RESUMO
Primary cilia are antenna-like structures protruding from the surface of various eukaryotic cells, and have distinct protein compositions in their membranes. This distinct protein composition is maintained by the presence of the transition zone (TZ) at the ciliary base, which acts as a diffusion barrier between the ciliary and plasma membranes. Defects in cilia and the TZ are known to cause a group of disorders collectively called the ciliopathies, which demonstrate a broad spectrum of clinical features, such as perinatally lethal Meckel syndrome (MKS), relatively mild Joubert syndrome (JBTS), and nonsyndromic nephronophthisis (NPHP). Proteins constituting the TZ can be grouped into the MKS and NPHP modules. The MKS module is composed of several transmembrane proteins and three soluble proteins. TMEM218 was recently reported to be mutated in individuals diagnosed as MKS and JBTS. However, little is known about how TMEM218 mutations found in MKS and JBTS affect the functions of cilia. In this study, we found that ciliary membrane proteins were not localized to cilia in TMEM218-knockout cells, indicating impaired barrier function of the TZ. Furthermore, the exogenous expression of JBTS-associated TMEM218 variants but not MKS-associated variants in TMEM218-knockout cells restored the localization of ciliary membrane proteins. In particular, when expressed in TMEM218-knockout cells, the TMEM218(R115H) variant found in JBTS was able to restore the barrier function of cells, whereas the MKS variant TMEM218(R115C) could not. Thus, the severity of symptoms of MKS and JBTS individuals appears to correlate with the degree of their ciliary defects at the cellular level.
Assuntos
Anormalidades Múltiplas , Cílios , Ciliopatias , Encefalocele , Anormalidades do Olho , Doenças Renais Císticas , Proteínas de Membrana , Mutação , Retina , Cílios/metabolismo , Cílios/genética , Cílios/patologia , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Ciliopatias/genética , Ciliopatias/metabolismo , Ciliopatias/patologia , Encefalocele/genética , Encefalocele/metabolismo , Encefalocele/patologia , Doenças Renais Císticas/genética , Doenças Renais Císticas/metabolismo , Doenças Renais Císticas/patologia , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/metabolismo , Anormalidades Múltiplas/patologia , Anormalidades do Olho/genética , Anormalidades do Olho/patologia , Anormalidades do Olho/metabolismo , Retina/metabolismo , Retina/anormalidades , Retina/patologia , Cerebelo/anormalidades , Cerebelo/metabolismo , Cerebelo/patologia , Doenças Cerebelares/genética , Doenças Cerebelares/metabolismo , Doenças Cerebelares/patologia , Animais , Membrana Celular/metabolismo , Camundongos , Transtornos da Motilidade Ciliar , Doenças Renais Policísticas , Retinose PigmentarRESUMO
Knobloch syndrome is an autosomal recessive phenotype mainly characterized by retinal detachment and encephalocele caused by biallelic pathogenic variants in the COL18A1 gene. However, there are patients clinically diagnosed as Knobloch syndrome with unknown molecular etiology not linked to COL18A1. We studied an historical pedigree (published in 1998) designated as KNO2 (Knobloch type 2 syndrome with intellectual disability, autistic behavior, retinal degeneration, encephalocele). Whole exome sequencing of the two affected siblings and the normal parents resulted in the identification of a PAK2 non-synonymous substitution p.(Glu435Lys) as a causative variant. The variant was monoallelic and apparently de novo in both siblings indicating a likely germ-line mosaicism in one of the parents; the mosaicism, however, could not be observed after deep sequencing of blood parental DNA. PAK2 encodes a member of a small group of serine/threonine kinases; these P21-activating kinases (PAKs) are essential in signal transduction and cellular regulation (cytoskeletal dynamics, cell motility, death and survival signaling and cell cycle progression). Structural analysis of the PAK2 p.(Glu435Lys) variant that is located in the kinase domain of the protein predicts a possible compromise in the kinase activity. Functional analysis of the p.(Glu435Lys) PAK2 variant in transfected HEK293T cells results in a partial loss of the kinase activity. PAK2 has been previously suggested as an autism-related gene. Our results show that PAK2-induced phenotypic spectrum is broad and not fully understood. We conclude that the KNO2 syndrome in the studied family is dominant and caused by a deleterious variant in the PAK2 gene.
Assuntos
Degeneração Retiniana , Descolamento Retiniano , Encefalocele/diagnóstico , Encefalocele/genética , Encefalocele/patologia , Células HEK293 , Humanos , Mutação , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Descolamento Retiniano/congênito , Descolamento Retiniano/genética , Quinases Ativadas por p21/genéticaRESUMO
BACKGROUND: Gorham-Stout disease (GSD) is a very rare disorder characterized by massive osteolysis of poorly understood aetiology. The association between GSD involving the skull base and cerebrospinal fluid (CSF) leakage has been reported in the literature. However, few cases of CSF leakage and Chiari-like tonsillar herniation in GSD involving the spine have been reported. CASE PRESENTATION: We present the case of a 20-year-old man with GSD involving the thoracic and lumbar spine, which caused CSF leakage and Chiari-like tonsillar herniation. The patient underwent four spinal surgeries for osteolytic lesions of the spine over a 10-year period. Here, we discuss the possible aetiology of the development of CSF leakage. Epidural blood patch (EBP) was performed at the T11-T12 level to repair the CSF leakage. After EBP treatment, rebound intracranial hypertension (RIH) developed, and tonsillar herniation disappeared 2 months later. CONCLUSIONS: GSD involving the spine with CSF leakage and Chiari-like tonsillar herniation is relatively rare. For patients who have undergone multiple spinal surgeries, minimally invasive treatment is an alternative treatment for CSF leakage. EBP can repair CSF leakage secondary to GSD and improve chronic brain sagging, with reversibility of Chiari-like malformations.
Assuntos
Malformação de Arnold-Chiari , Osteólise Essencial , Masculino , Humanos , Adulto Jovem , Adulto , Osteólise Essencial/complicações , Osteólise Essencial/cirurgia , Osteólise Essencial/patologia , Encefalocele/complicações , Encefalocele/cirurgia , Encefalocele/patologia , Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Encéfalo/patologia , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/cirurgiaRESUMO
BACKGROUND: Encephaloceles are neural tube defects characterized by herniation of meninges, neural tissue and cerebrospinal fluid, while atretic cephaloceles denote a rudimentary connection to the intracranial space with absence of herniated neural tissue and represent an infrequent dermatopathologic diagnosis. Limited reports of these entities confound the challenge in their histopathologic distinction. Accurate classification is important given associated anomalies and neurologic manifestations that impact prognosis. METHODS: We describe the clinicopathological and immunohistochemical [glial fibrillary acidic protein (GFAP), S100, epithelial membrane antigen (EMA), and somatostatin receptor subtype 2A (SSTR2A)] features in a retrospective series encountered at a single institution between 1994 and 2020. RESULTS: We identified 13 cases classified as atretic cephalocele (n = 11) and encephalocele (n = 2). Hamartomatous changes and multinucleated cells were unique to atretic cephaloceles while myxoid areas were unique to encephaloceles. At least focal staining for SSTRA was seen in all atretic cephaloceles with the majority (87.5%) staining for EMA; negative staining for GFAP and S100 confirmed absence of neural tissue. Encephaloceles were GFAP and S100 positive, and negative for SSTR2 and EMA. Atretic cephaloceles had a favorable prognosis compared to encephaloceles, with severe morbidity present in both encephalocele cases. CONCLUSION: Our study raises awareness of atretic cephalocele and encephalocele among dermatopathologists and reveals a mutually exclusive immunophenotype that facilitates their distinction for prognostication and management.
Assuntos
Encefalocele , Meninges , Humanos , Encefalocele/patologia , Estudos Retrospectivos , Meninges/patologia , PrognósticoRESUMO
OBJECTIVE: Encephaloceles are considered to result from defects in the developing skull through which meninges, and potentially brain tissue, herniate. The pathological mechanism underlying this process is incompletely understood. We aimed to describe the location of encephaloceles through the generation of a group atlas to determine whether they occur at random sites or clusters within distinct anatomical regions. METHODS: Patients diagnosed with cranial encephaloceles or meningoceles were identified from a prospectively maintained database between 1984 and 2021. Images were transformed to atlas space using non-linear registration. The bone defect, encephalocele and herniated brain contents were manually segmented allowing for a 3-dimensional heat map of encephalocele locations to be generated. The centroids of the bone defects were clustered utilising a K-mean clustering machine learning algorithm in which the elbow method was used to identify the optimal number of clusters. RESULTS: Of the 124 patients identified, 55 had volumetric imaging in the form of MRI (48/55) or CT (7/55) that could be used for atlas generation. Median encephalocele volume was 14,704 (IQR 3655-86,746) mm3 and the median surface area of the skull defect was 679 (IQR 374-765) mm2. Brain herniation into the encephalocele was found in 45% (25/55) with a median volume of 7433 (IQR 3123-14,237) mm3. Application of the elbow method revealed 3 discrete clusters: (1) anterior skull base (22%; 12/55), (2) parieto-occipital junction (45%; 25/55) and (3) peri-torcular (33%; 18/55). Cluster analysis revealed no correlation between the location of the encephalocele with gender (χ2 (2, n = 91) = 3.86, p = 0.15). Compared to expected population frequencies, encephaloceles were relatively more common in Black, Asian and Other compared to White ethnicities. A falcine sinus was identified in 51% (28/55) of cases. Falcine sinuses were more common (χ2 (2, n = 55) = 6.09, p = 0.05) whilst brain herniation was less common (χ2 (2, n = 55) = .16.24, p < 0.0003) in the parieto-occipital location. CONCLUSION: This analysis revealed three predominant clusters for the location of encephaloceles, with the parieto-occipital junction being the most common. The stereotypic location of encephaloceles into anatomically distinct clusters and the coexistence of distinct venous malformations at certain sites suggests that their location is not random and raises the possibility of distinct pathogenic mechanisms unique to each of these regions.
Assuntos
Encefalocele , Meningocele , Humanos , Encefalocele/patologia , Crânio/patologia , Meningocele/cirurgia , Encéfalo/patologia , Análise por ConglomeradosRESUMO
A 5-year-old girl came to the Tianjin Medical University Eye Hospital in May 2021 because of her poor eyesight after birth. The physical examination showed that she had high myopia, esotropia, horizontal tremor, and high myopia retinopathy of both eyes. After inquiring about her medical history, we found that the baby's occipital cystic mass swelled after birth, and CT examination showed that the occipital skull plate defect with meningocele, but without treatment, at present, the occipital mass had subsided by itself. Considering the eye manifestations and skull changes of the child, it may be conformed to Knobloch syndrome, after the detection of V4 by full exon gene, it was found that the child had the compound heterozygous variation of pathogenic gene COL18A1, and Knobloch syndrome was definite, Knobloch syndrome is a rare autosomal recessive hereditary disease with typical features of high myopia, retinal detachment and occipital encephalocele. At present, there is no clear treatment plan, and gene therapy may be an effective treatment for Knobloch syndrome in the future.
Assuntos
Miopia , Degeneração Retiniana , Descolamento Retiniano , Criança , Pré-Escolar , Encefalocele/diagnóstico , Encefalocele/genética , Encefalocele/patologia , Feminino , Humanos , Miopia/genética , Descolamento Retiniano/congênito , Descolamento Retiniano/diagnósticoRESUMO
Meckel syndrome (MKS) is a pre- or perinatal multisystemic ciliopathic lethal disorder with an autosomal recessive mode of inheritance. Meckel syndrome is usually manifested with meningo-occipital encephalocele, polycystic kidney dysplasia, postaxial polydactyly and hepatobiliary ductal plate malformation. Germline variants in CEP290 cause MKS4. In this study, we investigated a 35-years-old Chinese female who was 17+1 weeks pregnant. She had a history of adverse pregnancy of having foetus with multiple malformations. We performed ultrasonography and identified the foetus with occipital meningoencephalocele and enlarged cystic dysplastic kidneys. So, she decided to terminate her pregnancy and further genetic molecular analysis was performed. We identified the aborted foetus without postaxial polydactyly. Histological examination of foetal kidney showed cysts in kidney and thinning of the renal cortex with glomerular atrophy. Whole exome sequencing identified a novel homozygous variant (c.2144T>G; p.L715* ) in exon 21 of the CEP290 in the foetus. Sanger sequencing confirmed that both the parents of the foetus were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters of the foetus as well as in the 100 healthy individuals. Western blot analysis showed that this variant leads to the formation of truncated CEP290 protein with the molecular weight of 84 KD compared with the wild-type CEP290 protein of 290 KD. Hence, it is a loss-of-function variant. We also found that the mutant cilium appears longer in length than the wild-type cilium. Our present study reported the first variant of CEP290 associated with MKS4 in Chinese population.
Assuntos
Antígenos de Neoplasias/genética , Proteínas de Ciclo Celular/genética , Transtornos da Motilidade Ciliar/genética , Proteínas do Citoesqueleto/genética , Encefalocele/genética , Sequenciamento do Exoma , Mutação/genética , Doenças Renais Policísticas/genética , Retinose Pigmentar/genética , Adulto , Povo Asiático/genética , Sequência de Bases , Encefalocele/patologia , Feminino , Feto/diagnóstico por imagem , Homozigoto , Humanos , Rim/patologia , Masculino , Linhagem , Ultrassonografia Pré-NatalRESUMO
Meckel-Gruber syndrome (MKS) is a clinically and genetically heterogeneous ciliopathy characterized by a triad of occipital encephalocele, polycystic kidneys, and postaxial polydactyly. Pathogenesis of MKS is related to dysfunction of primary cilia. However, reports on MKS caused by Tectonic2 (TCTN2) mutations are scanty whilst. There is no direct evidence of ciliogenesis in such MKS patients. Here, we identified two novel nonsense variants of TCTN2 (c.343G > T, p.E115*; c.1540C > T, p.Q514*) in a Chinese MKS fetus. Compared to reported TCTN2-causing MKS patients, our case represented an endocardial pad defect, which was not reported previously. We also found primary cilia protruded normally from the surface of epithelial cells in the affected fetal kidney tubules compared to controls, indicating TCTN2 is not necessary for ciliogenesis in the kidney. To our knowledge, this is the first case of MKS fetus caused by TCTN2 mutations from China.
Assuntos
Transtornos da Motilidade Ciliar/genética , Encefalocele/genética , Predisposição Genética para Doença , Rim/metabolismo , Proteínas de Membrana/genética , Doenças Renais Policísticas/genética , Retinose Pigmentar/genética , China , Transtornos da Motilidade Ciliar/patologia , Códon sem Sentido/genética , Encefalocele/patologia , Feminino , Feto/patologia , Dedos/anormalidades , Heterogeneidade Genética , Humanos , Rim/patologia , Masculino , Linhagem , Doenças Renais Policísticas/patologia , Polidactilia , Retinose Pigmentar/patologia , Dedos do Pé/anormalidadesRESUMO
Knobloch Syndrome (KS) is a rare autosomal recessive hereditary disease. Despite its clinical heterogeneity, it is characterized by vitreoretinal degeneration and high myopia, with or without occipital skull defects. It is caused by mutations in the COL18A1 gene, which codifies for collagen XVIII, present in retina and vascular endothelium. Since the first description of the disease by doctors Knobloch and Layer in 1972, over 100 cases and 20 pathogenic or likely pathogenic mutations have been reported. We present the case of a child born from a consanguineous couple in Chile with congenital high myopia and dysmorphisms without an occipital skull defect. Whole exome sequencing analysis revealed an inherited homozygous variant in COL18A1, c.4224_4225delinsC, p.Pro1411Leufs*35.
Assuntos
Colágeno Tipo XVIII/genética , Encefalocele/genética , Predisposição Genética para Doença , Degeneração Retiniana/genética , Descolamento Retiniano/congênito , Criança , Encefalocele/complicações , Encefalocele/patologia , Feminino , Humanos , Mutação , Degeneração Retiniana/complicações , Degeneração Retiniana/patologia , Descolamento Retiniano/complicações , Descolamento Retiniano/genética , Descolamento Retiniano/patologia , Sequenciamento do ExomaRESUMO
OBJECTIVE: To investigate the etiology and longitudinal clinical, neuropsychological, psychosocial, and surgical outcome profile of patients with medication refractory epilepsy and temporal encephaloceles with a view to highlight diagnostic clues and management strategies. METHODS: The comprehensive epilepsy program databases at two surgical epilepsy centers from January 2000 to October 2018 were reviewed for this observational study, to identify patients with encephaloceles causing temporal lobe epilepsy (TLE) and treated with surgical resection. Their clinical, radiological, neuropsychological, psychiatric, and surgical data were obtained. Body mass index (BMI) data were also reviewed due to possible correlation between idiopathic intracranial hypertension and encephaloceles. RESULTS: Thirteen patients (eight female) were identified; only three were recognized on initial magnetic resonance imaging (MRI) report. Temporal encephaloceles were identified on the left in eight patients, on the right in three patients, and bilaterally in two patients. One patient had a strong family history of encephaloceles. The median BMI for patients with seizure onset ≤20 years of age was 22.4, whereas for patients with onset >20 years median BMI was 32.6 (P = .06). Five patients underwent a focal lesionectomy, three patients had limited temporal lobectomy, and five patients had standard anterior temporal lobectomy. Median postoperative follow-up was 5.5 years. All but one patient were free of disabling seizures. Nine of ten neuropsychologically tested patients had no discernable cognitive decline postoperatively. Postoperative psychosocial adjustment features were present in four patients. SIGNIFICANCE: Genetic factors and a possible association with idiopathic intracranial hypertension (given female predominance and elevated BMI) may contribute to the causation of temporal lobe encephaloceles. It is notable that a targeted surgical approach in the management of patients with TLE associated with encephaloceles has an excellent long-term clinical and neuropsychological outcome. Subtle encephaloceles should be actively searched for in patients with drug-resistant TLE because they significantly change surgical strategy and prognostication.
Assuntos
Encefalocele/diagnóstico , Adolescente , Adulto , Índice de Massa Corporal , Criança , Imagem de Difusão por Ressonância Magnética , Encefalocele/diagnóstico por imagem , Encefalocele/patologia , Encefalocele/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Temporal lobe encephaloceles (TE) are increasingly recognized as a cause of drug-resistant temporal lobe epilepsy. Improved recognition of these lesions offers an opportunity to treat them with a limited resection sparing the hippocampus. However, as they can be difficult to identify on imaging, additional clues pointing to the diagnosis can be helpful. We sought to understand the baseline cognitive/neuropsychological profile in patients with left temporal lobe epilepsy caused by encephaloceles compared with that caused by mesial temporal sclerosis (MTS), a common entity in the differential diagnosis. METHODS: Neuropsychological testing, including language (semantic and phonemic fluency and naming), verbal memory, intelligence quotient (IQ), and executive function measures were compared across two groups (five patients with left TE and five age- and gender-matched patients with left MTS). Other clinical variables related to cognition, including patient age, electroencephalographic characteristics, epilepsy duration, and factors related to antiseizure medication dosing, were also compared between groups. RESULTS: More patients with left MTS had atypical language lateralization (3/5 with right-sided language in the group with MTS compared with 0/5 in the group with TE). Patients with MTS had significantly worse scores on the Verbal Comprehension Index (VCI) subscore of the Wechsler Adult Intelligence Scale (WAIS; pâ¯=â¯0.026). General IQ was also worse in patients with MTS (pâ¯=â¯0.028). There was a trend towards worse executive function in patients with MTS as measured on Trails B (pâ¯=â¯0.096). Other measures related to language and verbal memory did not differ significantly between the groups nor did other relevant clinical variables, except epilepsy duration, which was significantly longer in patients with MTS (pâ¯=â¯0.0001). CONCLUSIONS: This pilot study demonstrates few significant differences between the groups with left MTS and TE surveyed. A higher rate of atypical language lateralization was noted in patients with left MTS. The higher baseline global IQ and VCI scores in patients with left TE compared with patients with MTS may be attributable to longer duration of epilepsy in patients with left MTS. Future work with a larger sample size will focus on establishing a unique neuropsychological profile related to epilepsy due to TE.
Assuntos
Epilepsia do Lobo Temporal , Adulto , Encefalocele/patologia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Projetos Piloto , Esclerose/patologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologiaRESUMO
OBJECTIVE: Nasal meningoencephalocele (encephalocele or cephalocele) is a rare condition with congenital, traumatic, or spontaneous origins. We investigated the clinicopathological characteristics of nasal encephaloceles to improve pathologists' and clinicians' understanding of this disease. METHODS: Sixteen patients with nasal encephaloceles were enrolled in this retrospective study investigating the condition's clinical and morphological features. RESULTS: Patients' average age was 37.8 (±20.8) years. The ratio of men to women was 2.2:1, patients' mean age was 47.4 (±11.8) years, and 10/16 patients had spontaneous encephaloceles. All patients with traumatic and spontaneous encephaloceles presented with cerebrospinal fluid leak. In 9/16 patients, the skull defect site occurred on the lateral wall of the sphenoid sinus. Both congenital patients experienced nasal obstruction. Histopathology, herniated tissues were brain and/or meningeal tissue, and the brain tissue was almost mature glial tissue. CONCLUSION: Nasal meningoencephalocele is a rare condition that can be challenging to diagnose. In patients with recurrent clear nasal discharge or in children with a unilateral nasal mass, a high index of suspicion for encephalocele is essential. In this study, spontaneous cases were most common in adults, and the lateral wall of the sphenoid sinus was the most common location.
Assuntos
Encefalocele/patologia , Meningocele/patologia , Nariz/patologia , Adulto , Rinorreia de Líquido Cefalorraquidiano/etiologia , Pré-Escolar , Encefalocele/diagnóstico , Feminino , Humanos , Lactente , Masculino , Meningocele/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Seio Esfenoidal/patologiaRESUMO
Chiari-like malformation (CM) and syringomyelia (SM) are common illnesses that can cause debilitating neuropathic pain in Cavalier King Charles spaniels (CKCS). The current imaging modality to screen CKCS for CM/SM is MRI of the brain and cervical spine. Magnetic resonance imaging provides good soft tissue detail and contrast of the cerebellum and cervical spinal cord. Computed tomography (CT) is another cross-sectional imaging technique that facilitates brain and neck evaluation; however, soft tissue resolution does not match that of MRI. Computed tomography benefits include identification of concurrent craniocervical junction anomalies (atlantooccipital overlap) and shorter imaging/anesthesia times with the ability to use only sedation. The aim of this retrospective, method comparison study is to assess the utility of multidetector CT for screening CM and SM in CKCS as compared to high-field MRI. Three groups of observers with different levels of experience graded CM and SM based on the British Veterinary Association/Kennel Club CM/SM classification criteria. Thirty CKCS underwent multidetector CT and 3 Tesla MRI studies. Computed tomography and MRI studies were reviewed at different timepoints to minimize bias. Computed tomography has lower Cohen's Kappa agreement for each observer group compared to MRI. The intraclass correlation coefficient averaging CM and SM for all groups was excellent using MRI, while CT was poor for SM and moderate for cerebellar herniation. Greater observer experience resulted in a higher agreement for CT and MRI. Magnetic resonance imaging should remain the standard for screening of CM and SM as CT can result in misclassification and greater disagreement.
Assuntos
Malformação de Arnold-Chiari/veterinária , Doenças do Cão/diagnóstico por imagem , Imageamento por Ressonância Magnética/veterinária , Tomografia Computadorizada Multidetectores/veterinária , Siringomielia/veterinária , Animais , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/patologia , Cerebelo/patologia , Cães , Encefalocele/patologia , Encefalocele/veterinária , Feminino , Imageamento por Ressonância Magnética/métodos , Masculino , Tomografia Computadorizada Multidetectores/métodos , Estudos Retrospectivos , Siringomielia/diagnóstico por imagem , Siringomielia/patologiaRESUMO
The placement of a ventriculoperitoneal (VP) shunt is frequently used in the management of chronic hydrocephalus. Failure of the shunt may occur due to physical obstruction, which is a recognized complication. Autopsy examination of deceased individuals with chronic disability is often not performed, which contributes to the difficulty in determining the frequency of mortality from VP shunts. Examination, when it does occur, should focus on the patency and positioning of the shunt, and this evaluation is especially important when the cause of death is poorly defined. In this report, we describe two cases of death caused by obstruction of VP shunts documented at autopsy. The first death was determined to be secondary to cerebellar edema with uncal and tonsillar herniation after posterior left VP shunt occlusion. The second was due to VP shunt occlusion resulting in diffuse cerebral edema and ventricular enlargement with compression and hemorrhage of the cerebellar tonsils and medulla.
Assuntos
Derivação Ventriculoperitoneal/efeitos adversos , Adolescente , Edema Encefálico/etiologia , Edema Encefálico/patologia , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/patologia , Encefalocele/etiologia , Encefalocele/patologia , Evolução Fatal , Feminino , Humanos , Hidrocefalia/terapia , Masculino , Adulto JovemRESUMO
Meckel syndrome (MKS) is a perinatally lethal, genetically heterogeneous, autosomal recessive condition caused by defective primary cilium formation leading to polydactyly, multiple cysts in kidneys and malformations of nervous system. We performed exome sequencing in six fetuses from six unrelated families with MKS. We identified seven novel variants in B9D2, TNXDC15, CC2D2A, CEP290 and TMEM67. We describe the second family with MKS due to a homozygous variant in B9D2 and fifth family with bi-allelic variant in TXNDC15. Our data validates the causation of MKS by pathogenic variation in B9D2 and TXNDC15 and also adds novel variants in CC2D2A, CEP290 and TMEM67 to the literature.
Assuntos
Transtornos da Motilidade Ciliar/genética , Transtornos da Motilidade Ciliar/patologia , Encefalocele/genética , Encefalocele/patologia , Feto/anormalidades , Mutação/genética , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/patologia , Retinose Pigmentar/genética , Retinose Pigmentar/patologia , Sequência de Aminoácidos , Sequência de Bases , Segregação de Cromossomos/genética , Transtornos da Motilidade Ciliar/diagnóstico por imagem , Estudos de Coortes , Encefalocele/diagnóstico por imagem , Feminino , Humanos , Masculino , Linhagem , Fenótipo , Doenças Renais Policísticas/diagnóstico por imagem , Retinose Pigmentar/diagnóstico por imagemRESUMO
BACKGROUND AND PURPOSE: Although advances in imaging have allowed earlier and more accurate diagnosis of various fetal anomalies, Dandy-Walker malformation (DWM) remains one of the more challenging central nervous system anomalies to diagnose accurately before birth. Basilar invagination (BI), which is a dislocation of the dens in an upward direction, is occasionally accompanied by Klippel-Feil syndrome (KFS). We report a pediatric case of BI caused by atlanto-occipital subluxation (AOS) in KFS, suspected of having DWM prenatally but head magnetic resonance images (MRI) showed no evidence of that at 7 months of age. CASE: At 28 weeks of gestation, fetal MRI study revealed a small cerebellar vermis, leading us to suspect a DWM. The patient was born at 40 weeks of gestation. Head CT showed inferior vermian hypoplasia without findings of hydrocephalus. Cervicothoracic CT showed cervical lamina assimilations, thoracic hemivertebrae, and cervicothoracic scoliosis. He was diagnosed with Dandy-Walker variant and KFS. At 7 months of age, head MRI showed near normal cerebellum and vermis and there was no evidence of the DWM. He did not have intellectual or developmental delay and imaging studies were performed periodically. At 9 years of age, an already existing cough headache deteriorated. Three-dimensional reconstructed images from CT scan showed C1 hypoplasia, fusion of C1 and C2, BI, and AOS. Sagittal T2-weighted MRI showed protrusion of cerebellar tonsils inferiorly to the level of the posterior arch of C2. Serum calcium, phosphate, and parathyroid hormone levels were normal. The diagnosis was tonsillar herniation related to BI following AOS in KFS. Posterior occipitocervical fixation was performed under traction. CONCLUSIONS: We found out two important clinical issues: DWM findings after birth can be disappearing and BI can present sequential deterioration because of AOS in KFS. Our observation indicated the possible prognosis of pediatric BI with long follow-up and can help us decide on its surgical treatment timing when associated with AOS.
Assuntos
Articulação Atlantoccipital/patologia , Síndrome de Dandy-Walker , Encefalocele/patologia , Luxações Articulares/patologia , Síndrome de Klippel-Feil , Humanos , Lactente , Recém-NascidoRESUMO
A 13-year-old male child was evaluated for headache and visual deterioration; he underwent routine MRI imaging which revealed a large craniopharyngeal canal, divided by an abnormal bony septum giving a bipartite appearance of the canal, with a lipoma and cephalocele on either side of the septum. The child had undergone a previous surgery for cleft palate repair at the age of 7. The child had normal pituitary function inspite of nonvisualization of pituitary gland in MRI. To best our knowledge, this is the first case with such a variation. We have also discussed the possible embryological hypothesis for this previously unreported entity. Knowledge about this rare variant might have surgical relevance in selected cases.
Assuntos
Encefalocele/patologia , Lipoma/patologia , Hipófise/patologia , Adolescente , Encefalocele/diagnóstico por imagem , Encefalocele/cirurgia , Humanos , Lipoma/diagnóstico por imagem , Lipoma/cirurgia , Imageamento por Ressonância Magnética , Masculino , Hipófise/diagnóstico por imagemRESUMO
Spontaneous cerebrospinal fluid (CSF) fistula is a rare entity, most commonly occurs at the ethmoid roof, cribriform plate, or the sphenoid sinus; at the perisella, inferolateral or pterygoid recesses. Imaging plays a major role in diagnosis, thereby guiding the treatment of a spontaneous CSF fistula, evolving multiple modalities. We report a case of a patient with spontaneous Meningio-encephalocele presented as an expansile lytic lesion in the left pterygoid body, this patient was successfully treated surgically.
Assuntos
Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem , Encefalocele/diagnóstico por imagem , Fístula/diagnóstico por imagem , Adulto , Vazamento de Líquido Cefalorraquidiano/patologia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Encefalocele/patologia , Encefalocele/cirurgia , Feminino , Fístula/patologia , Fístula/cirurgia , Humanos , Base do Crânio/diagnóstico por imagem , Osso Esfenoide/diagnóstico por imagemRESUMO
PURPOSE: The purpose of this study is to review a large series of frontoethmoidal encephalocele (FEE) regarding their clinical presentation, the progressiveness of the mass volume, the skin stigmata as well as its surgical approach and post-surgical complications. METHOD: Records of all FEE patients treated in Soetomo General Hospital, Surabaya, and Charity Foundation Program from 2008 to 2015 were reviewed. Detailed patient's demography, clinical findings, radiology results, operative procedures, and complications were documented. Follow-up was organized in weekly basis for the first 1 month after surgery or more often when situation or complication occurred. Wound healing, neurological assessment for new or progressive deficit, pseudomeningocele, skin breakdown, cerebrospinal fluid (CSF) leakage, exposed implant, recurrent mass, and cosmetic results were documented. Since most of the patients had no direct phone line at their hometown, we relied on social worker to contact them. RESULTS: One-stage surgery was performed for 400 patients with FEE (212 were male and 188 were female). Of 400 patients, 388 (97%) were younger than 18 years old. Most FEEs were nasoethmoidal, either isolated or combined with nasoorbital type (347 cases [86.75%]); nasofrontal subtypes were seen in 34 cases (8.5%) and nasoorbital in 14 cases (1.5%). The mean operative time was 2 h (range 30 min-3 h). There were only two patients (0.5%) needed postoperative blood transfusions. Mean hospitalization time was 5 days (range 4-7 days). Overall, complication rate in our series was 12.5%, mostly was CSF leakage and wound dehiscence. CONCLUSION: The current socioeconomic conditions and local facility should be considered to treat these specific disease processes. The refined and meticulous technique, especially in choosing the approach and handling the dural closure, is essential in lowering the complication rate.
Assuntos
Encefalocele/diagnóstico , Encefalocele/patologia , Encefalocele/cirurgia , Procedimentos Neurocirúrgicos/métodos , Osteotomia/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Procedimentos de Cirurgia Plástica/métodos , Adulto JovemRESUMO
Ciliopathies are a group of human disorders caused by dysfunction of primary cilia, ubiquitous microtubule-based organelles involved in transduction of extra-cellular signals to the cell. This function requires the concentration of receptors and channels in the ciliary membrane, which is achieved by complex trafficking mechanisms, in part controlled by the small GTPase RAB8, and by sorting at the transition zone located at the entrance of the ciliary compartment. Mutations in the transition zone gene CC2D2A cause the related Joubert and Meckel syndromes, two typical ciliopathies characterized by central nervous system malformations, and result in loss of ciliary localization of multiple proteins in various models. The precise mechanisms by which CC2D2A and other transition zone proteins control protein entrance into the cilium and how they are linked to vesicular trafficking of incoming cargo remain largely unknown. In this work, we identify the centrosomal protein NINL as a physical interaction partner of CC2D2A. NINL partially co-localizes with CC2D2A at the base of cilia and ninl knockdown in zebrafish leads to photoreceptor outer segment loss, mislocalization of opsins and vesicle accumulation, similar to cc2d2a-/- phenotypes. Moreover, partial ninl knockdown in cc2d2a-/- embryos enhances the retinal phenotype of the mutants, indicating a genetic interaction in vivo, for which an illustration is found in patients from a Joubert Syndrome cohort. Similar to zebrafish cc2d2a mutants, ninl morphants display altered Rab8a localization. Further exploration of the NINL-associated interactome identifies MICAL3, a protein known to interact with Rab8 and to play an important role in vesicle docking and fusion. Together, these data support a model where CC2D2A associates with NINL to provide a docking point for cilia-directed cargo vesicles, suggesting a mechanism by which transition zone proteins can control the protein content of the ciliary compartment.