-brain analysis was performed, yielding fixel-wise metrics for fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). Group differences were identified in a whole-brain analysis, followed by an analysis of tract-averaged metrics within a priori selected tracts associated with cognitive function. Both analyses were repeated while differentiating for postnatal hCMV infection status. Results: PT showed significant reductions of fixel metrics bilaterally in the cingulum, the genu corporis callosum and forceps minor, the capsula externa, and cerebellar and pontine structures. After including intracranial volume as a covariate, reductions remained significant in the cingulum. The tract-specific investigation revealed further reductions bilaterally in the superior longitudinal fasciculus and the uncinate fasciculus. When differentiating for hCMV infection status, no significant differences were found between CMV+ and CMV-. However, comparing CMV+ against HC, fixel metric reductions were of higher magnitude and of larger spatial extent than in CMV- against HC. Conclusion: Preterm birth can lead to long-lasting alterations of WM micro- and macrostructure, not visible on conventional MRI. Alterations are located predominantly in WM structures associated with cognitive function, likely underlying the cognitive deficits observed in our cohort. These observed structural alterations were more pronounced in preterms who suffered from early postnatal hCMV infection, in line with previous studies suggesting an additive effect.
RESUMO
Motion is a significant problem for the analysis of functional MRI data. This manuscript addresses the question of whether an individualized assessment of motion may be informative, and whether it may be beneficial with regard to explaining motion-related variance. Two independent datasets are used to explore and test this hypothesis, from a total of 21 healthy children, performing either no externally-cued task (resting state) or an active listening paradigm (beep story). Translations and rotations are combined into one single, individual measure of total displacement, which is demonstrated to be substantially different between brain regions as a function of their distance from the individual origin. An increasing number of covariates leads to a loss of detection power, but more so on the first than on the second level, and more so in less-powerful designs. Synthetic timeseries are calculated from which the direct effects of motion as well as motion*B0 effects can be isolated, allowing to extract individual timecourses which reflect both direct and indirect motion effects. Including three timecourses from such an individually-derived "motion fingerprint" into first-level statistical analyses explains variance to a similar degree as the commonly-used approach of including the realignment parameters, and performance is statistically equivalent to including the realignment parameters on the second level. A more individualized approach to explaining motion-related variance may therefore be beneficial, depending on the scenario.
Assuntos
Encéfalo/anatomia & histologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Movimento (Física) , Algoritmos , Artefatos , Criança , Simulação por Computador , Feminino , Humanos , Modelos Lineares , Masculino , Modelos EstatísticosRESUMO
In this study, we analyzed the structural connectivity of cortico-cortical and cortico-subcortical language networks in healthy children, using probabilistic tractography based on high angular resolution diffusion imaging. In addition to anatomically defining seed and target regions for tractography, we used fMRI to target inferior frontal and superior temporal cortical language areas on an individual basis. Further, connectivity between these cortical and subcortical (thalamus, caudate nucleus) language regions was assessed. Overall, data from 15 children (8f) aged 8-17 years (mean age 12.1 ±3 years) could be included. A slight but non-significant trend towards leftward lateralization was found in the arcuate fasciculus/superior longitudinal fasciculus (AF/SLF) using anatomically defined masks (p>.05, Wilcoxon rank test), while the functionally-guided tractography showed a significant lateralization to the left (p<.01). Connectivity of the thalamus with language regions was strong but not lateralized. Connectivity of the caudate nucleus with inferior-frontal language regions was also symmetrical, while connectivity with superior-temporal language regions was strongly lateralized to the left (p<.01). To conclude, we could show that tracking the arcuate fasciculus/superior longitudinal fasciculus is possible using both anatomically and functionally-defined seed and target regions. With the latter approach, we could confirm the presence of structurally-lateralized cortico-cortical language networks already in children, and finally, we could demonstrate a strongly asymmetrical connectivity of the caudate nucleus with superior temporal language regions. Further research is necessary in order to assess the usability of such an approach to assess language dominance in children unable to participate in an active fMRI study.