Zhipei Ling

Intraoperative MRI for optimizing electrode placement for deep brain stimulation of the subthalamic nucleus in Parkinson disease

OBJECT The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement. This study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes. METHODS Two hundred and six DBS electrodes were implanted in the subthalamic nucleus (STN) in 110 patients with Parkinson disease. All patients underwent iMRI after implantation to define the accuracy of lead placement. Fifty-six DBS electrode positions in 35 patients deviated from the center of the STN, according to the result of the initial postplacement iMRI scans. Thus, we adjusted the electrode positions for placement in the center of the STN and verified this by means of second or third iMRI scans. Recording was performed in adjusted parameters in the x-, y-, and z-axes. RESULTS Fifty-six (27%) of 206 DBS electrodes were adjusted as guided by iMRI. Electrode position was adjusted on the basis of iMRI 62 times. The sum of target coordinate adjustment was -0.5 mm in the x-axis, -4 mm in the y-axis, and 15.5 mm in the z-axis; the total of distance adjustment was 74.5 mm in the x-axis, 88 mm in the y-axis, and 42.5 mm in the z-axis. After adjustment with the help of iMRI, all electrodes were located in the center of the STN. Intraoperative MRI revealed 2 intraparenchymal hemorrhages in 2 patients, brain shift in all patients, and leads penetrating the lateral ventricle in 3 patients. CONCLUSIONS The iMRI technique can guide surgeons as they adjust deviated electrodes to improve the accuracy of implanting the electrodes into the correct anatomical position. The iMRI technique can also immediately demonstrate acute changes such as hemorrhage and brain shift during DBS surgery.

Deep brain stimulation for treatment of severe Alzheimer's disease: Study protocol for a prospective, self-controlled, phase I trial (case observation)

Background: With the aging of the global population, an increasing number of people are at risk of developing Alzheimers disease. There is currently no effective treatment to hinder or postpone the progression of Alzheimers disease. Cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist Memantine are the commonly prescribed drugs for this disease, but their therapeutic effects are still unsatisfactory. Therefore, there is an urgent need to investigate novel treatment methods. Many animal experiments have suggested that deep brain stimulation benefits Alzheimers disease, but clinical trials investigating this are still in their infancy. This study aims to investigate the safety and effectiveness of deep brain stimulation in the treatment of severe Alzheimers disease. Methods/Design: This study is a prospective, self-controlled, phase I trial (case observation), which will be performed in the Department of Neurosurgery, Chinese PLA General Hospital (Beijing, China). Six patients with severe Alzheimers disease will be enrolled to receive continuous bilateral deep brain stimulation of the fornix. Evaluations will be performed at baseline (prior to surgery) and at 1, 6, and 12 months after surgery. The primary outcome measures are disability and mortality rates during the 12-month deep brain stimulation trial period. Secondary outcome measures include the incidence of complications and Clinical Dementia Rating scale, Zarit Caregiver Burden Interview, Mini-Mental State Examination, and Barthel Index of Activities of Daily Living Scale scores. Patient recruitment will begin in August 2017, the analysis of primary outcome measures will be completed in October 2018, and the study will finish in June 2019. Discussion: The results of this study will help to determine the safety of deep brain stimulation for the treatment of severe Alzheimers disease. We will also assess whether deep brain stimulation can improve the cognition, symptoms, and activities of daily living of patients with Alzheimers disease. If the study succeeds, a novel option for patients with Alzheimers disease who respond poorly to current treatments may be provided. Trial registration: The study protocol is registered with ClinicalTrials.gov (identifier: NCT03115814). Ethics: The study protocol was approved by the Ethics Committee of Chinese PLA General Hospital (approval No. S2015-013-02) and will be performed in accordance with the Declaration of Helsinki formulated by the World Medical Association in 2013. Informed consent: Written informed consent will be obtained from each patients legal representative.

Partial improvement in performance of patients with severe Alzheimer's disease at an early stage of fornix deep brain stimulation

Deep brain stimulation is a therapy for Alzheimers disease (AD) that has previously been used for mainly mild to moderate cases. This study provides the first evidence of early alterations in performance induced by stimulation targeted at the fornix in severe AD patients. The performance of the five cases enrolled in this study was scored with specialized assessments including the Mini-Mental State Examination and Clinical Dementia Rating, both before and at an early stage after deep brain stimulation. The burden of caregivers was also evaluated using the Zarit Caregiver Burden Interview. As a whole, the cognitive performance of patients remained stable or improved to varying degrees, and caregiver burden was decreased. Individually, an improved mental state or social performance was observed in three patients, and one of these three patients showed remarkable improvement in long-term memory. The conditions of another patient deteriorated because of inappropriate antipsychotic medications that were administered by his caregivers. Taken together, deep brain stimulation was capable of improving some cognitive aspects in patients with severe AD, and of ameliorating their emotional and social performance, at least at an early stage. However, long-term effects induced by deep brain stimulation in patients with severe AD need to be further validated. More research should focus on clarifying the mechanism of deep brain stimulation. This study was registered with ClinicalTrials.gov (NCT03115814) on April 14, 2017.

[18F]ML-10 Imaging for Assessment of Apoptosis Response of Intracranial Tumor Early after Radiotherapy by PET/CT

[18F]ML-10 is a novel apoptosis radiotracer for positron emission tomography (PET). We assess the apoptosis response of intracranial tumor early after CyberKnife (CK) treatment by [18F]ML-10 PET imaging. 29 human subjects (30 lesions), diagnosed with intracranial tumors, underwent CK treatment at 14–24 Gy in 1–3 fractions, had [18F]ML-10 positron emission tomography/computed tomography (PET/CT) before (pre-CK) and 48 hours after (post-CK) CK treatment. Magnetic resonance imaging (MRI) scans were taken before and 8 weeks after CK treatment. Voxel-based analysis was used for the imaging analysis. Heterogeneous changes of apoptosis in tumors before and after treatment were observed on voxel-based analysis of PET images. A positive correlation was observed between the change in radioactivity (X) and subsequent tumor volume (Y) (r=0.862, p < 0.05), with a regression equation of Y=1.018∗X − 0.016. Malignant tumors tend to be more sensitive to CK treatment, but the treatment outcome is not affected by pre-CK apoptotic status of tumor cells; [18F]ML-10 PET imaging could be taken as an assessment 48 h after CK treatment.

Intracerebral Hemorrhage and Venous Infarction after Deep Brain Stimulation Lead Placement

To the Editor: Cerebral vascular events (intracerebral hemorrhage [ICH] or venous infarction) are the most feared complications of deep brain stimulation (DBS) surgery. The estimated risk of ICH in DBS surgery reportedly varies from 0.2% to 5.6%.[1‐3] ICH may develop at one of two sites depending on the puncture tract: (1) in the basal ganglia or target area or (2) in the puncture channel or cortex area. However, venous infarction in association with DBS surgery has rarely been described.[4‐6]

Integration of Functional MRI and White Matter Tractography in CyberKnife Radiosurgery

Purpose: To investigate the efficacy of the integration of functional magnetic resonance imaging and diffusion-tensor imaging tractography data into CyberKnife radiosurgery for intracranial tumor management. Materials and Methods: Functional neuroimaging, anatomical magnetic resonance imaging, and computed tomography images of patients with brain lesions in critical areas were acquired before radiosurgery. The acquired data sets were coregistered using the MIM image fusion software module and then were imported into the CyberKnife Robotic Radiosurgery System (Multiplan 4.0.2) for delineating the target, organs at risk, and possible nearby functionally relevant cortical and subcortical areas. Radiation dose distributions with and without the functionally relevant cortical and subcortical areas into the optimization process were developed and compared. Results: There were significant differences between the treatment plans with and without the functionally relevant cortical and subcortical areas into the optimization process. An average 22.71% reduction in the maximum dose to functional areas was observed. No neurological complication due to radiation damage was observed in the follow-up period. Conclusion: The functional neuroimaging could be easily and reliably integrated into the CyberKnife treatment planning. Consideration of functional structures and fiber tracts during treatment planning could clinically reduce the radiation doses to these critical structures, thereby preserving its unique function of brain.

Altered emotional prosody processing in patients with Parkinson’s disease after subthalamic nucleus stimulation

Background Patients with Parkinson’s disease (PD) exhibit deficits in recognizing and expressing vocal emotional prosody. The aim of this study was to explore emotional prosody processing in patients with PD shortly after subthalamic nucleus (STN) deep brain stimulation (DBS). Methods Two groups of patients with PD (pre-DBS and post-DBS) and one healthy control (HC) group were recruited as participants. All participants (PD and HC) were assessed using the Montreal Affective Voices database 50 Voices Recognition test. All participants were asked to nonverbally express five basic emotions (happiness, anger, fear, sadness, and neutral) to test emotional prosody expression. Fifteen native Chinese speakers were recruited as raters. We recorded the accuracy rate, reaction time, confidence level, and two acoustic parameters (mean pitch and mean intensity). Results The PD groups scored lower than the HC group in recognizing and expressing emotional prosody. STN DBS had no significant effect on the recognition of emotional prosody but had a significant effect on fear prosody expression. Pearson’s correlation analysis revealed significant correlations between performance on emotional prosody recognition tests and performance on emotional prosody expression tests in both the pre-DBS PD and post-DBS PD groups. Conclusion Shortly after STN DBS, the ability to recognize emotional prosody was not altered, but fear expression was impaired. We identified associations between abnormalities in emotional prosody recognition and expression deficits both before and after STN DBS, indicating that the processes involved in recognizing and expressing emotional prosody may share a common system.

Altered emotional recognition and expression in patients with Parkinson’s disease

Background Parkinson’s disease (PD) patients exhibit deficits in emotional recognition and expression abilities, including emotional faces and voices. The aim of this study was to explore emotional processing in pre-deep brain stimulation (pre-DBS) PD patients using two sensory modalities (visual and auditory). Methods Fifteen PD patients who needed DBS surgery and 15 healthy, age- and gender-matched controls were recruited as participants. All participants were assessed by the Karolinska Directed Emotional Faces database 50 Faces Recognition test. Vocal recognition was evaluated by the Montreal Affective Voices database 50 Voices Recognition test. For emotional facial expression, the participants were asked to imitate five basic emotions (neutral, happiness, anger, fear, and sadness). The subjects were required to express nonverbal vocalizations of the five basic emotions. Fifteen Chinese native speakers were recruited as decoders. We recorded the accuracy of the responses, reaction time, and confidence level. Results For emotional recognition and expression, the PD group scored lower on both facial and vocal emotional processing than did the healthy control group. There were significant differences between the two groups in both reaction time and confidence level. A significant relationship was also found between emotional recognition and emotional expression when considering all participants between the two groups together. Conclusion The PD group exhibited poorer performance on both the recognition and expression tasks. Facial emotion deficits and vocal emotion abnormalities were associated with each other. In addition, our data allow us to speculate that emotional recognition and expression may share a common system.

Protective effect of optic radiation reconstruction against the risk of visual field deficits in anterior temporal lobectomy

Objective To explore the clinical value of optic radiation reconstruction in protecting against visual field deficits (VFDs) in anterior temporal lobectomy (ATL). Methods We retrospectively analyzed 24 patients with medically refractory temporal lobe epilepsy undergoing ATL between January 2013 and June 2014. The surgical operations were aided by combining optic radiation reconstruction by diffusion tensor tractography (DTT), microscopy-based neuronavigation and intraoperative MRI (iMRI) techniques. ATL was performed according to the distance between Meyers loop and temporal pole. The visual fields were examined and seizure outcomes were evaluated by Engel class test in 3-month follow-up. Results The optic radiation was reconstructed in all patients. No bleeding was found in operative site or distant site by iMRI scan. The size of removed temporal lobe was 3.29 cm (1.90-5.10 cm). Visual field testing 3 months after operation showed no VFDs in 16 cases (66.67%) and mild VFDs (< 1/4 quadrant) in 8 cases (33.33% ). One case suffered mild VFD before operation, but did not aggravate after operation. Engel class test showed Engel classⅠin 19 patients (79.17%), class Ⅱ in 4 patients (16.67%) and class Ⅲ in one patient (4.17%). Conclusions For patients with medically refractory temporal lobe epilepsy, the techniques of combining optic radiation reconstruction, microscopy-based euronavigation and iMRI aided in precise mapping could reduce the risk of visual field deficits in anterior temporal lobectomy. DOI: 10.3969/j.issn.1672-6731.2015.09.005

Clinical study on deep brain electrode implantation assisted by ROSA system

Objective To evaluate the accuracy and safety of deep brain electrode implantation assisted by robotized stereotactic assistant (ROSA) system. Methods A total of 6 epileptic patients who had difficulty in positioning of epileptogenic focus underwent deep brain electrode implantation assisted by ROSA system. Record the maximum and minimum distance of electrode deviation according to postoperative CT and MRI and calculate the average distance, so as to evaluate the accuracy of operation. Record intraoperative electrode related bleeding events, postoperative electrode related bleeding or ischemic events and complications during the follow-up period, so as to evaluate the safety of operation. Results A total of 37 electrodes were successfully implanted in all 6 cases, with a success rate of 100%. Implanted electrodes were mainly located in medial temporal lobe, hippocampus and insular lobe (5 cases) and parieto-lobe (one case). The maximum deviation distance was 8.79 mm, and minimum was 1.14 mm, with an average of (3.65 ± 1.82) mm. Neither intraoperative electrode related bleeding event nor postoperative electrode related bleeding or ischemic event was found. No patient suffered from severe complications, such as intracranial infection, electrode disjunction, undesirable healing of scalp and wound infection, during the follow-up period from 3 to 5 months (mean 3.67 months). Conclusions Deep brain electrode implantation assisted by ROSA system is safe and accurate. DOI: 10.3969/j.issn.1672-6731.2015.09.006