RESUMO
BACKGROUND: Stereotactic approaches to diffuse intrinsic pontine gliomas (DIPGs) remain essential due to advances in molecular biology and management, necessitating tissue sampling. Here we present an effective technique with a biopsy by robot-assisted transcerebellar approach. METHOD: Our procedure was performed using the ROSA robotic system and the OARM CT scan, which provided stereotactic conditions for this transcerebellar approach to brainstem lesions. CONCLUSION: The robot-assisted transcerebellar stereotactic approach remains essential to provide complications for biopsy of brainstem lesions.
Assuntos
Neoplasias do Tronco Encefálico , Procedimentos Cirúrgicos Robóticos , Técnicas Estereotáxicas , Humanos , Neoplasias do Tronco Encefálico/cirurgia , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/patologia , Procedimentos Cirúrgicos Robóticos/métodos , Tronco Encefálico/cirurgia , Tronco Encefálico/patologia , Tronco Encefálico/diagnóstico por imagem , Glioma Pontino Intrínseco Difuso/cirurgia , Glioma Pontino Intrínseco Difuso/diagnóstico por imagem , Glioma Pontino Intrínseco Difuso/patologia , Masculino , Cerebelo/cirurgia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , FemininoRESUMO
OBJECTIVE: To present the ultrasound imaging and genetic diagnosis of a fetus with prenatal lethal form of Gaucher disease. CASE REPORT: A 37-year-old primiparous woman was pregnant at her 23 weeks of gestation and the prenatal fetal ultrasound revealed hydrops fetalis, cerebellum hypoplasia, and fetal immobility. The pregnancy was terminated due to major fetal anomaly, and whole exome sequencing (WES) analysis of fetal tissue and parental blood unveiled a pathogenic variant in exon 10 of the GBA gene (NM_001005741.3: c.1265T > G: p.L422R) originating from the mother. Additionally, a novel CNV (chr1: 155204785-155205635 deletion, 0.85 kb) spanning exon 10-12 in the GBA gene was identified from the father. This compound heterozygosity confirmed the diagnosis of prenatal lethal form of Gaucher disease and was informative for genetic counseling. CONCLUSION: WES is a powerful tool to detect pathogenic variants among fetuses with nonimmune hydrops fetalis and complex abnormality from prenatal ultrasound. Compound heterozygosity consisted of single nucleotide variants (SNV) and copy number variations (CNVs) may lead rare inherited metabolic disorders including prenatal lethal form of Gaucher disease.
Assuntos
Cerebelo , Variações do Número de Cópias de DNA , Sequenciamento do Exoma , Doença de Gaucher , Hidropisia Fetal , Ultrassonografia Pré-Natal , Humanos , Feminino , Doença de Gaucher/genética , Doença de Gaucher/diagnóstico , Doença de Gaucher/complicações , Gravidez , Adulto , Hidropisia Fetal/genética , Hidropisia Fetal/diagnóstico , Cerebelo/anormalidades , Cerebelo/diagnóstico por imagem , Heterozigoto , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/diagnóstico , Polimorfismo de Nucleotídeo Único , Glucosilceramidase/genética , Deficiências do DesenvolvimentoRESUMO
Methylmercury (MeHg) is a well-known neurotoxicant that induces various cellular functions depending on cellular- and developmental-specific vulnerabilities. MeHg has a high affinity for selenol and thiol groups, thus impairing the antioxidant system. Such affinity characteristics of MeHg led us to develop sensor vectors to assess MeHg toxicity. In this study, MeHg-mediated defects in selenocysteine (Sec) incorporation were demonstrated using thioredoxin reductase 1 cDNA fused with the hemagglutinin tag sequence at the C-terminus. Taking advantage of such MeHg-mediated defects in Sec incorporation, a cDNA encoding luciferase with a Sec substituted for cysteine-491 was constructed. This construct showed MeHg-induced decreases in signaling in a dose-dependent manner. To directly detect truncated luciferase under MeHg exposure, we further constructed a new sensor vector fused with a target for proteasomal degradation. However, this construct was inadequate because of the low rate of Sec insertion, even in the absence of MeHg. Finally, a Krab transcriptional suppressor fused with Sec was constructed and assessed to demonstrate MeHg-dependent increases in signal intensity. We confirmed that the vector responded specifically and in a dose-dependent manner to MeHg in cultured cerebellar granule cells. This vector is expected to allow monitoring of MeHg-specific toxicity via spatial and temporal imaging.
Assuntos
Compostos de Metilmercúrio , Compostos de Metilmercúrio/toxicidade , Animais , Humanos , Camundongos , Técnicas Biossensoriais/métodos , Luciferases/metabolismo , Luciferases/genética , Cerebelo/metabolismo , Cerebelo/efeitos dos fármacosRESUMO
LINE-1 and Alu retrotransposons are components of the human genome and have been implicated in many human diseases. These elements can influence human transcriptome plasticity in various mechanisms. Chimeric transcripts derived from LINE-1 and Alu can also impact the human transcriptome, such as exonization and post-transcriptional modification. However, its specific role in ASD neuropathology remains unclear, particularly in the cerebellum tissues. We performed RNA-sequencing of post-mortem cerebellum tissues from ASD and unaffected individuals for transposable elements profiling and chimeric transcript identification. The majority of free transcripts of transposable elements were not changed in the cerebellum tissues of ASD compared with unaffected individuals. Nevertheless, we observed that chimeric transcripts derived from LINE-1 and Alu were embedded in the transcripts of differentially expressed genes in the cerebellum of ASD, and these genes were related to developments and abnormalities of the cerebellum. In addition, the expression levels of these genes were correlated with the significantly decreased thickness of the molecular layer in the cerebellum of ASD. We also found that global methylation and expression of LINE-1 and Alu elements were not changed in ASD, but observed in the ASD sub-phenotypes. Our findings showed associations between transposable elements and cerebellar abnormalities in ASD, particularly in distinct phenotypic subgroups. Further investigations using appropriate models are warranted to elucidate the structural and functional implications of LINE-1 and Alu elements in ASD neuropathology.
Assuntos
Elementos Alu , Transtorno do Espectro Autista , Cerebelo , Elementos Nucleotídeos Longos e Dispersos , Humanos , Cerebelo/metabolismo , Cerebelo/patologia , Elementos Nucleotídeos Longos e Dispersos/genética , Elementos Alu/genética , Transtorno do Espectro Autista/genética , Masculino , Feminino , Retroelementos/genética , Metilação de DNA , Transcriptoma , AdultoRESUMO
Packet information encoding of neural signals was proposed for vision about 50 years ago and has recently been revived as a plausible strategy generalizable to natural and artificial sensory systems. It involves discrete image segmentation controlled by feedback and the ability to store and compare packets of information. This article shows that neurons of the cerebellum-like electrosensory lobe (EL) of the electric fish Gymnotus omarorum use spike-count and spike-timing distribution as constitutive variables of packets of information that encode one-by-one the electrosensory images generated by a self-timed series of electric organ discharges (EODs). To evaluate this hypothesis, extracellular unitary activity was recorded from the centro-medial map of the EL. Units recorded in high-decerebrate preparations were classified into six types using hierarchical cluster analysis of post-EOD spiking histograms. Cross-correlation analysis indicated that each EOD strongly influences the unit firing probability within the next inter-EOD interval. Units of the same type were similarly located in the laminar organization of the EL and showed similar stimulus-specific changes in spike count and spike timing after the EOD when a metal object was moved close by, along the fish's body parallel to the skin, or when the longitudinal impedance of a static cylindrical probe placed at the center of the receptive field was incremented in a stepwise manner in repetitive trials. These last experiments showed that spike-counts and the relative entropy, expressing a comparative measure of information before and after the step, were systematically increased with respect to a control in all unit types. The post-EOD spike-timing probability distribution and the relatively independent contribution of spike-timing and number to the content of information in the transmitted packet suggest that these are the constitutive image-encoding variables of the packets. Comparative analysis suggests that packet information transmission is a general principle for processing superposition images in cerebellum-like networks.
Assuntos
Cerebelo , Animais , Cerebelo/fisiologia , Potenciais de Ação/fisiologia , Órgão Elétrico/fisiologia , Neurônios/fisiologia , Peixe Elétrico/fisiologia , Gimnotiformes/fisiologia , Rede Nervosa/fisiologiaRESUMO
Both cortical and cerebellar developmental differences have been implicated in attention-deficit/hyperactivity disorder (ADHD). Recently accumulating neuroimaging studies have highlighted hierarchies as a fundamental principle of brain organization, suggesting the importance of assessing hierarchy abnormalities in ADHD. A novel gradient-based resting-state functional connectivity analysis was applied to investigate the cerebro-cerebellar disturbed hierarchy in children and adolescents with ADHD. We found that the interaction of functional gradient between diagnosis and age was concentrated in default mode network (DMN) and visual network (VN). At the same time, we also found that the opposite gradient changes of DMN and VN caused the compression of the cortical main gradient in ADHD patients, implicating the co-occurrence of both low- (visual processing) and high-order (self-related thought) cognitive dysfunction manifesting in abnormal cerebro-cerebellar organizational hierarchy in ADHD. Our study provides a neurobiological framework to better understand the co-occurrence and interaction of both low-level and high-level functional abnormalities in the cortex and cerebellum in ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Cerebelo , Córtex Cerebral , Conectoma , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Adolescente , Criança , Masculino , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Feminino , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologiaRESUMO
The behavioral effects of α-synuclein oligomers were studied at various times after its chronic intranasal administration to 75-day-old C57BL/6J mice in comparison with the dynamics of changes in the transcriptional activity of caspases genes (Casp9, Casp8, and Casp3) in the hippocampus, frontal cortex, and cerebellum. The negative effects of α-synuclein oligomers on exploratory activity and short-term memory in the novel object recognition test were most pronounced after 90 days from the end of administration, while after 1 and 270 days, partial compensation of the studied cognitive functions was observed. Analysis of the expression of caspase genes suggests that early compensatory mechanisms are associated with suppression of the effector caspase-3 gene expression along with increased activity of the genes encoding initiator caspases-9 and -8. Late compensation processes are associated with a decrease in the activity of initiator caspases in the frontal cortex and cerebellum.
Assuntos
Caspase 3 , Caspase 8 , Caspase 9 , Cerebelo , Disfunção Cognitiva , Hipocampo , Camundongos Endogâmicos C57BL , alfa-Sinucleína , Animais , Camundongos , Caspase 3/genética , Caspase 3/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Hipocampo/metabolismo , Cerebelo/metabolismo , Lobo Frontal/metabolismo , Masculino , Modelos Animais de Doenças , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/metabolismo , Memória de Curto Prazo/efeitos dos fármacosRESUMO
BACKGROUND: Parkinson's disease (PD) is often accompanied by gait disorders and freezing of gait (FoG), disabling symptoms that are resistant to conventional dopamine treatments. Given the cerebellum's connectivity with the motor cortex and basal ganglia, and its implication in PD, combining transcranial direct current stimulation targeting the cerebellum (ctDCS) with physical exercise might improve gait and balance. OBJECTIVE: This study aimed to evaluate the effectiveness of a novel rehabilitation approach that combines noninvasive cerebellar stimulation with motor-cognitive training via an augmented reality treadmill (C-Mill VR+) in individuals with PD and FoG. METHODS: Seventeen individuals with PD exhibiting FoG were enrolled in a randomized controlled trial. The participants were randomly assigned to a group receiving motor-cognitive training on the C-Mill VR+ with either ctDCS or sham ctDCS. Assessments were conducted pre-intervention (T0), post-intervention (T1) after 10 sessions, and at 4-week follow-up (T2), using various clinical scales. Additionally, C-Mill assessments of postural stability and gait were conducted at T0 and T1. RESULTS: Although no significant time*group interactions were observed for any of the clinical variables measured, some were found in the C-Mill measures. Specifically, right lower limb sway in static conditions, both with eyes open (OAD) and eyes closed (OCD), significantly improved at T1 in the ctDCS group compared with the sham group. CONCLUSIONS: C-Mill outcomes indicate that the combined treatment may enhance motor control. Participants who received ctDCS along with augmented reality motor-cognitive training showed better postural stability.
Assuntos
Cerebelo , Transtornos Neurológicos da Marcha , Doença de Parkinson , Estimulação Transcraniana por Corrente Contínua , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/reabilitação , Masculino , Feminino , Transtornos Neurológicos da Marcha/reabilitação , Transtornos Neurológicos da Marcha/etiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Estimulação Transcraniana por Corrente Contínua/instrumentação , Idoso , Pessoa de Meia-Idade , Realidade Aumentada , Terapia por Exercício/métodos , Terapia por Exercício/instrumentação , Equilíbrio Postural/fisiologia , Resultado do TratamentoRESUMO
Neuronal development is a highly regulated process that is dependent on the correct coordination of cellular responses to extracellular cues. In response to semaphorin axon guidance proteins, the MICAL1 protein is stimulated to produce reactive oxygen species that oxidize actin on specific methionine residues, leading to filamentous actin depolymerization and consequent changes in neuronal growth cone dynamics. Crossing genetically modified mice homozygous for floxed Mical1 (Mical1fl/fl) alleles with transgenic mice expressing Cre recombinase under the control of a tyrosinase gene enhancer/promoter (Tyr::Cre) enabled conditional Mical1 deletion. Immunohistochemical analysis showed Mical1 expression in the cerebellum, which plays a prominent role in the coordination of motor movements, with reduced Mical1 expression in Mical1fl/fl mice co-expressing Tyr::Cre. Analysis of the gaits of mice running on a treadmill showed that both male and female Mical1fl/fl, Tyr::Cre mutant mice had significant alterations to their striding patterns relative to wild-type mice, although the specific aspects of their altered gaits differed between the sexes. Additional motor tests that involved movement on a rotating rod, descending a vertical pole, or crossing a balance beam did not show significant differences between the genotypes, suggesting that the effect of the Mical1fl/fl, Tyr::Cre genetic modifications was only manifested during specific highly coordinated movements that contribute to running. These findings indicate that there is a behavioral consequence in Mical1fl/fl, Tyr::Cre mutant mice that affects motor control as manifested by alterations in their gait.
Assuntos
Monofenol Mono-Oxigenase , Animais , Camundongos , Feminino , Masculino , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , Marcha/genética , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Camundongos Transgênicos , Cerebelo/metabolismo , Corrida/fisiologia , Camundongos Endogâmicos C57BLAssuntos
Revascularização Cerebral , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/diagnóstico por imagem , Revascularização Cerebral/métodos , Cerebelo/irrigação sanguínea , Cerebelo/cirurgia , Cerebelo/diagnóstico por imagem , Procedimentos Neurocirúrgicos/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Artéria Vertebral/cirurgia , Artéria Vertebral/diagnóstico por imagem , Resultado do TratamentoRESUMO
Among ruptured intracranial aneurysms, aneurysms of the vertebral artery(VA) and posterior inferior cerebellar artery(PICA) are relatively rare, and they exhibit distinct characteristics. These include: 1) a high frequency of diverse aneurysmal morphologies, such as fusiform or dissecting aneurysms; 2) proximity to the lower cranial nerves; 3) the presence of perforators to the medulla oblongata; and, 4) obstruction to the surgical approach by specific bony structures, such as the occipital condyle and jugular tubercle. Consequently, these aneurysms often require interventions that are more complex than simple clipping or coiling, which is typical for anterior circulation aneurysms. Interventions include skull base techniques such as the far-lateral approach and revascularization procedures such as occipital artery(OA)-PICA bypass. Despite these complexities, the rarity of these aneurysms and the recent advancements in endovascular procedures pose challenges for young neurosurgeons in acquiring adequate microsurgical experience. This narrative review addresses the clinical features of VA and PICA aneurysms, the history and variations in the lateral suboccipital approach for these aneurysms, and several bypass techniques for reconstructing the PICA. Lastly, we illustrate our current microsurgical practices through a case presentation accompanied by a surgical video showcasing both the far-lateral approach and the OA-PICA bypass.
Assuntos
Craniotomia , Aneurisma Intracraniano , Microcirurgia , Artéria Vertebral , Humanos , Aneurisma Intracraniano/cirurgia , Craniotomia/métodos , Microcirurgia/métodos , Artéria Vertebral/cirurgia , Cerebelo/irrigação sanguínea , Cerebelo/cirurgiaRESUMO
Background and Objectives: Typically, the vertebral arteries (VAs) enter the posterior fossa through dural rings and further unite, forming the basilar artery. The posterior inferior cerebellar artery (PICA) is usually a branch of the V4 segment of the VA (intradural origin). It may also leave the V3 suboccipital segment of the VA (extradural origin). The transdural origin of the PICA within the VA's dural ring has been consistently overlooked. A study was designed to determine the topographical patterns of the PICA's origin. Materials and Methods: Determinations were performed in a retrospective sample of 225 computed tomography angiograms. Four types of PICA origin were documented: type 0, absent PICA; type 1, the extradural origin of the PICA from the V3 segment of the VA; type 2, the transdural origin of the PICA within the dural ring; and type 3, the intradural origin of the PICA from the V4 segment of the VA. The bilateral symmetry of types was also investigated. Results: Out of 450 VAs, type 0 (absent PICA) was found in 36%, type 1 (extradural) in 0.44%, type 2 (transdural) in 5.56%, and typical type 3 in just 58%. In types 1 and 2, the PICA entered the posterior fossa through the dural ring and the marginal sinus. In the overall group (N = 225), the type combinations 1_1, 1_2 and 1_3 were not found. Bilaterally absent PICAs occurred in 18.67%. The bilateral combinations 0_1/0_2/0_3/2_2/2_3/3_3 were found, respectively, in 0.89%/3.11%/30.67%/1.78%/4.44%/40.44%. Four of the seventy-eight PICAs opposite to an absent one, three intradural and one transdural, were true bihemispheric PICAs. Conclusions: The PICAs with extradural or transdural origins are facultative contents of the dural ring and are at risk during neurosurgical approaches in the foramen magnum. Rare bihemispheric PICAs could originate either intradurally or within the dural ring.
Assuntos
Artéria Vertebral , Humanos , Estudos Retrospectivos , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/anormalidades , Artéria Vertebral/anatomia & histologia , Masculino , Feminino , Pessoa de Meia-Idade , Cerebelo/irrigação sanguínea , Cerebelo/diagnóstico por imagem , Idoso , Prevalência , Adulto , Angiografia por Tomografia Computadorizada/métodosRESUMO
Psychiatric symptoms are common in neurodevelopmental movement disorders, including some types of dystonia. However, research has mainly focused on motor manifestations and underlying circuits. Myoclonus-dystonia is a rare and homogeneous neurodevelopmental condition serving as an illustrative paradigm of childhood-onset dystonias, associated with psychiatric symptoms. Here, we assessed the prevalence of psychiatric disorders and the severity of depressive symptoms in patients with myoclonus-dystonia and healthy volunteers (HV). Using resting-state functional neuroimaging, we compared the effective connectivity within and among non-motor and motor brain networks between patients and HV. We further explored the hierarchical organization of these networks and examined the relationship between their connectivity and the depressive symptoms. Comparing 19 patients to 25 HV, we found a higher prevalence of anxiety disorders and more depressive symptoms in the patient group. Patients exhibited abnormal modulation of the cerebellum on the cerebral cortex in the sensorimotor, dorsal attention, salience, and default mode networks. Moreover, the salience network activity was directed by the cerebellum in patients and was related to depressive symptoms. Altogether, our findings highlight the role of the cerebellar drive on both motor and non-motor cortical areas in this disorder, suggesting cerebellar involvement in the complex phenotype of such neurodevelopmental movement disorders.
Assuntos
Cerebelo , Córtex Cerebral , Distúrbios Distônicos , Humanos , Masculino , Feminino , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Distúrbios Distônicos/fisiopatologia , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Adulto , Fenótipo , Depressão/fisiopatologia , Adulto Jovem , Imageamento por Ressonância Magnética , Adolescente , Transtornos do Neurodesenvolvimento/fisiopatologiaRESUMO
The human cerebellum is activated by a wide variety of cognitive and motor tasks. Previous functional atlases have relied on single task-based or resting-state fMRI datasets. Here, we present a functional atlas that integrates information from seven large-scale datasets, outperforming existing group atlases. The atlas has three further advantages. First, the atlas allows for precision mapping in individuals: the integration of the probabilistic group atlas with an individual localizer scan results in a marked improvement in prediction of individual boundaries. Second, we provide both asymmetric and symmetric versions of the atlas. The symmetric version, which is obtained by constraining the boundaries to be the same across hemispheres, is especially useful in studying functional lateralization. Finally, the regions are hierarchically organized across three levels, allowing analyses at the appropriate level of granularity. Overall, the present atlas is an important resource for the study of the interdigitated functional organization of the human cerebellum in health and disease.
Assuntos
Mapeamento Encefálico , Cerebelo , Imageamento por Ressonância Magnética , Humanos , Cerebelo/fisiologia , Cerebelo/diagnóstico por imagem , Cerebelo/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodos , Masculino , Feminino , Adulto , Atlas como Assunto , Adulto Jovem , Processamento de Imagem Assistida por Computador/métodos , Lateralidade Funcional/fisiologiaRESUMO
The concept of forward models in the brain, classically applied to describing on-line motor control, can in principle be extended to action planning, i.e. assuming forward sensory predictions are issued during the mere preparation of movements. To test this idea, we combined a delayed movement task with a virtual reality based manipulation of visuomotor congruence during functional magnetic resonance imaging. Participants executed simple hand movements after a delay. During the delay, two aspects of the upcoming movement could be cued: the movement type and the visuomotor mapping (i.e. congruence of executed hand movements and visual movement feedback by a glove-controlled virtual hand). Frontoparietal areas showed increased delay period activity when preparing pre-specified movements (cued > uncued). The cerebellum showed increased activity during the preparation for incongruent > congruent visuomotor mappings. The left anterior intraparietal sulcus showed an interaction effect, responding most strongly when a pre-specified (cued) movement was prepared under expected visuomotor incongruence. These results suggest that motor planning entails a forward prediction of visual body movement feedback, which can be adjusted in anticipation of nonstandard visuomotor mappings, and which is likely computed by the cerebellum and integrated with state estimates for (planned) control in the anterior intraparietal sulcus.
Assuntos
Mapeamento Encefálico , Cerebelo , Lobo Frontal , Imageamento por Ressonância Magnética , Movimento , Lobo Parietal , Desempenho Psicomotor , Humanos , Masculino , Feminino , Adulto , Cerebelo/fisiologia , Cerebelo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Lobo Parietal/fisiologia , Lobo Parietal/diagnóstico por imagem , Adulto Jovem , Desempenho Psicomotor/fisiologia , Lobo Frontal/fisiologia , Lobo Frontal/diagnóstico por imagem , Movimento/fisiologia , Mapeamento Encefálico/métodos , Mãos/fisiologia , Sinais (Psicologia) , Realidade Virtual , Retroalimentação Sensorial/fisiologiaRESUMO
RATIONALE: Hemifacial spasm (HFS) is triggered by neurovascular compression mostly at the root entry/exit zone of the facial nerve. HFS with the responsible blood vessel located in the internal auditory canal (IAC) is a very rare occurrence. In our case, the HFS was triggered by compression of the anterior inferior cerebellar artery (AICA) loop on the facial nerve in the IAC. PATIENT CONCERNS: A 27-year-old female presented with a 5-year history of right-sided facial twitching with no obvious course. The frequency and severity of the attacks increases when the patient was anxious or agitated which severely affected her quality of life. DIAGNOSIS: Preoperative 3D-TOF magnetic resonance imaging (MRI) evaluation of cranial nerves showed that the right AICA loop had a tortuous course within the IAC and compressed the facial nerve. INTERVENTION: Microvascular decompression (MVD) surgery was carried out to separate the tortuous AICA loop and facial nerve in the IAC using a Teflon pad. OUTCOMES: The abnormal muscle response disappeared intraoperatively and 2-years follow-up revealed no recurrence of her symptomatology. She is current well and go about her daily activities with no neurological deficits. LESSON: The attachment of the facial nerve to the tortuous AICA loop coupled with the pulsatile impulse of tortuous AICA loop may have resulted in the entrapment and compression of the CN VII in the IAC.
Assuntos
Nervo Facial , Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Humanos , Feminino , Espasmo Hemifacial/cirurgia , Espasmo Hemifacial/etiologia , Adulto , Nervo Facial/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Síndromes de Compressão Nervosa/cirurgia , Síndromes de Compressão Nervosa/etiologia , Orelha Interna/irrigação sanguínea , Cerebelo/irrigação sanguínea , Cerebelo/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
INTRODUCTION: The cerebellar response has been studied for years with different models of alteration of other brain structures to understand its complex functioning and its relationship with the rest of the body. Studies in patients with Parkinson's disease (PD) showed that the cerebellar function is modified by deficit of the basal ganglia; which supports the hypothesis that both structures are related anatomically and functionally. METHODS: In our study, the ventrolateral striatum (VLS) of the basal ganglia was altered by an electrolytic lesion, in order to produce a similar jaw frequency of jaw tremor movements presented in parkinsonism, thereafter we analyzed the effect of the lesion on the expression of multiunit activity (MUA) of the cerebellum. RESULTS: We found cerebellar activation during mandibular movements and increment during oral jaw tremor movements. In addition, the amplitude of baseline MUA registered in animals with alteration of the VLS decreased with respect to the intact group. CONCLUSIONS: Accordingly, we conclude that cerebellar changes in MUA may be due to a decrease in the cerebellar inflectional or as a possible compensatory function between cerebellum and basal ganglia.
Assuntos
Gânglios da Base , Cerebelo , Transtornos Parkinsonianos , Cerebelo/fisiopatologia , Gânglios da Base/fisiopatologia , Animais , Transtornos Parkinsonianos/fisiopatologia , Modelos Animais de Doenças , Masculino , Tremor/fisiopatologiaRESUMO
SNCA/PARK1 encodes α-synuclein, which is associated with familial Parkinson's disease. Despite its abundance in presynaptic terminals, the aggregation mechanism of α-synuclein and its relationship with Parkinson's disease have not yet been elucidated. Moreover, the ultrastructures of α-synuclein localization sites in neuronal presynaptic terminals remain unclear. Therefore, we herein generated transgenic mice expressing human α-synuclein tagged with mKate2 (hSNCA-mKate2 mice). These mice exhibited normal growth and fertility and had no motor dysfunction relative to their wild-type littermates, even at one year old. α-Synuclein-mKate2 accumulated in presynaptic terminals, particularly between Purkinje cells in the cerebellum and neurons in cerebellar nuclei. α-Synuclein-mKate2 was associated with the presynaptic marker, synaptophysin. In-resin CLEM and immunoelectron or electron microscopy revealed that α-synuclein-mKate2 localized on the surface of synaptic vesicles that were tightly arranged and assembled to form large synaptic pools in the cerebellum with negligible effects on the active zone. These results suggest that α-synuclein-associated ultrastructures in the presynaptic terminals of hSNCA-mKate2 mice reflect the structures of α-synuclein-assembled synaptic vesicle pools, and the size of vesicle pools increased. This transgenic mouse model will be a valuable tool for studying α-synuclein-associated synaptic vesicle pools.
Assuntos
Camundongos Transgênicos , Terminações Pré-Sinápticas , Vesículas Sinápticas , alfa-Sinucleína , Animais , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/ultraestrutura , Vesículas Sinápticas/metabolismo , Vesículas Sinápticas/ultraestrutura , Camundongos , Humanos , Células de Purkinje/metabolismo , Células de Purkinje/ultraestrutura , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Cerebelo/metabolismo , Cerebelo/ultraestrutura , Sinaptofisina/metabolismo , Sinaptofisina/genética , MasculinoRESUMO
Hemispherotomy is an effective surgery for treating refractory epilepsy from diffuse unihemispheric lesions. To date, postsurgery neuroplastic changes supporting behavioral recovery after left or right hemispherotomy remain unclear. In the present study, we systematically investigated changes in gray matter volume (GMV) before and after surgery and further analyzed their relationships with behavioral scores in two large groups of pediatric patients with left and right hemispherotomy (29 left and 28 right). To control for the dramatic developmental effect during this stage, age-adjusted GMV within unaffected brain regions was derived voxel by voxel using a normative modeling approach with an age-matched reference cohort of 2115 healthy children. Widespread GMV increases in the contralateral cerebrum and ipsilateral cerebellum and GMV decreases in the contralateral cerebellum were consistently observed in both patient groups, but only the left hemispherotomy patients showed GMV decreases in the contralateral cingulate gyrus. Intriguingly, the GMV decrease in the contralateral cerebellum was significantly correlated with improvement in behavioral scores in the right but not the left hemispherotomy patients. Importantly, the preoperative voxelwise GMV features can be used to significantly predict postoperative behavioral scores in both patient groups. These findings indicate an important role of the contralateral cerebellum in the behavioral recovery following right hemispherotomy and highlight the predictive potential of preoperative imaging features in postoperative behavioral performance.
Assuntos
Epilepsia Resistente a Medicamentos , Substância Cinzenta , Hemisferectomia , Imageamento por Ressonância Magnética , Humanos , Hemisferectomia/métodos , Feminino , Masculino , Criança , Pré-Escolar , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Adolescente , Cerebelo/diagnóstico por imagem , Cerebelo/cirurgia , Cerebelo/patologia , Plasticidade Neuronal/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Encéfalo/patologia , Lateralidade Funcional/fisiologiaRESUMO
BACKGROUND: The Zic family of transcription factors (TFs) promote both proliferation and maturation of cerebellar granule neurons (CGNs), raising the question of how a single, constitutively expressed TF family can support distinct developmental processes. Here we use an integrative experimental and bioinformatic approach to discover the regulatory relationship between Zic TF binding and changing programs of gene transcription during postnatal CGN differentiation. RESULTS: We first established a bioinformatic pipeline to integrate Zic ChIP-seq data from the developing mouse cerebellum with other genomic datasets from the same tissue. In newborn CGNs, Zic TF binding predominates at active enhancers that are co-bound by developmentally regulated TFs including Atoh1, whereas in mature CGNs, Zic TF binding consolidates toward promoters where it co-localizes with activity-regulated TFs. We then performed CUT&RUN-seq in differentiating CGNs to define both the time course of developmental shifts in Zic TF binding and their relationship to gene expression. Mapping Zic TF binding sites to genes using chromatin looping, we identified the set of Zic target genes that have altered expression in RNA-seq from Zic1 or Zic2 knockdown CGNs. CONCLUSIONS: Our data show that Zic TFs are required for both induction and repression of distinct, developmentally regulated target genes through a mechanism that is largely independent of changes in Zic TF binding. We suggest that the differential collaboration of Zic TFs with other TF families underlies the shift in their biological functions across CGN development.