Assuntos
Encefalopatias , Encéfalo , Obesidade , Redução de Peso , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Redução de Peso/fisiologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/etiologia , Encefalopatias/fisiopatologiaRESUMO
OBJECTIVE: This study aimed to predict occurrence of acute encephalopathy syndromes (AES) immediately after febrile status epilepticus in children and to explore the usefulness of electroencephalogram (EEG) in the early diagnosis of AES. METHODS: We reviewed data from 120 children who had febrile status epilepticus lasting >30 min and were admitted to our hospital between 2012 and 2019. AES with reduced diffusion on brain magnetic resonance imaging was diagnosed in 11 of these patients. EEG and serum cytokines were analyzed in AES patients. Clinical symptoms and laboratory data were compared between AES and non-AES patients. Logistic regression analysis was used to identify early predictors of AES. RESULTS: Multivariate logistic regression identified serum creatinine as a risk factor for developing AES. A scoring model to predict AES in the post-ictal phase that included serum creatinine, sodium, aspartate aminotransferase, and glucose was developed, and a score of 2 or more predicted AES with sensitivity of 90.9% and specificity of 71.6%. Post-ictus EEG revealed non-convulsive status epilepticus in four of the seven AES patients. CONCLUSION: Children with febrile status epilepticus may be at risk of developing severe AES with reduced diffusion. Post-ictus EEG and laboratory data can predict the occurrence of severe AES.
Assuntos
Encefalopatias , Convulsões Febris , Estado Epiléptico , Criança , Humanos , Encefalopatias/diagnóstico por imagem , Encefalopatias/epidemiologia , Encefalopatias/fisiopatologia , Creatinina/sangue , Eletroencefalografia , Convulsões Febris/complicações , Convulsões Febris/diagnóstico , Estado Epiléptico/complicações , Estado Epiléptico/diagnóstico , Síndrome , Imageamento por Ressonância Magnética , Medição de Risco , Valor Preditivo dos TestesRESUMO
Can we construct a model of brain function that enables an understanding of whole-brain circuit mechanisms underlying neurological disease and use it to predict the outcome of therapeutic interventions? How are pathologies in neurological disease, some of which are observed to have spatial spreading mechanisms, associated with circuits and brain function? In this review, we discuss approaches that have been used to date and future directions that can be explored to answer these questions. By combining optogenetic functional magnetic resonance imaging (fMRI) with computational modeling, cell type-specific, large-scale brain circuit function and dysfunction are beginning to be quantitatively parameterized. We envision that these developments will pave the path for future therapeutics developments based on a systems engineering approach aimed at directly restoring brain function.
Assuntos
Encefalopatias , Encéfalo , Imageamento por Ressonância Magnética , Rede Nervosa , Optogenética , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Simulação por Computador , Imageamento por Ressonância Magnética/métodos , Optogenética/métodos , Encefalopatias/diagnóstico por imagem , Encefalopatias/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologiaRESUMO
Event-related potentials (ERPs) are a common approach for investigating the neural basis of cognition and disease. There exists a vast and growing literature of ERP-related articles, the scale of which motivates the need for efficient and systematic meta-analytic approaches for characterizing this research. Here we present an automated text-mining approach as a form of meta-analysis to examine the relationships between ERP terms, cognitive domains and clinical disorders. We curated dictionaries of terms, collected articles of interest, and measured co-occurrence probabilities in published articles between ERP components and cognitive and disorder terms. Collectively, this literature dataset allows for creating data-driven profiles for each ERP, examining key associations of each component, and comparing the similarity across components, ultimately allowing for characterizing patterns and associations between topics and components. Additionally, by examining large literature collections, novel analyses can be done, such as examining how ERPs of different latencies relate to different cognitive associations. This openly available dataset and project can be used both as a pedagogical tool, and as a method of inquiry into the previously hidden structure of the existing literature. This project also motivates the need for consistency in naming, and for developing a clear ontology of electrophysiological components.
Assuntos
Encefalopatias/fisiopatologia , Encéfalo/fisiopatologia , Cognição , Mineração de Dados , Potenciais Evocados , Transtornos Neurocognitivos/fisiopatologia , Animais , Automação , Bibliometria , Encefalopatias/diagnóstico , Encefalopatias/psicologia , Eletroencefalografia , Humanos , Transtornos Neurocognitivos/diagnóstico , Reconhecimento Automatizado de PadrãoRESUMO
N-acetyl-aspartyl-glutamate (NAAG) is the most abundant dipeptide in the brain, where it acts as a neuromodulator of glutamatergic synapses by activating presynaptic metabotropic glutamate receptor 3 (mGluR3). Recent data suggest that NAAG is selectively localized to postsynaptic dendrites in glutamatergic synapses and that it works as a retrograde neurotransmitter. NAAG is released in response to glutamate and provides the postsynaptic neuron with a feedback mechanisms to inhibit excessive glutamate signaling. A key regulator of synaptically available NAAG is rapid degradation by the extracellular enzyme glutamate carboxypeptidase II (GCPII). Increasing endogenous NAAG-for instance by inhibiting GCPII-is a promising treatment option for many brain disorders where glutamatergic excitotoxicity plays a role. The main effect of NAAG occurs through increased mGluR3 activation and thereby reduced glutamate release. In the present review, we summarize the transmitter role of NAAG and discuss the involvement of NAAG in normal brain physiology. We further present the suggested roles of NAAG in various neurological and psychiatric diseases and discuss the therapeutic potential of strategies aiming to enhance NAAG levels.
Assuntos
Encefalopatias/metabolismo , Encéfalo/fisiologia , Dipeptídeos/metabolismo , Animais , Encéfalo/metabolismo , Encefalopatias/fisiopatologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/fisiopatologia , Dipeptídeos/fisiologia , Glutamato Carboxipeptidase II/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Transtornos Mentais/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Neurônios/metabolismo , Neurotransmissores/metabolismo , Receptores de Glutamato Metabotrópico/metabolismoAssuntos
Encefalopatias , Transtornos Mentais , Receptores de Ácido Caínico/fisiologia , Animais , Encefalopatias/metabolismo , Encefalopatias/fisiopatologia , Humanos , Transtornos Mentais/metabolismo , Transtornos Mentais/fisiopatologia , Plasticidade Neuronal/fisiologia , Receptores de Ácido Caínico/metabolismo , Transmissão Sináptica/fisiologiaRESUMO
Awake craniotomy enables mapping and monitoring of brain functions. For successful procedures, rapid awakening and the precise evaluation of consciousness are required. A prospective, observational study conducted to test whether intraoperative hand strength could be a sensitive indicator of consciousness during the awake phase of awake craniotomy. Twenty-three patients who underwent awake craniotomy were included. Subtle changes of the level of consciousness were assessed by the Japan Coma Scale (JCS). The associations of hand strength on the unaffected side with the predicted plasma concentration (Cp) of propofol, the bispectral index (BIS), and the JCS were analyzed. Hand strength relative to the preoperative maximum hand strength on the unaffected side showed significant correlations with the Cp of propofol (ρ = - 0.219, p = 0.007), the BIS (ρ = 0.259, p = 0.002), and the JCS (τ = - 0.508, p = 0.001). Receiver operating characteristic curve analysis for discriminating JCS 0-1 and JCS ≥ 2 demonstrated that the area under the curve was 0.76 for hand strength, 0.78 for Cp of propofol, and 0.66 for BIS. With a cutoff value of 75% for hand strength, the sensitivity was 0.76, and the specificity was 0.67. These data demonstrated that hand strength is a useful indicator for assessing the intraoperative level of consciousness during awake craniotomy.
Assuntos
Encefalopatias/cirurgia , Força da Mão , Mãos/fisiologia , Adulto , Idoso , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/sangue , Encefalopatias/fisiopatologia , Encefalopatias/psicologia , Estado de Consciência , Craniotomia , Feminino , Humanos , Consciência no Peroperatório , Japão , Masculino , Pessoa de Meia-Idade , Propofol/administração & dosagem , Propofol/sangue , Estudos Prospectivos , VigíliaAssuntos
Encefalopatias/diagnóstico , Encefalopatias/etiologia , Circulação Cerebrovascular/fisiologia , Corpo Caloso/patologia , Doença Aguda , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Criança , Humanos , Nefrite/complicações , Nefrite/diagnósticoRESUMO
BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic seizures and white matter lesions with reduced diffusion, which are often accompanied by involuntary movements. The neurological outcomes of AESD vary from normal to mild or severe sequelae, including intellectual disability, paralysis, and epilepsy. The present study aimed to clarify the prognostic factors of AESD, including involuntary movements. METHODS: We enrolled 29 patients with AESD admitted to Tottori University Hospital from 1991 to 2020 and retrospectively analyzed their clinical data. Neurological outcomes were assessed by the Pediatric Cerebral Performance Category score and cerebral paralysis as neurological sequelae. RESULTS: Of the 29 patients, 12 had favorable outcomes and 17 had unfavorable outcomes. Univariate analysis revealed that the presence of underlying diseases, a decline in Glasgow Coma Scale (GCS) score 12-24 h after early seizures, and involuntary movements were associated with unfavorable outcomes. In multivariate analysis, a decline in GCS score and involuntary movements were associated with unfavorable outcomes. The sensitivities and specificities of underlying diseases, a decline of ≥ 3 points in GCS score 12-24 h after early seizures, and involuntary movements for unfavorable outcomes were 53% and 92%, 92% and 65%, and 59% and 92%, respectively. CONCLUSIONS: The appearance of involuntary movements may be associated with unfavorable outcomes of AESD. The prognostic factors identified herein are comparable with previously known prognostic factors of consciousness disturbances after early seizures.
Assuntos
Encefalopatias/diagnóstico , Discinesias/diagnóstico , Convulsões/diagnóstico , Encefalopatias/complicações , Encefalopatias/fisiopatologia , Pré-Escolar , Discinesias/etiologia , Discinesias/fisiopatologia , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/fisiopatologiaRESUMO
One of the current problems of modern radiobiology is determine the characteristics of the manifestation of radiation-induced effects not only at different dose loads, but also at different stages of development of the organism. In previous reports, we have summarized available evidence that at certain ages there is a comparative acceleration of radiation-induced pathological changes in the eye and brain, and the study and assessment of the risk of possible ophthalmic and neurological pathology in remote periods after contamination of radioactive areas. Data of irradiated in utero individuals are possible on the basis of observation of the state of the visual analyzer in persons who underwent intrauterine irradiation in 1986. Therefore, a parallel study of retinal morphometric parameters, amplitude and latency of components of evoked visual potentials in irradiated in utero individuals was performed. OBJECTIVE: to evaluate the retinal morphometric parameters, amplitude and latency components of the evoked visual potentials in intrauterine irradiated persons. MATERIALS AND METHODS: The results of surveys of 16 people irradiated in utero in the aftermath of the Chornobyl disaster were used; the comparison group were residents of Kyiv of the corresponding age (25 people). Optical coherence tomography was performed on a Cirrus HD-OCT, Macular Cube 512x128 study technique was used. At the same time, the study of visual evoked potentials on the inverted pattern was performed, and occipital leads wereanalyzed. Visual evoked potentials were recorded on a reversible chess pattern (VEP) - an electrophysiological test, which is a visual response to a sharp change in image contrast when presenting a reversible image of a chessboard. RESULTS: In those irradiated in utero at the age of 22-25 years, there was a probable increase in retinal thickness in the fovea, there was a tendency to increase the thickness of the retina in the areas around the fovea. When recording visual evoked potentials on a reversible chess pattern in this group, there was a tendency to decrease the amplitudes of components (N75, P100, N145, P200) in the right and left parieto-occipital areas and asymmetric changes in latency of these components. CONCLUSIONS: Early changes of fovea recorded in OCT and decreasing amplitudes of components of visual evoked potentials on the reversible chess pattern at the age of 22 25 years may indicate a risk of development in patients irradiated in utero, early age-related macular degeneration, as well as increased risk and increased risk structures of the visual analyzer.
Assuntos
Anormalidades Induzidas por Radiação/fisiopatologia , Acidente Nuclear de Chernobyl , Potenciais Evocados Visuais/efeitos da radiação , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Radiação Ionizante , Retina/anatomia & histologia , Retina/efeitos da radiação , Adulto , Encefalopatias/fisiopatologia , Oftalmopatias/fisiopatologia , Feminino , Humanos , Masculino , Gravidez , Ucrânia , Adulto JovemRESUMO
Precision treatments for epilepsy targeting the underlying genetic diagnoses are becoming a reality. Historically, the goal of epilepsy treatments was to reduce seizure frequency. In the era of precision medicine, however, outcomes such as prevention of epilepsy progression or even improvements in cognitive functions are both aspirational targets for any intervention. Developing methods, both in clinical trial design and in novel endpoints, will be necessary for measuring, not only seizures, but also the other neurodevelopmental outcomes that are predicted to be targeted by precision treatments. Biomarkers that quantitatively measure disease progression or network level changes are needed to allow for unbiased measurements of the effects of any gene-level treatments. Here, we discuss some of the promising electrophysiological biomarkers that may be of use in clinical trials of precision therapies, as well as the difficulties in implementing them.
Assuntos
Encefalopatias/genética , Encefalopatias/fisiopatologia , Epilepsia/genética , Epilepsia/fisiopatologia , Medicina de Precisão/métodos , Anticonvulsivantes/uso terapêutico , Biomarcadores , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Encefalopatias/diagnóstico , Encefalopatias/terapia , Epilepsia/diagnóstico , Epilepsia/terapia , Potenciais Evocados Visuais/fisiologia , Humanos , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/fisiopatologia , Transtornos do Neurodesenvolvimento/terapiaRESUMO
Coenzyme Q10 (ubiquinone or CoQ10) is a lipid molecule that acts as an electron mobile carrier of the electron transport chain and also contains antioxidant properties. Supplementation of CoQ10 has been very useful to treat mitochondrial diseases. CoQ10 along with its synthetic analogue, idebenone, is used largely to treat various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Friedreich's ataxia and additional brain disease condition like autism, multiple sclerosis, epilepsy, depression, and bipolar disorder, which are related to mitochondrial impairment. In this article, we have reviewed numerous physiological functions of CoQ10 and the rationale for its use in clinical practice in different brain disorders.
Assuntos
Encefalopatias/tratamento farmacológico , Doenças Mitocondriais/tratamento farmacológico , Ubiquinona/análogos & derivados , Animais , Antioxidantes/farmacologia , Encefalopatias/fisiopatologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Doenças Mitocondriais/fisiopatologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/fisiopatologia , Ubiquinona/farmacologiaRESUMO
RATIONALE: Progressive encephalopathy with brain edema and/or leukoencephalopathy-1 is an infantile, lethal neurometabolic disorder caused by a NAD(P)HX epimerase (NAXE) gene mutation. It is characterized by a fluctuating disease course with repeated episodes of improvement and regression. In this report, we present a rare case of NAXE gene mutation-related encephalopathy with unexpected neurological recovery and long survival time. PATIENT CONCERNS: A 20-month-old girl presented with progressively unsteady gait and bilateral hand tremors after a trivial febrile illness. Her disease rapidly progressed to consciousness disturbance, 4-limb weakness (muscle power: 1/5 on the Medical Research Council scale), and respiratory failure. The patient gradually recovered 2âmonths later. However, another episode of severe fever-induced encephalopathy developed 2âyears after the initial presentation. DIAGNOSES: Results of laboratory investigations, including complete blood count, blood chemistry, inflammatory markers, and cerebral spinal fluid analysis were unremarkable. Electroencephalography and nerve conduction velocity studies yielded normal results. Brain magnetic resonance imaging on diffusion-weighted imaging revealed abnormal sysmmetric hyperintensity in the bilateral middle cerebellar peduncles. A genetic study using whole exome sequencing confirmed the diagnosis of NAXE gene mutation-related encephalopathy. INTERVENTIONS: Pulse therapy with methylprednisolone, intravenous immunoglobulin, coenzyme Q10, and carnitine were initially introduced. After a NAXE gene defect was detected, the vitamin B complex and coenzyme Q10 were administered. A continuous rehabilitation program was also implemented. OUTCOMES: NAXE gene mutation-related encephalopathy is usually regarded as a lethal neurometabolic disorder. However, the outcome in this case is better than that in the previous cases. She showed progressive neurological recovery and a longer survival time. The muscle power of the 4 limbs recovered to grade 4. At present (age of 5.5âyears old), she can walk with an unsteady gait and go to school. LESSONS: Although NAXE gene mutation-related encephalopathy is rare, it should be considered as a differential diagnosis of early onset progressive encephalopathy.
Assuntos
Encefalopatias/genética , Encefalopatias/fisiopatologia , Racemases e Epimerases/genética , Suplementos Nutricionais , Feminino , Humanos , Lactente , Ubiquinona/análogos & derivados , Ubiquinona/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Sequenciamento do ExomaRESUMO
BACKGROUND: Tanycytic ependymoma (TE) (WHO grade II) is a rare and morphologically distinct variant of ependymoma with only 77 cases reported worldwide so far. Variable clinical and radio-pathological features lead to misdiagnosis as WHO grade 1 tumors. On imaging, differentials of either schwannoma, meningioma, low-grade glial (like angiocentric glioma), or myxopapillary ependymoma are considered. In this study, we aim to discuss clinical, radiological, and pathological features of TE from our archives. METHOD: We report clinicopathological aspects of six cases of TE from archives of tertiary care center between 2016 and 2018. Detailed histological assessment in terms of adequate tissue sampling and immunohistochemistry was done for each case. RESULT: The patient's age ranged between 10 and 53 years with a slight male predilection. Intraspinal location was seen in two cases (intramedullary and extramedullary), three cases were cervicomedullary (intramedullary), and one was intracranial. One case was associated with neurofibromatosis type 2. Four cases mimicked as either schwannoma or low-grade glial tumor on squash smears. On imaging, ependymoma as differential was kept in only two cases and misclassified remaining either as low-grade glial or schwannoma. DISCUSSION: In initial published reports, the spine is the most common site (50.4%) followed by intracranial (36.4%) and cervicomedullary (3.9%). They have also highlighted the challenges in diagnosing them intraoperatively and radiologically. Treatment is similar to conventional ependymoma if diagnosed accurately. A multidisciplinary approach with the integration of neurosurgeon, neuroradiologist, and neuropathologist is required for accurate diagnosis and better treatment of patients.
Assuntos
Encefalopatias/fisiopatologia , Ependimoma/diagnóstico , Ependimoma/fisiopatologia , Ependimoma/terapia , Imuno-Histoquímica/métodos , Neoplasias Epiteliais e Glandulares/fisiopatologia , Doenças da Medula Espinal/fisiopatologia , Adolescente , Adulto , Encefalopatias/diagnóstico por imagem , Criança , Ependimoma/diagnóstico por imagem , Feminino , Técnicas Histológicas , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Doenças da Medula Espinal/diagnóstico por imagem , Adulto JovemRESUMO
Heart rate has natural fluctuations that are typically ascribed to autonomic function. Recent evidence suggests that conscious processing can affect the timing of the heartbeat. We hypothesized that heart rate is modulated by conscious processing and therefore dependent on attentional focus. To test this, we leverage the observation that neural processes synchronize between subjects by presenting an identical narrative stimulus. As predicted, we find significant inter-subject correlation of heart rate (ISC-HR) when subjects are presented with an auditory or audiovisual narrative. Consistent with our hypothesis, we find that ISC-HR is reduced when subjects are distracted from the narrative, and higher ISC-HR predicts better recall of the narrative. Finally, patients with disorders of consciousness have lower ISC-HR, as compared to healthy individuals. We conclude that heart rate fluctuations are partially driven by conscious processing, depend on attentional state, and may represent a simple metric to assess conscious state in unresponsive patients.
Assuntos
Estado de Consciência/fisiologia , Frequência Cardíaca/fisiologia , Estimulação Acústica , Adolescente , Adulto , Idoso , Atenção , Teorema de Bayes , Encefalopatias/fisiopatologia , Análise por Conglomerados , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Taxa Respiratória , Adulto JovemAssuntos
Estado Terminal , Eletroencefalografia/normas , Pessoas Famosas , Lógica , Estado Epiléptico/fisiopatologia , Administração Intravenosa , Benzodiazepinonas/administração & dosagem , Encefalopatias/diagnóstico , Encefalopatias/tratamento farmacológico , Encefalopatias/fisiopatologia , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Humanos , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamento farmacológicoRESUMO
OBJECTIVE: Mild encephalopathy with reversible splenial lesion (MERS) is associated with a variety of infections and anti-epileptic drug withdrawal. Here we report the clinical characteristics of H1N1 influenza A-associated MERS based on our experience of four pediatric cases. METHODS: A detailed retrospective analysis of four patients with H1N1 influenza A-associated MERS was performed at Guangzhou Women and Children's Medical Center. RESULTS: All patients exhibited mild influenza-like illness and seizures. Three patients presented with a new-onset seizure with fever after 5 years of age. 75% patients had altered mental status. For all four patients, influenza A (H1N1) viral RNA was detected in throat swab specimens at least twice. Brain magnetic resonance images revealed similar ovoid lesions in the corpus callosum, mainly in the splenium and for one patient in the splenium and genu of the corpus callosum. Only one patient had an abnormal electroencephalogram tracing. Cells and protein in the cerebrospinal fluid were normal in all patients. All patients received oseltamivir and one patient received intravenous immunoglobulin. As a result, all patients fully recovered after 2 months and showed no neurologic sequelae at discharge. CONCLUSION: This case series provides insight towards clinical features of H1N1 influenza A-associated MERS.
Assuntos
Encefalopatias/diagnóstico , Encéfalo/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Vírus da Influenza A Subtipo H1N1/patogenicidade , Encéfalo/fisiopatologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/fisiopatologia , Encefalopatias/virologia , Criança , Pré-Escolar , Corpo Caloso/fisiopatologia , Feminino , Humanos , Influenza Humana/complicações , Influenza Humana/diagnóstico , Influenza Humana/fisiopatologia , Influenza Humana/virologia , Imageamento por Ressonância Magnética , MasculinoRESUMO
Developmental and epileptic encephalopathies (DEE) are a heterogenous group of conditions characterized by the co-occurrence of epilepsy and intellectual/developmental disability. Despite several known DEE-related genes, including these encoding ion channels, still many cases remain without molecular diagnosis. Here, we present a 2-year-old girl with severe DEE in whom whole exome sequencing revealed de novo p.(Val471Leu) variant in the KCNC2 encoding Kv3.2, a voltage-gated potassium channel. To the best of our knowledge, this is the third DEE case due to KCNC2 mutation. Our clinical and molecular findings, particularly the recurrence of p.(Val471Leu) in patient with similar clinical phenotype, further support KCNC2 as a novel DEE-associated gene.
Assuntos
Encefalopatias/genética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Canais de Potássio Shaw/genética , Encefalopatias/fisiopatologia , Pré-Escolar , Deficiências do Desenvolvimento/fisiopatologia , Epilepsia , Feminino , Predisposição Genética para Doença , Humanos , Deficiência Intelectual/fisiopatologia , Mutação de Sentido Incorreto/genética , Fenótipo , Sequenciamento do ExomaRESUMO
The field of neuromodulation, at its essence, aims to apply electrical stimulation to the brain to ameliorate various pathology. Many methods of applying this stimulation exist, including invasive and non-invasive means. In the realm of invasive stimulation, stimulation of the cortex remains one of the earliest techniques investigated, yet one of the most underutilized today. Evidence for the efficacy of direct invasive cortical stimulation continues to mount, especially in recent years. In this chapter we will review the evidence for the use of invasive cortical stimulation as it applies to neuropathic pain, epilepsy, psychiatric disease, movement disorders, tinnitus, and post-stroke recovery, as well explore some potential mechanisms and future directions of the technique.
Assuntos
Encefalopatias , Estimulação Encefálica Profunda , Encefalopatias/fisiopatologia , Encefalopatias/terapia , Humanos , Resultado do TratamentoRESUMO
Over the past 20 years, analyses of single brain cell genomes have revealed that the brain is composed of cells with myriad distinct genomes: the brain is a genomic mosaic, generated by a host of DNA sequence-altering processes that occur somatically and do not affect the germline. As such, these sequence changes are not heritable. Some processes appear to occur during neurogenesis, when cells are mitotic, whereas others may also function in post-mitotic cells. Here, we review multiple forms of DNA sequence alterations that have now been documented: aneuploidies and aneusomies, smaller copy number variations (CNVs), somatic repeat expansions, retrotransposons, genomic cDNAs (gencDNAs) associated with somatic gene recombination (SGR), and single nucleotide variations (SNVs). A catch-all term of DNA content variation (DCV) has also been used to describe the overall phenomenon, which can include multiple forms within a single cell's genome. A requisite step in the analyses of genomic mosaicism is ongoing technology development, which is also discussed. Genomic mosaicism alters one of the most stable biological molecules, DNA, which may have many repercussions, ranging from normal functions including effects of aging, to creating dysfunction that occurs in neurodegenerative and other brain diseases, most of which show sporadic presentation, unlinked to causal, heritable genes.