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1.
Neurol Sci ; 45(4): 1557-1563, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37926747

RESUMO

INTRODUCTION: Door-to-needle time (DNT) is an established predictor of outcome in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). Several strategies have been proposed to streamline in-hospital pathways, among which treatment at CT/MR bed. AIM: To explore the impact of treatment at CT/MR bed, here defined as imaging area (IA), on functional outcome in stroke patients treated with IVT alone. METHODS: All AIS patients treated with IVT alone at our center in 2020, 2021, and 2022 were included. Patients with any previous disability were excluded. The cohort was divided into two groups, depending on the treatment site. One group received IVT at IA, the other at emergency room or stroke unit (non-IA). Regression analysis assessed the association between treatment site and 3-month outcome. RESULTS: A total of 327 patients who received IVT alone were included in the analysis. One hundred thirty-three (40.7%) were in the IA group and 194 (59.3%) in the non-IA group. The groups showed similar baseline characteristics. In the IA group, DNT was 45 min shorter. Despite similar rates of functional independence (mRS 0-2), the IA group showed higher rates of excellent outcome (mRS 0-1) compared to the non-IA group (60.1% vs 42.8%, p<0.01). Immediate treatment at IA was independently associated to excellent outcome (OR 1.78 [1.03-3.08]). CONCLUSIONS: Thrombolytic treatment at IA lowers DNT and is an independent predictor of excellent outcome after AIS. Our study emphasizes the importance of immediate thrombolytic treatment at IA, soon after radiological eligibility is confirmed. Immediate treatment at IA should be a standard-of-care for AIS.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/etiologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Terapia Trombolítica/métodos , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
2.
Semin Musculoskelet Radiol ; 28(5): 641-650, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39406226

RESUMO

Metabolic bone diseases (MBDs), including osteoporosis, osteomalacia, and Paget's disease, represent a significant challenge in medical imaging and intervention. Interventional radiologists play a pivotal role in managing these conditions, due to the crucial role of detailed and precise imaging in diagnosing and treating MBDs. This article offers comprehensive recommendations aimed at optimizing interventional radiologic practices for patients with MBDs, highlighting the importance of using advanced imaging modalities, including dual-energy X-ray absorptiometry and magnetic resonance imaging, essential for accurate assessment of bone mineral density and architecture, guiding effective intervention strategies. We also discuss the use of minimally invasive procedures like vertebroplasty and biopsy, vital for both diagnostic and therapeutic purposes, to enhance diagnostic accuracy and therapeutic outcomes, ensuring high-quality patient management in the context of MBDs.


Assuntos
Doenças Ósseas Metabólicas , Humanos , Doenças Ósseas Metabólicas/diagnóstico por imagem , Radiologia Intervencionista/métodos , Radiografia Intervencionista/métodos , Absorciometria de Fóton/métodos
3.
Childs Nerv Syst ; 40(8): 2457-2464, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38573550

RESUMO

PURPOSE: Deep brain stimulation (DBS) of nucleus ventralis intermedius thalami (Vim) is a validated technique for the treatment of essential tremor (ET) in adults. Conversely, its use for post traumatic tremor (PTT) and in paediatric patients is still debated. We evaluated the efficacy of Vim-DBS for lesional tremor in three paediatric patients with drug-resistant post-traumatic unilateral tremor. METHODS: We retrospectively collected data regarding three patients with unilateral tremor due to severe head injury, with no MRI evidence of basal ganglia lesions. The three patients underwent stereotactic frame-based robot-assisted DBS of Vim contralateral to the tremor side. RESULTS: Mean follow-up was 48 months (range: 36-60 months). Tremor was reduced in all patients with a better control of voluntary movements and improvement of functional status (mean FIM scale improvement + 7 points). No surgical complications occurred. CONCLUSION: Unilateral contralateral DBS of Vim could be efficacious in post-traumatic tremor, even in paediatric patients and should be offered in PTT drug-resistant patients.


Assuntos
Estimulação Encefálica Profunda , Tremor , Núcleos Ventrais do Tálamo , Humanos , Estimulação Encefálica Profunda/métodos , Masculino , Tremor/etiologia , Tremor/terapia , Criança , Estudos Retrospectivos , Feminino , Adolescente , Resultado do Tratamento
4.
Pediatr Neurosurg ; 59(1): 35-43, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38262396

RESUMO

INTRODUCTION: Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm that affects patients, predominantly males aged 40-70 years, with very heterogeneous clinical presentation and prognosis. In 2020, Goyal et al. proposed consensus recommendations for the management of patients with ECD, remarking on the exceptional presentation of the disease in the pediatric population. CASE PRESENTATION: The first patient, a 20-year-old male, underwent cervical laminectomy and partial removal of a cervical spine lesion, initially apparently consistent with cervical schwannomas. The second patient, a 9-year-old female, received surgery for an extra-axial lesion of the greater sphenoid wing, radiologically consistent with a meningioma. CONCLUSION: At present, 15 pediatric cases have been reported in the literature with involvement of the central nervous system, with no consensus on the diagnostic and therapeutic management, as Pegoraro et al. evidenced in their pediatric multicenter case series. The present article adds two new cases of ECD with onset in childhood and young adulthood, who received the diagnosis after neurosurgical procedures.


Assuntos
Doença de Erdheim-Chester , Neoplasias Meníngeas , Meningioma , Masculino , Feminino , Humanos , Criança , Adulto Jovem , Adulto , Doença de Erdheim-Chester/diagnóstico por imagem , Doença de Erdheim-Chester/cirurgia , Prognóstico , Sistema Nervoso Central , Estudos Multicêntricos como Assunto
5.
Am J Med Genet A ; 191(2): 540-545, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36321570

RESUMO

Nuclear Factor I B (NFIB) haploinsufficiency has recently been identified as a cause of intellectual disability (ID) and macrocephaly. Here we report on two new individuals carrying a microdeletion in the chromosomal region 9p23-p22.3 containing NFIB. The first is a 7-year 9-month old boy with developmental delays, ID, definite facial anomalies, and brain and spinal cord magnetic resonance imaging findings including periventricular nodular heterotopia, hypoplasia of the corpus callosum, arachnoid cyst in the left middle cranial fossa, syringomyelia in the thoracic spinal cord and distal tract of the conus medullaris, and a stretched appearance of the filum terminale. The second is a 32-year-old lady (the proband' mother) with dysmorphic features, and a history of learning disability, hypothyroidism, poor growth, left inguinal hernia, and panic attacks. Her brain magnetic resonance imaging findings include a dysmorphic corpus callosum, and a small cyst in the left choroidal fissure that marks the hippocampal head. Array-based comparative genomic hybridization identified, in both, a 232 Kb interstitial deletion at 9p23p22.3 including several exons of NFIB and no other known genes. Our two individuals add to the knowledge of this rare disorder through the addition of new brain and spinal cord MRI findings and dysmorphic features. We propose that NFIB haploinsufficiency causes a clinically recognizable malformation-ID syndrome.


Assuntos
Anormalidades Múltiplas , Deficiência Intelectual , Feminino , Humanos , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Encéfalo/patologia , Deleção Cromossômica , Hibridização Genômica Comparativa , Corpo Caloso/patologia , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Fatores de Transcrição NFI/genética , Fenótipo , Masculino , Criança , Adulto
6.
Childs Nerv Syst ; 39(3): 711-720, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36443473

RESUMO

INTRODUCTION: Loculated hydrocephalus is a complex condition in which different non-communicating compartments form within the ventricular system due to different etiology, mainly intraventricular hemorrhage and infection. Since the end of the twentieth century, neuroendoscopy has been explored as a therapeutic option for loculated hydrocephalus with non-univocal results. METHODS: We performed a retrospective analysis of 90 patients who underwent endoscopic treatment for loculated hydrocephalus from January 1997 to January 2021 (mean age: 2 years, range 7-21). We included 37 (41.1%) children with multiloculated hydrocephalus, 37 (41.1%) with isolated lateral ventricle, 13 (14.4%) with excluded temporal horn, and 3 (3.3%) with isolated fourth ventricle. We compared our results with those available in literature. RESULTS: A mean of 1.91 endoscopic procedure/patient were performed (only one endoscopy in 42.2% of cases). Complications of neuroendoscopy and of shunt surgeries were recorded in 17 (18.9%) and 52 (57.8%) children, respectively. Twenty-six (28.9%) children were shunt-free at the last follow-up, 47.8% have only one shunt. DISCUSSION: The first goal of neuroendoscopy is to increase the rate of shunt-free patients but, when it is not possible, it aims at simplifying shunt system and reducing the number of surgical procedures. In our series, neuroendoscopy was able to achieve both these goals with an acceptable complication rate. Thus, our results confirmed neuroendoscopy as a valid tool in the long-term management of loculated hydrocephalus. Neuronavigation and intraoperative ultrasound could increase the success rate in cases with distorted anatomy.


Assuntos
Hidrocefalia , Neuroendoscopia , Terceiro Ventrículo , Criança , Humanos , Lactente , Adolescente , Adulto Jovem , Adulto , Neuroendoscopia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Ventriculostomia/métodos , Hidrocefalia/cirurgia , Hidrocefalia/etiologia , Terceiro Ventrículo/cirurgia , Quarto Ventrículo/cirurgia
7.
Childs Nerv Syst ; 39(9): 2493-2497, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37526681

RESUMO

PURPOSE: During the last decade, there has been renewed interest in stereotactic approaches to diffuse intrinsic pontine gliomas (DIPGs) in children, due to the development of new concepts in molecular biology and management, and subsequent need for tissue sampling. Stereotactic frame-based and robot-assisted techniques are associated with reduced target error and have been incorporated into standard practice at our institution. METHODS: Four children (age 2-7 years) underwent a robot-assisted frame-based transcerebellar approach using the Leksell G frame coupled with Renishaw's neuromate® stereotactic robot. The procedures included 3 biopsies (two brainstem tumors and one cerebellar hemispheric lesion) and 1 depth electrode implantation into a low-grade tumor remnant (ganglioglioma) of the middle cerebellar peduncle causing drug-resistant epilepsy in a young girl. Targeting was based on MRI, and in one case, 18F-FET-PET was coregistered to MRI to improve sampling accuracy. The frame was applied 180° rotated compared to standard orientation, and patients were positioned prone during surgery and stereotactic preoperative CT scan. Postoperative CT scan ruled out complications and was coregistered to preoperative MRI to check the target accuracy. RESULTS: No complications occurred, and targeting was accurate in all cases. All tissue samplings provided proper histology; depth electrode EEG exploration was diagnostic and led subsequent resective surgery. CONCLUSIONS: According to our experience, the transcerebellar frame-based robotic stereotactic approach to the cerebellum and the brainstem is feasible, safe, and effective even in young children.


Assuntos
Neoplasias do Tronco Encefálico , Robótica , Feminino , Humanos , Criança , Pré-Escolar , Técnicas Estereotáxicas , Biópsia/métodos , Neoplasias do Tronco Encefálico/patologia
8.
Cell Mol Neurobiol ; 42(8): 2863-2892, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34709498

RESUMO

Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response.


Assuntos
Astrocitoma , Esclerose Tuberosa , Humanos , Astrocitoma/metabolismo , Metilação de DNA/genética , Sirolimo/uso terapêutico , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genética , Esclerose Tuberosa/patologia
9.
Neurol Sci ; 43(2): 1311-1326, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34097175

RESUMO

BACKGROUND: Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and treatment of CM1 in children. METHODS: A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale ("strongly disagree," "disagree," "agree," "strongly agree"). Statements that were endorsed ("agree" or "strongly agree") by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three). RESULTS: Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the "definition of radiological failure 24 month post-surgery." CONCLUSIONS: The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient population.


Assuntos
Malformação de Arnold-Chiari , Siringomielia , Malformação de Arnold-Chiari/diagnóstico , Malformação de Arnold-Chiari/terapia , Criança , Consenso , Técnica Delphi , Humanos , Itália
10.
Semin Musculoskelet Radiol ; 26(4): 510-520, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36103892

RESUMO

Spinal cord evaluation is an integral part of spine assessment, and its reliable imaging work-up is mandatory because even localized lesions may produce serious effects with potentially irreversible sequelae. Spinal cord alterations are found both incidentally during spine evaluation in otherwise neurologically asymptomatic patients or during neurologic/neuroradiologic assessment in myelopathic patients. Myelopathy (an umbrella term for any neurologic deficit that refers to spinal cord impairment) can be caused by intrinsic lesions or extrinsic mechanical compression, and its etiology may be both traumatic and/or nontraumatic. The symptoms largely depend on the size/extension of lesions, ranging from incontinence to ataxia, from spasticity to hyperreflexia, from numbness to weakness. Magnetic resonance imaging is the reference imaging modality in spinal cord evaluation, ensuring the best signal and spatial resolution. We provide an overview of the most common spinal cord disorders encountered by radiologists and describe the technical measures that offer optimal spinal cord visualization.


Assuntos
Compressão da Medula Espinal , Doenças da Medula Espinal , Humanos , Imageamento por Ressonância Magnética , Compressão da Medula Espinal/diagnóstico , Compressão da Medula Espinal/etiologia , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/diagnóstico por imagem , Coluna Vertebral
11.
Pediatr Neurosurg ; 57(2): 133-137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34823255

RESUMO

INTRODUCTION: Although still considered quite harmless, nonpowder guns (NPG) may cause severe head injuries in children. We present the case of a depressed skull fracture with superior sagittal sinus involvement following NPG injury. Decision-making and surgical management are discussed, and the current literature concerning NPG-related pediatric head injuries is reviewed. CASE PRESENTATION: A 4-year-old boy hit by a compressed-air rifle came to our center. CT scan showed a depressed skull fracture of the occipital bone on the midline and intracranial penetration of some fragments of the pellet. CT angiography documented a compression of the superior sagittal sinus without thrombosis. Soon after hospital admission, the patient showed deterioration of the neurological status suggesting intracranial hypertension. Surgery was performed with fracture elevation, removal of metal fragments, and wound debridement. The patient had a full recovery without subsequent neurological deficits. DISCUSSION/CONCLUSION: Modern airguns may produce severe penetrating head injuries in children. Parents and physicians should be aware of the danger of NPG. Depressed skull fracture and dural venous sinus involvement can occur, and even a stable neurological condition may worsen. In such instances, a thorough preoperative assessment including vascular imaging is mandatory. The surgical risk is not negligible due to the possible injury of the sinus wall and subsequent intraoperative bleeding. This has to be weighted against potential complications of the penetrating injury, such as infection, sinus thrombosis, and intracranial hypertension. Our case suggests that prompt surgical treatment can be a safe and effective option.


Assuntos
Traumatismos Craniocerebrais , Hipertensão Intracraniana , Trombose dos Seios Intracranianos , Fratura do Crânio com Afundamento , Criança , Pré-Escolar , Traumatismos Craniocerebrais/complicações , Humanos , Hipertensão Intracraniana/complicações , Masculino , Trombose dos Seios Intracranianos/complicações , Fratura do Crânio com Afundamento/diagnóstico por imagem , Fratura do Crânio com Afundamento/cirurgia , Seio Sagital Superior/diagnóstico por imagem , Seio Sagital Superior/cirurgia
12.
Pediatr Neurosurg ; 57(6): 389-395, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36167051

RESUMO

BACKGROUND: Acute traumatic epidural hematoma (EDH) is a complication in 2-3% of pediatric head injuries. Surgery is mandatory in symptomatic cases; otherwise, conservative treatment is a valid approach, especially in the pediatric population. Ossified epidural hematomas (OEHs) have been reported in the pediatric population as a rare complication of conservative EDH management, although the exact incidence remains unknown. The progressive increase in conservative management may lead to increases in the OEH incidence over the next few years. Our study aimed to systematically review OEH incidence, management strategies, characteristics (thickness, inner/outer calcifications), complication rates, time to surgery after the EDH diagnosis, and clinical outcomes. SUMMARY: A systematic review was conducted in accordance with the PRISMA guidelines. Studies reporting diagnoses and clear descriptions of OEH after EDH in pediatric patients were considered eligible. Sixteen studies, including 18 pediatric patients aged 0-18 years, were included. Head trauma was the most common cause of OEH. Seven (38.8%) OEHs were treated less than 1 month after EDH diagnosis. Surgery was performed in 17 cases (94.44%), while 1 asymptomatic case (5.56%) was managed conservatively. KEY MESSAGES: Surgery was the most commonly used treatment for OEH. Data for conservative treatment of OEH are limited. Magnetic resonance imaging or ultrasound within the first 2 months, to check for EDH resolution, may be crucial to rule out complications in pediatric patients.


Assuntos
Calcinose , Traumatismos Craniocerebrais , Hematoma Epidural Craniano , Criança , Humanos , Tratamento Conservador , Estudos Retrospectivos , Hematoma Epidural Craniano/diagnóstico por imagem , Hematoma Epidural Craniano/etiologia , Hematoma Epidural Craniano/cirurgia , Traumatismos Craniocerebrais/complicações , Tomografia Computadorizada por Raios X/efeitos adversos
13.
Hum Genet ; 140(4): 625-647, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33337535

RESUMO

Type 1 Chiari malformation (C1M) is characterized by cerebellar tonsillar herniation of 3-5 mm or more, the frequency of which is presumably much higher than one in 1000 births, as previously believed. Its etiology remains undefined, although a genetic basis is strongly supported by C1M presence in numerous genetic syndromes associated with different genes. Whole-exome sequencing (WES) in 51 between isolated and syndromic pediatric cases and their relatives was performed after confirmation of the defect by brain magnetic resonance image (MRI). Moreover, in all the cases showing an inherited candidate variant, brain MRI was performed in both parents and not only in the carrier one to investigate whether the defect segregated with the variant. More than half of the variants were Missense and belonged to the same chromatin-remodeling genes whose protein truncation variants are associated with severe neurodevelopmental syndromes. In the remaining cases, variants have been detected in genes with a role in cranial bone sutures, microcephaly, neural tube defects, and RASopathy. This study shows that the frequency of C1M is widely underestimated, in fact many of the variants, in particular those in the chromatin-remodeling genes, were inherited from a parent with C1M, either asymptomatic or with mild symptoms. In addition, C1M is a Mendelian trait, in most cases inherited as dominant. Finally, we demonstrate that modifications of the genes that regulate chromatin architecture can cause localized anatomical alterations, with symptoms of varying degrees.


Assuntos
Malformação de Arnold-Chiari/genética , Montagem e Desmontagem da Cromatina/genética , Sequenciamento do Exoma , Mutação de Sentido Incorreto , Adolescente , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Sistema de Sinalização das MAP Quinases/genética , Imageamento por Ressonância Magnética , Masculino , Microcefalia/genética , Adulto Jovem
14.
Brain ; 143(1): 131-149, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834371

RESUMO

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. In the CNS, TSC is characterized by cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs). SEGAs may lead to impaired circulation of CSF resulting in hydrocephalus and raised intracranial pressure in patients with TSC. Currently, surgical resection and mTORC1 inhibitors are the recommended treatment options for patients with SEGA. In the present study, high-throughput RNA-sequencing (SEGAs n = 19, periventricular control n = 8) was used in combination with computational approaches to unravel the complexity of SEGA development. We identified 9400 mRNAs and 94 microRNAs differentially expressed in SEGAs compared to control tissue. The SEGA transcriptome profile was enriched for the mitogen-activated protein kinase (MAPK) pathway, a major regulator of cell proliferation and survival. Analysis at the protein level confirmed that extracellular signal-regulated kinase (ERK) is activated in SEGAs. Subsequently, the inhibition of ERK independently of mTORC1 blockade decreased efficiently the proliferation of primary patient-derived SEGA cultures. Furthermore, we found that LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5 were overexpressed at both gene and protein levels in SEGA compared to control tissue. Taken together LAMTOR1-5 can form a complex, known as the 'Ragulator' complex, which is known to activate both mTORC1 and MAPK/ERK pathways. Overall, this study shows that the MAPK/ERK pathway could be used as a target for treatment independent of, or in combination with mTORC1 inhibitors for TSC patients. Moreover, our study provides initial evidence of a possible link between the constitutive activated mTORC1 pathway and a secondary driver pathway of tumour growth.


Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , MAP Quinases Reguladas por Sinal Extracelular/genética , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Esclerose Tuberosa/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrocitoma/etiologia , Astrocitoma/metabolismo , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/metabolismo , Butadienos/farmacologia , Criança , Pré-Escolar , Inibidores Enzimáticos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Perfilação da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Nitrilas/farmacologia , RNA-Seq , Análise de Sequência de RNA , Esclerose Tuberosa/complicações , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Células Tumorais Cultivadas , Adulto Jovem
15.
Childs Nerv Syst ; 37(9): 2727-2734, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34128119

RESUMO

PURPOSE: Cerebellar mutism syndrome (CMS) represents a major complication affecting many children that undergo surgery for posterior fossa lesions. Etiology and pathophysiology are still not fully understood. CMS deeply influences quality of life and recovery of these patients. An effective treatment has not been defined yet. This case-based review aims at analyzing the available evidence and knowledge to better delineate this phenomenon and to determine whether CMS can be successfully treated with pharmacological therapy. METHODS: Systematic research and retrieval of databases were conducted analyzing all papers where medical treatment of CMS was reported. A summary of the latest understanding and reports regarding definition, clinical manifestations, pathophysiology, management, and outcome of CMS has been conducted. RESULTS: Consensus on definition of this syndrome is lacking. CMS is the term accepted by the Posterior Fossa Society in 2016. Pathophysiology is still poorly understood but the most likely mechanism is injury along proximal components of the efferent cerebellar pathway. Nine papers describing positive effects of pharmacological therapy for CMS have been identified. Fluoxetine, zolpidem, bromocriptine, and midazolam are the drugs that seem to alleviate symptoms of CMS and improve recovery. To date, cognitive rehabilitation and physiotherapy are the only treatment options available. CONCLUSION: CMS has deep impact on affected children and their families. Despite attempts to identify preventive measures and treatment, cases still occur on a regular basis. Pharmacological treatments have been proposed to help reduce the symptoms of CMS with some promising results, but reports are limited; therefore, further studies are needed.


Assuntos
Doenças Cerebelares , Neoplasias Cerebelares , Mutismo , Cerebelo , Criança , Humanos , Mutismo/tratamento farmacológico , Mutismo/etiologia , Complicações Pós-Operatórias , Qualidade de Vida
16.
Pediatr Neurosurg ; 56(5): 471-476, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34320505

RESUMO

INTRODUCTION: Achondroplasia is a genetic disorder characterized by defects in the development of endochondral bone resulting in skeletal abnormalities like stenosis of the foramen magnum and of the spine, shortened limb bones, and macrocephaly. Congenital spinal stenosis is frequent and due to premature fusion of the pedicles to the laminae. CASE PRESENTATION: We report a case of neurogenic bladder and fecal incontinence due to lumbar stenosis successfully treated with L1-L5 partial laminectomy and foraminotomy in a 7-year-old achondroplasic child. DISCUSSION/CONCLUSION: To our knowledge, this is the first case report of exclusive neurogenic bladder and fecal incontinence in an achondroplasic child. Neurogenic bladder and fecal incontinence without motor impairment may be early and exclusive clinical findings of lumbar stenosis in children with achondroplasia.


Assuntos
Incontinência Fecal , Bexiga Urinaria Neurogênica , Criança , Descompressão Cirúrgica , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/cirurgia
17.
Ann Diagn Pathol ; 54: 151774, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34182416

RESUMO

Dysembryoplastic neuroepithelial tumors (DNT) is a benign (World Health Organisation, WHO, grade I) glioneuronal tumor and it represent one of the most frequent neoplasm in patient affected by seizures. The epileptic neuronal activity can be determined by abnormal synchronization, excessive glutamate excitation and\or inadequate GABA inhibition. Increasing evidence suggests that the astrocytes might be involved in this process even if neurons play a relevant role. In particular astrocytes promote the clearance of glutamate, a potent excitatory neurotransmitter of the central nervous system. Indeed, elevated concentrations of extracellular glutamate may determine iper-excitability and seizures as well as other neurological disorders. So, astrocytes, converting glutamate into glutamine via the enzyme glutamine synthetase (GS), could play a protective anti-seizures role. In the present study, we analyzed the immunohistochemical expression of GS in 20 DNTs specimens documenting a constant immunoistochemical expression of GS in astrocytes of the lesional tissue and of the cerebral cortex.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Glutamato-Amônia Ligase/metabolismo , Neoplasias Neuroepiteliomatosas/metabolismo , Adolescente , Astrócitos/metabolismo , Astrócitos/patologia , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Feminino , Glioma/patologia , Humanos , Imuno-Histoquímica/métodos , Masculino , Neoplasias Neuroepiteliomatosas/patologia , Neurônios/patologia , Adulto Jovem
19.
Childs Nerv Syst ; 36(5): 951-960, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31853898

RESUMO

BACKGROUND: Subependymal giant cell astrocytomas (SEGA) are benign tumors characteristic of tuberous sclerosis complex (TSC) that may cause hydrocephalus. Various treatments are nowadays available as mTOR inhibitors or surgery. Surgery is still a valid option especially for symptomatic and larger tumors. METHODS: From January 1994 to December 2015, 31 TSC patients harboring SEGA underwent surgery at the Department of Neurosurgery of the Meyer Pediatric Hospital, Florence. Indications for surgery were tumor size and location, growth and cystization/hemorrhage, and hydrocephalus. Clinical data, preoperative and postoperative MRI, recurrence rate, further surgical procedures, and related complications were analyzed. RESULTS: A total of 44 surgeries were performed in 31 TSC patients affected by SEGA, achieving gross total removal (GTR) and subtotal removal (STR), respectively, in 36 and 8 patients. Recurrences occurred in 11 patients; 9 of them underwent further surgical procedures and 2 were treated with mTOR pathway inhibitors. Surgical morbidity and mortality were, respectively, 22.7% and 2.3%. After a mean follow-up of 4.9 years, 90% of patients were tumor-free with good neurological status in 93.3%; twelve (40%) had a ventriculo-peritoneal shunt (VPS) for hydrocephalus. CONCLUSIONS: The present series confirms that the surgical approach, combined with mTOR inhibitors, is still a valid option for the treatment of SEGAs.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Esclerose Tuberosa , Astrocitoma/complicações , Astrocitoma/diagnóstico por imagem , Astrocitoma/cirurgia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Criança , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico por imagem , Esclerose Tuberosa/cirurgia
20.
Childs Nerv Syst ; 36(9): 1845-1851, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32613424

RESUMO

PURPOSE: To investigate the effects of deep brain stimulation (DBS) electrodes on the brain of a dystonic pediatric patient submitted to bilateral DBS of the globus pallidus internus (GPI). METHODS: An 8-year-old male patient underwent bilateral DBS of GPI for status dystonicus. He died 2 months later due to multiorgan failure triggered by bacterial pneumonia. A post-mortem pathological study of the brain was done. RESULTS: At visual inspection, no grossly apparent softening, hemorrhage, or necrosis of the brain adjacent to the DBS lead tracts was detected. High-power microscopic examination of the tissue surrounding the electrode trajectories showed lymphocyte infiltration, astrocytic gliosis, microglia, macrophages, and clusters of multinucleate giant cells. Significant astrocytosis was confirmed by GFAP staining in the electrode site. The T cell lymphocyte activity was overexpressed with activated macrophages detected with CD3, CD20, CD45, and CD68 stains respectively. There was no gliosis or leukocyte infiltration away from the surgical tracks of the electrodes. CONCLUSION: This is the first post-mortem examination of a child's brain after bilateral DBS of GPI. The comparison with adult post-mortem reports showed no significant differences and confirms the safety of DBS implantation in the pediatric population too.


Assuntos
Estimulação Encefálica Profunda , Globo Pálido , Autopsia , Criança , Humanos , Masculino , Resultado do Tratamento
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