RESUMO
Rubinstein-Taybi syndrome (RSTS) is a rare neurodevelopmental disorder caused by mutations in CREBBP or EP300 genes encoding CBP/p300 lysine acetyltransferases. We investigated the efficacy of the histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) in ameliorating morphological abnormalities of iPSC-derived young neurons from P149 and P34 CREBBP-mutated patients and hypoexcitability of mature neurons from P149. Neural progenitors from both patients' iPSC lines were cultured one week with TSA 20 nM and, only P149, for 6 weeks with TSA 0.2 nM, in parallel to neural progenitors from controls. Immunofluorescence of MAP2/TUJ1 positive cells using the Skeletonize Image J plugin evidenced that TSA partially rescued reduced nuclear area, and decreased branch length and abnormal end points number of both 45 days patients' neurons, but did not influence the diminished percentage of their neurons with respect to controls. Patch clamp recordings of TSA-treated post-mitotic P149 neurons showed complete/partial rescue of sodium/potassium currents and significant enhancement of neuron excitability compared to untreated replicas. Correction of abnormalities of P149 young neurons was also affected by valproic acid 1 mM for 72 h, with some variation, with respect to TSA, on the morphological parameter. These findings hold promise for development of an epigenetic therapy to attenuate RSTS patients cognitive impairment.
Assuntos
Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Adolescente , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Criança , Proteína p300 Associada a E1A/genética , Eletroencefalografia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/fisiologia , Imageamento por Ressonância Magnética , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/genética , Mutação , Neurônios/metabolismo , Neurônios/fisiologia , Técnicas de Patch-Clamp , Síndrome de Rubinstein-Taybi/diagnóstico por imagem , Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/fisiopatologiaRESUMO
BACKGROUND: Intracranial pressure (ICP) monitoring is essential after subarachnoid hemorrhage (SAH) to prevent secondary brain insults and to tailor individualized treatments. Optic nerve sheath diameter (ONSD), measured using ultrasound (US), could serve as a noninvasive bedside tool to estimate ICP, avoiding the risks of hemorrhage or infection related to intracranial catheters. The aims of this study were twofold: first, to explore the reliability of US for measuring ONSD; second, to establish whether the US-ONSD can be considered a proxy for ICP in SAH patients early after bleeding. For the first aim, we compared the ONSD measurements given by magnetic resonance imaging (MRI-ONSD) with the US-ONSD findings. For the second aim, we analyzed the relationship between US-ONSD measurements and ICP values. METHODS: Adult patients with diagnosis of aneurysmal SAH and external ventricular drainage system (EVD) were included. Ten patients were examined by MRI to assess ONSD, and the results were compared to the diameter given by US. In 20 patients, the US-ONSD values were related to ICP measured simultaneously through EVD. In ten of these patients, we explored the changes in the US-ONSD at the time of controlled and fairly rapid changes in ICP after cerebrospinal fluid (CSF) drainage. RESULTS: US-ONSD measurements at the bedside were accurate, very similar to the diameters measured by MRI (the mean difference in the Bland-Altman plot was 0.08 mm, 95% limits of agreement: - 1.13; + 1.23 mm). No clear relationship was detectable between the ICP and US-ONSD, and a linear regression model showed an angular coefficient very close to 0 (p > 0.05). US-ONSD and ICP values were in agreement after CSF drainage and shifts in ICP in a limited number of patients. CONCLUSIONS: US-ONSD measurement does not accurately estimate ICP in SAH patients in the intensive care unit.
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Hipertensão Intracraniana , Hemorragia Subaracnóidea , Adulto , Humanos , Hipertensão Intracraniana/diagnóstico por imagem , Hipertensão Intracraniana/etiologia , Pressão Intracraniana , Nervo Óptico/diagnóstico por imagem , Estudos Prospectivos , Reprodutibilidade dos Testes , Hemorragia Subaracnóidea/diagnóstico por imagem , UltrassonografiaRESUMO
Kleefstra syndrome (KS) is a rare genetic condition resulting from either 9q34.3 microdeletions or mutations in the EHMT1 gene located in the same genomic region. To date, approximately 100 patients have been reported, thereby allowing the core phenotype of KS to be defined as developmental delay/intellectual disability, generalized hypotonia, neuropsychiatric anomalies, and a distinctive facial appearance. Here, to further expand the knowledge on genotype and phenotype of this condition, we report 2 novel cases: one patient carrying a 46-kb 9q34.3 deletion and showing macrocephaly never described in KS, and a second patient carrying a classic 9q34.3 deletion, presenting with a previously unreported skeletal feature (postaxial polydactyly of the right foot) and an unusual brain anomaly (olfactory bulb hypoplasia) observed via magnetic resonance imaging. Further, we provide a review of the current literature regarding KS and compare these 2 patients with those previously described, thereby confirming that the genotype-phenotype correlation in KS remains difficult to determine.
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Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Megalencefalia/patologia , Bulbo Olfatório/patologia , Polidactilia/patologia , Dedos do Pé/anormalidades , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Deleção Cromossômica , Cromossomos Humanos Par 9/genética , Anormalidades Craniofaciais/diagnóstico por imagem , Fácies , Genótipo , Cardiopatias Congênitas/diagnóstico por imagem , Histona-Lisina N-Metiltransferase/genética , Humanos , Lactente , Deficiência Intelectual/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Megalencefalia/diagnóstico por imagem , Megalencefalia/genética , Mutação , Bulbo Olfatório/diagnóstico por imagem , Fenótipo , Polidactilia/genéticaRESUMO
PURPOSE: To describe normal foetal brain development with high resolution post-mortem MRI (PMMRI) of non-fixed foetal brains. METHODS: We retrospectively collected PMMRIs of foetuses without intracranial abnormalities and chromosomal aberrations studied after a termination of pregnancy due to extracranial abnormalities or after a spontaneous intrauterine death. PMMRIs were performed on a 3-T scanner without any fixation and without removing the brain from the skull. All PMMRIs were evaluated in consensus by two neuroradiologists. RESULTS: Our analysis included ten PMMRIs (median gestational age (GA): 21 weeks; range: 17-28 weeks). At 19 and 20 weeks of GA, the corticospinal tracts are recognisable in the medulla oblongata, becoming less visible from 21 weeks. Prior to 20 weeks the posterior limb of the internal capsule (PLIC) is more hypointense than surrounding deep grey nuclei; starting from 21 weeks the PLIC becomes isointense, and is hyperintense at 28 weeks. From 19-22 weeks, the cerebral hemispheres show transient layers: marginal zone, cortical plate, subplate, and intermediate, subventricular and germinal zones. CONCLUSION: PMMRI of non-fixed in situ foetal brains preserves the natural tissue contrast and skull integrity. We assessed foetal brain development in a small cohort of foetuses, focusing on 19-22 weeks of gestation. KEY POINTS: ⢠Post-mortem magnetic resonance imaging (PMMRI) of non-fixed head is feasible. ⢠PMMRI of unfixed in situ foetal brains preserves the natural tissue contrast. ⢠PMMRI provide a good depiction of the normal foetal brain development. ⢠PMMRI of unfixed in situ foetal brains preserves the skull integrity. ⢠PMMRI pattern of foetal brain development at early gestational age is described.
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Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Segundo Trimestre da Gravidez , Autopsia , Encéfalo/embriologia , Feminino , Idade Gestacional , Humanos , Masculino , Gravidez , Valores de Referência , Estudos RetrospectivosRESUMO
Rubinstein-Taybi syndrome is a rare, autosomal dominant, plurimalformative disorder that is clinically characterized by intellectual disability and a wide spectrum of congenital anomalies; facial dysmorphisms are typical, and broad thumbs and great toes are particularly distinctive. Its genetic basis is only partially known, with a detection rate of approximately 65-70%; specifically, microdeletions or mutations in the CREBBP or EP300 genes can be found. Much is known about its clinical features and health-care protocols, but some areas of clinical knowledge are currently unsolved. In particular, few efforts have been made until now to understand the variability in the neuropsychological and neurobehavioral profile and to deepen knowledge of the neuroradiological malformative pattern. Consequently, little is known about the possible genotype-phenotype correlations of these issues. Here, we report clinical and genetic data from a cohort of 23 RSTS Italian patients. The most common features in brain magnetic resonance imaging (MRI) were dysmorphic aspects of the corpus callosum (73.6%) with or without minor dysmorphisms of cerebellar vermis, periventricular posterior white matter hyperintensity, and other less common anomalies. The most interesting feature on the whole spine MRI scans was the tendency for a low-lying conus medullaris without terminal filum thickening. These data will help to improve neuropsychiatric and neuroradiological knowledge and highlight specific genotype-phenotype correlations.
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Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/fisiopatologia , Adolescente , Encéfalo/diagnóstico por imagem , Proteína de Ligação a CREB/genética , Criança , Pré-Escolar , Estudos de Coortes , Proteína p300 Associada a E1A/genética , Feminino , Estudos de Associação Genética , Humanos , Lactente , Itália , Imageamento por Ressonância Magnética , Masculino , Mutação , Neuropsiquiatria/métodos , Fenótipo , Adulto JovemAssuntos
Doenças Desmielinizantes , Hipofosfatemia , Leucoencefalopatias , Doenças Desmielinizantes/diagnóstico por imagem , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Humanos , Hipofosfatemia/etiologia , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/etiologia , SíndromeRESUMO
Balò's concentric sclerosis (BCS) is considered a rare demyelinating disease and regarded as an aggressive variant of multiple sclerosis (MS). We describe three cases (one male and two females) with neuroimaging features suggestive of BCS and heterogeneous symptoms, with benign long-term clinical course upon treatment with natalizumab and fingolimod. Neurological examination, blood and cerebrospinal fluid analyses, brain and spinal cord magnetic resonance imaging (MRI) and brain proton magnetic resonance spectroscopy were performed. At onset, patient #1 showed predominant cognitive impairment with consciousness disturbances; patient #2 presented with left hemiparesis; patient #3 demonstrated hesitance in speech and in written word production, along with right central facial palsy. All patients showed the typical MRI changes associated with BCS, such as concentric rings or a whorled appearance on T2-weighted and contrast-enhanced T1-weighted images. They were treated with high dosage i.v. steroid with clinical improvement and followed-up for 3 years with different clinical course. Two patients fulfilled the revised McDonald criteria for MS and received preventive therapy, natalizumab and fingolimod, respectively, whereas the third patient is still stable without clinical and radiological evolution. All of them did not have new exacerbations or MRI lesions over 2-4 year follow-up. Our descriptions demonstrate the heterogeneity of clinical presentation of BCS. Moreover, these case reports suggest that BCS may neither be rapidly progressive nor fatal and may be considered part of the MS spectrum. In line with this hypothesis, current treatments for MS were effective in our patients.
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Doenças Desmielinizantes/patologia , Esclerose Cerebral Difusa de Schilder/diagnóstico , Esclerose Cerebral Difusa de Schilder/tratamento farmacológico , Esclerose Múltipla/diagnóstico , Esteroides/uso terapêutico , Adulto , Encéfalo/patologia , Doenças Desmielinizantes/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/tratamento farmacológico , Exame Neurológico/métodos , Medula Espinal/patologiaRESUMO
PURPOSE: To understand the meaning of diffuse excessive high signal intensity (DEHSI) of white matter (WM), a frequently observed finding on MR in VLBW infants at a corrected term age. METHODS: This is a retrospective study. Qualitative visual assessment of cerebral WM signal intensity on T2WI was performed by two readers on 78 VLBW infants, scanned on a 1.5 T-MRI at term equivalent age. ADC values were then measured in six regions of interest: four in frontal and parietal periventricular and two in parietal subcortical WM. Mean ADC values were then compared with qualitative visual assessment and with mean ADC values obtained ten term healthy babies. Both periventricular and subcortical mean ADC values were correlated with the neurological follow-up, evaluated with the Griffith's mental developmental scale at 36 months. RESULTS: There was no agreement between the visual qualitative assessment of white matter DEHSI and corresponding ADC values (P values = 0.42 for periventricular WM; P values = 0.18 for subcortical WM). Mean ADC values were higher in preterms than in term babies (P values <0.001). No significant correlation was found between ADC values and the developmental quotient at 36 months (P values >0.05). CONCLUSIONS: DEHSI in VLBW infants is a MR finding poorly defined with conventional T2 MRI. The presence of T2 hyperintensities weakly correlates with ADC, and ADC values are not associated with the neurological long-term outcome at 3 years, demonstrating that DEHSI should not be considered as a WM disease.
Assuntos
Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Imageamento por Ressonância Magnética/métodos , Substância Branca/anatomia & histologia , Pré-Escolar , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Intracranial haemorrhage (ICH) in term newborns has been increasingly recognised but the occurrence in late preterm infants and the clinical presentation are still unclear. OBJECTIVE: To investigate the appearance of intracranial haemorrhage at MRI in a cohort of infants born at 34 weeks' gestation or more and to correlate MRI findings with neonatal symptoms. MATERIALS AND METHODS: We retrospectively reviewed neonatal brain MRI scans performed during a 3-year period. We included neonates ≥34 weeks' gestation with intracranial haemorrhage and compared findings with those in babies without intracranial haemorrhage. Babies were classified into three groups according to haemorrhage location: (1) infratentorial, (2) infra- and supratentorial, (3) infra- and supratentorial + parenchymal involvement. RESULTS: Intracranial haemorrhage was observed in 36/240 babies (15%). All of these 36 had subdural haemorrhage. Sixteen babies were included in group 1; 16 in group 2; 4 in group 3. All infants in groups 1 and 2 were asymptomatic except one who was affected by intraventricular haemorrhage grade 3. Among the infants in group 3, who had intracranial haemorrhage with parenchymal involvement, three of the four (75%) presented with acute neurological symptoms. Uncomplicated spontaneous vaginal delivery was reported in 20/36 neonates (56%), vacuum extraction in 4 (11%) and caesarean section in 12 (33%). Babies with intracranial haemorrhage had significantly higher gestational age (38 ± 2 weeks vs. 37 ± 2 weeks) and birth weight (3,097 ± 485 g vs. 2,803 ± 741 g) compared to babies without intracranial haemorrhage and were more likely to be delivered vaginally than by caesarian section. CONCLUSION: Mild intracranial haemorrhage (groups 1 and 2) is relatively common in late preterm and term infants, although it mostly represents an incidental finding in clinically asymptomatic babies; early neurological symptoms appear to be related to parenchymal involvement.
Assuntos
Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/patologia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Itália/epidemiologia , Masculino , Prevalência , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To define a method of quantifying axial proptosis in patients with Graves' orbitopathy (GO) and to validate a score that correlates with the orbital involvement and helps determine the degree of proptosis correction for elective orbital decompression. DESIGN: Retrospective, case series. PARTICIPANTS: The study included 50 patients (group A) and 29 control subjects who underwent orbital computed tomography (CT). The method was then validated in another group of 21 patients with GO (group B). METHODS: The orbital area (OA) was measured manually on the central axial section of the CT scan at a level where the lens is visualized. The OA intersects the projection of the globe and delimitates the chord of an arch (globe chord [OC]). The area of the circular sector under the chord (CA) represents the portion of the globe within the orbit. MAIN OUTCOME MEASURES: A CA-to-OA ratio was calculated to reduce the error due to variability of the measurements and to perform correlations with some of the clinical parameters of GO. RESULTS: Measurement error was low (<2%). We did not observe significant differences in the mean OA of patients with GO (783.6 ± 12.1 mm(2)) and controls (758.5 ± 20.4 mm(2); P = not significant). The OC value in patients with GO was 130.2 ± 11.5 mm(2), significantly lower than in controls (281.8 ± 9.7 mm(2); P<0.0001). The CA-to-OA ratio also was lower in patients with GO than in controls (0.16 ± 0.01 vs. 0.38 ± 0.01; P<0.0001). A significant correlation was found in patients with GO between the CA-to-OA ratio and proptosis (P<0.001), lid fissure (P = 0.004), and intraocular pressure (P<0.001). In group B, the CA-to-OA ratio was 0.18 ± 0.02, significantly different from that of controls (P<0.0001) and inversely correlated with proptosis (P<0.0001) and lid fissure (P<0.045). CONCLUSIONS: By measuring the CA-to-OA ratio, we were able to quantify the degree of axial proptosis in patients with GO. The significant correlation of CA/OA with some orbital parameters confirms that this parameter also may be used as a measure of orbital involvement in GO. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Assuntos
Exoftalmia/patologia , Adolescente , Adulto , Idoso , Análise de Variância , Estudos de Casos e Controles , Feminino , Doença de Graves/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Spinal neurofibromatosis (SNF), a phenotypic subclass of neurofibromatosis 1 (NF1), is characterized by bilateral neurofibromas involving all spinal roots. In order to deepen the understanding of SNF's clinical and genetic features, we identified 81 patients with SNF, 55 from unrelated families, and 26 belonging to 19 families with at least 1 member affected by SNF, and 106 NF1 patients aged >30 years without spinal tumors. A comprehensive NF1 mutation screening was performed using NGS panels, including NF1 and several RAS pathway genes. The main features of the SNF subjects were a higher number of internal neurofibromas (p < 0.001), nerve root swelling (p < 0.001), and subcutaneous neurofibromas (p = 0.03), while hyperpigmentation signs were significantly less frequent compared with the classical NF1-affected cohorts (p = 0.012). Fifteen patients underwent neurosurgical intervention. The histological findings revealed neurofibromas in 13 patients and ganglioneuromas in 2 patients. Phenotypic variability within SNF families was observed. The proportion of missense mutations was higher in the SNF cases than in the classical NF1 group (21.40% vs. 7.5%, p = 0.007), conferring an odds ratio (OR) of 3.34 (CI = 1.33−10.78). Two unrelated familial SNF cases harbored in trans double NF1 mutations that seemed to have a subclinical worsening effect on the clinical phenotype. Our study, with the largest series of SNF patients reported to date, better defines the clinical and genetic features of SNF, which could improve the management and genetic counseling of NF1.
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Usually overlooked by physicians, olfactory abnormalities are not uncommon. Olfactory malformations have recently been reported in an emerging group of genetic disorders called Mendelian Disorders of the Epigenetic Machinery (MDEM). This study aims to determine the prevalence of olfactory malformations in a heterogeneous group of subjects with MDEM. We reviewed the clinical data of 35 patients, 20 females and 15 males, with a mean age of 9.52 years (SD 4.99). All patients had a MDEM and an already available high-resolution brain MRI scan. Two experienced neuroradiologists reviewed the MR images, noting abnormalities and classifying olfactory malformations. Main findings included Corpus Callosum, Cerebellar vermis, and olfactory defects. The latter were found in 11/35 cases (31.4%), of which 7/11 had Rubinstein-Taybi syndrome (RSTS), 2/11 had CHARGE syndrome, 1/11 had Kleefstra syndrome (KLFS), and 1/11 had Weaver syndrome (WVS). The irregularities mainly concerned the olfactory bulbs and were bilateral in 9/11 patients. With over 30% of our sample having an olfactory malformation, this study reveals a possible new diagnostic marker for MDEM and links the epigenetic machinery to the development of the olfactory bulbs.
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The occurrence of optic pathway gliomas (OPGs) in children with neurofibromatosis type 1 (NF1) still raises many questions regarding screening and surveillance because of the lack of robust prognostic factors. Recent studies of an overall cohort of 381 patients have suggested that the genotype may be the main determinant of the development of OPG, with the risk being higher in patients harbouring NF1 mutations in the 5' tertile and the cysteine/serine-rich domain. In an attempt to confirm this hypothesis, we used strict criteria to select a large independent cohort of 309 NF1 patients with defined constitutional NF1 mutations and appropriate brain images (255 directly enrolled and 54 as a result of a literature search). One hundred and thirty-two patients had OPG and 177 did not. The association of the position (tertiles and functional domains) and type of NF1 mutation with the development of OPG was analysed using the χ2 test and Fisher's exact probability test; odds ratios (ORs) with 95% confidence intervals were calculated, and Bonferroni's correction for multiple comparisons was applied; multiple logistic regression was also used to study genotype-phenotype associations further. Our findings show no significant correlation between the site/type of NF1 mutation and the risk of OPG, and thus do not support the hypothesis that certain constitutional mutations provide prognostic information in this regard. In addition, we combined our cohort with a previously described cohort of 381 patients for a total of 690 patients and statistically re-analysed the results. The re-analysis confirmed that there were no correlations between the site (tertile and domain) and the risk of OPG, thus further strengthening our conclusions.
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We report a case of a 57-year-old man with bilateral masses in the internal auditory canal. The peculiar findings at magnetic resonance imaging with tridimensional fluid-attenuated inversion recovery sequence combined with clinical data provided new insights into understanding the pathophysiology of the hearing loss.
Assuntos
Orelha Interna/patologia , Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Súbita/diagnóstico por imagem , Perda Auditiva Súbita/etiologia , Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Melanoma/secundário , Neoplasias Cutâneas/patologia , Audiometria de Tons Puros , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Compostos OrganometálicosRESUMO
Ulnar-mammary syndrome (UMS) is characterized by ulnar defects, and nipple or apocrine gland hypoplasia, caused by TBX3 haploinsufficiency. Signs of hypogonadism were repeatedly reported, but the mechanisms remain elusive. We aim to assess the origin of hypogonadism in two families with UMS. UMS was suspected in two unrelated probands referred to an academic center with delayed puberty because of the evident ulnar ray and breast defects in their parents. Clinical, biochemical and genetic investigations proved the existence of congenital normosmic IHH (nIHH) associated with pituitary hypoplasia in the two probands who were heterozygous for novel TBX3 pathogenic variants. The mutations co-segregated with delayed puberty, midline defects (nose, teeth and tongue anomalies) and other variable features of UMS in the two families (absent axillary hairs and nipple hypoplasia, asymmetrical features including unilateral ulnar or renal abnormalities). The combined analysis of these findings and of the previous UMS reports showed delayed puberty and other signs of hypogonadism in 79 and 37% of UMS males, respectively. Proband 1 was followed up to adulthood with persistence of nIHH. In conclusion, UMS should be suspected in patients with delayed puberty and midline defects, including pituitary hypoplasia, in the presence of mild cues for TBX3 mutation, even in the absence of limb malformations. In addition, TBX3 should be included among candidate genes for congenital nIHH.
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One patient with Graves' hyperthyroidism and ophthalmopathy in its active phase and unresponsive to steroid, was treated with the anti-CD20 monoclonal antibody, rituximab (RTX), as part of an open study. The effect of RTX in the thyroid and the orbital tissues was studied. The ophthalmopathy responded to RTX therapy by ameliorating the eye signs with a decrease in the clinical activity score from 5 to 2 in 3 months, while the patient had peripheral B-cell depletion. Hyperthyroidism did not improve during the 6 months of B-cell depletion and serum TSH-receptor antibodies (TRAb) levels did not significantly change after RTX therapy. Therefore, the patient underwent total thyroidectomy and few B-cells were found in the thyroid tissue specimens. While the patient eye disease remained stable (clinical activity score = 2), we performed corrective orbital decompression and we found absence of lymphocytes in the orbital tissue specimens. We believe that RTX treatment in Graves' disease may cause amelioration of ophthalmopathy by depleting total lymphocytes population in the orbit. The persistence of Graves' hyperthyroidism suggests that a single cycle of RTX does not result in complete lymphocyte depletion in thyroid tissue and thus no decline in serum TRAb was observed.
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Anticorpos Monoclonais/uso terapêutico , Linfócitos B/imunologia , Oftalmopatia de Graves/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Imunossupressores/administração & dosagem , Órbita/imunologia , Anticorpos Monoclonais Murinos , Autoanticorpos/sangue , Linfócitos B/patologia , Feminino , Doença de Graves/sangue , Doença de Graves/patologia , Doença de Graves/cirurgia , Oftalmopatia de Graves/imunologia , Oftalmopatia de Graves/patologia , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide , Imuno-Histoquímica , Contagem de Linfócitos , Subpopulações de Linfócitos , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Órbita/patologia , Receptores da Tireotropina/sangue , Rituximab , Linfócitos T/patologia , Tireoidectomia , Tireotropina/sangue , Tiroxina/sangueRESUMO
Commissural embryology mechanisms are not yet completely understood. The study and comprehension of callosal dysgenesis can provide remarkable insights into embryonic or fetal commissural development. The diffusion tensor imaging (DTI) technique allows the in vivo analyses of the white-matter microstructure and is a valid tool to clarify the disturbances of brain connections in patients with dysgenesis of the corpus callosum (CC). The segmental callosal agenesis (SCAG) is a rare partial agenesis of the corpus callosum (ACC). In a newborn with SCAG the DTI and tractography analyses proved that the CC was made of two separate segments consisting respectively of the ventral part in the genu and body of the CC, connecting the frontal lobes, and the dorsal part in the CC splenium and the attached hippocampal commissure (HC), connecting the parietal lobes and the fornix. These findings support the embryological thesis of a separated origin of the ventral and the dorsal parts of the CC.
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Agenesia do Corpo Caloso/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Imagem de Tensor de Difusão , Processamento de Imagem Assistida por Computador , Corpo Caloso/embriologia , Feminino , Humanos , Masculino , GravidezRESUMO
OBJECTIVE: Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder (1:125.000) characterized by growth retardation, psychomotor developmental delay, microcephaly and dysmorphic features. In 25% of patients seizures have been described, and in about 66% a wide range of EEG abnormalities, but studies on neurological features are scant and dated. The aim of this study is to describe the electroclinical phenotype of twenty-three patients with RSTS, and to try to correlate electroclinical features with neuroradiological, cognitive and genetic features. PATIENTS AND METHODS: Electroclinical features of twenty-three patients with RSTS (age between18months and 20years) were analyzed. Sleep and awake EEG was performed in twenty-one patients, and brain MRI in nineteen patients. All subjects received cognitive evaluation. RESULTS: EEG abnormalities were observed in 76% (16/21) of patients. A peculiar pattern prevalent in sleep, characterized by slow monomorphic activity on posterior regions was also observed in 33% (7/21) of patients. Almost no patient presented seizures. Eighty-four percentage of patients had brain MRI abnormalities, involving corpus callosum and/or posterior periventricular white matter. Average General Quotient (GQ) was 52, while average IQ was 55, corresponding to mild Intellectual Disability. The homogeneous electroclinical pattern was observed mainly in patients with more severe neuroradiologic findings and moderate Intellectual Disability/Developmental Disability (ID/DD). No genotype-phenotype correlations were found. CONCLUSION: The specific electroclinical and neuroradiological features described may be part of a characteristic RSTS phenotype. Wider and longitudinal studies are needed to verify its significance and impact on diagnosis, prognosis and clinical management of RSTS patients.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Síndrome de Rubinstein-Taybi/diagnóstico por imagem , Síndrome de Rubinstein-Taybi/fisiopatologia , Adolescente , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Testes de Inteligência , Imageamento por Ressonância Magnética , Masculino , Fenótipo , Síndrome de Rubinstein-Taybi/genética , Sono/fisiologia , Vigília/fisiologia , Adulto JovemRESUMO
BACKGROUND: Sex chromosomal aneuploidies in males are rare diseases with an overwhelming involvement of endocrinological and auxological issues; less frequently, other anomalies are observed. Neuroradiological issues are often not taken into account in single patients, and neuroradiological examinations are rarely performed. CASE PRESENTATION: Here, we report a boy with 48,XXXY/49,XXXXY mosaicism, phenotypically characterized by hypotonia, intellectual disability, ventricular septal defect, micropenis, and with mild hypertelorism, inverted nipples, a congenital hip dysplasia, and some neuroradiological features so far not described. The Magnetic Resonance Imaging showed white matter abnormalities and enlargement of lateral ventricles with never described dysmorphisms of cranio-cervical junction and posterior fossa. A cranio-cervical Computerized Tomography confirmed a dysmorphic aspect of the posterior fossa and occipital condyles, slight morphological asymmetry of C1 and slight lateralization to the right of the odontoid's apex. CONCLUSIONS: Considering the possible relevant clinical impact of these findings, the neuroradiological assessment seems potentially useful to the diagnostic approach of these patients.