Etienne Holl

MRI-guided STN DBS in Parkinson's disease without microelectrode recording: efficacy and safety.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinsons disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology and Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording. Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6) mm. There were no haemorrhagic complications. At a median follow-up period of 12 months, there was a mean improvement in the off-medication motor part of the Unified Parkinsons Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition, there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre-operatively, to 1.56 (SD 1.92) post-operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinsons disease Questionnaire 39 summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity.

Effects of subthalamic stimulation on speech of consecutive patients with Parkinson disease

Objective: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limiting its beneficial effect. Here we prospectively examined the short- and long-term speech response to STN-DBS in a consecutive series of patients to identify clinical and surgical factors associated with speech change. Methods: Thirty-two consecutive patients were assessed before surgery, then 1 month, 6 months, and 1 year after STN-DBS in 4 conditions on- and off-medication with on- and off-stimulation using established and validated speech and movement scales. Fifteen of these patients were followed up for 3 years. A control group of 12 patients with PD were followed up for 1 year. Results: Within the surgical group, speech intelligibility significantly deteriorated by an average of 14.2% ± 20.15% off-medication and 16.9% ± 21.8% on-medication 1 year after STN-DBS. The medical group deteriorated by 3.6% ± 5.5% and 4.5% ± 8.8%, respectively. Seven patients showed speech amelioration after surgery. Loudness increased significantly in all tasks with stimulation. A less severe preoperative on-medication motor score was associated with a more favorable speech response to STN-DBS after 1 year. Medially located electrodes on the left STN were associated with a significantly higher risk of speech deterioration than electrodes within the nucleus. There was a strong relationship between high voltage in the left electrode and poor speech outcome at 1 year. Conclusion: The effect of STN-DBS on speech is variable and multifactorial, with most patients exhibiting decline of speech intelligibility. Both medical and surgical issues contribute to deterioration of speech in STN-DBS patients. Classification of evidence: This study provides Class III evidence that STN-DBS for PD results in deterioration in speech intelligibility in all combinations of medication and stimulation states at 1 month, 6 months, and 1 year compared to baseline and to control subjects treated with best medical therapy.

Improving Targeting in Image-Guided Frame-Based Deep Brain Stimulation

BACKGROUND: Deep brain stimulation (DBS) is commonly used in the treatment of movement disorders such as Parkinson disease (PD), dystonia, and other tremors. OBJECTIVE: To examine systematic errors in image-guided DBS electrode placement and to explore a calibration strategy for stereotactic targeting. METHODS: Pre- and postoperative stereotactic MR images were analyzed in 165 patients. The perpendicular error between planned target coordinates and electrode trajectory was calculated geometrically for all 312 DBS electrodes implanted. Improvement in motor unified PD rating scale III subscore was calculated for those patients with PD with at least 6 months of follow-up after bilateral subthalamic DBS. RESULTS: Mean (standard deviation) scalar error of all electrodes was 1.4(0.9) mm with a significant difference between left and right hemispheres. Targeting error was significantly higher for electrodes with coronal approach angle (ARC) ≥10° (P < .001). Mean vector error was X: −0.6, Y: −0.7, and Z: −0.4 mm (medial, posterior, and superior directions, respectively). Targeting error was significantly improved by using a systematic calibration strategy based on ARC and target hemisphere (mean: 0.6 mm, P < .001) for 47 electrodes implanted in 24 patients. Retrospective theoretical calibration for all 312 electrodes would have reduced the mean (standard deviation) scalar error from 1.4(0.9) mm to 0.9(0.5) mm (36% improvement). With calibration, 97% of all electrodes would be within 2 mm of the intended target as opposed to 81% before calibration. There was no significant correlation between the degree of error and clinical outcome from bilateral subthalamic nucleus DBS (R2 = 0.07). CONCLUSION: After calibration of a systematic targeting error an MR image-guided stereotactic approach would be expected to deliver 97% of all electrodes to within 2 mm of the intended target point with a single brain pass.

Minimizing Brain Shift in Stereotactic Functional Neurosurgery

BACKGROUND Stereotactic functional neurosurgical interventions depend on precise anatomic targeting before lesioning or deep brain stimulation (DBS) electrode placement. OBJECTIVE To examine the degree of subcortical brain shift observed when adopting an image-guided approach to stereotactic functional neurosurgery. METHODS Coordinates for the anterior and posterior commissural points (AC and PC) were recorded on thin-slice stereotactic magnetic resonance imaging (MRI) scans performed before and immediately after DBS electrode implantation in 136 procedures. The changes in length of AC-PC and in stereotactic coordinates for AC and PC were calculated for each intervention. In patients with Parkinson disease undergoing bilateral subthalamic nucleus (STN) DBS with at least 6 months of follow-up, pre- and postoperative scores of the motor part of the Unified Parkinsons Disease Rating Scale (UPDRS-III) were reviewed. RESULTS Mean (SD) change in AC-PC length (ΔAC-PC) was 0.6 (0.4) mm. There was no statistically significant difference in ΔAC-PC between groups when examining anatomic target subgroups (P =.95), age subgroups (P = .63), sex (P = .59), and unilateral versus bilateral implantation (P =.15). The mean (SD) vector changes for the commissural points were: −0.1 (0.3) mm in X, −0.4 (0.6) mm in Y, and −0.1 (0.7) mm in Z for the AC; and −0.1 (0.3) mm in X, −0.2 (0.7) mm in Y, and 0.0 (0.7) mm in Z for the PC. There was a negligible correlation between the magnitude of brain shift and percentage improvement in UPDRS-III off-medication in patients undergoing STN DBS for PD (R2 <0.01). CONCLUSION Brain shift has long been considered an issue in stereotactic targeting during DBS procedures. However, with the image-guided approach and surgical technique used in this study, subcortical brain shift was extremely limited and did not appear to adversely affect clinical outcome.

Value of subthalamic nucleus local field potentials recordings in predicting stimulation parameters for deep brain stimulation in Parkinson's disease

Objectives Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be a highly effective treatment for Parkinsons disease. However, therapeutic efficacy can be limited by inconsistent targeting of this nucleus. It was shown previously that an increase in local field potential (LFP) power over the beta frequency band may provide intraoperative confirmation of STN targeting. Whether the depth of this focal increase also helps predict the depth and voltage chosen for chronic stimulation is tested here. Methods LFPs were recorded from the contacts of 57 DBS electrodes as the latter were advanced in 2 mm steps from above to below the intended surgical target point in STN. Results A spectral peak in the bipolar LFP was recorded in the 11–35 Hz band at the lowest contact pair that underwent a steep but focal change during electrode descent in all but three sides. The depth of the initial intraoperative step increase in beta correlated with the depth of the contact independently chosen for chronic DBS (Spearmans rho=0.35, p=0.01). In addition, the absolute difference between the depths of the initial increase in beta and the contact chosen for chronic DBS correlated with the voltage used for chronic stimulation (rho=0.322, p=0.017). Thus more voltage had to be employed if a depth was selected for chronic stimulation that differed from that of the beta generator. Conclusions Online spectral analysis of LFPs recorded from the DBS electrode may help identify the optimal therapeutic target in the STN region for DBS.

Therapeutic subthalamic nucleus deep brain stimulation reverses cortico-thalamic coupling during voluntary movements in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted treatment for patients experiencing the motor complications of Parkinsons disease (PD). While its successes are becoming increasingly apparent, the mechanisms underlying its action remain unclear. Multiple studies using radiotracer-based imaging have investigated DBS-induced regional changes in neural activity. However, little is known about the effect of DBS on connectivity within neural networks; in other words, whether DBS impacts upon functional integration of specialized regions of cortex. In this work, we report the first findings of fMRI in 10 subjects with PD and fully implanted DBS hardware receiving efficacious stimulation. Despite the technical demands associated with the safe acquisition of fMRI data from patients with implanted hardware, robust activation changes were identified in the insula cortex and thalamus in response to therapeutic STN DBS. We then quantified the neuromodulatory effects of DBS and compared sixteen dynamic causal models of effective connectivity between the two identified nodes. Using Bayesian model comparison, we found unequivocal evidence for the modulation of extrinsic (between region), i.e. cortico-thalamic and thalamo-cortical connections. Using Bayesian model parameter averaging we found that during voluntary movements, DBS reversed the effective connectivity between regions of the cortex and thalamus. This casts the therapeutic effects of DBS in a fundamentally new light, emphasising a role in changing distributed cortico-subcortical interactions. We conclude that STN DBS does impact upon the effective connectivity between the cortex and thalamus by changing their sensitivities to extrinsic afferents. Furthermore, we confirm that fMRI is both feasible and is tolerated well by these patients provided strict safety measures are adhered to.

Tremor associated with Klinefelter syndrome – A case series and review of the literature

BACKGROUND Previous case series suggested a link between Klinefelter syndrome (KS) and essential tremor (ET) or an ET-like syndrome. METHODS We investigated three KS-patients with tremor including tremor-analyzes and discuss our data in context to findings from a literature review. The clinical outcome after deep brain stimulation (DBS) is also reviewed. RESULTS Tremor in KS is predominantly a postural and kinetic tremor that resembles ET. Our patients were further characterized by absent family history for tremor in first degree relatives, lack of subjective alcohol responsiveness inquired by history, and tremor onset in childhood. One of our patients and two cases from literature improved after DBS of the ventral intermediate nucleus (VIM) of the thalamus. CONCLUSIONS Tremor in KS shares several features with ET. If other characteristics such as family history, alcohol responsiveness, and age at tremor onset may serve as discriminating factors from ET, needs to be further investigated. First observations suggest that VIM-DBS may be efficacious.

Skewering the Subthalamic Nucleus via a Parietal Approach

Background/Aims: A frontal burr hole around the level of the coronal suture is the conventional entry point when performing subthalamic nucleus (STN) deep brain stimulation (DBS). However, alternative approaches may sometimes be necessary. Methods: We present a report of delayed hardware erosion through the scalp in the left frontal region after successful bilateral STN DBS for Parkinson’s disease. The left STN was retargeted via a parietal entry point. Results: Significant improvement in UPDRS motor score (59%) was obtained with bilateral stimulation 6 months after re-operation. The literature was examined for similar approaches and the rationale, risks and benefits of non-frontal entry points in functional neurosurgery were explored. Conclusion: Together with a brief review of STN anatomy, this report demonstrates that the parietal approach to the STN remains a viable option in addition to the more traditional frontal access.

P5-19 Value of subthalamic nucleus local field potentials recording in predicting stimulation parameters for deep brain stimulation in Parkinson's disease

hand tip position. All the parameters were then evaluated by comparing the UPDRS scores related to characteristics of akinesia and bradykinesia. Results: Parameter of reaction time became larger value according to the UPDRS score increased. Concerning the parameters on correctness, some patterns were observed for each subject. Correlations to UPDRS scores were recognized for some parameters on reaction time and correctness. Conclusions: Some of movement characteristics on PD patients were extracted from the measurement data of visual tracking test. The test adopted in this study was easy to utilize in daily life and hospital. The proposed method will be effective for simple evaluation of movement disorders such as PD.