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OBJECTIVE: The study aims at comparing the diagnostic accuracy of qualitative and quantitative assessment of the susceptibility in the precentral gyrus in detecting amyotrophic lateral sclerosis (ALS) with predominance of upper motor neuron (UMN) impairment. METHODS: We retrospectively collected clinical and 3T MRI data of 47 ALS patients, of whom 12 with UMN predominance (UMN-ALS). We further enrolled 23 healthy controls (HC) and 15 ALS Mimics (ALS-Mim). The Motor Cortex Susceptibility (MCS) score was qualitatively assessed on the susceptibility-weighted images (SWI) and automatic metrics were extracted from the quantitative susceptibility mapping (QSM) in the precentral gyrus. MCS scores and QSM-based metrics were tested for correlation, and ROC analyses. RESULTS: The correlation of MCS score and susceptibility skewness was significant (Rho = 0.55, p < 0.001). The susceptibility SD showed an AUC of 0.809 with a specificity and positive predictive value of 100% in differentiating ALS and ALS Mim versus HC, significantly higher than MCS (Z = -3.384, p-value = 0.00071). The susceptibility skewness value of -0.017 showed specificity of 92.3% and predictive positive value of 91.7% in differentiating UMN-ALS versus ALS mimics, even if the performance was not significantly better than MCS (Z = 0.81, p = 0.21). CONCLUSION: The MCS and susceptibility skewness of the precentral gyrus show high diagnostic accuracy in differentiating UMN-ALS from ALS-mimics subjects. The quantitative assessment might be preferred being an automatic measure unbiased by the reader. CLINICAL RELEVANCE STATEMENT: The clinical diagnostic evaluation of ALS patients might benefit from the qualitative and/or quantitative assessment of the susceptibility in the precentral gyrus as imaging marker of upper motor neuron predominance. KEY POINTS: ⢠Amyotrophic lateral sclerosis diagnostic work-up lacks biomarkers able to identify upper motor neuron involvement. ⢠Susceptibility-weighted imaging/quantitative susceptibility mapping-based measures showed good diagnostic accuracy in discriminating amyotrophic lateral sclerosis with predominant upper motor neuron impairment from patients with suspected motor neuron disorder. ⢠Susceptibility-weighted imaging/quantitative susceptibility mapping-based assessment of the magnetic susceptibility provides a diagnostic marker for amyotrophic lateral sclerosis with upper motor neuron predominance.
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Esclerose Lateral Amiotrófica , Córtex Motor , Doença dos Neurônios Motores , Humanos , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Córtex Motor/diagnóstico por imagem , Estudos Retrospectivos , Neurônios Motores , Doença dos Neurônios Motores/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
INTRODUCTION/AIMS: Becker muscular dystrophy (BMD) is characterized by variable disease severity and progression, prompting the identification of biomarkers for clinical trials. We used data from an ongoing phase II study to provide a comprehensive characterization of a cohort of patients with BMD, and to assess correlations between histological and magnetic resonance imaging (MRI) markers with muscle function and strength. METHODS: Eligible patients were ambulatory males with BMD, aged 18 to 65 years (200 to 450 meters on 6-minute walk test). The following data were obtained: function test results, strength, fat-fraction quantification using chemical shift-encoded MRI (whole thigh and quadriceps), and fibrosis and muscle fiber area (MFA) of the brachial biceps. RESULTS: Of 70 patients screened, 51 entered the study. There was substantial heterogeneity between patients in muscle morphology (histology and MRI), with high fat replacement. Total fibrosis correlated significantly and mostly moderately with all functional endpoints, including both upper arm strength assessments (left and right elbow flexion rho -.574 and -.588, respectively [both P < .0001]), as did MRI fat fraction (whole thigh and quadriceps), for example, with four-stair-climb velocity -.554 and -.550, respectively (both P < .0001). Total fibrosis correlated significantly and moderately with both MRI fat fraction assessments (.500 [P = .0003] and .423 [.0024], respectively). DISCUSSION: In this BMD cohort, micro- and macroscopic morphological muscle parameters correlated moderately with each other and with functional parameters, potentially supporting the use of MRI fat fraction and histology as surrogate outcome measures in patients with BMD, although additional research is required to validate this.
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Distrofia Muscular de Duchenne , Adolescente , Adulto , Idoso , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Distrofia Muscular de Duchenne/diagnóstico por imagem , Coxa da Perna , Adulto JovemRESUMO
BACKGROUND: Pallister-Hall syndrome (OMIM #146510) is a rare autosomal dominant condition caused by a mutation in the GLI3 gene. The cardinal feature of Pallister-Hall syndrome is the presence of hypothalamic hamartomas, which may manifest with seizures, panhypopituitarism and visual impairment. In Pallister-Hall syndrome, dysplastic histogenetic processes responsible for hypothalamic hamartomas are thought to disrupt early craniofacial development. The clinical presentation of Pallister-Hall syndrome may include: characteristic facies (low-set and posteriorly angulated ears, short nose with flat nasal bridge), cleft palate and uvula, bifid epiglottis and laryngotracheal cleft, limb anomalies (e.g., polysyndactyly, short limbs and nail dysplasia), anal atresia, genitourinary abnormalities and congenital heart defects. CASE PRESENTATION: We report the case of two monochorionic diamniotic twins diagnosed with Pallister-Hall syndrome during the neonatal period, after the identification of a hypothalamic hamartoma on day 1 by cerebral ultrasound scan, later confirmed by brain magnetic resonance imaging. Cerebral ultrasound and magnetic resonance imaging presentations were identical in both twins. DISCUSSION AND CONCLUSIONS: We review previously published cases (four reports) of hypothalamic hamartomas identified via cerebral ultrasound and compare reported ultrasonographic features. Main differential diagnoses based on cerebral ultrasound findings are discussed. Full description of typical magnetic resonance imaging appearance is also provided. This is the first case reported in the literature of monochorionic diamniotic twins affected by genetically confirmed Pallister-Hall syndrome with identical hypothalamic hamartomas at cerebral ultrasound and magnetic resonance imaging. Moreover, this paper adds to the existing literature on the sonographic appearance of hypothalamic hamartomas. Considering the consistency in hypothalamic hamartomas' sonographic appearance, we support the use of cerebral ultrasound as a first-line neuroimaging modality in case of clinical suspicion of Pallister-Hall syndrome.
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Doenças Hipotalâmicas , Síndrome de Pallister-Hall , Hamartoma , Humanos , Doenças Hipotalâmicas/complicações , Doenças Hipotalâmicas/diagnóstico por imagem , Recém-Nascido , Neuroimagem , Síndrome de Pallister-Hall/complicações , Síndrome de Pallister-Hall/diagnóstico por imagem , Síndrome de Pallister-Hall/genética , Gêmeos MonozigóticosRESUMO
OBJECTIVES: To reach a molecular diagnosis for a family with two consecutive fetuses presenting with multiple congenital anomalies. METHODS: The two fetuses underwent prenatal ultrasound, autopsy, radiologic, and genetic investigation. Genetic analysis included karyotype and array-CGH for both fetuses and trio-based whole exome sequencing (WES) only for the second fetus. RESULTS: WES results, initially focusing on recessive or dominant de novo variants, were negative.However, as a result of new relevant information regarding family history, the variant c.648_651dup in the PTCH1 gene was identified as causative of the fetal phenotype. CONCLUSIONS: This case further highlights how WES data analysis and interpretation strongly rely on family history and robust genotype-phenotype correlation. This is even more relevant in the prenatal setting, where access to fetal phenotype is limited and prenatal recognition of many morbid genes is not fully explored. We also provide a detailed description of the prenatal manifestations of Basal Cell Nevus Syndrome.
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Síndrome do Nevo Basocelular , Exoma , Síndrome do Nevo Basocelular/diagnóstico , Síndrome do Nevo Basocelular/genética , Feminino , Feto/anormalidades , Feto/diagnóstico por imagem , Humanos , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Sequenciamento do Exoma/métodosRESUMO
We describe 3 cases of solitary sclerosis (SS), a rare condition characterized by a single inflammatory demyelinating lesion in the white matter of the brain or spinal cord. All patients had progressive limb motor impairment (patient 1, 66-year-old female: left spastic hemiparesis; patient 2, 39-year-old male: right spastic hemiparesis; patient 3, 42-year-old female: proximally predominant left upper limb weakness with amyotrophy and fasciculations). In all patients, MRI disclosed a single small T2-hyperintense demyelinating lesion: in the right anterior paramedian upper medulla, in the median-left paramedian anterior lower medulla, and in the left paramedian anterior cervical spinal cord at C4 level, respectively. In patients 1 and 2, transcranial magnetic stimulation (TMS) demonstrated altered motor evoked potentials (MEPs) and increased central motor conduction time (CMCT) in the affected limbs; in patient 3, needle EMG revealed chronic neurogenic changes in C5-C7 muscles of left upper limb. Patients 1 and 2 had normal brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). CSF analysis demonstrated IgG oligoclonal bands in all patients. In patients 2 and 3, levels of neurofilament light chain (NFL) in CSF and serum, respectively, were within normal limits. The three cases were consistent with the diagnosis of SS. Notably, while the first two cases mimicked Mills' syndrome (the hemiparetic variant of primary lateral sclerosis, PLS), the third one was rather reminiscent of amyotrophic lateral sclerosis (ALS). This suggests including SS in the differential diagnosis not only of PLS, but also of ALS. We also report the first quantification of NFL levels in SS.
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Esclerose Lateral Amiotrófica , Doença dos Neurônios Motores , Humanos , Masculino , Feminino , Idoso , Adulto , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/patologia , Bandas Oligoclonais , Esclerose/patologia , Espasticidade Muscular , Doença dos Neurônios Motores/diagnóstico , Doença dos Neurônios Motores/patologia , Neurônios Motores/patologia , Síndrome , ParesiaRESUMO
OBJECTIVES: To distinguish amyotrophic lateral sclerosis (ALS) and its subtypes from ALS mimics and healthy controls based on the assessment of iron-related hypointensity of the primary motor cortex in susceptibility-weighted imaging (SWI). METHODS: We enrolled 64 patients who had undergone magnetic resonance imaging studies with clinical suspicions of ALS. The ALS group included 48 patients; the ALS-mimicking disorder group had 16 patients. The ALS group was divided into three subgroups according to the prevalence of upper motor neuron (UMN) or lower motor neuron (LMN) impairment, with 12 subjects in the UMN-predominant ALS group (UMN-ALS), 16 in the LMN-predominant ALS group (LMN-ALS), and 20 with no prevalent impairment (C-ALS). The Motor Cortex Susceptibility (MCS) score was defined according to the hypointensity of the primary motor cortex in the SWI sequence. Its diagnostic accuracy in differentiating groups was evaluated. RESULTS: The MCS was higher in the ALS group than in the healthy control and ALS-mimicking disorder groups (p < 0.001). Among ALS subgroups, the MCS was significantly higher in the UMN-ALS group than in the healthy control (p < 0.001), ALS-mimicking disorder (p = 0.002), and LMN-ALS groups (p = 0.002) and higher in the C-ALS group than in the healthy control group (p = 0.019). An MCS value ≥ 2 showed specificity and a positive predictive value of 100% in the detection of both UMN-ALS and C-ALS patients. CONCLUSIONS: The assessment of MCS in the SWI sequence could be a useful tool in supporting diagnosis in patients suspicious for ALS with prevalent signs of UMN impairment or with no prevalence signs of UMN or LMN impairment. KEY POINTS: ⢠The hypointensity of the primary motor cortex in susceptibility-weighted imaging could support the diagnosis of ALS. ⢠Our new qualitative score called MCS shows high specificity and positive predictive value in differentiating ALS patients with upper motor neuron impairment from patients with ALS-mimicking disorders and healthy controls.
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Esclerose Lateral Amiotrófica , Córtex Motor , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Córtex Motor/diagnóstico por imagem , Neurônios Motores , FenótipoRESUMO
OBJECTIVES: The aim of our study was to investigate whether the magnetic susceptibility varies according to the amyotrophic lateral sclerosis (ALS) phenotypes based on the predominance of upper motor neuron (UMN)/lower motor neuron (LMN) impairment. METHODS: We retrospectively collected imaging and clinical data of 47 ALS patients (12 with UMN predominance (UMN-ALS), 16 with LMN predominance (LMN-ALS), and 19 with no clinically defined predominance (Np-ALS)). We further enrolled 23 healthy controls (HC) and 15 ALS mimics (ALS-Mim). These participants underwent brain 3-T magnetic resonance imaging (3-T MRI) with T1-weighted and gradient-echo multi-echo sequences. Automatic segmentation and quantitative susceptibility mapping (QSM) were performed. The skewness of the susceptibility values in the precentral cortex (SuscSKEW) was automatically computed, compared among the groups, and correlated to the clinical variables. RESULTS: The Kruskal-Wallis test showed significant differences in terms of SuscSKEW among groups (χ2(3) = 24.2, p < 0.001), and pairwise tests showed that SuscSKEW was higher in UMN-ALS compared to those in LMN-ALS (p < 0.001), HC (p < 0.001), Np-ALS (p = 0.012), and ALS-Mim (p < 0.001). SuscSKEW was highly correlated with the Penn UMN score (Spearman's rho 0.612, p < 0.001). CONCLUSION: This study demonstrates that the clinical ALS phenotypes based on UMN/LMN sign predominance significantly differ in terms of magnetic susceptibility properties of the precentral cortex. Combined MRI-histopathology investigations are strongly encouraged to confirm whether this evidence is due to iron overload in UMN-ALS, unlike in LMN-ALS. KEY POINTS: ⢠Magnetic susceptibility in the precentral cortex reflects the prevalence of UMN/LMN impairment in the clinical ALS phenotypes. ⢠The degree of UMN/LMN impairment might be well described by the automatically derived measure of SuscSKEW in the precentral cortex. ⢠Increased SuscSKEW in the precentral cortex is more relevant in UMN-ALS patients compared to those in Np-ALS and LMN-ALS patients.
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Esclerose Lateral Amiotrófica , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Neurônios Motores , Fenótipo , Estudos RetrospectivosRESUMO
OBJECTIVES: We investigated whether prenatal magnetic resonance imaging (MRI) within 26 weeks of gestation (GW) may predict the fate of isolated upward rotation of the cerebellar vermis (URCV). METHODS: This retrospective multicentre observational study included foetuses diagnosed with isolated URCV in prenatal MRI performed within 26 GW. Isolated URCV was defined by a brainstem-vermis angle (BVA) ≥ 12° in the MR midline sagittal view without abnormalities of the supratentorial structures, brainstem, or cerebellum hemispheres. The assessments included the BVA, clival-supraoccipital angle, transverse diameter of the posterior cranial fossa, tentorial angle, width of the cisterna magna (WCM), ventricular width, vermian diameters, hypointense stripes, and cerebellar tail sign. Late prenatal or postnatal MRI was used as a reference standard to assess the final vermian fate (rotated/de-rotated). RESULTS: Forty-five foetuses (mean GW at prenatal MRI = 21.5 ± 1.4 weeks) were included. In the reference standard, the vermis was de-rotated in 26 cases (57.7%). At least two of the following criteria were used to predict the persistence of URCV at imaging follow-up: BVA ≥ 23°, WCM ≥ 9 mm, and the cerebellar tail sign. The results were a sensitivity of 84.21% (95% CI, 60.4-96.6%), specificity of 80.8% (95% CI, 60.6-93.4%), positive predictive value of 76% (95% CI, 58.7-87.8%), and negative predictive value of 87.5% (95% CI, 70.9-95.2%). CONCLUSIONS: MRI within 26 GW on foetuses diagnosed with isolated URCV may predict delayed cerebellar vermis de-rotation, which is associated with good neurodevelopmental outcome in most cases. KEY POINTS: ⢠Foetal MRI is a valuable tool in predicting the fate of isolated upward-rotated cerebellar vermis. ⢠A wider angle between the brainstem and vermis is associated with higher risk of persistence of vermian rotation. ⢠The presence of ≥ 2 factors among a brainstem-to-vermis angle ≥ 23°, width of the cisterna magna ≥ 9 mm, and the presence of the "cerebellar tail sign" has a sensitivity of 84.21% (95% CI, 60.4-96.6%) and specificity of 80.8% (95% CI, 60.6-93.4%) in predicting the persistence of the vermian rotation at imaging follow-up.
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Vermis Cerebelar/diagnóstico por imagem , Idade Gestacional , Anormalidade Torcional/diagnóstico por imagem , Tronco Encefálico , Vermis Cerebelar/anormalidades , Vermis Cerebelar/embriologia , Cerebelo/diagnóstico por imagem , Fossa Craniana Posterior , Diagnóstico Diferencial , Feminino , Feto , Humanos , Imageamento por Ressonância Magnética/métodos , Gravidez , Diagnóstico Pré-Natal , Remissão Espontânea , Estudos Retrospectivos , Sensibilidade e Especificidade , Anormalidade Torcional/embriologiaRESUMO
BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a rare disorder characterized by recurrent epistaxis, telangiectasias and systemic arteriovenous malformations (AVMs). HHT is associated with mutations in genes encoding for proteins involved in endothelial homeostasis such as ENG (endoglin) and ACVRL1 (activin receptor-like kinase-1). CASE PRESENTATION: Here we describe a 22-year-old male presenting with a transient episode of slurred speech and left arm paresis. Brain MRI displayed polymicrogyria. A right-to-left shunt in absence of an atrial septum defect was noted. Chest CT revealed multiple pulmonary AVMs, likely causing paradoxical embolism manifesting as a transient ischemic attack. The heterozygous ENG variant, c.3G > A (p.Met1lle), was detected in the patient. This variant was also found in patient's mother and in his younger brother who displayed cortical dysplasia type 2. CONCLUSIONS: The detection of cortical development malformations in multiple subjects from the same pedigree may expand the phenotypic features of ENG-related HHT patients. We suggest considering HHT in young patients presenting with acute cerebral ischemic events of unknown origin.
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Endoglina/genética , Malformações do Desenvolvimento Cortical/genética , Telangiectasia Hemorrágica Hereditária/diagnóstico , Receptores de Activinas Tipo II/genética , Fístula Arteriovenosa/diagnóstico , Malformações Arteriovenosas/genética , Heterozigoto , Humanos , Masculino , Mutação , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Telangiectasia Hemorrágica Hereditária/genética , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
In this case report, we describe the first PCR-confirmed case of HSV2 myeloradiculitis with a purely motor presentation, occurring in a 68-year-old liver transplant recipient. The patient reported ascending weakness with no sensory nor sphincteric symptoms, thereby resembling acute demyelinating inflammatory neuropathy, or Guillain-Barré syndrome. HSV2 was detected in cerebrospinal fluid by PCR, and the patient was successfully treated with intravenous Acyclovir.
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Síndrome de Guillain-Barré/virologia , Herpes Simples/líquido cefalorraquidiano , Transplante de Fígado/efeitos adversos , Aciclovir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 2 , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: The importance of predicting disease progression in multiple sclerosis (MS) has increasingly been recognized, and hence reliable biomarkers are needed. OBJECTIVES: To investigate the prognostic role of cerebrospinal fluid (CSF) amyloid beta1-42 (Aß) levels by the determination of a cut-off value to classify patients in slow and fast progressors. To evaluate possible association with white matter (WM) and grey matter (GM) damage at early disease stages. METHODS: Sixty patients were recruited and followed up for 3-5 years. Patients underwent clinical assessment, brain magnetic resonance imaging (MRI; at baseline and after 1 year), and CSF analysis to determine Aß levels. T1-weighted volumes were calculated. T2-weighted scans were used to quantify WM lesion loads. RESULTS: Lower CSF Aß levels were observed in patients with a worse follow-up Expanded Disability Status Scale (EDSS; r = -0.65, p < 0.001). The multiple regression analysis confirmed CSF Aß concentration as a predictor of patients' EDSS increase (r = -0.59, p < 0.0001). Generating a receiver operating characteristic curve, a cut-off value of 813 pg/mL was determined as the threshold able to identify patients with worse prognosis (95% confidence interval (CI): 0.690-0.933, p = 0.0001). No differences in CSF tau and neurofilament light chain (NfL) levels were observed (p > 0.05). CONCLUSION: Low CSF Aß levels may represent a predictive biomarker of disease progression in MS.
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Peptídeos beta-Amiloides/líquido cefalorraquidiano , Progressão da Doença , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico por imagem , Fragmentos de Peptídeos/líquido cefalorraquidiano , Substância Branca/diagnóstico por imagem , Adulto , Biomarcadores/líquido cefalorraquidiano , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Somatoform disorders (SDs) are a heterogeneous group of psychiatric syndromes characterized by common symptoms, which may mimic a physical condition but they are not explained by a medical condition. Although the biologic nature of this disorder has been widely accepted, the neuroanatomical correlates characterizing SDs are still inconclusive. OBJECTIVE: This study aims to explore gray matter (GM) volume alterations in SD patients compared to healthy controls and their possible association with clinical and cognitive measures. METHOD: We used voxel-based morphometry to examine regional GM volumes in 20 inpatients with SDs and 24-matched healthy controls. Only for SD patients, we employed multiple instruments to assess psychopathology and cognitive functioning, which were then used to explore their association with GM volume deficits. RESULTS: Compared to healthy controls, SD patients showed GM volume reductions in the hypothalamus, left fusiform gyrus, right cuneus, left inferior frontal gyrus, left posterior cingulate, and right amygdala (p < 0.05, cluster Family Wise Error corrected). Additionally, in SD, Symptom Checklist-90-Phobia and Hamilton Depressive Rating Scale scores negatively correlated with specific fronto-temporoparietal regions whereas Symptom Checklist-90-Sleep scores positively correlated with anterior cingulate cortex. Lastly, the Boston Naming Test negatively correlated with fronto-temporoparietal and striatal volumes whereas Free and Cued Selective Reminding Test and Stroop scores positively correlated with superior temporal gyrus and cuneus, respectively (all p < 0.05, cluster Family Wise Error corrected). CONCLUSION: Our results suggest that SDs might be characterized by selective impairments in specific cortico-limbic regions associated to two overlapping circuits, the neuromatrix of pain and the emotion regulation system.
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Encéfalo/diagnóstico por imagem , Transtornos Somatoformes/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Transtornos Somatoformes/diagnóstico , Transtornos Somatoformes/patologiaRESUMO
OBJECTIVE: Children exposed to chemotherapy in the prenatal period demonstrate normal neurocognitive development at 3 years but concerns regarding fetal brain growth remain high considering its vulnerability to external stimuli. Our aim was to evaluate the impact of in-utero chemotherapy exposure on brain growth and its effects on neurodevelopmental outcome. METHODS: The protocol was approved by the local ethics committee. Brain regional volumes at term postmenstrual age were measured by MRI in children exposed to in-utero chemotherapy and compared with normal MRI controls. Brain segmentation was performed by Advanced Normalization Tools (ANTs)-based transformations of the Neonatal Brain Atlas (ALBERT). Neurodevelopmental assessment (Bayley-III scales) was performed at 18 months corrected age in both exposed infants and in a group of healthy controls. Multiple linear regressions and false discovery rate correction for multiple comparisons were performed. RESULTS: Twenty-one newborns prenatally exposed to chemotherapy (epirubicin administered in 81% of mothers) were enrolled in the study: the mean gestational age was 36.4±2.4 weeks and the mean birthweight was 2,753±622 g. Brain MRI was performed at mean postmenstrual age of 41.1±1.4 weeks. No statistically significant differences were identified between the children exposed to chemotherapy and controls in both the total (398±55 cm3 vs 427±56 cm3, respectively) and regional brain volumes. Exposed children showed normal Bayley-III scores (cognitive 110.2±14.5, language 99.1±11.3, and motor 102.6±7.3), and no significant correlation was identified between the brain volumes and neurodevelopmental outcome. CONCLUSION: Prenatal exposure to anthracycline/cyclophosphamide-based chemotherapy does not impact fetal brain growth, thus supporting the idea that oncological treatment in pregnant women seems to be feasible and safe for the fetus.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Desenvolvimento Fetal/efeitos dos fármacos , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Neoplasias/tratamento farmacológico , GravidezRESUMO
BACKGROUND: Elderly bipolar disorder (BD) and behavioural variant of frontotemporal dementia (bvFTD) may exhibit similar symptoms and both disorders are characterized by selective abnormalities in cortical and subcortical regions that are associated with cognitive and emotional impairments. We aimed to investigate common and distinct neural substrates of BD and bvFTD by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques. METHODS: 3-Tesla MRI and 18 fluorodeoxyglucose-PET scans were acquired for 16 elderly BD patients, 23 bvFTD patients with mild cognitive impairments and 68 healthy controls (48 for PET and 20 for MRI analyses). RESULTS: BD and bvFTD patients exhibit a different localization of grey matter reductions in the lateral prefrontal cortex, with the first group showing grey matter decrease in the ventrolateral prefrontal cortex and the latter group showing grey matter reductions in the dorsolateral prefrontal cortex as well as unique grey matter and metabolic alterations within the orbitofrontal cortex. The bvFTD group also displayed unique volumetric shrinkage in regions within the temporo-parietal network together with greater metabolic impairments within the temporal cortex and more extensive volumetric and metabolic abnormalities within the limbic lobe. Finally, while the BD group showed greater grey matter volumes in caudate nucleus, bvFTD subjects displayed lower metabolism. CONCLUSION: This MRI-PET study explored, for the first time to the best of our knowledge, structural and functional abnormalities in bvFTD and elderly BD patients, with the final aim of identifying the specific biological signature of these disorders, which might have important implications not only in prevention but also in differential diagnosis and treatment.
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Envelhecimento , Transtorno Bipolar , Córtex Cerebral , Demência Frontotemporal , Substância Cinzenta , Imageamento por Ressonância Magnética , Rede Nervosa , Tomografia por Emissão de Pósitrons , Idoso , Envelhecimento/metabolismo , Envelhecimento/patologia , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/metabolismo , Transtorno Bipolar/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Feminino , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/metabolismo , Demência Frontotemporal/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/metabolismo , Substância Cinzenta/patologia , Humanos , Masculino , Imagem Multimodal , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/metabolismo , Rede Nervosa/patologiaRESUMO
OBJECTIVE: Recent trials have shown the safety and benefits of fetoscopic treatment of myelomeningocele (MMC). The authors' aim was to report their preliminary results of prenatal fetoscopic treatment of MMC using a biocellulose patch, focusing on neurological outcomes, fetal and maternal complications, neonatal CSF leakage, postnatal hydrocephalus, and radiological outcomes. METHODS: Preoperative assessment included clinical examination, ultrasound imaging, and MRI of the fetus. Patients underwent purely fetoscopic in utero MMC repair, followed by postoperative in utero and postnatal MRI. All participants received multidisciplinary follow-up. RESULTS: Five pregnant women carrying fetuses affected by MMC signed informed consent for the fetoscopic treatment of the defect. The mean MMC size was 30.4 mm (range 19-49 mm). Defect locations were L1 (2 cases), L5 (2 cases), and L4 (1 case). Hindbrain herniation and ventriculomegaly were documented in all cases. The mean gestational age at surgery was 28.2 weeks (range 27.8-28.8 weeks). Fetoscopic repair was performed in all cases. The mean gestational age at delivery was 33.9 weeks (range 29.3-37.4 weeks). After surgery, reversal of hindbrain herniation was documented in all cases. Three newborns developed signs of hydrocephalus requiring CSF diversion. Neurological outcomes in terms of motor level were favorable in all cases, but a premature newborn died due to CSF infection and sepsis. CONCLUSIONS: The authors' preliminary results suggest that fetoscopic treatment of MMC is feasible, reproducible, and safe for mothers and their babies. Neurological outcomes were favorable and similar to those in the available literature. As known, prematurity was the greatest complication.
Assuntos
Hidrocefalia/cirurgia , Meningomielocele/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Adulto , Feminino , Fetoscopia/métodos , Idade Gestacional , Humanos , Recém-Nascido , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Gravidez , Resultado do TratamentoRESUMO
OBJECTIVE: To assess whether structured reports (SRs) of MRI in patients with inherited neuromuscular disorders (IND) provide more clinically relevant information than non-structured reports (NSRs) and whether neuroradiologists' expertise affects completeness of reports. MATERIAL AND METHODS: Lower limbs' MRI reports of patients with IND produced by neuroradiologists with different level of expertise (> 15 years vs. < 15 years of experience in reading IND-MRI) before and after implementation of a SR template were included. Reports were assessed for the presence of 9 key features relevant for IND management. Reports and images were evaluated by neurologists who assessed: disease-specific muscular involvement pattern; presence of sufficient information to order the appropriate genetic/diagnostic tests; presence of sufficient information to make therapeutic decision/perform biopsy and necessity to review MRI images. Mann-Whitney and Fisher's exact tests were used to compare the number of key features for NSR and SR and neurologists' answers for reports produced by neuroradiologists with different experience. RESULTS: Thirty-one SRs and 101 NSRs were reviewed. A median of 8 and 6 key features was present in SR and NSR, respectively (p value < 0.0001). When reports were produced by less expert neuroradiologists, neurologists recognized muscular involvement pattern, had sufficient information for clinical decision-making/perform biopsy more often with SR than NSR (p values: < 0.0001), and needed to evaluate images less often with SR (p value: 0.0001). When reports produced by expert neuroradiologists were evaluated, no significant difference in neurologists' answers was observed. CONCLUSION: SR of IND-MRI contained more often clinically relevant information considered important for disease management than NSR. Radiologist's expertise affects completeness of NSR reports.
Assuntos
Extremidade Inferior , Imageamento por Ressonância Magnética/métodos , Prontuários Médicos/normas , Doenças Neuromusculares/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
We describe a mother and son with focal epilepsy, mild cognitive impairment, and pachygyria, which was parieto-occipital in the mother and with remarkable posterior greater than anterior severity in the son. Overall clinical manifestations, although overlapping in type, were likewise slightly more severe in the son. Using targeted resequencing through a gene panel for malformations of cortical development, we identified the c.655 T > A [p.(Trp219Arg)] novel missense variant in the LIS1 gene, segregating in the proband and in his mother. Western Blot analysis, qPCR gene expression and RT-PCR disclosed no significant differences between proband, his parents, and controls. Epilepsy and mild cognitive impairment can be the only clinical presentation of constitutional LIS1 mutations, which can therefore be inherited if the associated phenotype implies limited or no reproductive disadvantage. Parents of patients harboring LIS1 mutations should be assessed for their mutation carrier status.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Síndromes Epilépticas/diagnóstico , Síndromes Epilépticas/genética , Lisencefalia/diagnóstico , Lisencefalia/genética , Proteínas Associadas aos Microtúbulos/genética , Mutação , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Criança , Análise Mutacional de DNA , Éxons , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , FenótipoRESUMO
Gillespie syndrome (GLSP) is a rare congenital disorder characterized by partial aniridia, hypotonia, progressive cerebellar hypoplasia, nonprogressive ataxia, and intellectual disability. All causative variants to date affect the central or the 3'-terminal domains of ITPR1 gene and exhibit autosomal recessive or dominant inheritance pattern. We investigated by exome sequencing the molecular cause of GLSP in a family composed by consanguineous healthy parents, two affected siblings and one healthy son. We found the novel splice site variant c.278_279 + 2delACGT located at the 5'-end of ITPR1. The affected siblings were homozygotes, their parents heterozygous carriers and the variant was absent in the healthy son, indicating a recessive inheritance pattern. The deletion abolished the splice-donor site at exon 5/intron 5 junction, causing the skipping of exon 5 and the generation of a premature STOP codon. The mutation is predicted to result in the synthesis of a 64-amino acids nonfunctional protein. The mutant transcript comprised >96% of ITPR1 mRNA in the affected siblings, indicating that a small amount of wild-type transcript was still present. The novel autosomal recessive mutation here reported is the first variant affecting the ITPR1 N-terminal suppressor domain, thus extending the spectrum of the pathogenetic variants in GLSP and the range of the associated clinical manifestations.
Assuntos
Aniridia/genética , Ataxia Cerebelar/genética , Mutação da Fase de Leitura , Receptores de Inositol 1,4,5-Trifosfato/genética , Deficiência Intelectual/genética , Sítios de Splice de RNA/genética , Adolescente , Aniridia/etiologia , Ataxia Cerebelar/etiologia , Criança , Códon sem Sentido , Éxons , Feminino , Genes Recessivos , Homozigoto , Humanos , Receptores de Inositol 1,4,5-Trifosfato/química , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Deficiência Intelectual/etiologia , Masculino , Linhagem , Domínios ProteicosRESUMO
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.
Assuntos
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
BACKGROUND: The effects and potential hazards of brain magnetic resonance imaging (MRI) at 3 T in newborns are debated. OBJECTIVE: Assess the impact of 3-T MRI in newborns on body temperature and physiological parameters. MATERIAL AND METHODS: Forty-nine newborns, born preterm and at term, underwent 3-T brain MRI at term-corrected age. Rectal and skin temperature, oxygen saturation and heart rate were recorded before, during and after the scan. RESULTS: A statistically significant increase in skin temperature of 0.6 °C was observed at the end of the MRI scan (P<0.01). There was no significant changes in rectal temperature, heart rate or oxygen saturation. CONCLUSION: Core temperature, heart rate and oxygen saturation in newborns were not affected by 3-T brain MR scanning.