Keyoumars Ashkan

Adaptive Deep Brain Stimulation In Advanced Parkinson Disease

Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof‐of‐principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS.

Deep brain stimulation can suppress pathological synchronisation in parkinsonian patients

Background Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective therapeutic intervention in severe Parkinsons disease, its mechanism of action remains unclear. One possibility is that DBS suppresses local pathologically synchronised oscillatory activity. Methods To explore this, the authors recorded from DBS electrodes implanted in the STN of 16 patients with Parkinsons disease during simultaneous stimulation (pulse width 60 μs; frequency 130 Hz) of the same target using a specially designed amplifier. The authors analysed data from 25 sides. Results The authors found that DBS progressively suppressed peaks in local field potential activity at frequencies between 11 and 30 Hz as voltage was increased beyond a stimulation threshold of 1.5 V. Median peak power had fallen to 54% of baseline values by a stimulation intensity of 3.0 V. Conclusion The findings suggest that DBS can suppress pathological 11–30 Hz activity in the vicinity of stimulation in patients with Parkinsons disease. This suppression occurs at stimulation voltages that are clinically effective.

Effect of electrode contact location on clinical efficacy of pallidal deep brain stimulation in primary generalised dystonia.

Objectives: To determine the effect of electrode contact location on efficacy of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for primary generalised dystonia (PGD). Subjects and methods: A consecutive series of 15 patients with PGD (10 females, mean age 42 years, seven DYT1) who underwent bilateral GPi DBS, were assessed using the Burke–Fahn–Marsden (BFM) dystonia scale before and 6 months after surgery. The position of the stimulated electrode contact(s) was determined from the postoperative stereotactic MRI. Contralateral limb and total axial BFM subscores were compared with the location of the stimulated contact(s) within the GPi. Results: The mean total BFM score decreased from 38.9 preoperatively to 11.9 at 6 months, an improvement of 69.5% (p<0.00001). Cluster analysis of the stimulated contact coordinates identified two groups, distributed along an anterodorsal to posteroventral axis. Clinical improvement was greater for posteroventral than anterodorsal stimulation for the arm (86% vs 52%; p<0.05) and trunk (96% vs 65%; p<0.05) and inversely correlated with the y coordinate. For the leg, posteroventral and anterodorsal stimulation were of equivalent efficacy. Overall clinical improvement was maximal with posteroventral stimulation (89% vs 67%; p<0.05) and inversely correlated with the y (A-P) coordinate (r = −0.62, p<0.05). Conclusion: GPi DBS is effective for PGD but outcome is dependent on contact location. Posteroventral GPi stimulation provides the best overall effect and is superior for the arm and trunk. These results may be explained by the functional anatomy of GPi and its outflow tracts.

Intra-operative recordings of local field potentials can help localize the subthalamic nucleus in Parkinson's disease surgery

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be a highly effective treatment for Parkinsons disease (PD). However, therapeutic efficacy is limited by difficulties in consistently and correctly targeting this nucleus. Increasing evidence suggests that there is abnormal synchronization of beta frequency band activity (approximately 20 Hz) in the STN of PD patients, as reflected in the oscillatory nature of the local field potential (LFP). We hypothesized that an increase in the power of the LFP beta activity may provide intra-operative confirmation of STN targeting in patients undergoing STN implantation for the treatment of advanced PD. Accordingly, we recorded LFPs from the four contacts of DBS electrodes as the latter were advanced in 2 mm steps from a point 4-6 mm above the intended surgical target point in the STN, to a point 4 mm below this. Contacts were configured to give three bipolar recordings of LFPs. These were analyzed on 16 sides in 9 patients. The power in the 13-35 Hz band recorded at the lowest contact pair underwent a steep but focal increase during electrode descent. The depth of the peak beta activity showed excellent agreement with the level of the intra-operative clinical stun effect (k coefficient = 0.792). The depth of peak beta activity also showed 100% specificity and 100% sensitivity for placement within STN in comparison to pre- and Post-operative stereotactic MRI. Functional physiological localization of STN by the on-line spectral analysis of LFPs is quick to perform and may provide information directly relevant to the position of the electrode contact actually used for DBS.

Variability of the subthalamic nucleus: The case for direct MRI guided targeting

Because of concerns about direct visualization of the subthalamic nucleus (STN) on magnetic resonance imaging (MRI), many functional neurosurgeons continue to rely on atlas-based coordinates to reach this target. T2-weighted MRI does allow direct visualisation of the STN. In order to compare the coordinates of the target point within the visualised STN with those obtained from standard brain atlases, the preoperative stereotactic T2-weighted MRI used to implant 55 deep brain stimulation electrodes in the visualised STN of 29 consecutive patients with Parkinsons disease treated in two European centres were studied. The coordinates of the directly visualised STN were significantly different from those of the atlas target. Variability of the position of the STN may render direct visualisation a more accurate means of targeting this nucleus.

Microvascular decompression for trigeminal neuralgia in the elderly: A review of the safety and efficacy

OBJECTIVE:To critically examine the efficacy and safety of microvascular decompression (MVD) for trigeminal neuralgia (TN) in elderly patients. METHODS:We performed a retrospective review of medical records, followed by prospective follow-up. The outcome data from 44 MVD operations for TN performed in 40 consecutive patients with a mean age of 65 years (range, 60–75 yr) in the period 1991 to 2001 were compared with those from 40 younger control subjects (mean age, 46 yr; range, 20–59 yr) operated on during the same period. RESULTS:The median time from diagnosis of TN to MVD in the older patients was 7 years (range, 1–22 yr), compared with 3 years (range, 3 mo to 20 yr) in the younger group (P = 0.02). With the exception of one, all patients in this study were classified as American Society of Anesthesiologist Grade 1 or 2. Initial pain relief was achieved in 98 and 100% of the patients in the study and control groups, respectively. There were no operative mortalities or life-threatening morbidities. Transient facial numbness and diplopia occurred in both groups. Headaches, nausea, and vomiting were more frequent in the younger patients, whereas wound infection and confusion were more common in the older patients. The mean length of hospital stay was 5.4 days (range, 3–10 d) for the older patients, compared with 5.3 days (range, 3–9 d) for the control group (P = 0.4). After average follow-ups of 30 and 33 months, the pain recurred in 24 and 27% of the patients in the elderly and control groups, respectively. CONCLUSION:MVD is underused in the elderly despite being both safe and effective. Fitness and not age should be the key in deciding the treatment options. It is proposed that any patient with medically refractory TN who is fit for general anesthesia should be given the opportunity to choose MVD.

Benign central neurocytoma

“Central neurocytoma” is classically considered as an intraventricular benign tumor, largely based on data from small retrospective series. The authors present prospective data on 12 patients with tumors diagnosed as central neurocytoma, to highlight the diverse nature of this tumor and challenge the classic notion.

Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment

This study explores whether near‐infrared (NIr) light treatment neuroprotects dopaminergic cells in the substantia nigra pars compacta (SNc) and the zona incerta‐hypothalamus (ZI‐Hyp) from degeneration in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated mice. BALB/c albino mice were divided into four groups: 1) Saline, 2) Saline‐NIr, 3) MPTP, 4) MPTP‐NIr. The injections were intraperitoneal and they were followed immediately by NIr light treatment (or not). Two doses of MPTP, mild (50 mg/kg) and strong (100 mg/kg), were used. Mice were perfused transcardially with aldehyde fixative 6 days after their MPTP treatment. Brains were processed for tyrosine hydroxylase (TH) immunochemistry. The number of TH+ cells was estimated using the optical fractionator method. Our major finding was that in the SNc there were significantly more dopaminergic cells in the MPTP‐NIr compared to the MPTP group (35%–45%). By contrast, in the ZI‐Hyp there was no significant difference in the numbers of cells in these two groups. In addition, our results indicated that survival in the two regions after MPTP insult was dose‐dependent. In the stronger MPTP regime, the magnitude of loss was similar in the two regions (≈60%), while in the milder regime cell loss was greater in the SNc (45%) than ZI‐Hyp (≈30%). In summary, our results indicate that NIr light treatment offers neuroprotection against MPTP toxicity for dopaminergic cells in the SNc, but not in the ZI‐Hyp. J. Comp. Neurol. 518:25–40, 2010.

Proportion of life lived with dystonia inversely correlates with response to pallidal deep brain stimulation in both primary and secondary childhood dystonia

The aim of this study was to examine the impact of dystonia aetiology and duration, contracture, and age at deep brain stimulation (DBS) surgery on outcome in a cohort of children with medically refractory, disabling primary, secondary‐static, or secondary‐progressive dystonias, including neurodegeneration with brain iron accumulation (NBIA).

CT/MR Image Fusion in the Postoperative Assessment of Electrodes Implanted for Deep Brain Stimulation

Background/Aims: Stereotactic postoperative imaging is essential for verification of the position of electrodes implanted for deep brain stimulation (DBS). MRI offers superior visualisation of the DBS targets relative to CT, but previous adverse incidents have heightened concerns about risks of postoperative MRI. Preoperative MRI fused with postoperative CT offers an alternative method for evaluating electrode position, but before this method can be clinically applied, the image registration accuracy must be established. The purpose of this study was to quantitatively assess the accuracy of three different image registration and fusion methods. Methods: Preoperative stereotactic MRI and postoperative stereotactic CT were acquired from 20 patients under- going DBS surgery (35 electrodes in total). The postoperative CT was registered and fused with the preoperative MRI, using three different registration algorithms. The position of each electrode tip was determined in stereotactic coordinates both in the (unfused) postoperative CT and the fused CT/MRI. The difference in tip position between the CT and fused CT/MRI was used to evaluate the registration accuracy. Results: The mean error along the lateral, anteroposterior, and vertical axes was 0.5, 0.5, and 1 mm, respectively. Conclusions: CT/MRI fusion provides a safe, practical technique for postoperative identification of DBS electrodes.