Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 2.

The field of neuromodulation has evolved significantly over the past decade. Developments include novel indications and innovations of hardware, software, and stimulation techniques leading to an expansion in scope and role of these techniques as powerful therapeutic interventions. In this review, which is the second part of an effort to document and integrate the basic fundamentals and recent successful developments in the field, we will focus on classic paradigms for electrode placement as well as new exploratory targets, mechanisms of neuromodulation using this technique and new developments, including focused ultrasound driven ablative procedures.

O campo da neuromodulação evoluiu significativamente na última década. Esse progresso inclui novas indicações e inovações de hardware, software e técnicas de estimulação, levando a uma expansão das áreas clínicas cobertas e no papel dessas técnicas como intervenções terapêuticas eficazes. Nesta revisão, que é a segunda parte de um esforço para documentar e integrar os fundamentos básicos e os desenvolvimentos recentes e bem-sucedidos no campo, vamos nos concentrar em paradigmas clássicos para colocação de eletrodos, bem como em novos alvos exploratórios, mecanismos de neuromodulação usados por esta técnica e novos desenvolvimentos, incluindo procedimentos ablativos orientados por ultrassom focalizado.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1.

Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Nas últimas três décadas, a estimulação cerebral profunda (ECP) se tornou um tratamento bem estabelecido para doença de Parkinson (DP) e outros transtornos do movimento. A eficácia a longo prazo na DP foi bem documentada para a melhora dos sintomas motores cardinais da DP e das complicações induzidas pelo uso do levodopa, como as flutuações motoras e as discinesias. O momento da seleção do paciente é crucial para se obter os benefícios ideais da ECP, antes que as complicações da DP se tornem irreversíveis. O objetivo desta primeira parte da revisão é examinar os conceitos fundamentais da ECP na prática clínica, discutindo os aspectos históricos, a seleção de pacientes, os potenciais efeitos da ECP nos sintomas motores e não motores da doença e o manejo prático dos pacientes após a cirurgia.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1 / Princípios da estimulação cerebral profunda na doença de Parkinson na prática clínica: parte 1

Abstract Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Resumo Nas últimas três décadas, a estimulação cerebral profunda (ECP) se tornou um tratamento bem estabelecido para doença de Parkinson (DP) e outros transtornos do movimento. A eficácia a longo prazo na DP foi bem documentada para a melhora dos sintomas motores cardinais da DP e das complicações induzidas pelo uso do levodopa, como as flutuações motoras e as discinesias. O momento da seleção do paciente é crucial para se obter os benefícios ideais da ECP, antes que as complicações da DP se tornem irreversíveis. O objetivo desta primeira parte da revisão é examinar os conceitos fundamentais da ECP na prática clínica, discutindo os aspectos históricos, a seleção de pacientes, os potenciais efeitos da ECP nos sintomas motores e não motores da doença e o manejo prático dos pacientes após a cirurgia.

Design and validation of looping assistance methods in robotic-assisted neonatal surgical suturing in a chest model.

BACKGROUND: Neonate patients have a reduced thoracic cavity, making thoracoscopic procedures even more challenging than their adult counterparts. METHODS: We evaluated five control strategies for robot-assisted thoracoscopic surgical looping in simulations and experiments with a physical robotic system in a neonate surgical phantom. The strategies are composed of state-of-the-art constrained optimization and a novel looping force feedback term. RESULTS: All control strategies allowed users to successfully perform looping. A user study in simulation showed that the proposed strategy was superior in terms of Physical demand p < 0.05 $\left(p< 0.05\right)$ and task duration p < 0.05 $\left(p< 0.05\right)$ . The cumulative sum analysis of inexperienced users shows that the proposed looping force feedback can speed up the learning. Results with surgeons did not show a significant difference among control strategies. CONCLUSIONS: Assistive strategies in looping show promise and further work is needed to extend these benefits to other subtasks in robot-aided surgical suturing.

The effects of different levels of realism on the training of CNNs with only synthetic images for the semantic segmentation of robotic instruments in a head phantom.

PURPOSE: The manual generation of training data for the semantic segmentation of medical images using deep neural networks is a time-consuming and error-prone task. In this paper, we investigate the effect of different levels of realism on the training of deep neural networks for semantic segmentation of robotic instruments. An interactive virtual-reality environment was developed to generate synthetic images for robot-aided endoscopic surgery. In contrast with earlier works, we use physically based rendering for increased realism. METHODS: Using a virtual reality simulator that replicates our robotic setup, three synthetic image databases with an increasing level of realism were generated: flat, basic, and realistic (using the physically-based rendering). Each of those databases was used to train 20 instances of a UNet-based semantic-segmentation deep-learning model. The networks trained with only synthetic images were evaluated on the segmentation of 160 endoscopic images of a phantom. The networks were compared using the Dwass-Steel-Critchlow-Fligner nonparametric test. RESULTS: Our results show that the levels of realism increased the mean intersection-over-union (mIoU) of the networks on endoscopic images of a phantom ([Formula: see text]). The median mIoU values were 0.235 for the flat dataset, 0.458 for the basic, and 0.729 for the realistic. All the networks trained with synthetic images outperformed naive classifiers. Moreover, in an ablation study, we show that the mIoU of physically based rendering is superior to texture mapping ([Formula: see text]) of the instrument (0.606), the background (0.685), and the background and instruments combined (0.672). CONCLUSIONS: Using physical-based rendering to generate synthetic images is an effective approach to improve the training of neural networks for the semantic segmentation of surgical instruments in endoscopic images. Our results show that this strategy can be an essential step in the broad applicability of deep neural networks in semantic segmentation tasks and help bridge the domain gap in machine learning.

SmartArm: Integration and validation of a versatile surgical robotic system for constrained workspaces.

BACKGROUND: With the increasing presence of surgical robots minimally invasive surgery, there is a growing necessity of a versatile surgical system for deep and narrow workspaces. METHODS: We developed a versatile system for constrained workspaces called SmartArm. It has two industrial-type robotic arms with flexible tools attached to its distal tip, with a total of nine active degrees-of-freedom. The system has a control algorithm based on constrained optimization that allows the safe generation of task constraints and intuitive teleoperation. RESULTS: The SmartArm system is evaluated in a master-slave experiment in which a medically untrained user operates the robot to suture the dura mater membrane at the skull base of a realistic head phantom. Our results show that the user could accomplish the task proficiently, with speed and accuracy comparable to manual suturing by surgeons. Conclusions We demonstrated the integration and validation of the SmartArm.

Virtual reality simulation of robotic transsphenoidal brain tumor resection: Evaluating dynamic motion scaling in a master-slave system.

BACKGROUND: Integrating simulators with robotic surgical procedures could assist in designing and testing of novel robotic control algorithms and further enhance patient-specific pre-operative planning and training for robotic surgeries. METHODS: A virtual reality simulator, developed to perform the transsphenoidal resection of pituitary gland tumours, tested the usability of robotic interfaces and control algorithms. It used position-based dynamics to allow soft-tissue deformation and resection with haptic feedback; dynamic motion scaling control was also incorporated into the simulator. RESULTS: Neurosurgeons and residents performed the surgery under constant and dynamic motion scaling conditions (CMS vs DMS). DMS increased dexterity and reduced the risk of damage to healthy brain tissue. Post-experimental questionnaires indicated that the system was well-evaluated by experts. CONCLUSION: The simulator was intuitively and realistically operated. It increased the safety and accuracy of the procedure without affecting intervention time. Future research can investigate incorporating this simulation into a real micro-surgical robotic system.

Autonomous Positioning of Eye Surgical Robot Using the Tool Shadow and Kalman Filtering.

Vitreoretinal surgery is one of the most difficult surgical operations, even for experienced surgeons. Thus, a master-slave eye surgical robot has been developed to assist the surgeon in safely performing vitreoretinal surgeries; however, in the master-slave control, the robotic positioning accuracy depends on the surgeon's coordination skills. This paper proposes a new method of autonomous robotic positioning using the shadow of the surgical instrument. First, the microscope image is segmented into three regions-namely, a micropipette, its shadow, and the eye ground-using a Gaussian mixture model (GMM). The tips of the micropipette and its shadow are then extracted from the contour lines of the segmented regions. The micropipette is then autonomously moved down to the simulated eye ground until the distance between the tips of micropipette and its shadow in the microscopic image reaches a predefined threshold. To handle possible occlusions, the tip of the shadow is estimated using a Kalman filter. Experiments to evaluate the robotic positioning accuracy in the vertical direction were performed. The results show that the autonomous positioning using the Kalman filter enhanced the accuracy of robotic positioning.

Impacto da estimulação cerebral profunda na qualidade de vida e humor em pacientes com doença de Parkinson / Impact of deep brain stimulation on quality of life and mood in patients with Parkinson's disease

A doença de Parkinson (DP) é uma doença neurodegenerativa deri¬vada de uma redução da produção de dopamina. O seu tratamento é basicamente por medidas farmacológicas. No entanto, nos está¬dios avançados da doença, especialmente devido às flutuações do motor, o tratamento farmacológico por si só não é completamente bem-sucedido. Assim, surge a possibilidade de benefícios ao pacien¬te pela técnica de estimulação cerebral profunda (DBS). O objetivo deste estudo foi analisar o impacto do DBS palidal ou subtalâmica sobre a qualidade de vida desses pacientes (QoL). Para tanto, em¬pregaram-se duas escalas, comparando os resultados pré e pós-ope¬ratórios: o Inventário de Depressão de Beck - BDI (avalia o aspecto emocional dos pacientes) e o PDQ-39 (avalia os aspectos motores e as relações sociais). Podemos observar que a avaliação do BDI apon¬tou para uma melhora média de 9,5% e os escores do PDQ-39 me¬lhoraram 10,28%. Há evidências que pacientes submetidos à técnica de DBS subalâmicos ou paliativos mostraram uma QoL de melhoria importante, assim, o DBS surge como um adjuvante na luta contra a doença de Parkinson. (AU)

Parkinson's disease (PD) is a neurodegenerative disorder derived from a reduction of dopamine production. The treatment of PD is basically by pharmacological measures. However, in the advanced stages of the disease, especially due to motor fluctuations, phar¬macological treatment by itself is not completely successful. At that moment, the possibility of the patient´s benefits by the technique of deep brain stimulation (DBS) comes up. The aim of this study was to analyze the impact of pallidal or subthalamic DBS on PD patients' quality of life (QoL). To do so, two scales were employed, comparing the pre and post-operative results: Beck Depression Inventory - BDI (evaluates the patients' emotional aspect) and PDQ-39 (evaluates mo¬tor aspects and social relations). We could observe that BDI evalua¬tion pointed to an average improvement of 9.5% and PDQ-39 scores improved 10.28%. We can conclude that patients who have undergo¬ne the technique of subthalamic or pallidal DBS showed an important improvement QoL. DBS comes up as an adjuvant in the fight against Parkinson's disease. (AU)

On the use of discrete steps in robot-aided flexible needle insertion.

Needle steering devices present great potential for improving the safety and accuracy of medical interventions with percutaneous access. Despite significant advances in the field, needle steerability remains an issue to be solved by the scientific community. In this paper, we propose the use of discrete steps in flexible needle insertion, inspired by the manual procedure performed by physicians. Conceptually, the method relies in alternating between two motions: grasp-push and release-retreat. For experimental evaluation, a modified gripper is used along with a 6DOF robotic manipulator to control needle insertion velocity, rotation and grasping. Preliminary results indicate that the use of discrete steps minimizes some negative effects, such as slippage and needle buckling, observed on alternative methods, while preserving their functional advantages.

Hemispheric surgery for refractory epilepsy in children and adolescents: outcome regarding seizures, motor skills and adaptive function.

PURPOSE: The aim of the study was to report the seizure outcome, motor skills and adaptive motor functions in a series of children and adolescents who underwent hemispheric surgery, analysing the risk-benefits of surgery. METHODS: The clinical course, seizure and motor function outcomes of 15 patients who underwent hemispheric surgery were reviewed. RESULTS: The mean age at surgery was 9.5, with 1-9 years follow-up. The underlying pathologies were Rasmussen encephalitis, vascular disorders, and hemimegalencephaly. All the patients presented with severe epilepsy and different degrees of hemiparesis, although motor functionality was preserved in 80% of the patients. At last follow-up, 67% were seizure free, and 20% rarely experienced seizures. Antiepileptic drugs were reduced in 60%, and complete withdrawal from such drugs was successful in 20% of the patients. The motor outcome following the surgery varied between the patients. Despite the motor deficit after surgery, the post-operative motor function showed unchanged for gross motor function in most (60%), while 27% improved. Similar results were obtained for the ability to handle objects in daily life activities. Sixty percent of the children were capable of handling objects, with somewhat reduced coordination and/or motor speed. CONCLUSION: Pre-surgical motor function continues to play a role in the pre-surgical evaluation process in order to provide a baseline for outcome. Hemispheric surgery, once regarded as a radical intervention and last treatment resource, may become routinely indicated for refractory hemispheric epilepsy in children and adolescents, with oftentime favourable motor outcomes.

Corpus callosotomy in a patient with startle epilepsy.

Startle epilepsy is a syndrome of reflex epilepsy in which the seizures are precipitated by a sudden and surprising, usually auditory, stimulus. We describe herein a girl who had been suffering with startle-induced seizures since 2 years of age. She had focal, tonic and tonic-clonic seizures, refractory to antiepileptic treatment. Daily tonic seizures led to very frequent falls and morbidity. Neurologically, she had no deficit. Interictal EEG showed slow waves and epileptiform discharges in central and fronto-central regions. Video-polygraphic recordings of seizures, triggered by stimuli, showed generalised symmetric tonic posturing with ictal EEG, characterised by an abrupt and diffuse electrodecremental pattern of fast activity, followed by alpha-theta rhythm superimposed by epileptic discharges predominantly over the vertex and anterior regions. Magnetic resonance imaging showed no abnormalities. Corpus callosotomy was performed when the patient was 17. Since surgery, the patient (one year follow-up) has remained seizure-free. Corpus callosotomy may be considered in patients with startle epilepsy and tonic seizures, in the absence of focal lesions amenable to surgery. [Published with video sequences].

Granule cell dispersion is not a predictor of surgical outcome in temporal lobe epilepsy with mesial temporal sclerosis.

The aim of this retrospective study of a series of patients with mesial temporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS) was to analyze the association of granule cell dispersion (GCD) with surgical prognosis, patterns of MTS and clinical data. Hippocampal specimens from 66 patients with MTLE and unilateral MTS and from 13 controls were studied. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patients' clinical data, types of MTS and surgical outcome were reviewed. GCD occurred in 45.5% of cases and was not correlated with clinical variable. More severe neuronal loss was observed in patients with GCD. Except for MTS Type 2 - observed only in four no- GCD patients - groups did not differ with respect to the types of MTS. Surgical outcome was similar in both groups. In conclusion, GCD was associated with the degree of hippocampal cell loss, but was not a predictor of surgical outcome.

Granule cell dispersion is associated with memory impairment in right mesial temporal lobe epilepsy.

PURPOSE: We analyzed the association of granule cell dispersion (GCD) with memory performance, clinical data and surgical outcome in a series of patients with mesial temporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS). METHOD: Hippocampal specimens from 54 patients with MTLE (27 patients with right MTLE and 27 with left MTLE) and unilateral MTS, who were separated into GCD and no-GCD groups and thirteen controls were studied. Quantitative neuropathological evaluation was performed using hippocampal sections stained with NeuN. Patients' neuropsychological measures, clinical data, type of MTS and surgical outcome were reviewed. RESULTS: GCD occurred in 28 (51.9%) patients. No correlation between GCD and MTS pattern, clinical data or surgical outcome was found. The presence of GCD was correlated with worse visuospatial memory performance in right MTLE, but not with memory performance in left MTLE. CONCLUSION: GCD may be related to memory impairment in right MTLE-MTS patients. However, the role of GCD in memory function is not precisely defined.

Major depressive disorder as a predictor of a worse seizure outcome one year after surgery in patients with temporal lobe epilepsy and mesial temporal sclerosis.

PURPOSE: The association between pre-surgical psychiatric disorders (PDs) and worse seizure outcome in patients with refractory epilepsy submitted to surgery has been increasingly recognized in the literature. The present study aimed to verify the impact of pre- and post-surgical PD on seizure outcome in a series of patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS). METHOD: Data from 115 TLE-MTS patients (65 females; 56.5%) who underwent cortico-amygdalohippocampectomy (CAH) were analyzed. Pre- and post-surgical psychiatric evaluations were performed using DSM-IV and ILAE criteria. The outcome subcategory Engel IA was considered as corresponding to a favorable prognosis. A multivariate logistic regression model was applied to identify possible risk factors associated with a worse seizure outcome. RESULTS: Pre-surgical PDs, particularly major depressive disorder (MDD), anxiety and psychotic disorders, were common, being found in 47 patients (40.8%). Fifty-six patients (48.7%) were classified as having achieved an Engel IA one year after CAH. According to the logistic regression model, the presence of pre-surgical MDD (OR=5.23; p=0.003) appeared as the most important risk factor associated with a non-favorable seizure outcome. CONCLUSION: Although epilepsy surgery may be the best treatment option for patients with refractory TLE-MTS, our findings emphasize the importance of performing a detailed psychiatric examination as part of the pre-surgical evaluation protocol.

Pre-surgical predictors for psychiatric disorders following epilepsy surgery in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis.

Psychiatric outcomes of patients submitted to epilepsy surgery have gained particular interest given the high prevalence of pre-surgical psychiatric disorders (PD) in this population. The present study aimed to verify the possible pre-surgical predictors for psychiatric disorders following epilepsy surgery in a homogeneous series of patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS). Data from 115 TLE-MTS patients (65 females; 56.5%) who underwent cortico-amygdalohippocampectomy were included. Pre- and post-surgical psychiatric evaluations were performed using DSM-IV criteria. Pre-surgical PD - particularly mood, anxiety and psychotic disorders - were diagnosed in 47 patients (40.8%). Twenty-seven patients (54% of those with pre-surgical PD) demonstrated a remission of psychiatric symptoms on post-surgical psychiatric evaluation. Eleven patients (9.6%) developed de novo PD. The presence of pre-surgical depression (OR=3.32; p=0.008), pre-surgical interictal psychosis (OR=4.39; p=0.009) and epileptiform discharges contralateral to the epileptogenic zone (OR=2.73; p=0.01) were risk factors associated with post-surgical PD. Although epilepsy surgery is considered to be the best treatment option for patients with refractory TLE-MTS, the relatively high psychiatric comorbidities observed in surgical candidates and their possible negative impact on post-surgical outcomes require a careful pre-surgical evaluation of clinical, sociodemographic and psychiatric factors.

Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss as a predictor of surgical outcome.

OBJECTIVE: To analyze retrospectively a series of patients with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS), and the association of patterns of hippocampal sclerosis with clinical data and surgical prognosis. METHOD: Sixty-six patients with medically refractory TLE with unilateral MTS after anterior temporal lobectomy were included. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patient's clinical data and surgical outcome were reviewed. RESULTS: Occurrence of initial precipitating insult (IPI), as well as better postoperative seizure control (i.e. Engel class 1), were associated with classical and severe patterns of hippocampal sclerosis (MTS type 1a and 1b, respectively). CONCLUSION: Quantitative evaluation of hippocampal neuronal loss patterns predicts surgical outcome in patients with TLE-MTS.

Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss as a predictor of surgical outcome / Epilepsia do lobo temporal com esclerose mesial temporal: o padrão da perda neuronal hipocampal como preditor do prognóstico cirúrgico

OBJECTIVE: To analyze retrospectively a series of patients with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS), and the association of patterns of hippocampal sclerosis with clinical data and surgical prognosis. METHOD: Sixty-six patients with medically refractory TLE with unilateral MTS after anterior temporal lobectomy were included. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patient's clinical data and surgical outcome were reviewed. RESULTS: Occurrence of initial precipitating insult (IPI), as well as better postoperative seizure control (i.e. Engel class 1), were associated with classical and severe patterns of hippocampal sclerosis (MTS type 1a and 1b, respectively). CONCLUSION: Quantitative evaluation of hippocampal neuronal loss patterns predicts surgical outcome in patients with TLE-MTS.

OBJETIVO: Analisar retrospectivamente uma série de pacientes com epilepsia do lobo temporal (ELT) e esclerose mesial temporal (EMT), bem como correlacionar os padrões de esclerose hipocampal com os dados clínicos e o prognóstico cirúrgico. MÉTODOS: Foram incluídos neste estudo 66 pacientes com ELT refratária a tratamento medicamentoso e com EMT unilateral submetidos à lobectomia temporal anterior. A análise neuropatológica quantitativa foi realizada em seções hipocampais imunomarcadas com NeuN. Dados clínicos e resultados do acompanhamento pós-cirúrgico foram revisados. RESULTADOS: Ocorrência de evento precipitante inicial e melhor controle de crises após a cirurgia (i.e. classe 1 de Engel) foram associados aos padrões clássico (EMT tipo 1a) e severo (EMT tipo 1b) de esclerose hipocampal. CONCLUSÃO: A análise quantitativa do padrão de perda neuronal do hipocampo é capaz de predizer o prognóstico cirúrgico em pacientes com ELT-EMT.

Auras in temporal lobe epilepsy with hippocampal sclerosis: relation to seizure focus laterality and post surgical outcome.

We examined the relationship between presence and frequency of different types of auras and side of lesion and post surgical outcomes in 205 patients with medically intractable mesial temporal lobe epilepsy (MTLE) with unilateral hippocampal sclerosis (HS). With respect to the number of auras, multiple auras were not associated with side of lesion (p=0.551). The side of HS was not associated with the type of auras reported. One hundred fifty-seven patients were operated. The occurrence of multiple auras was not associated with post-surgical outcome (p=0.740). The presence of extratemporal auras was significantly higher in patients with poor outcome. In conclusion, this study suggests that the presence of extratemporal auras in patients with MTLE-HS possibly reflects extratemporal epileptogenicity in these patients, who otherwise showed features suggestive of TLE. Therefore, TLE-HS patients undergoing pre-surgical evaluation and presenting clinical symptoms suggestive of extratemporal involvement should be more extensively evaluated to avoid incomplete resection of the epileptogenic zone.