Long-term follow-up of pallidal deep brain stimulation for craniocervical dystonia: is the globus pallidus internus the best target?

OBJECTIVE: Craniocervical dystonia (CCD) is a common type of segmental dystonia, which is a disabling disease that has been frequently misdiagnosed. Blepharospasm or cervical dystonia is the most usual symptom initially. Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been widely used for treating CCD, its clinical outcome has been primarily evaluated in small-scale studies. This research examines the sustained clinical effectiveness of DBS of the GPi in individuals diagnosed with CCD. METHODS: The authors report 24 patients (14 women, 10 men) with refractory CCD who underwent DBS of the GPi between 2016 and 2023. The severity and disability of the dystonia were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The BFMDRS scores were collected preoperatively, 6 months postoperatively, and at the most recent follow-up visit. RESULTS: The mean age at onset was 52.0 ± 11.0 years (range 33-71 years) and the mean disease duration was 63.3 ± 73.3 months (range 7-360 months) (values for continuous variables are expressed as the mean ± SD). The mean follow-up period was 37.5 ± 23.5 months (range 6-84 months). The mean total BFMDRS motor scores at the 3 different time points were 13.3 ± 9.4 preoperatively, 5.0 ± 4.7 (55.3% improvement, p < 0.001) at 6 months, and 4.5 ± 3.6 (56.6% improvement, p < 0.001) at last follow-up. The outcomes were deemed poor in 6 individuals. CONCLUSIONS: Inferences drawn from the findings suggest that DBS of the GPi has long-lasting effectiveness and certain limitations in managing refractory CCD. The expected stability of the clinical outcome is not achieved. Patients with specific types of dystonia might consider targets other than GPi for a more precise therapy.

A microfluidic concentration gradient colorimetric system for rapid detection of nitrite in surface water.

A microfluidic concentration gradient colorimetric detection system consisting of a microfluidic concentration gradient colorimetric detection chip, a self-built colorimetric signal acquisition box and a self-written smartphone APP was constructed for the rapid, in-field and visual quantitative detection of nitrite. Specifically, nitrite with initial concentration of C0 can be automatically diluted into 8 concentration gradients characterized by arithmetic series, and the concentrations are 0, 0.20 C0, 0.33 C0, 0.46 C0, 0.59 C0, 0.72 C0, 0.86 C0 and C0. The colorimetric signal acquisition box avoided the interference of light spots on data acquisition. Under the optimal experimental conditions, the quantitative detection of nitrite was achieved by the proposed two-step colorimetric method based on the inhibition of AuNPs signal amplification, and the limit of detection (LOD) was 0.14 mg/L. The microfluidic concentration gradient colorimetric detection system was able to detect nitrite as low as 0.43 mg/L and showed a good specificity. The practical application was investigated by analyzing 10 actual samples of river and lake water, pure water and tap water. The recoveries of the microfluidic concentration gradient colorimetric detection system ranged from 94.92% to 105.60%, which indicates that the method had a good application prospect in the detection of practical samples.

Techniques of Frameless Robot-Assisted Deep Brain Stimulation and Accuracy Compared with the Frame-Based Technique.

BACKGROUND: Frameless robot-assisted deep brain stimulation (DBS) is an innovative technique for leads implantation. This study aimed to evaluate the accuracy and precision of this technique using the Sinovation SR1 robot. METHODS: 35 patients with Parkinson's disease who accepted conventional frame-based DBS surgery (n = 18) and frameless robot-assisted DBS surgery (n = 17) by the same group of neurosurgeons were analyzed. The coordinate of the tip of the intended trajectory was recorded as xi, yi, and zi. The actual position of lead implantation was recorded as xa, ya, and za. The vector error was calculated by the formula of √(xi - xa)2 + (yi - ya)2 + (zi - za)2 to evaluate the accuracy. RESULTS: The vector error was 1.52 ± 0.53 mm (range: 0.20-2.39 mm) in the robot-assisted group and was 1.77 ± 0.67 mm (0.59-2.98 mm) in the frame-based group with no significant difference between two groups (p = 0.1301). In 10.7% (n = 3) frameless robot-assisted implanted leads, the vector error was greater than 2.00 mm with a maximum offset of 2.39 mm, and in 35.5% (n = 11) frame-based implanted leads, the vector error was larger than 2.00 mm with a maximum offset of 2.98 mm. Leads were more posterior than planned trajectories in the robot-assisted group and more medial and posterior in the conventional frame-based group. CONCLUSIONS: Awake frameless robot-assisted DBS surgery was comparable to the conventional frame-based technique in the accuracy and precision for leads implantation.

Efficacy of caudal pedunculopontine nucleus stimulation on postural instability and gait disorders in Parkinson's disease.

OBJECTIVES: Gait-related symptoms like postural instability and gait disorders (PIGD) inexorably worsen with Parkinson's disease (PD) deterioration and become refractory to current available medical treatment and deep brain stimulation (DBS) of conventional targets. Pedunculopontine nucleus (PPN) deep brain stimulation (DBS) is a promising method to treat PIGD. This prospective study aimed to clarify the clinical application of PPN-DBS and to explore effects of caudal PPN stimulation on PIGD. METHODS: Five consecutive PD patients with severe medication-resistant postural instability and gait disorders accepted caudal PPN-DBS. LEAD-DBS toolbox was used to reconstruct and visualize the electrodes based on pre- and postoperative images. Outcomes were assessed with Movement Disorder Society (MDS)-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), gait-specific questionnaires, and objective gait analysis with GAITRite system. RESULTS: MDS-UPDRS subitems 35-38 scores were improved at postoperative 6 months (mean, 4.40 vs 11.00; p = 0.0006) and 12 months (mean, 5.60 vs 11.00; p = 0.0013) compared with baseline, and scores at 6 months were slightly lower than scores at 12 months (mean, 4.40 vs 5.60; p = 0.0116). Gait and Falls Questionnaire, New Freezing of Gait Questionnaire, and Falls Questionnaire scores also significantly improved at postoperative 6 months and 12 months compared with baseline. In addition, cadence, bilateral step length, and bilateral stride length significantly increased when PPN On-stimulation compared with Off-stimulation. CONCLUSIONS: This study suggested that caudal PPN low-frequency stimulation improved PIGD for PD patients at the 6- and 12-month period.

Limb loss experience evoked by electric cortical stimulation.

Limb loss experience is a type of body illusion characterized by the sensation of a missing limb or body part. We aimed to investigate the brain areas involved in this unusual somatosensory experience evoked by electric cortical stimulation with stereo-electroencephalography electrodes. We retrospectively reviewed the data of patients with medical intractable epilepsy, from October 2015 to December 2020, who underwent stereo-electroencephalography implantation and electric cortical stimulation in order to locate the epileptogenic zone and obtain a functional map. We included patients who reported experiences of limb loss during the process of electric cortical stimulation for functional mapping. Three patients reported experiences of limb loss in the process of electric cortical stimulation. Limb loss experience (including the right hand, right upper limb and right side of the body) occurred when the cortex of the left posterior insula, posterior dorsal cingulate and parietal operculum were stimulated. Limb loss experience can be evoked by electric cortical stimulation of the posterior insula, parietal operculum, and posterior cingulate cortex, and provides additional evidence that these cortices play a role in the integration of body sensory perception.

Direct Targeting of the Anterior Nucleus of the Thalamus via 3 T Quantitative Susceptibility Mapping.

Objective: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a potentially effective, minimally invasive, and reversible method for treating epilepsy. The goal of this study was to explore whether 3 T quantitative susceptibility mapping (QSM) could delineate the ANT from surrounding structures, which is important for the direct targeting of DBS surgery. Methods: We obtained 3 T QSM, T1-weighted (T1w), and T2-weighted (T2w) images from 11 patients with Parkinson's disease or dystonia who received subthalamic nucleus (STN) or globus pallidus interna (GPi) DBS surgery in our center. The ANT and its surrounding white matter structures on QSM were compared with available atlases. The contrast-to-noise ratios (CNRs) of ANT relative to the external medullary lamina (eml) were compared across the three imaging modalities. Additionally, the morphology and location of the ANT were depicted in the anterior commissure (AC)-posterior commissure (PC)-based system. Results: ANT can be clearly distinguished from the surrounding white matter laminas and appeared hyperintense on QSM. The CNRs of the ANT-eml on QSM, T1w, and T2w images were 10.20 ± 4.23, 1.71 ± 1.03, and 1.35 ± 0.70, respectively. One-way analysis of variance (ANOVA) indicated significant differences in CNRs among QSM, T1w, and T2w imaging modalities [F(2) = 85.28, p < 0.0001]. In addition, both the morphology and location of the ANT were highly variable between patients in the AC-PC-based system. Conclusion: The potential utility of QSM for the visualization of ANTs in clinical imaging is promising and may be suitable for targeting the ANT for DBS to treat epilepsy.

Direct visualization of deep brain stimulation targets in patients with Parkinson's disease via 3-T quantitative susceptibility mapping.

BACKGROUND: The direct visualization of brain nuclei on magnetic resonance (MR) images is important for target localization during deep brain stimulation (DBS) in patients with Parkinson's disease (PD). We demonstrated the superiority of 3-T high-resolution submillimeter voxel size quantitative susceptibility mapping (QSM) for delineating the subthalamic nucleus (STN) and the globus pallidus internus (GPi). METHODS: Preoperative 3-T QSM and T2 weighted (T2w) images were obtained from ten patients with PD. Qualitative visualization scores were analyzed by two neurosurgeons on both images using a 4-point and 5-point scale, respectively. Images were also compared with regard to contrast-to-noise ratios (CNRs) and edge detection power for the STN and GPi. The Wilcoxon rank-sum test and the signed-rank test were used to compare measurements between the two images. RESULTS: Visualization scores for the STN and GPi, the mean CNR of the STN relative to the zona incerta (ZI) and the substantia nigra, and the mean CNR of the GPi relative to the internal capsule (IC) and the globus pallidum externum, were significantly higher on QSM images than on T2w images (P < 0.01). The edge detection powers of the STN-ZI and GPi-IC on QSM were significantly larger (by 2.6- and 3.8-fold, respectively) than those on T2w images (P < 0.01). QSM detected asymmetry of the STN in two patients. CONCLUSIONS: QSM images provided improved delineation ability for the STN and GPi when compared to T2w images. Our findings are important for patients with PD who undergo DBS surgery, particularly those with asymmetric bilateral nuclei.

Effects of pedunculopontine nucleus deep brain stimulation on gait disorders in Parkinson's Disease: A meta-analysis of the literature.

OBJECTIVES: The pedunculopontine nucleus (PPN) is considered a promising target to alleviate gait disorders. We aimed to evaluate the effects of PPN stimulation on motor symptoms and gait disorders in patients with Parkinson's disease (PD) to help assess the potential role of PPN-DBS treatment in gait disorders. METHODS: Studies were searched for low-frequency PPN stimulation to treat gait disorders and freezing of gait (FOG) in the PubMed, Embase, Cochrane Library, Web of Science, and ClinicalKey up to April 2020. Outcomes of Unified Parkinson's Disease Rating Scale (UPDRS) part III, subitems 27-30; UPDRS subitems 13 and 14; the Freezing of Gait Questionnaire (FOGQ), and the Gait and Falls Questionnaire (GFQ) were extracted and evaluated during PPN On-stimulation compared to preoperation or Off-stimulation in both Off- and On-medication states. RESULTS: There was a significant improvement in subitems 27-30 with PPN On-stimulation versus Off-stimulation in Off-medication and On-medication states, but no improvement in UPDRS part III. The occurrence of FOG and falls also declined between PPN On-stimulation and presurgery, with a significant improvement in subitem 13 and subitem 14 in Off-medication and On-medication states, GFQ, and FQGQ. Heterogeneity in stimulation frequency, follow-up, electrode location, and unilateral or bilateral stimulation existed among the included studies. CONCLUSIONS: In some conditions and in some selective PD patients, low-frequency PPN-DBS has beneficial effects on FOG and falls but no wider benefits on rigidity, resting tremor, or bradykinesia.

Mirth and laughter induced by electrical stimulation of the posterior insula.

Laughter induced in the insula is uncommon. In this case-report we present a description of a patient with drug-resistant focal epilepsy for whom laughter with mirth was elicited when the posterior insula (PI) was stimulated by intracranial electrodes. We attempted to analyze the progression of laughter in the insula and suggest a possible pathway for the expression of laughter.

Electrical stimulation of the insulo-opercular region: visual phenomena and altered body-ownership symptoms.

PURPOSE: Using direct intracerebral electrical stimulation (ES) in epileptic patients to evoke symptoms to help identify the functional neuroanatomy of the insular lobe and opercula. METHODS: We selected 43 patients who had at least 1 electrode inserted into the insula or opercula via an oblique approach among 135 patients with intractable epilepsy. Bipolar stimulation was chosen, and the stimulation parameters of the biphasic waves included a pulse width of 0.2 ms, a frequency of 50 Hz, a duration of 3 s, and an intensity gradually increasing from 0.5 to 4 mA. RESULTS: In total, 93 electrodes were implanted into the insula or insular opercula, and 169 of 281 contacts (60.1%) evoked 212 responses by ES of the insula. 142 responses were induced by stimulating the insular opercula in 126 of 343 sites (36.7%). Usual responses, such as somatosensory, visceral sensory, speech, auditory, and motor responses, were evoked. In addition, rarely reported responses, including cardiovascular symptoms (tachycardia), visual symptoms evoked by ES of the parietal and temporal opercula, and vestibular symptoms (like the loss of ownership of the body) evoked following stimulation of the posterior insula and parietal operculum, were also induced in our study. CONCLUSIONS: The insula and opercula perform various and complicated functions. The posterior insula and parietal operculum could play important roles in body-ownership symptoms. The complicated visual phenomena were partially related to the temporal operculum.

Out-of-body experience in the anterior insular cortex during the intracranial electrodes stimulation in an epileptic child.

The authors present a case of an out-of- body experience (OBE) that occurred in a child with intractable epilepsy when stimulating the anterior insular cortex (AIC) by intracranial electrodes. After destroying several sites precisely located at the left AIC by radiofrequency thermocoagulation, the patient's seizures disappeared, and the OBE could not be reproduced when repeatedly stimulating these sites. To our knowledge, it has never been reported that an OBE occurred in the AIC. We analyze the mechanism of an OBE mostly appearing in temporo-parietal junction (TPJ) and propose two perspectives for a possible mechanism involving the AIC causing the OBE.

Spontaneous breakup of extended monodisperse polymer melts.

We apply continuum mechanical based, numerical modeling to study the dynamics of extended monodisperse polymer melts during the relaxation. The computations are within the ideas of the microstructural "interchain pressure" theory. The computations show a delayed necking resulting in a rupture, as a result of small initial sample imperfections. These ruptures agree with experimental observations.