Monitoring cognitive functions during deep brain stimulation (DBS) interventions by Real Time Neuropsychological Testing (DBS-RTNT).

Objective: We monitored cognition during Deep brain stimulation (DBS) surgery, when the electrode is positioned at the target subthalamic nucleus (i.e., STN motor area) in 14 PD patients. Methods: We present the Real Time Neuropsychological Testing (DBS-RTNT) protocol, our preliminary experience, along with patients' performance comparing intraoperative results with baseline data. Results: Compared to baseline, DBS-RTNT in the target area showed a significantly decreased performance at some tasks belonging to memory and executive functions domains. Significantly decreased short-term memory and sequencing scores were found for right (vs. left) hemisphere DBS-RTNT. Conclusions: PD patients' performance should be monitored during DBS surgery as STN-DBS may induce changes in cognitive performance. These preliminary data contribute to improve, during DBS-surgery the anatomo-functional topography of the STN in order to identify, in future approaches, in the individual patient the best site producing positive motor effects, without causing negative cognitive and/or emotional changes. Medications (i.e., the patients underwent surgery in a levodopa off state) could in principle have influenced our results therefore future studies are needed to address possible confounding effect of levodopa use.

Deep brain stimulation for Parkinson's disease in practice: results of the survey by the Italian Neurosurgery Society.

BACKGROUND: Deep brain stimulation (DBS) is a safe and effective treatment for patients with advanced Parkinson's disease (PD) and many neurosurgical centers in Italy have a DBS program. Considering the prevalence of PD and criteria for DBS implantation, about 3200-10,350 PD patients may benefit from DBS in Italy. The global management of patients underwent DBS is complex and it can be supposed that many differences exist between centers in clinical practice. The Italian Neurosurgery Society (SINch) designed this survey to investigate the state of the art of DBS for PD in Italy. METHODS: A 26-item closed-ended question survey was designed and sanded by email at all Italian Neurosurgery centers. The main topic investigated was DBS teams, anatomical target selection, surgical procedure, neuroimaging, intraoperative target localization, DBS device and patients' follow-up. RESULTS: A total of 23 neurosurgery centers completed the survey. There are mainly low-to medium-volume centers (<20 annual DBS procedures) with dedicated DBS teams. The principal anatomical target used is subthalamic nucleus (STN) and, relative to the surgical technique, it emerges that in Italy DBS are bilaterally implanted in a single-step session with awake anesthesia and with frame-based technique. Final leads positioning is defined by microelectrode recordings (MER) and microstimulation (MS), with limited role of intraoperative neuroimaging (MRI and O-Arm). The stimulation is started at 15 or 30 days from procedure. CONCLUSIONS: Many centers of neurosurgery in Italy have a well-established DBS program for patients with advanced PD and some practical differences in technique between centers exist. Further investigation is needed to investigate specific criteria for selecting one technique over another.

Deep Brain Stimulation in childhood-onset dystonia due to brain pathology. A long-term study.

BACKGROUND: Pallidal Deep Brain Stimulation (DBS) is an established treatment option for isolated, inherited or idiopathic dystonia, however data on its safety and efficacy in other forms of dystonia are more limited. OBJECTIVES: Retrospective analysis of motor and non-motor outcomes in pediatric onset refractory dystonia due to static or progressive brain disorders in a cohort of patients with a DBS treatment duration ≥12 months. METHODS: Multidisciplinary assessments including standardised scales/tests of motor function, pain, quality of life, cognition and language were carried out before implantation and longitudinally afterwards. RESULTS: 9 patients were included, 7 had cerebral palsy. Mean age at implantation was 209 months ± 156, mean treatment duration 84 ± 37 months. DBS was well tolerated and positively affected both motor and non-motor functions. In particular, statistically significant improvements were documented in Burke-Fahn-Marsden Scale scores (- 19.9% p 0.01031) at 12 months and in long-term quality of life (+28.6%, p 0.0292). CONCLUSIONS: DBS may be a useful treatment option in generalized dystonia associated with brain pathology. Even when the motor benefits are limited, improvements in quality of life and non-motor functions, or the possible prevention of serious dystonia-related complications, may have a significant impact on overall clinical status.

Globus Pallidus Internus Deep Brain Stimulation Using Frame-Based vs. Frameless Stereotaxy in Dystonia: A Single-Center Experience.

Objective: Bilateral globus pallidus internus deep brain stimulation (GPi-DBS) is an established and effective therapy for primary refractory dystonia. However, the comparison of frameless vs. frame-based DBS surgery technique is still controversial. This retrospective study aims to compare the clinical outcome of two GPi-DBS surgical techniques for patients affected by primary generalized or multi-segmental dystonia. Methods: For lead's stereotaxic placement, 10 patients underwent frame-based surgery and the other 10 subjects DBS surgery with a frameless technique. Clinical features were evaluated at baseline and 6 and 12 months after surgery by means of the Burke-Fahn-Marsden Dystonia Rating Scale. Results: Frame-based GPi-DBS and frameless stereotaxic group revealed a comparable clinical outcome with no surgical complications. Conclusions: Frameless technique is safe and well-tolerated by patients and showed similar effectiveness of the frame-based stereotaxic surgery during GPi-DBS for primary dystonia. Notably, it could be a valid alternative solution because of the great advantage in improving the patient's discomfort during awake surgery.

Brain impedance variation of directional leads implanted in subthalamic nuclei of Parkinsonian patients.

OBJECTIVE: Conventional deep brain stimulation (DBS) systems with ring-shaped leads generate spherical electrical fields. In contrast, novel directional leads use segmented electrodes. Aim of this study was to quantify the impedance variations over time in subjects with the directional Cartesia-Boston® system. METHODS: Impedance records, programming settings, and clinical data of 11 consecutive Parkinsonian patients implanted with DBS directional leads in two Italian centers (Udine and Vicenza) were retrospectively evaluated. Data were collected before starting stimulation (in the operating room and at days 5 and 40) and after switching stimulation on at the successive follow-up visits (1, 6 and 12 months). RESULTS: Directional leads have significantly higher impedance than ring leads. Stimulated contacts had always lower impedance compared to non-stimulated contacts. Before DBS-on, all contacts had higher impedance in the operating room, with an initial decrease five days post-surgery and a subsequent increase at day 40, more evident for directional contacts. The impedance of directional leads increased post-implantation at 1 and 6 months with a plateau at 12 months. CONCLUSIONS: There was a significant difference between the directional and ring leads at baseline (before activation of DBS) and during follow-up (chronic DBS). SIGNIFICANCE: Our study reveals new information about the impedance of segmented electrodes that is useful for patient management during the initial test period, as well as during long-term DBS follow-up.

Frameless Deep Brain Stimulation Surgery: A Single-Center Experience and Retrospective Analysis of Placement Accuracy of 220 Electrodes in a Series of 110 Patients.

BACKGROUND: Proper lead placement is considered one of the key factors in achieving a good clinical outcome in deep brain stimulation (DBS), but there is still considerable controversy surrounding the accuracy of the frameless in comparison to the frame-based technique. OBJECTIVE: We report our single-center experience with DBS electrode placement to evaluate the accuracy of the frameless stereotactic system. METHODS: We prospectively analyzed the data of 110 patients who underwent DBS surgery for Parkinson disease, dystonia, essential tremor, or refractory epilepsy. The final targets (FTs) of the 220 leads were: subthalamic nucleus, globus pallidus pars interna, ventralis intermedius nucleus, and anterior nuclei of thalamus in thalamus. A bilateral stereotactic approach using a combined identification of target based on preoperative images (MRI and CT scan fusion) and intra-operative micro-electrode recording (MER) were done. We collected and compared the coordinates of planned target (PT), the definitive expected target (ET) during MER, and the effective final location (FT) of the lead using the postoperative CT. Accuracy was assessed by both vector error (VE) and deviation from the PT. RESULTS: The mean and SD from PTs was 0.78 ± 0.43 mm in the x direction, 0.68 ± 0.41 mm in the y direction, and 0.76 ± 0.41 mm in the z direction. Global VE was 1.43 ± 0.37. CONCLUSION: Frameless systems appear to be a reliable and accurate technique.

To move or not to move: subthalamic deep brain stimulation effects on implicit motor simulation.

We explored implicit motor simulation processes in Parkinson's Disease (PD) patients with ON-OFF subthalamic deep brain stimulation (DBS) of the sub-thalamic nucleus (STN). Participants made lexical decisions about hand action-related verbs, abstract verbs, and pseudowords presented either within a positive (e.g., "Do …") or a negative (e.g., "Don't …") sentence context. Healthy controls showed significantly slower responses for hand-action verbs (vs. abstract verbs) in the negative (vs. positive) context, which suggests that negative contexts may suppress motor simulation or preparation processes. The STN-DBS improves cortical motor functions, thus patients are expected to perform at the same level as unimpaired subjects in the ON condition. By contrast, the 50% reduced DBS is expected to result in a reduced activation for motor information, which in turn might cause a reduced, if not absent, context modulation. PD patients exhibited the same pattern as controls when their DBS was at 100% ON; however, reducing the DBS to 50% had a deleterious outcome on the positive faster than negative context effect, suggesting that the altered inhibition mechanism in PD could be responsible for the missed effect. In addition, our results confirm the view that implicit motor simulation mechanisms behind action-related verb processing are flexible and context-dependent.

Microsubthalamotomy improves sleep in patients affected by advanced Parkinson's disease.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves sleep in patients affected by Parkinson's disease (PD). Since microsubthalamotomy (mSTN) shows positive effects on motor symptoms, it could improve sleep in PD patients. Our goals were: to assess the effects of mSTN on sleep in patients affected by advanced PD; and to look for a correlation between sleep and motor features after the neurosurgical procedure. METHODS: Fifteen patients who underwent bilateral STN-DBS were enrolled. Subjective sleep evaluation was assessed using the Parkinson's Disease Sleep Scale (PDSS). Data on sleep schedule and presence of restless legs syndrome (RLS) were obtained. Objective sleep features were investigated by polysomnography (PSG). To evaluate the mSTN effect, we compared motor state and sleep features before and after the neurosurgical procedure, before the programmable pulse generator was switched on. RESULTS: mSTN had beneficial effects on motor state and sleep features. After the surgery, the mean total PDSS score increased from 84.0±25.2 to 115.2±16.6 (P<0.001). PD patients reported longer total sleep time duration, decreased daytime sleepiness, and improvement in RLS symptoms. PSG data showed an increase in total sleep time and sleep efficiency with a decrease in wakefulness after sleep onset and arousal index. No correlation between motor improvements and sleep features modifications was observed after mSTN. CONCLUSIONS: mSTN improves sleep quality and ameliorates several sleep complaints, as well as motor symptoms, in advanced PD patients who have undergone STN-DBS.

Emotion recognition in Parkinson's disease after subthalamic deep brain stimulation: differential effects of microlesion and STN stimulation.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) has acquired a relevant role in the treatment of Parkinson's disease (PD). Despite being a safe procedure, it may expose patients to an increased risk to experience cognitive and emotional difficulties. Impairments in emotion recognition, mediated both by facial and prosodic expressions, have been reported in PD patients treated with such procedure. However, it is still unclear whether the STN per se is responsible for such changes or whether others factors like the microlesion produced by the electrode implantation may also play a role. In this study we evaluated facial emotions discrimination and emotions recognition using both facial and prosodic expressions in 12 patients with PD and 13 matched controls. Patients' were tested in four conditions: before surgery, both in on and off medication, and after surgery, respectively few days after STN implantation before turning stimulator on and few months after with stimulation on. We observed that PD patients were impaired in discriminating and recognizing facial emotions, especially disgust, even before DBS implant. Microlesion caused by surgical procedure was found to influence patients' performance on the discrimination task and recognition of sad facial expression while, after a few months of STN stimulation, impaired disgust recognition was again prominent. No impairment in emotional prosody recognition was observed both before and after surgery. Our study confirms that PD patients may experience a deficit in disgust recognition and provides insight into the differential effect of microlesion and stimulation of STN on several tasks assessing emotion recognition.

Deep brain stimulation: Subthalamic nucleus electrophysiological activity in awake and anesthetized patients.

OBJECTIVE: The purpose of this study was to evaluate changes in subthalamic nucleus (STN) neuronal activity in Parkinson's disease (PD) patients during deep brain stimulation (DBS) surgery under general anesthesia, and to compare these data with those recorded in the same subjects during previous surgery under local anesthesia. METHODS: Five patients with advanced PD, who had previously undergone bilateral STN-DBS under local anesthesia, underwent re-implantation under general anesthesia (with an anesthetic protocol based on the intravenous infusion of remifentanyl and ketamine) owing to surgical device complications. The microelectrode recording (MER) data obtained were analyzed by an off-line spike-sorting software. Neurophysiological data (number of spikes detected, mean firing rate, pause index and burst index) obtained under local and general anesthesia were then evaluated and compared by means of statistical analysis. RESULTS: We found no statistically significant difference between the first and second surgical procedures in any of the neurophysiological parameters analyzed. CONCLUSIONS: Bilateral STN-DBS for advanced PD with MER guidance is possible and reliable under a ketamine-based anesthetic protocol. SIGNIFICANCE: General anesthesia can be proposed for those patients who do not accept an "awake surgery" for clinical reasons, such as excessive fear, poor cooperation or severe "off"-medication effects.

Surgery of insular nonenhancing gliomas: volumetric analysis of tumoral resection, clinical outcome, and survival in a consecutive series of 66 cases.

BACKGROUND: Despite intraoperative technical improvements, the insula remains a challenging area for surgery because of its critical relationships with vascular and neurophysiological functional structures. OBJECTIVE: To retrospectively investigate the morbidity profile in insular nonenhancing gliomas, with special emphasis on volumetric analysis of tumoral resection. METHODS: From 2000 to 2010, 66 patients underwent surgery. All surgical procedures were conducted under cortical-subcortical stimulation and neurophysiological monitoring. Volumetric scan analysis was applied on T2-weighted magnetic resonance images (MRIs) to establish preoperative and postoperative tumoral volume. RESULTS: The median preoperative tumor volume was 108 cm. The median extent of resection was 80%. The median follow-up was 4.3 years. An immediate postoperative worsening was detected in 33.4% of cases; a definitive worsening resulted in 6% of cases. Patients with extent of resection of > 90% had an estimated 5-year overall survival rate of 92%, whereas those with extent of resection between 70% and 90% had a 5-year overall survival rate of 82% (P < .001). The difference between preoperative tumoral volumes on T2-weighted MRI and on postcontrast T1-weighted MRI ([T2 - T1] MRI volume) was computed to evaluate the role of the diffusive tumoral growing pattern on overall survival. Patients with preoperative volumetric difference < 30 cm demonstrated a 5-year overall survival rate of 92%, whereas those with a difference of > 30 cm had a 5-year overall survival rate of 57% (P = .02). CONCLUSION: With intraoperative cortico-subcortical mapping and neurophysiological monitoring, a major resection is possible with an acceptable risk and a significant result in the follow-up.

Autism and motor acts: experimental analysison mylohyoid muscle emg recordingsduring grasping-to-eat action - biomed 2010.

Most neuroscience studies do not pay enough attention to bio-mechanical related problems, such as the kinematic aspects of movements, that pose important boundary conditions, but are in general not sufficiently taken into consideration. In this work, using an experimental protocol based on measurements of mylohyoid (MH) muscle activity during grasping-to-eat actions, we debate the existence of impairments of action chains in children with autism spectrum disorders (ASD). We re-examine the results of an electromyographic (EMG) experiment on MH muscle presented in a previous study; and we compare them to the results of a new, similar experiment in order to study the electromyographic activity of MH in typically developing (TD) children and in children with ASD executing grasping-to-eat actions. Our results are remarkably different from the original work and seem to indicate that there is no clear experimental evidence of different action organization in children with ASD.

Semantic access dysphasia resulting from left temporal lobe tumours.

Unlike semantic degradation disorders, the mechanisms and the anatomical underpinnings of semantic access disorders are still unclear. We report the results of a case series study on the effects of temporal lobe gliomas on semantic access abilities of a group of 20 patients. Patients were tested 1-2 days before and 4-6 days after the removal of the tumour. Their semantic access skills were assessed with two spoken word-to-picture matching tasks, which aimed to separately control for rate of presentation, consistency and serial position effects (Experiment 1) and for word frequency and semantic distance effects (Experiment 2). These variables have been held to be critical in characterizing access in contrast to degraded-store semantic deficits, with access deficits characterized by inconsistency of response, better performance with slower presentation rates and with semantically distant stimuli, in the absence of frequency effects. Degradation deficits show the opposite pattern. Our results showed that low-grade slowly growing tumours tend not to produce signs of access problems. However, high-grade tumours especially within the left hemisphere consistently produce strong semantic deficits of a clear access type: response inconsistency and strong semantic distance effects in the absence of word frequency effects were detected. However, effects of presentation rate and serial position were very weak, suggesting non-refractory behaviour in the tumour patients tested. This evidence, together with the results of lesion overlapping, suggests the presence of a type of non-refractory semantic access deficit. We suggest that this deficit could be caused by the disconnection of posterior temporal lexical input areas from semantic system.

The neural basis of temporal preparation: Insights from brain tumor patients.

When foreperiods (FPs) of different duration vary on a trial-by-trial basis equiprobably but randomly, the RT is faster as the FP increases (variable FP effect), and becomes slower as the FP on the preceding trial gets longer (sequential effects). It is unclear whether the two effects are due to a common mechanism or to two different ones. Patients with lesions on the right lateral prefrontal cortex do not show the typical FP effect, suggesting a deficit in monitoring the FP adequately [Stuss, D. T., Alexander, M. P., Shallice, T., Picton, T. W., Binns, M. A., Macdonald, R., et al. (2005). Multiple frontal systems controlling response speed. Neuropsychologia, 43, 396-417]. The aim of this study was two-fold: (1) to replicate this neuropsychological result testing cerebral tumor patients before and after surgical removal of the tumor located unilaterally in the prefrontal, premotor or parietal cortex, respectively and (2) to investigate whether the sequential effects would change together with the FP effect (supporting single-process accounts) or the two effects can be dissociated across tumor locations (suggesting dual-process views). The results of an experiment with a variable FP paradigm show a significant reduction of the FP effect selectively after excision of tumors on right prefrontal cortex. On the other hand, the sequential effects were reliably reduced especially after surgical removal of tumors located in the left premotor region, despite a normal FP effect. The latter dissociation between the two effects supports a dual-process account of the variable FP phenomena. This study demonstrates that testing acute cerebral tumor patients represents a viable neuropsychological approach for the fractionation and localisation of cognitive processes.

Mental rotation in a patient with an implanted electrode grid in the motor cortex.

We investigated the effects of cortical stimulation on mental rotation tasks in a patient with an electrode array placed over his left primary motor cortex. The array was implanted to relieve chronic pain resulting from right brachial plexus damage. Tasks involving motor imagery were slowed down by cortical stimulation, whereas those involving visual imagery were not. When the patient performed the motor-imagery task, the interference effect on response times disappeared if the stimulator was switched off. We also probed two of the sites (anterior-lateral and posterior-medial position), and found that stimulation of the more anterior-lateral one consistently disrupted motor imagery.