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1.
Transl Stroke Res ; 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612482

RESUMO

In genetic studies of cerebrovascular diseases, the optimal vessels to use as controls remain unclear. Our goal is to compare the transcriptomic profiles among 3 different types of control vessels: superficial temporal artery (STA), middle cerebral arteries (MCA), and arteries from the circle of Willis obtained from autopsies (AU). We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed upregulation of genes associated with tRNA/rRNA processing. Moreover, our results suggest that the matched case-control study design, which involves control STA samples collected from the same subjects of matched aneurysm samples in our study, can improve the identification of non-inherited disease-associated genes. Given the challenges associated with obtaining fresh intracranial arteries from healthy individuals, our study suggests that using MCA, AU, or paired STA samples as controls are feasible strategies for future large-scale studies investigating cerebral vasculopathies. However, the intrinsic differences of each type of control should be taken into consideration when interpreting the results. With the limitations of each control type, it may be most optimal to use multiple tissues as controls.

2.
Mov Disord Clin Pract ; 10(6): 987-991, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37332654

RESUMO

Background: Technological advancements in deep brain stimulation (DBS) require methodological changes in programming. Fractionalization poses significant practical challenges for the most common approach for assessing DBS efficacy, monopolar review (MR). Objectives: Two DBS programming methods: MR and fixed parameter vertical and horizontal fractionalization (FPF) were compared. Methods: A two-phase process of vertical and horizontal FPF was performed. MR was conducted thereafter. After a short wash-out period, both optimal configurations determined by MR and FPF were tested in a double-blind randomized manner. Results: Seven PD patients were enrolled, providing 11 hemispheres to compare the two conditions. In all subjects, the blinded examiner selected a directional or fractionalization configuration. There was no significant difference in clinical benefits between MR and FPF. FPF was the preferred method for initial programming as selected by subject and clinician. Conclusions: FPF programming is a viable and efficient methodology that may be incorporated into clinical practice.

3.
J Parkinsons Dis ; 13(3): 415-419, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36911947

RESUMO

Deep brain stimulation (DBS), a treatment of Parkinson's disease (PD), has been associated with suicidality. We conducted a case-control study comparing suicide in four pairs of cohorts: PD patients with DBS or not, epilepsy patients with resection surgery or not, subjects with BMI≥30 with bariatric surgery or not, and patients with chronic kidney disease with transplantation or not. PD patients with DBS demonstrated a lower risk of suicide relative to PD patients without DBS. Findings from other elective surgeries indicate that patients receiving operative treatments do not possess predictable differences in suicide rates relative to their medically managed counterparts.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Suicídio , Humanos , Doença de Parkinson/complicações , Estudos Retrospectivos , Estudos de Casos e Controles , Estimulação Encefálica Profunda/efeitos adversos , Resultado do Tratamento
4.
Neurol Genet ; 8(6): e200040, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36475054

RESUMO

Background and Objectives: While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms. Methods: We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results. Results: Somatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway. Discussion: We propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.

5.
Front Surg ; 9: 863921, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211256

RESUMO

Advanced Parkinson's disease (PD) is characterized by increasingly debilitating impaired movements that include motor fluctuations and dyskinesias. At this stage of the disease, pharmacological management can result in unsatisfactory clinical benefits and increase the occurrence of adverse effects, leading to the consideration of advanced therapies. The scope of this review is to provide an overview of currently available therapies for advanced PD, specifically levodopa-carbidopa intestinal gel, continuous subcutaneous apomorphine infusion, radiofrequency ablation, stereotactic radiosurgery, MRI-guided focused ultrasound, and deep brain stimulation. Therapies in clinical trials are also discussed, including novel formulations of subcutaneous carbidopa/levodopa, gene-implantation therapies, and cell-based therapies. This review focuses on the clinical outcomes and adverse effects of the various therapies and also considers patient-specific characteristics that may influence treatment choice. This review can equip providers with updated information on advanced therapies in PD to better counsel patients on the available options.

6.
PLoS One ; 17(10): e0275490, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36264986

RESUMO

Optimal placement of deep brain stimulation (DBS) therapy for treating movement disorders routinely relies on intraoperative motor testing for target determination. However, in current practice, motor testing relies on subjective interpretation and correlation of motor and neural information. Recent advances in computer vision could improve assessment accuracy. We describe our application of deep learning-based computer vision to conduct markerless tracking for measuring motor behaviors of patients undergoing DBS surgery for the treatment of Parkinson's disease. Video recordings were acquired during intraoperative kinematic testing (N = 5 patients), as part of standard of care for accurate implantation of the DBS electrode. Kinematic data were extracted from videos post-hoc using the Python-based computer vision suite DeepLabCut. Both manual and automated (80.00% accuracy) approaches were used to extract kinematic episodes from threshold derived kinematic fluctuations. Active motor epochs were compressed by modeling upper limb deflections with a parabolic fit. A semi-supervised classification model, support vector machine (SVM), trained on the parameters defined by the parabolic fit reliably predicted movement type. Across all cases, tracking was well calibrated (i.e., reprojection pixel errors 0.016-0.041; accuracies >95%). SVM predicted classification demonstrated high accuracy (85.70%) including for two common upper limb movements, arm chain pulls (92.30%) and hand clenches (76.20%), with accuracy validated using a leave-one-out process for each patient. These results demonstrate successful capture and categorization of motor behaviors critical for assessing the optimal brain target for DBS surgery. Conventional motor testing procedures have proven informative and contributory to targeting but have largely remained subjective and inaccessible to non-Western and rural DBS centers with limited resources. This approach could automate the process and improve accuracy for neuro-motor mapping, to improve surgical targeting, optimize DBS therapy, provide accessible avenues for neuro-motor mapping and DBS implantation, and advance our understanding of the function of different brain areas.


Assuntos
Estimulação Encefálica Profunda , Aprendizado Profundo , Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Estimulação Encefálica Profunda/métodos , Fenômenos Biomecânicos , Estudo de Prova de Conceito , Extremidade Superior
7.
Sci Rep ; 12(1): 18120, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36302865

RESUMO

The expanding application of deep brain stimulation (DBS) therapy both drives and is informed by our growing understanding of disease pathophysiology and innovations in neurosurgical care. Neurophysiological targeting, a mainstay for identifying optimal, motor responsive targets, has remained largely unchanged for decades. Utilizing deep learning-based computer vision and related computational methods, we developed an effective and simple intraoperative approach to objectively correlate neural signals with movements, automating and standardizing the otherwise manual and subjective process of identifying ideal DBS electrode placements. Kinematics are extracted from video recordings of intraoperative motor testing using a trained deep neural network and compared to multi-unit activity recorded from the subthalamic nucleus. Neuro-motor correlations were quantified using dynamic time warping with the strength of a given comparison measured by comparing against a null distribution composed of related neuro-motor correlations. This objective measure was then compared to clinical determinations as recorded in surgical case notes. In seven DBS cases for treatment of Parkinson's disease, 100 distinct motor testing epochs were extracted for which clear clinical determinations were made. Neuro-motor correlations derived by our automated system compared favorably with expert clinical decision making in post-hoc comparisons, although follow-up studies are necessary to determine if improved correlation detection leads to improved outcomes. By improving the classification of neuro-motor relationships, the automated system we have developed will enable clinicians to maximize the therapeutic impact of DBS while also providing avenues for improving continued care of treated patients.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Estimulação Encefálica Profunda/métodos , Vigília , Resultado do Tratamento , Núcleo Subtalâmico/fisiologia , Doença de Parkinson/cirurgia , Doença de Parkinson/tratamento farmacológico
8.
Neurosurg Rev ; 45(4): 2593-2613, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35511309

RESUMO

The neurosurgical treatment of movement disorders, primarily via deep brain stimulation (DBS), is a rapidly expanding and evolving field. Although conventional targets including the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) for Parkinson's disease and ventral intermediate nucleus of the thalams (VIM) for tremor provide substantial benefit in terms of both motor symptoms and quality of life, other targets for DBS have been explored in an effort to maximize clinical benefit and also avoid undesired adverse effects associated with stimulation. These novel targets primarily include the rostral zona incerta (rZI), caudal zona incerta (cZI)/posterior subthalamic area (PSA), prelemniscal radiation (Raprl), pedunculopontine nucleus (PPN), substantia nigra pars reticulata (SNr), centromedian/parafascicular (CM/PF) nucleus of the thalamus, nucleus basalis of Meynert (NBM), dentato-rubro-thalamic tract (DRTT), dentate nucleus of the cerebellum, external segment of the globus pallidus (GPe), and ventral oralis (VO) complex of the thalamus. However, reports of outcomes utilizing these targets are scattered and disparate. In order to provide a comprehensive resource for researchers and clinicians alike, we have summarized the existing literature surrounding these novel targets, including rationale for their use, neurosurgical techniques where relevant, outcomes and adverse effects of stimulation, and future directions for research.


Assuntos
Estimulação Encefálica Profunda , Núcleos Intralaminares do Tálamo , Doença de Parkinson , Núcleo Subtalâmico , Estimulação Encefálica Profunda/métodos , Humanos , Doença de Parkinson/terapia , Qualidade de Vida , Núcleo Subtalâmico/cirurgia
9.
J Neurol Neurosurg Psychiatry ; 93(4): 386-394, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35193951

RESUMO

OBJECTIVE: The severity of motor symptoms in Parkinson's disease (PD) depends on environmental conditions. For example, the presence of external patterns such as a rhythmic tone can attenuate bradykinetic impairments. However, the neural mechanisms for this context-dependent attenuation (e.g., paradoxical kinesis) remain unknown. Here, we investigate whether context-dependent symptom attenuation is reflected in single-unit activity recorded in the operating room from the substantia nigra pars reticulata (SNr) of patients with PD undergoing deep brain stimulation surgery. The SNr is known to influence motor planning and execution in animal models, but its role in humans remains understudied. METHODS: We recorded SNr activity while subjects performed cued directional movements in response to auditory stimuli under interleaved 'patterned' and 'unpatterned' contexts. SNr localisation was independently confirmed with expert intraoperative assessment as well as post hoc imaging-based reconstructions. RESULTS: As predicted, we found that motor performance was improved in the patterned context, reflected in increased reaction speed and accuracy compared with the unpatterned context. These behavioural differences were associated with enhanced responsiveness of SNr neurons-that is, larger changes in activity from baseline-in the patterned context. Unsupervised clustering analysis revealed two distinct subtypes of SNr neurons: one exhibited context-dependent enhanced responsiveness exclusively during movement preparation, whereas the other showed enhanced responsiveness during portions of the task associated with both motor and non-motor processes. CONCLUSIONS: Our findings indicate the SNr participates in motor planning and execution, as well as warrants greater attention in the study of human sensorimotor integration and as a target for neuromodulatory therapies.


Assuntos
Doença de Parkinson , Parte Reticular da Substância Negra , Animais , Humanos , Hipocinesia , Neurônios/fisiologia , Doença de Parkinson/complicações , Substância Negra
10.
Clin Neurol Neurosurg ; 208: 106842, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34339900

RESUMO

OBJECTIVE: To determine how neuropsychiatric comorbidity, modulatory indication, demographics, and other characteristics affect inpatient deep brain stimulation (DBS) outcomes. METHODS: This is a retrospective study of 45 months' worth of data from the National Inpatient Sample. Patients were aged ≥ 18 years old and underwent DBS for Parkinson Disease (PD), essential tremor (ET), general dystonia and related disorders, other movement disorder (non-PD/ET), or obsessive-compulsive disorder (OCD) at a US hospital. Primary endpoints were prolonged length of stay (PLOS), high-end hospital charges (HEHCs), unfavorable disposition, and inpatient complications. Logistic models were constructed with odds ratios under 95% confidence intervals. A p-value of 0.05 determined significance. RESULTS: Of 214,098 records, there were 27,956 eligible patients. Average age was 63.9 ± 11.2 years, 17,769 (63.6%) were male, and 10,182 (36.4%) patients were female. Most of the cohort was White (51.1%), Medicare payer (64.3%), and treated at a large-bed size (80.7%), private non-profit (76.9%), and metro-teaching (94.0%) hospital. Neuropsychiatric comorbidity prevalence ranged from 29.9% to 47.7% depending on indication. Compared with PD, odds of complications and unfavorable disposition were significantly higher with other movement disorders and dystonia, whereas OCD conferred greater risk for HEHCs (p < 0.05). Patients with ET had favorable outcomes. Neuropsychiatric comorbidity, Black race, and Charlson Comorbidity Index > 0 were significantly associated with unfavorable outcomes (p < 0.05). CONCLUSION: The risk of adverse inpatient outcomes for DBS in the United States is independently correlated with non-PD/ET disorders, neuropsychiatric comorbidity, and non-White race, reflecting the heterogeneity and infancy of widespread DBS for these patients.


Assuntos
Distúrbios Distônicos/terapia , Tremor Essencial/terapia , Transtorno Obsessivo-Compulsivo/terapia , Doença de Parkinson/terapia , Idoso , Bases de Dados Factuais , Estimulação Encefálica Profunda , Distúrbios Distônicos/complicações , Tremor Essencial/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/complicações , Doença de Parkinson/complicações , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos
11.
Stereotact Funct Neurosurg ; 99(5): 443-450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33902054

RESUMO

INTRODUCTION: Deep brain stimulation of the zona incerta is effective at treating tremor and other forms of parkinsonism. However, the structure is not well visualized with standard MRI protocols making direct surgical targeting unfeasible and contributing to inconsistent clinical outcomes. In this study, we applied coronal gradient echo MRI to directly visualize the rostral zona incerta in Parkinson's disease patients to improve targeting for deep brain stimulation. METHODS: We conducted a prospective study to optimize and evaluate an MRI sequence to visualize the rostral zona incerta in patients with Parkinson's disease (n = 31) and other movement disorders (n = 13). We performed a contrast-to-noise ratio analysis of specific regions of interest to quantitatively assess visual discrimination of relevant deep brain structures in the optimized MRI sequence. Regions of interest were independently assessed by 2 neuroradiologists, and interrater reliability was assessed. RESULTS: Rostral zona incerta and subthalamic nucleus were well delineated in our 5.5-min MRI sequence, indicated by excellent interrater agreement between neuroradiologists for region-of-interest measurements (>0.90 intraclass coefficient). Mean contrast-to-noise ratio was high for both rostral zona incerta (6.39 ± 3.37) and subthalamic nucleus (17.27 ± 5.61) relative to adjacent white matter. There was no significant difference between mean signal intensities or contrast-to-noise ratio for Parkinson's and non-Parkinson's patients for either structure. DISCUSSION/CONCLUSION: Our optimized coronal gradient echo MRI sequence delineates subcortical structures relevant to traditional and novel deep brain stimulation targets, including the zona incerta, with high contrast-to-noise. Future studies will prospectively apply this sequence to surgical planning and postimplantation outcomes.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Zona Incerta , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapia , Estudos Prospectivos , Reprodutibilidade dos Testes , Zona Incerta/diagnóstico por imagem
12.
Front Neurol ; 11: 320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477236

RESUMO

Electrical stimulation mapping (ESM) using stereoelectroencephalography (SEEG) is an essential component in the workup of surgical epilepsy. Since the initial application of ESM in the mid-1960s, it remains unparalleled in defining eloquent brain areas and delimiting seizure foci for the purposes of surgical planning. Here, we briefly review the current state of SEEG stimulation, with a focus on the techniques used for identifying the epileptogenic zone and eloquent cortex. We also summarize clinical data on the efficacy of SEEG stimulation in surgical outcomes and functional mapping. Finally, we briefly highlight future applications of SEEG ESM, including novel functional mapping approaches, identifying rare seizure semiologies, neurophysiologic investigations for understanding cognitive function, and its role in SEEG-guided radiofrequency thermal coagulation.

13.
Stereotact Funct Neurosurg ; 95(4): 229-235, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28728152

RESUMO

OBJECTIVE: The success of deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) depends on accurately placing the electrode into the GPi motor territory. Direct targeting can be difficult as GPi laminar borders are not always clearly identifiable on MRI. Here, we report a method for using the putamen (PUT) as a surrogate anatomical marker to target the GPi. METHODS: We developed a PUT-based GPi targeting using the FGATIR (fast gray matter acquisition T1-weighted inversion recovery) MRI sequence and compared it with consensus coordinate-based indirect targeting. Stereotactic target coordinates were obtained and analyzed. RESULTS: In our GPi DBS case sequences, GPi borders were unresolvable on T2-weighted MRI. However, in all cases, application of the PUT-based method resulted in consistently localized GPi targets, which were confirmed by merging the T2-weighted MRI with the FGATIR MRI. Significant differences were noted in the target coordinates between the PUT-based method and indirect targeting based on both the distance from the anterior commissure and the distance from the intercommissural plane. The mean differences for mediolateral distance and anteroposterior distance were 1.4 and 1.42 mm, respectively. In addition, the PUT-based method estimated a target that was closer to the nearest implanted electrode. CONCLUSION: Our PUT-based method allows consistent and precise patient-specific GPi targeting. Further study is planned to correlate PUT-based GPi targeting with microelectrode recording, location of active contact of the DBS electrode and clinical outcome.


Assuntos
Estimulação Encefálica Profunda/métodos , Globo Pálido/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapia , Putamen/diagnóstico por imagem , Idoso , Eletrodos Implantados , Feminino , Globo Pálido/anatomia & histologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Microeletrodos , Pessoa de Meia-Idade , Putamen/anatomia & histologia , Estudos Retrospectivos
14.
JCI Insight ; 2(7): e90133, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-28405611

RESUMO

BACKGROUND. We report the 12-month clinical and imaging data on the effects of bilateral delivery of the glutamic acid decarboxylase gene into the subthalamic nuclei (STN) of advanced Parkinson's disease (PD) patients. METHODS. 45 PD patients were enrolled in a 6-month double-blind randomized trial of bilateral AAV2-GAD delivery into the STN compared with sham surgery and were followed for 12 months in open-label fashion. Subjects were assessed with clinical outcome measures and 18F-fluorodeoxyglucose (FDG) PET imaging. RESULTS. Improvements under the blind in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores in the AAV2-GAD group compared with the sham group continued at 12 months [time effect: F(4,138) = 11.55, P < 0.001; group effect: F(1,35) = 5.45, P < 0.03; repeated-measures ANOVA (RMANOVA)]. Daily duration of levodopa-induced dyskinesias significantly declined at 12 months in the AAV2-GAD group (P = 0.03; post-hoc Bonferroni test), while the sham group was unchanged. Analysis of all FDG PET images over 12 months revealed significant metabolic declines (P < 0.001; statistical parametric mapping RMANOVA) in the thalamus, striatum, and prefrontal, anterior cingulate, and orbitofrontal cortices in the AAV2-GAD group compared with the sham group. Across all time points, changes in regional metabolism differed for the two groups in all areas, with significant declines only in the AAV2-GAD group (P < 0.005; post-hoc Bonferroni tests). Furthermore, baseline metabolism in the prefrontal cortex (PFC) correlated with changes in motor UPDRS scores; the higher the baseline PFC metabolism, the better the clinical outcome. CONCLUSION. These findings show that clinical benefits after gene therapy with STN AAV2-GAD in PD patients persist at 12 months. TRIAL REGISTRATION. ClinicalTrials.gov NCT00643890. FUNDING. Neurologix Inc.


Assuntos
Terapia Genética/métodos , Glutamato Descarboxilase/genética , Doença de Parkinson/terapia , Adulto , Idoso , Dependovirus , Método Duplo-Cego , Feminino , Seguimentos , Técnicas de Transferência de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Parvovirinae , Tomografia por Emissão de Pósitrons , Núcleo Subtalâmico/diagnóstico por imagem , Núcleo Subtalâmico/fisiopatologia , Resultado do Tratamento , Estados Unidos
15.
Stereotact Funct Neurosurg ; 95(2): 107-113, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28324881

RESUMO

BACKGROUND/AIMS: Laser interstitial thermal therapy (LITT) has become an alternative to open-resective surgery for refractory mesial temporal lobe epilepsy (MTLE). Occurrence of visual field defects (VFDs) following open surgery for MTLE is reported at 52-100%. We examined the rate of VFDs following LITT for amygdalohippocampectomy (AHE) and correlated the occurrence of VFDs with damage to the optic radiations, assessed by diffusion tensor tractography (DTI). METHODS: We performed a retrospective analysis of 5 patients who underwent LITT-AHE for medically refractory MTLE. We examined the association between VFDs and optic radiation damage by correlating postprocedural visual field testing with qualitative assessment of optic radiation fiber tracts. RESULTS: Postoperative assessments showed that 4 patients had normal visual field testing, and 1 had a right superior quadrantanopsia (20%). We performed 3-dimensional reconstruction of the optic radiation, laser probe trajectory, and ablation volume. Damage to Meyer's loop was determined consistent with the VFD. CONCLUSIONS: Short-term follow-up in our series suggests that laser ablation AHE may be associated with a lower rate of VFD than has been reported for open AHE. Our results suggest that incorporating optic radiation mapping through DTI may preoperatively help to minimize the risk of VFD following laser ablation AHE.


Assuntos
Tonsila do Cerebelo/cirurgia , Imagem de Tensor de Difusão/métodos , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/cirurgia , Terapia a Laser/tendências , Transtornos da Visão/etiologia , Adulto , Idoso , Tonsila do Cerebelo/diagnóstico por imagem , Epilepsia do Lobo Temporal/diagnóstico por imagem , Feminino , Seguimentos , Hipocampo/diagnóstico por imagem , Humanos , Terapia a Laser/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transtornos da Visão/diagnóstico por imagem , Campos Visuais/fisiologia , Vias Visuais/diagnóstico por imagem
16.
Lancet Neurol ; 10(4): 309-19, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21419704

RESUMO

BACKGROUND: Gene transfer of glutamic acid decarboxylase (GAD) and other methods that modulate production of GABA in the subthalamic nucleus improve basal ganglia function in parkinsonism in animal models. We aimed to assess the effect of bilateral delivery of AAV2-GAD in the subthalamic nucleus compared with sham surgery in patients with advanced Parkinson's disease. METHODS: Patients aged 30-75 years who had progressive levodopa-responsive Parkinson's disease and an overnight off-medication unified Parkinson's disease rating scale (UPDRS) motor score of 25 or more were enrolled into this double-blind, phase 2, randomised controlled trial, which took place at seven centres in the USA between Nov 17, 2008, and May 11, 2010. Infusion failure or catheter tip location beyond a predefined target zone led to exclusion of patients before unmasking for the efficacy analysis. The primary outcome measure was the 6-month change from baseline in double-blind assessment of off-medication UPDRS motor scores. This trial is registered with ClinicalTrials.gov, NCT00643890. FINDINGS: Of 66 patients assessed for eligibility, 23 were randomly assigned to sham surgery and 22 to AAV2-GAD infusions; of those, 21 and 16, respectively, were analysed. At the 6-month endpoint, UPDRS score for the AAV2-GAD group decreased by 8·1 points (SD 1·7, 23·1%; p<0·0001) and by 4·7 points in the sham group (1·5, 12·7%; p=0·003). The AAV2-GAD group showed a significantly greater improvement from baseline in UPDRS scores compared with the sham group over the 6-month course of the study (RMANOVA, p=0·04). One serious adverse event occurred within 6 months of surgery; this case of bowel obstruction occurred in the AAV2-GAD group, was not attributed to treatment or the surgical procedure, and fully resolved. Other adverse events were mild or moderate, likely related to surgery and resolved; the most common were headache (seven patients in the AAV2-GAD group vs two in the sham group) and nausea (six vs two). INTERPRETATION: The efficacy and safety of bilateral infusion of AAV2-GAD in the subthalamic nucleus supports its further development for Parkinson's disease and shows the promise for gene therapy for neurological disorders. FUNDING: Neurologix.


Assuntos
Técnicas de Transferência de Genes , Terapia Genética/métodos , Glutamato Descarboxilase/genética , Doença de Parkinson/terapia , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Subtalâmico/fisiopatologia , Resultado do Tratamento
17.
J Neurosurg ; 112(4): 829-31, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19558306

RESUMO

Discontinuity in the silicone insulation over an electrode of a left vagus nerve stimulator (VNS) allowed the aberrant leak of current to the phrenic nerve and other structures. This resulted in ipsilateral diaphragmatic dysfunction, inability to vocalize, and severe radiating pain into the jaw and upper incisor for the duration of each stimulation. The device was explanted and a new device was implanted. All stimulation-related symptoms ceased immediately. A similar discontinuity in the silicone insulation is the likely explanation for several prior reports of poorly understood pains and phrenic nerve stimulation in patients with VNSs. The findings and analysis of this case establish a rationale for consideration of replacement of the VNS lead in all similarly symptomatic patients.


Assuntos
Eletrodos Implantados/efeitos adversos , Dor Facial/etiologia , Silicones , Estimulação do Nervo Vago/efeitos adversos , Estimulação do Nervo Vago/instrumentação , Diafragma/inervação , Diafragma/fisiopatologia , Condutividade Elétrica , Falha de Equipamento , Dor Facial/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Nervo Frênico/fisiopatologia , Retratamento , Distúrbios da Fala/etiologia , Distúrbios da Fala/fisiopatologia
18.
J Neurosurg Spine ; 4(3): 246-50, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16572625

RESUMO

Epithelioid angiosarcoma of bone is a rare, high-grade lesion that is highly vascular and can be associated with a bleeding diathesis. An association has been reported in angiosarcomas in other locations with coagulopathy from tumor-related disseminated intravascular coagulopathy and fibrinolysis. The authors report the case of a rare occurrence of a primary sacral epithelioid angiosarcoma associated with a large epidural hematoma and a severe bleeding diathesis. A 25-year-old woman presented with weakness, fatigue, neck and low-back pain, and progressive left S-1 radiculopathy. Imaging studies revealed a large ventral epidural hematoma extending from the sacral region rostrally to C-2 and a vascular tumor located in the sacrum. The patient underwent a sacral laminectomy, complicated by postoperative bleeding from the wound, and required massive transfusions. Ultimately, multimodal therapy was required to obtain hemostasis, including the use of endovascular embolization, radiation therapy, and an infusion of epsilon-aminocaproic acid with heparin. This case represents the first report of a primary epithelioid angiosarcoma in the sacrum and emphasizes that the coagulopathy seen in angiosarcoma is also a feature of this epithelioid variant.


Assuntos
Neoplasias Ósseas/complicações , Hemangiossarcoma/complicações , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transfusão de Sangue , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Terapia Combinada , Doxorrubicina/administração & dosagem , Embolização Terapêutica , Feminino , Hemangiossarcoma/tratamento farmacológico , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Hematoma Epidural Espinal , Transtornos Hemorrágicos , Hemostasia , Humanos , Ifosfamida/administração & dosagem , Laminectomia , Imageamento por Ressonância Magnética , Sacro/patologia , Sacro/cirurgia , Resultado do Tratamento
19.
Neurologist ; 11(3): 187-9, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15860143

RESUMO

BACKGROUND: Herpes simplex encephalitis (HSE) still carries a high morbidity and mortality. REVIEW SUMMARY: The authors report a 27-year-old patient who presented with an HSE manifested by a high temperature, seizures, and headaches. His hospitalization course was complicated by a pulmonary embolism. After anticoagulation was started, the patient developed a right temporal hematoma at the same region of the abnormal signal on magnetic resonance imaging. The patient underwent a craniotomy and evacuation of the hematoma with an uneventful postoperative outcome. CONCLUSION: The safety of anticoagulation in HSE has not been raised in the literature previously, and it needs further study.


Assuntos
Anticoagulantes/efeitos adversos , Encefalite por Herpes Simples/complicações , Acidentes de Trânsito , Adulto , Craniotomia , Encefalite por Herpes Simples/patologia , Encefalite por Herpes Simples/cirurgia , Humanos , Hemorragias Intracranianas/induzido quimicamente , Imageamento por Ressonância Magnética , Masculino , Embolia Pulmonar/complicações , Embolia Pulmonar/tratamento farmacológico , Convulsões/etiologia , Lobo Temporal , Tomografia Computadorizada por Raios X , Filtros de Veia Cava
20.
J Neurosurg ; 99(2): 311-8, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12924706

RESUMO

OBJECT: Broca identified the posterior third of the inferior frontal gyrus as a locus essential for the production of fluent speech. The authors have conducted this retrospective analysis in an attempt to find readily identifiable landmarks on magnetic resonance (MR) imaging that correspond to intraoperative cortical stimulation-induced speech arrest. These landmarks demonstrate novel structural-functional relationships that can be used preoperatively to predict the location of the Broca area. METHODS: Using a neuronavigation system, sites where stimulation produced speech arrest (Broca area) were recorded in a consecutive series of patients undergoing awake tumor resections in the perisylvian territory of the dominant hemisphere. The authors reviewed 33 consecutive patients by projecting the MR imaging data sets and marking the site where the Broca area was identified. Sulcus topography was analyzed with respect to this site by scrolling into neighboring planes and classifying the frontal operculum into one of the four schemes of sulcus variability described by Ebeling, et al. The following categories of frontal opercula were found: 18 (69%) of 26 were Type I, eight (31%) of 26 were Type III, and seven cases eluded classification because of sulcal effacement. For patients with Type I anatomy, the Broca area was adjacent to, and distributed evenly around, the inferior precentral sulcus (IPS). Quantitatively, the site of speech arrest was located a mean of 2.4 +/- 0.25 cm from the anteroinferior aspect of the pars opercularis, where it abuts the subarachnoid space surrounding the apex of the pars triangularis. For all patients with Type III anatomy, the Broca area was adjacent to the accessory sulcus that lies immediately posterior to the IPS. In these patients the mean distance from the anterior inferior pars opercularis was 2.3 +/- 0.29 cm. The mean distance from the Broca area to the edge of the tumor for the 26 patients with clear sulcal anatomy was 1.29 +/- 0.12 cm. CONCLUSIONS: The results indicate a correlation between the structure of the frontal operculum as seen on MR imaging and the functional localization of speech arrest in the dominant hemisphere. Additionally, sulcal landmarks that can be used preoperatively to predict the location of the Broca area within the inferior frontal gyrus are described based on the patient population. This information will allow the surgeon to determine if an awake craniotomy is necessary to identify the Broca area when planning a surgical procedure near the dominant frontal operculum.


Assuntos
Mapeamento Encefálico , Lobo Frontal/anatomia & histologia , Lobo Frontal/cirurgia , Cuidados Intraoperatórios , Imageamento por Ressonância Magnética , Córtex Motor/anatomia & histologia , Cuidados Pré-Operatórios , Adulto , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Feminino , Lobo Frontal/patologia , Lateralidade Funcional/fisiologia , Glioma/patologia , Glioma/cirurgia , Humanos , Magnetoencefalografia/métodos , Masculino , Pessoa de Meia-Idade , Córtex Motor/patologia , Córtex Motor/cirurgia , Fala/fisiologia , Vigília
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