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1.
NMR Biomed ; 37(5): e5101, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38303627

RESUMO

1H-magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single-voxel MRS (point-resolved single-voxel spectroscopy sequence, 1.5 T: echo time [TE] 23-37 ms/135-144 ms, repetition time [TR] 1500 ms; 3 T: TE 37-41 ms/135-144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann-Whitney U-tests and Kruskal-Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Humanos , Criança , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Imageamento por Ressonância Magnética
2.
Br J Haematol ; 201(1): 114-124, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36329651

RESUMO

Brain injury is a common complication of sickle cell anaemia (SCA). White matter (WM) and cortical and subcortical grey matter (GM), structures may have reduced volume in patients with SCA. This study focuses on whether silent cerebral infarction (SCI), vasculopathy or anaemia affects WM and regional GM volumes in children living in Africa. Children with SCA (n = 144; aged 5-20 years; 74 male) and sibling controls (n = 53; aged 5-17 years; 29 male) underwent magnetic resonance imaging. Effects of SCI (n = 37), vasculopathy (n = 15), and haemoglobin were assessed. Compared with controls, after adjusting for age, sex and intracranial volume, patients with SCA had smaller volumes for WM and cortical, subcortical and total GM, as well as bilateral cerebellar cortex, globus pallidus, amygdala and right thalamus. Left globus pallidus volume was further reduced in patients with vasculopathy. Putamen and hippocampus volumes were larger in patients with SCA without SCI or vasculopathy than in controls. Significant positive effects of haemoglobin on regional GM volumes were confined to the controls. Patients with SCA generally have reduced GM volumes compared with controls, although some subcortical regions may be spared. SCI and vasculopathy may affect the trajectory of change in subcortical GM and WM volume. Brain volume in non-SCA children may be vulnerable to contemporaneous anaemia.


Assuntos
Anemia Falciforme , Acidente Vascular Cerebral , Substância Branca , Humanos , Masculino , Criança , Tanzânia , Imageamento por Ressonância Magnética/métodos , Neuroimagem , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia
3.
Stroke ; 51(4): 1166-1173, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32138633

RESUMO

Background and Purpose- Widespread reductions in white matter integrity are associated with cognitive dysfunction in sickle cell anemia. Silent cerebral infarction (SCI), vasculopathy (VSC), and low hemoglobin concentration (Hb) are implicated; we aimed to determine independent contributions to microstructural white matter injury and whether white matter integrity differs across arterial territories. Methods- Sixty two children with sickle cell anemia aged 6 to 19 years were prospectively studied at Muhimbili National Hospital, Tanzania. SCI± and VSC± were identified on magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) scans by 2 neuroradiologists. Tract-based spatial statistics tested for voxel-wise differences in diffusion tensor imaging metrics (ie, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) between SCI± and VSC± groups, with correlations between diffusion tensor imaging metrics and Hb. In tract-based spatial statistics analyses, potentially mediating factors (ie, age, sex, as well as Hb, SCI, and/or vasculopathy) were covariates. Differences in mean diffusion tensor imaging metrics across regions of interest in arterial territories were explored. Results- Compared with SCI- patients (n=45), SCI+ patients (n=17) exhibited increased radial diffusivity in multiple regions; negative relationships were observed between mean diffusivity, axial diffusivity, and Hb (P<0.005). Compared with VSC- patients (n=49), mild (n=6) or moderate (n=7) VSC+ patients exhibited reduced fractional anisotropy in widespread regions (P<0.05) including the anterior longitudinal fasciculi, corpus callosum, internal capsule, corona radiata, and corticospinal tracts. Overall, the posterior cerebral arterial territory had higher mean mean diffusivity and mean radial diffusivity than the anterior and middle cerebral arterial territories, although no patient had vasculopathy in this area. There was an interaction between territory and vasculopathy. Conclusions- SCI, vasculopathy, and Hb are independent risk factors, and thus treatment targets, for diffuse white matter injury in patients with sickle cell anemia. Exacerbation of hemodynamic stress may play a role.


Assuntos
Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/epidemiologia , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão/tendências , Angiografia por Ressonância Magnética/tendências , Substância Branca/diagnóstico por imagem , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos Prospectivos , Tanzânia/epidemiologia , Adulto Jovem
4.
Stroke ; 50(7): 1719-1726, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31195937

RESUMO

Background and Purpose- We determined prevalences of neurological complications, vascular abnormality, and infarction in Tanzanian children with sickle cell disease. Methods- Children with sickle cell disease were consecutively enrolled for transcranial Doppler; those with slightly elevated (>150 cm/s), low (<50 cm/s) or absent cerebral blood flow velocity (CBFv) were invited for brain magnetic resonance imaging and magnetic resonance angiography. Results- Of 200 children (median age 9; range 6-13 years; 105 [2.5%] boys), 21 (11%) and 15 (8%) had previous seizures and unilateral weakness, respectively. Twenty-eight (14%) had elevated and 39 (20%) had low/absent CBFv, all associated with lower hemoglobin level, but not higher indirect bilirubin level. On multivariable analysis, CBFv>150 cm/s was associated with frequent painful crises and low hemoglobin level. Absent/low CBFv was associated with low hemoglobin level and history of unilateral weakness. In 49 out of 67 children with low/absent/elevated transcranial Doppler undergoing magnetic resonance imaging, 43% had infarction, whereas 24 out of 48 (50%) magnetic resonance angiographies were abnormal. One had hemorrhagic infarction; none had microbleeds. Posterior circulation infarcts occurred in 14%. Of 11 children with previous seizure undergoing magnetic resonance imaging, 10 (91%) had infarction (5 silent) compared with 11 out of 38 (29%) of the remainder ( P=0.003). Of 7 children with clinical stroke, 2 had recurrent stroke and 3 died; 4 out of 5 had absent CBFv. Of 193 without stroke, 1 died and 1 had a stroke; both had absent CBFv. Conclusions- In one-third of Tanzanian children with sickle cell disease, CBFv is outside the normal range, associated with frequent painful crises and low hemoglobin level, but not hemolysis. Half have abnormal magnetic resonance angiography. African children with sickle cell disease should be evaluated with transcranial Doppler; those with low/absent/elevated CBFv should undergo magnetic resonance imaging/magnetic resonance angiography.


Assuntos
Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/epidemiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Adolescente , Anemia Falciforme/complicações , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/epidemiologia , Circulação Cerebrovascular , Criança , Feminino , Hemoglobinas/análise , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Dor/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/complicações , Tanzânia/epidemiologia , Ultrassonografia Doppler Transcraniana
5.
Am J Hum Genet ; 95(5): 611-21, 2014 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-25439728

RESUMO

Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum.


Assuntos
Ataxia Cerebelar/genética , Deficiência Intelectual/genética , Nexinas de Classificação/genética , Sequência de Bases , Ataxia Cerebelar/patologia , Mapeamento Cromossômico , Códon sem Sentido/genética , Feminino , Fibroblastos/ultraestrutura , Redes Reguladoras de Genes/genética , Genes Recessivos/genética , Humanos , Deficiência Intelectual/patologia , Masculino , Microscopia Eletrônica , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
6.
Eur Radiol ; 26(7): 2327-36, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26489748

RESUMO

OBJECTIVES: To compare the diagnostic yield of whole-body post-mortem computed tomography (PMCT) imaging to post-mortem magnetic resonance (PMMR) imaging in a prospective study of fetuses and children. METHODS: We compared PMCT and PMMR to conventional autopsy as the gold standard for the detection of (a) major pathological abnormalities related to the cause of death and (b) all diagnostic findings in five different body organ systems. RESULTS: Eighty two cases (53 fetuses and 29 children) underwent PMCT and PMMR prior to autopsy, at which 55 major abnormalities were identified. Significantly more PMCT than PMMR examinations were non-diagnostic (18/82 vs. 4/82; 21.9 % vs. 4.9 %, diff 17.1 % (95 % CI 6.7, 27.6; p < 0.05)). PMMR gave an accurate diagnosis in 24/55 (43.64 %; 95 % CI 31.37, 56.73 %) compared to 18/55 PMCT (32.73 %; 95 % CI 21.81, 45.90). PMCT was particularly poor in fetuses <24 weeks, with 28.6 % (8.1, 46.4 %) more non-diagnostic scans. Where both PMCT and PMMR were diagnostic, PMMR gave slightly higher diagnostic accuracy than PMCT (62.8 % vs. 59.4 %). CONCLUSION: Unenhanced PMCT has limited value in detection of major pathology primarily because of poor-quality, non-diagnostic fetal images. On this basis, PMMR should be the modality of choice for non-invasive PM imaging in fetuses and children. KEY POINTS: • Overall 17.1 % more PMCT examinations than PMMR were non-diagnostic • 28.6 % more PMCT were non-diagnostic than PMMR in fetuses <24 weeks • PMMR detected almost a third more pathological abnormalities than PMCT • PMMR gave slightly higher diagnostic accuracy when both were diagnostic.


Assuntos
Autopsia/métodos , Feto/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Imagem Corporal Total/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes
7.
Dev Med Child Neurol ; 58(1): 63-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26502795

RESUMO

AIM: Review a series of children with posterior circulation arterial ischaemic stroke (PCAIS) to identify diagnostic modality and associations in cases of vertebral artery dissection (VAD). METHOD: Retrospective analysis of 30 cases of childhood PCAIS identified from two tertiary centres over 11 years. Clinical and demographic details were recorded. Brain and cerebrovascular imaging were reviewed. Aetiology was classified using the Childhood Arterial Ischaemic Stroke Standardized Classification and Diagnostic Evaluation criteria. Outcome was evaluated using standardized paediatric stroke outcome scores. Logistic regression was used to explore variables associated with diagnosis. RESULTS: Twenty-three patients were male (77%) and 7 were female (23%). VAD was the most commonly identified aetiology, in 15 cases (50%). Aetiology was undetermined in 12 (40%), probable cardioembolism in two, and reversible cerebral vasoconstriction syndrome in one. In those with VAD, diagnosis was made on initial magnetic resonance angiography (MRA) in six (40%). Further cases of VAD were diagnosed with catheter angiography (n=6), computed tomographic angiography (n=1), or follow-up MRA (n=2). Presence of multiple infarcts was associated with a diagnosis of VAD. INTERPRETATION: Endoluminal cerebrovascular imaging increases the rate of diagnosis of VAD in childhood PCAIS and should especially be considered if there are multiple infarcts.


Assuntos
Isquemia Encefálica/etiologia , Circulação Cerebrovascular/fisiologia , Acidente Vascular Cerebral/etiologia , Dissecação da Artéria Vertebral/complicações , Adolescente , Isquemia Encefálica/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Dissecação da Artéria Vertebral/diagnóstico
8.
NMR Biomed ; 28(4): 468-85, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25802212

RESUMO

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra-voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences. An ice-water phantom and nine healthy volunteers were scanned across fives centres on eight scanners (four Siemens 1.5T, four Philips 3T). The mean ADC, IVIM parameters (diffusion coefficient D and perfusion fraction f) and DTI parameters (mean diffusivity MD and fractional anisotropy FA), were measured in grey matter, white matter and specific brain sub-regions. A mixed effect model was used to measure the intra- and inter-scanner coefficient of variation (CV) for each of the five parameters. ADC, D, MD and FA had a good intra- and inter-scanner reproducibility in both grey and white matter, with a CV ranging between 1% and 7.4%; mean 2.6%. Other brain regions also showed high levels of reproducibility except for small structures such as the choroid plexus. The IVIM parameter f had a higher intra-scanner CV of 8.4% and inter-scanner CV of 24.8%. No major difference in the inter-scanner CV for ADC, D, MD and FA was observed when analysing the 1.5T and 3T scanners separately. ADC, D, MD and FA all showed good intra-scanner reproducibility, with the inter-scanner reproducibility being comparable or faring slightly worse, suggesting that using data from multiple scanners does not have an adverse effect compared with using data from the same scanner. The IVIM parameter f had a poorer inter-scanner CV when scanners of different field strengths were combined, and the parameter was also affected by the scan acquisition resolution. This study shows that the majority of diffusion MRI derived parameters are robust across 1.5T and 3T scanners and suitable for use in multi-centre clinical studies and trials.


Assuntos
Encéfalo/anatomia & histologia , Imagem de Difusão por Ressonância Magnética/métodos , Neuroimagem/métodos , Adulto , Anisotropia , Água Corporal , Difusão , Imagem de Tensor de Difusão/métodos , Humanos , Gelo , Modelos Teóricos , Movimento (Física) , Imagens de Fantasmas , Reprodutibilidade dos Testes , Água , Substância Branca/anatomia & histologia
10.
Lancet ; 382(9888): 223-33, 2013 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-23683720

RESUMO

BACKGROUND: Post-mortem MRI is a potential diagnostic alternative to conventional autopsy, but few large prospective studies have compared its accuracy with that of conventional autopsy. We assessed the accuracy of whole-body, post-mortem MRI for detection of major pathological lesions associated with death in a prospective cohort of fetuses and children. METHODS: In this prospective validation study, we did pre-autopsy, post-mortem, whole-body MRI at 1·5 T in an unselected population of fetuses (≤24 weeks' or >24 weeks' gestation) and children (aged <16 years) at two UK centres in London between March 1, 2007 and Sept 30, 2011. With conventional autopsy as the diagnostic gold standard, we assessed MRI findings alone, or in conjunction with other minimally invasive post-mortem investigations (minimally invasive autopsy), for accuracy in detection of cause of death or major pathological abnormalities. A radiologist and pathologist who were masked to the autopsy findings indicated whether the minimally invasive autopsy would have been adequate. The primary outcome was concordance rate between minimally invasive and conventional autopsy. FINDINGS: We analysed 400 cases, of which 277 (69%) were fetuses and 123 (31%) were children. Cause of death or major pathological lesion detected by minimally invasive autopsy was concordant with conventional autopsy in 357 (89·3%, 95% CI 85·8-91·9) cases: 175 (94·6%, 90·3-97·0) of 185 fetuses at 24 weeks' gestation or less, 88 (95·7%, 89·3-98·3) of 92 fetuses at more than 24 weeks' gestation, 34 (81·0%, 66·7-90·0) [corrected] of 42 newborns aged 1 month or younger, 45 (84·9%, 72·9-92·1) of 53 infants aged older than 1 month to 1 year or younger, and 15 (53·6%, 35·8-70·5) of 28 children aged older than 1 year to 16 years or younger. The dedicated radiologist or pathologist review of the minimally invasive autopsy showed that in 165 (41%) cases a full autopsy might not have been needed; in these cases, concordance between autopsy and minimally invasive autopsy was 99·4% (96·6-99·9). INTERPRETATION: Minimally invasive autopsy has accuracy similar to that of conventional autopsy for detection of cause of death or major pathological abnormality after death in fetuses, newborns, and infants, but was less accurate in older children. If undertaken jointly by pathologists and radiologists, minimally invasive autopsy could be an acceptable alternative to conventional autopsy in selected cases. FUNDING: Policy research Programme, Department of Health, UK.


Assuntos
Autopsia/métodos , Imageamento por Ressonância Magnética/métodos , Adolescente , Autopsia/normas , Causas de Morte , Criança , Pré-Escolar , Morte Fetal/patologia , Humanos , Lactente , Imageamento por Ressonância Magnética/normas , Estudos Prospectivos , Sensibilidade e Especificidade , Imagem Corporal Total/métodos , Imagem Corporal Total/normas
11.
Brain ; 136(Pt 6): 1708-17, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23687123

RESUMO

Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.


Assuntos
Encéfalo/metabolismo , Proteínas de Transporte/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Ferro/metabolismo , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Adolescente , Adulto , Estudos de Coortes , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Doenças Neurodegenerativas/diagnóstico , Adulto Jovem
12.
Br J Haematol ; 163(3): 373-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23889205

RESUMO

Sickle cell anaemia (SCA) is associated with silent cerebral infarction (SCI), affecting white and cortical grey matter, but there are few data on subcortical volumes. We analysed retrospective magnetic resonance imaging (MRI) data in 26 SCA patients and 20 controls, comparing mean subcortical volumes between three groups: controls, SCA with SCI (n = 13) and SCA without visible abnormality (n = 13). Specific volumetric differences were found in the hippocampus, amygdala, pallidum, caudate, putamen, thalamus, and cerebellum. This is the first study to demonstrate subcortical volume change in SCA, with the most severe volumetric deficits occurring in children with SCI seen on MRI.


Assuntos
Anemia Falciforme/complicações , Infarto Encefálico/etiologia , Encéfalo/patologia , Adolescente , Anemia Falciforme/patologia , Gânglios da Base/patologia , Infarto Encefálico/patologia , Cerebelo/patologia , Criança , Feminino , Seguimentos , Humanos , Sistema Límbico/patologia , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Estudos Retrospectivos , Tálamo/patologia , Adulto Jovem
13.
Am J Med Genet A ; 161A(9): 2124-33, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23824879

RESUMO

5q14.3 deletions spanning and flanking MEF2C as well as intragenic MEF2C mutations have recently been described as a cause of severe intellectual disability, epilepsy, and muscular hypotonia, with variable brain and other anomalies. With an increasing number of patients described, the clinical presentation of the patients appears to be relatively uniform, however the structural brain phenotypes described are variable. We describe two unrelated patients with overlapping de novo interstitial deletions of 4.1 and 1.9 Mb, including MEF2C in 5q14.3, one of whom had a complex brain malformation which could be best described as microcephaly with simplified gyral pattern (MSG). Expression analysis in both patients confirmed haploinsufficiency for MEF2C, decreased MECP2 expression and increased C3ORF58 (DIA1) expression, which is a new finding. A detailed analysis of brain and white matter abnormalities reported in patients with 5q14.3 deletion syndrome to date revealed a greater number of reported abnormalities in patients with deletions not including MEF2C than those with deletions or mutations directly affecting MEF2C. Screening an additional 43 patients with malformations of cerebral cortical development (MCD) for mutations in MEF2C and/or deletions in 5q14.3q15, did not detect any additional mutations, allowing us to conclude that 5q14.3 deletion syndrome is a rare cause of microcephaly with simplified gyral pattern.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 5 , Malformações do Desenvolvimento Cortical/genética , Encéfalo/patologia , Pré-Escolar , Hibridização Genômica Comparativa , Fácies , Humanos , Fatores de Transcrição MEF2/genética , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/diagnóstico
14.
Brain ; 135(Pt 8): 2506-14, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22831780

RESUMO

Mutations in the ACTA2 gene lead to diffuse and diverse vascular diseases; the Arg179His mutation is associated with an early onset severe phenotype due to global smooth muscle dysfunction. Cerebrovascular disease associated with ACTA2 mutations has been likened to moyamoya disease, but appears to have distinctive features. This study involved the analysis of neuroimaging of 13 patients with heterozygous missense mutations in ACTA2 disrupting Arg179. All patients had persistent ductus arteriosus and congenital mydriasis, and variable presentation of pulmonary hypertension, bladder and gastrointestinal problems associated with this mutation. Distinctive cerebrovascular features were dilatation of proximal internal carotid artery, occlusive disease of terminal internal carotid artery, an abnormally straight course of intracranial arteries, and absent basal 'moyamoya' collaterals. Patterns of brain injury supported both large and small vessel disease. Key differences from moyamoya disease were more widespread arteriopathy, the combination of arterial ectasia and stenosis and, importantly, absence of the typical basal 'moyamoya' collaterals. Evaluation of previously published cases suggests some of these features are also seen in the ACTA2 mutations disrupting Arg258. The observation that transition from dilated to normal/stenotic arterial calibre coincides with where the internal carotid artery changes from an elastic to muscular artery supports the hypothesis that abnormal smooth muscle cell proliferation caused by ACTA2 mutations is modulated by arterial wall components. Patients with persistent ductus arteriosus or congenital mydriasis with a label of 'moyamoya' should be re-evaluated to ensure the distinctive neuroimaging features of an ACTA2 mutation have not been overlooked. This diagnosis has prognostic and genetic implications, and mandates surveillance of other organ systems, in particular the aorta, to prevent life-threatening aortic dissection.


Assuntos
Actinas/genética , Arginina/genética , Heterozigoto , Doença de Moyamoya/genética , Mutação de Sentido Incorreto/genética , Fenótipo , Adolescente , Adulto , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Doença de Moyamoya/diagnóstico
16.
Dev Med Child Neurol ; 55(4): 385-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23066702

RESUMO

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinicoradiological diagnosis comprising 'thunderclap' headaches and reversible segmental vasoconstriction of cerebral arteries, occasionally complicated by ischaemic or haemorrhagic stroke. We report a case of RCVS in a 13-year-old male with severe thunderclap headaches and no focal neurological signs. Brain imaging showed multiple posterior circulation infarcts; cerebral computed tomography, magnetic resonance imaging, and catheter angiography showed multifocal irregularity and narrowing, but in different arterial segments. Laboratory studies did not support a diagnosis of vasculitis. Symptoms resolved over 3 weeks; magnetic resonance angiography 3 months later was normal and remained so after 2 years. We highlight the typical clinical features of RCVS in this case and suggest that the diagnosis should be considered in children with thunderclap headaches or stroke syndromes where headache is a prominent feature, especially if cerebrovascular imaging studies appear to be evolving or discrepant.


Assuntos
Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico , Cefaleia/etiologia , Vasoespasmo Intracraniano/complicações , Vasoespasmo Intracraniano/diagnóstico , Adolescente , Cateterismo , Angiografia Cerebral , Artérias Cerebrais/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologia , Diagnóstico Diferencial , Cefaleia/tratamento farmacológico , Cefaleia/terapia , Humanos , Angiografia por Ressonância Magnética , Masculino , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Síndrome , Tomografia Computadorizada por Raios X , Vasoconstrição , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/patologia , Vasoespasmo Intracraniano/fisiopatologia
17.
J Craniofac Surg ; 24(1): 242-6, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23348293

RESUMO

BACKGROUND: The frontofacial monobloc advancement with osteogenic distraction is increasingly used as a surgical treatment for children with complex craniosynostosis-associated syndromes. However, the subfrontal osteotomy cuts to free the facial skeleton from the skull base require extradural retraction of the frontal lobes. The purpose of this study was to determine the frequency and degree of radiologically identifiable frontal lobe changes and whether any such changes affected the patients' outcome. METHODS: The clinical records and preoperative and postoperative computed tomography imaging of all patients undergoing monobloc frontofacial distraction advancement (with or without bipartition) were reviewed. A retrospective medical notes review was undertaken to assess any patient or surgically related factors that might predispose to frontal lobe changes and evaluate outcome from surgery. Where available, magnetic resonance imaging scans were reviewed to compare outcome with that on computed tomography. RESULTS: Fifty cases were identified as suitable for the study. Eighteen patients (36%) had no frontal lobe changes. Thirty-two cases (64%) did have changes that appeared related to the position of maximum retraction during subfrontal osteotomy cuts. There were no changes in the incidence/extent of these changes over time or of any link to the patients' diagnosis, age at surgery, phenotype severity, surgery type, or any surgical or postoperative adverse events. We found no evidence that these changes were responsible for neurologic problems (eg, epilepsy) or reduced cognitive function. CONCLUSIONS: This study reveals a high incidence of frontal lobe changes demonstrable on neuroimaging following the frontofacial monobloc procedure reflecting the retraction points during surgery. Although no postoperative disability was reported, it is clearly important to consider more detailed neuropsychologic testing and review current surgical techniques to ensure that such changes are kept to a minimum.


Assuntos
Craniossinostoses/cirurgia , Lobo Frontal/lesões , Osteogênese por Distração/efeitos adversos , Adolescente , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Osteogênese por Distração/métodos , Osteotomia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
18.
Blood Adv ; 7(11): 2297-2308, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35947137

RESUMO

In sickle cell disease, the relative importance of reduced hemoglobin (Hb) and peripheral oxygen saturation on brain structure remains uncertain. We applied graph-theoretical analysis to diffusion magnetic resonance imaging data to investigate the effect of structural brain connectivity on cognitive function, alongside the presence or absence, number, and volume of silent cerebral infarction. In patients, we investigated the relationships between network properties, blood oxygenation, and cognition (working memory and processing speed indices). Based on streamline counts and fractional anisotropy, we identified a subnetwork with weakened connectivity in 92 patients with sickle cell disease (91 homozygous for HbS [HbSS], 1 heterozygote with HbSß0 thalassemia; 49 males; aged 8.0 to 38.8 y), compared with 54 control subjects (22 males; aged 6.7 to 30.6 y). Multiple regression analyses showed a significant effect of Hb on full-network edge density (P < .05) and of peripheral oxygen saturation on streamline-weighted subnetwork efficiency (P < .01). There were effects of fractional anisotropy-weighted full-network and subnetwork efficiency on working memory index (both P < .05), and of streamline-weighted subnetwork efficiency on processing speed index (P = .05). However, there were no effects of presence, number or volume of silent cerebral infarcts. Streamline-weighted efficiency was progressively lower with lower oxygen saturation, with a downstream effect on the processing speed index. In path analysis, indirect relationships between blood oxygenation and cognition, mediated by network properties, were better supported than direct alternatives, with an indirect relationship between low oxygen saturation and processing speed index in patients, mediated by structural connectivity efficiency in a subnetwork of the brain differing from control subjects. Our findings are consistent with the notion that cognitive impairment is primarily mediated by hypoxic-ischemic effects on normal-appearing white matter and highlight the utility of network-based methods in providing biomarkers of cognitive dysfunction in patients with sickle cell disease.


Assuntos
Anemia Falciforme , Substância Branca , Masculino , Humanos , Cognição , Encéfalo/patologia , Substância Branca/patologia , Substância Branca/fisiologia , Imagem de Difusão por Ressonância Magnética/métodos , Anemia Falciforme/patologia
19.
Eur Radiol ; 22(2): 447-57, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21918916

RESUMO

OBJECTIVE: To determine if histograms of apparent diffusion coefficients (ADC) can be used to differentiate paediatric brain tumours. METHODS: Imaging of histologically confirmed tumours with pre-operative ADC maps were reviewed (54 cases, 32 male, mean age 6.1 years; range 0.1-15.8 years) comprising 6 groups. Whole tumour ADC histograms were calculated; normalised for volume. Stepwise logistic regression analysis was used to differentiate tumour types using histogram metrics, initially for all groups and then for specific subsets. RESULTS: All 6 groups (5 dysembryoplastic neuroectodermal tumours, 22 primitive neuroectodermal tumours (PNET), 5 ependymomas, 7 choroid plexus papillomas, 4 atypical teratoid rhabdoid tumours (ATRT) and 9 juvenile pilocytic astrocytomas (JPA)) were compared. 74% (40/54) were correctly classified using logistic regression of ADC histogram parameters. In the analysis of posterior fossa tumours, 80% of ependymomas, 100% of astrocytomas and 94% of PNET-medulloblastoma were classified correctly. All PNETs were discriminated from ATRTs (22 PNET and 4 supratentorial ATRTs) (100%). CONCLUSIONS: ADC histograms are useful in differentiating paediatric brain tumours, in particular, the common posterior fossa tumours of childhood. PNETs were differentiated from supratentorial ATRTs, in all cases, which has important implications in terms of clinical management. Key Points • MR based apparent diffusion coefficient histograms can help differentiate paediatric brain tumours • ADC histogram parameters correctly classified the great majority of posterior fossa tumours.


Assuntos
Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Ependimoma/diagnóstico , Processamento de Imagem Assistida por Computador/métodos , Oncologia/métodos , Tumores Neuroectodérmicos Primitivos/diagnóstico , Papiloma do Plexo Corióideo/diagnóstico , Tumor Rabdoide/diagnóstico , Adolescente , Astrocitoma/patologia , Criança , Pré-Escolar , Difusão , Ependimoma/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Meduloblastoma/diagnóstico , Meduloblastoma/patologia , Tumores Neuroectodérmicos Primitivos/patologia , Papiloma do Plexo Corióideo/patologia , Análise de Regressão , Estudos Retrospectivos , Tumor Rabdoide/patologia
20.
J Inherit Metab Dis ; 35(3): 459-67, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22086604

RESUMO

Pontocerebellar hypoplasia type 6 (PCH6) (MIM #611523) is a recently described disorder caused by mutations in RARS2 (MIM *611524), the gene encoding mitochondrial arginyl-transfer RNA (tRNA) synthetase, a protein essential for translation of all mitochondrially synthesised proteins. This case confirms that progressive cerebellar and cerebral atrophy with microcephaly and complex epilepsy are characteristic features of PCH6. Additional features of PCH subtypes 2 and 4, including severe dystonia, optic atrophy and thinning of the corpus callosum, are demonstrated. Congenital lactic acidosis can be present, but respiratory chain dysfunction may be mild or absent, suggesting that disordered mitochondrial messenger RNA (mRNA) translation may not be the only mechanism of impairment or that a secondary mechanism exists to allow some translation. We report two novel mutations and expand the phenotypic spectrum of this likely underdiagnosed PCH variant, where recognition of the characteristic neuroradiological phenotype could potentially expedite genetic diagnosis and limit invasive investigations.


Assuntos
Aminoacil-tRNA Sintetases/genética , Arginina-tRNA Ligase/genética , Mitocôndrias/metabolismo , Mutação , Atrofias Olivopontocerebelares/genética , Acidose Láctica/genética , Atrofia/patologia , Encéfalo/patologia , Encefalopatias/genética , Pré-Escolar , Transporte de Elétrons , Feminino , Humanos , Fenótipo , Biossíntese de Proteínas , RNA Mensageiro/metabolismo
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