Dentate nucleus deep brain stimulation: Technical note of a novel methodology assisted by tractography.

BACKGROUND: The cerebellum has emerged as an attractive and promising target for neuromodulation in movement disorders due to its vast connection with important cortical and subcortical areas. Here, we describe a novel technique of deep brain stimulation (DBS) of the dentate nucleus (DN) aided by tractography. METHODS: Since 2015, patients with movement disorders including dystonia, ataxia, and tremor have been treated with DN DBS. The cerebellar target was initially localized using coordinates measured from the fastigial point. The target was adjusted with direct visualization of the DN in the susceptibility-weighted imaging and T2 sequences of the MRI and finally refined based on the reconstruction of the dentatorubrothalamic tract (DRTT). RESULTS: Three patients were treated with this technique. The final target was located in the anterior portion of DN in close proximity to the DRTT, with the tip of the lead on the white matter and the remaining contacts on the DN. Clinical outcomes were variable and overall positive, with no major side effect. CONCLUSION: Targeting the DN based on tractography of the DRTT seems to be feasible and safe. Larger studies will be necessary to support our preliminary findings.

Petroclival Meningiomas: Factors Determining the Choice of Approach.

Objectives To review a surgical series of petroclival meningiomas and the factors considered in the choice of approach. Design Retrospective review. Setting The study was conducted in a university hospital in southern Brazil. Participants Twenty-two patients with petroclival meningioma originating from the upper two-thirds of the clivus medial to the fifth cranial nerve. Main Outcome Measures Gross-total resection, mortality, major morbidity, new cranial nerve deficits and tumor progression or recurrence. Results Retrosigmoid approach was used in tumors <3 cm and in those at or below the internal auditory meatus. Posterior petrosectomy was performed for tumors extending into the middle fossa. Gross-total resection was performed in 11 patients (50%). The mean follow-up time was 32 months (6-75 months). There were four cases of tumor progression or recurrence, which were treated with radiosurgery. Conclusions Resection of petroclival meningiomas remains challenging. In most cases, the retrosigmoid approach was sufficient, without affecting the degree of tumor resection. Petrosal approaches were reserved for patients with tumor extension into the middle fossa.

Petroclival meningiomas: Remaining controversies in light of minimally invasive approaches.

Surgical resection of petroclival meningiomas remains challenging due to their deep location and relationship to vital neurovascular structures. Although the natural history of these tumors involves a slow course, the incidence of cranial nerve deficits and the extent of tumor resection vary widely in the literature. Some reviews on this topic have been conducted, but data remain fragmentary and based on retrospective case series, which hinders attempts at meta-analysis. Within this context, research into the use of minimally invasive approaches, including in neuroendoscopy, continues to emerge. The objective of this narrative review is to analyze the available literature on the surgical treatment of petroclival meningiomas, with a focus on attempts at endoscopy-assisted resection.

Microvascular decompression of the posterior inferior cerebellar artery for intermediate nerve neuralgia.

BACKGROUND: Intermediate nerve neuralgia (INN) is an extremely rare craniofacial pain disorder mainly caused by neurovascular compression. CASE DESCRIPTION: We present the case of a 48-year-old female with a 20-month history of intractable paroxysmal INN on the right side. The patient described feeling paroxysmal pain in her auditory canal, pinna, deep in the jaw, and adjacent retromastoid area on the right side. She described the pain as being like a burning sensation. Magnetic resonance imaging showed the right posterior cerebellar artery crossing the cerebellopontine cistern in close contact with the right VII and VIII nerves. Surgical exploration via retromastoid craniotomy revealed vascular compression of the intermediate nerve by the posterior cerebellar artery. We therefore performed microvascular nerve decompression to relieve pain, and the patient remained pain-free at the 6-month follow-up visit. CONCLUSION: INN should be considered as a differential diagnosis in cases with atypical facial neuralgia, and microvascular decompression is an effective treatment option that can provide optimal pain relief.

Intraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies.

Several studies published to date about glioma surgery have addressed the validity of using novel technologies for intraoperative guidance and potentially improved outcomes. However, most of these reports are limited by questionable methods and/or by their retrospective nature. In this work, we performed a systematic review of the literature to address the impact of intraoperative assistive technologies on the extent of resection (EOR) in glioma surgery, compared to conventional unaided surgery. We were also interested in two secondary outcome variables: functional status and progression-free survival. We primarily used PubMed to search for relevant articles. Studies were deemed eligible for our analysis if they (1) were prospective controlled studies; (2) used EOR as their primary target outcome, assessed by MRI volumetric analysis; and (3) had a homogeneous study population with clear inclusion criteria. Out of 493 publications identified in our initial search, only six matched all selection criteria for qualitative synthesis. Currently, the evidence points to 5-ALA, DTI functional neuronavigation, neurophysiological monitoring, and intraoperative MRI as the best tools for improving EOR in glioma surgery. Our sample and conclusions were limited by the fact that studies varied in terms of population characteristics and in their use of different volumetric analyses. We were also limited by the low number of prospective controlled trials available in the literature. Additional evidence-based high-quality studies assessing cost-effectiveness should be conducted to better determine the benefits of intraoperative assistive technologies in glioma surgery.

Diferenciação neuronal in vitro de células-tronco mesenquimais humanas para uso em transplante neural / Neuronal differentiation of human mesenchymal stem cells in vitro for neural transplantation

Introdução. O transplante de células é possibilidade terapêutica promissora para muitas doenças neurológicas. Nos últimos anos, a possibilidade do isolamento de células-tronco dos tecidos adultos, por exemplo da medula-óssea, atrai a atenção da comunidade científica, estratégia que minimiza os problemas éticos relativos ao uso de tecido fetal para implantes visando ao tratamento de doenças neurológicas. Entretanto, a eficiência da transdiferenciação de células-tronco mesenquimais em neurônios, bem como os mecanismos envolvidos nesse processo, permanecem desconhecidos. A obtenção de neurônios maduros ocorreu somente em sistemas de co-cultura, o que induz a questão se a diferenciação representa um potencial das células per si, ou se é possível somente devido à fusão com neurônios maduros. Objetivos. No presente trabalho, pretendeu-se verificar o potencial de as células-tronco mesenquimais tornarem-se neurônios e esclarecer os possíveis mecanismos envolvidos nesse processo. Material e métodos. Células-tronco mesenquimais foram isoladas de 20 doadores voluntários normais e caracterizadas por análise de separação celular ativada por fluorescência. A multipotencialidade foi investigada ao se diferenciar as células em condrócitos e osteócitos. A capacidade de auto-renovação foi confirmada pelo ensaio de incorporação de BrdU. Ulteriormente, as células foram diferenciadas por uma semana em meio contendo AMPc, IBMX, ou combinação de ambos, e os resultados foram comparados com o cultivo em meio básico. Diferentes bloqueadores de Ca2+ ou inibidores de PKA foram usados como tentativa de se impedir a diferenciação, ocorrência que foi mensurada com imunocitoquímica para NF-200 (marcador de neurônios maduros). O registro eletrofisiológico por meio de patch clamp foi usado para se confirmar o fenótipo neuronal. As figuras foram configuradas em microscopia confocal. Para análise estatística foi utilizada ANOVA com teste post-hoc. Resultados. As células isoladas...

Introduction. Cell transplantation has been considered a promising therapeutic approach for many neurological diseases. The possibility of isolation of stem cells from adult tissues, i.e. bone marrow, has attracted the attention of the scientific community in the recent years. This strategy is interesting on avoiding the ethical issues regarding the use of fetal tissue for neural implants. Moreover, the efficiency of the transdifferentiation of mesenchymal stem cells (MSCs) into neurons, and the mechanisms involved in this process remain largely unknown. The obtention of mature neurons was described only in coculture systems, what raised the question if the differentiation is a potential of the cells itself, or if it is possible only due to fusion with mature neurons. Objectives. In the present investigation, we aimed to verify the potential of MSCs to differentiate into neurons, and also to clarify the possible mechanisms involved on it. Material and methods. MSCs were isolated from 20 healthy human subjects and characterized by FACS-analysis. Multipotentiality was addressed by differentiating them into chondrocytes and osteocytes. The self-renewal capacity was confirmed with BrdU-incorporation assay. Afterwards, cells were differentiated for 1 week in a medium containing cAMP, IBMX, or a combination of both, and the results were compared with cells treated in basal-medium condition. Different Ca2+-blockers and PKA-inhibitor peptide were used on an attempt to impair differentiation, which was quantified with NF-200 immunostaining (a marker of mature neurons). Patch-clamp recording was used to confirm neuronal phenotype. Pictures were taken in confocal microscope. For statistical analysis ANOVA with a post-hoc test was used. Results. The isolated cells expressed CD90, 105, 44, and 13, but were negative for CD34 and 45, meaning that they were non-hematopoiethic; 98.74 ± 0.43 % of them incorporated BrdU in 6hs. After isolation, they differentiated into...

Iatrogenic Creutzfeldt-Jakob disease following human growth hormone therapy: case report.

We report the case of a 41-year-old man with iatrogenic Creutzfeldt-Jakob disease (CJD) acquired after the use of growth hormone (GH) obtained from a number of pituitary glands sourced from autopsy material. The incubation period of the disease (from the midpoint of treatment to the onset of clinical symptoms) was rather long (28 years). Besides the remarkable cerebellar and mental signs, the patient exhibited sleep disturbance (excessive somnolence) from the onset of the symptoms, with striking alteration of the sleep architecture documented by polysomnography. 14-3-3 protein was detected in the CSF, and MRI revealed increased signal intensity bilaterally in the striatum, being most evident in diffusion-weighted (DW-MRI) sequences. This is the second case of iatrogenic CJD associated with the use of GH reported in Brazil.

Iatrogenic Creutzfeldt-Jakob disease following human growth hormone therapy: case report

We report the case of a 41-year-old man with iatrogenic Creutzfeldt-Jakob disease (CJD) acquired after the use of growth hormone (GH) obtained from a number of pituitary glands sourced from autopsy material. The incubation period of the disease (from the midpoint of treatment to the onset of clinical symptoms) was rather long (28 years). Besides the remarkable cerebellar and mental signs, the patient exhibited sleep disturbance (excessive somnolence) from the onset of the symptoms, with striking alteration of the sleep architecture documented by polysomnography. 14-3-3 protein was detected in the CSF, and MRI revealed increased signal intensity bilaterally in the striatum, being most evident in diffusion-weighted (DW-MRI) sequences. This is the second case of iatrogenic CJD associated with the use of GH reported in Brazil