Philippe De Vloo, Luka Milosevic, Robert M. Gramer, David Hernán Aguirre-Padilla, Robert F. Dallapiazza, Darrin J. Lee, William D. Hutchison, Alfonso Fasano and Andres M. Lozano
The authors report on a female patient with left-dominant Parkinson’s disease with motor fluctuations and levodopa-induced dyskinesias and comorbid postherpetic neuralgia (PHN), who underwent a right-sided pallidotomy. Besides a substantial improvement in her Parkinson’s symptoms, she reported an immediate and complete disappearance of PHN. This neuralgia had been long-standing, pharmacologically refractory, and severe (preoperative Brief Pain Inventory [BPI] pain severity score of 8.0, BPI pain interference score of 7.3, short-form McGill Pain Questionnaire sensory pain rating index of 7 and affective pain rating index of 10, Present Pain Intensity rank value of 4, and visual analog scale score of 81 mm; all postoperative scores were 0). She continued to be pain free at 16 months postoperatively.
This peculiar finding adds substantially to the largely unrecognized evidence for the role of the pallidum in pain processing, based on previous electrophysiological, metabolic, anatomical, pharmacological, and clinical observations. Therefore, the potential of the pallidum as a neurosurgical target for neuropathic pain warrants further investigation.
Zang-Hee Cho, Hoon-Ki Min, Se-Hong Oh, Jae-Yong Han, Chan-Woong Park, Je-Geun Chi, Young-Bo Kim, Sun Ha Paek, Andres M. Lozano and Kendall H. Lee
A challenge associated with deep brain stimulation (DBS) in treating advanced Parkinson disease (PD) is the direct visualization of brain nuclei, which often involves indirect approximations of stereotactic targets. In the present study, the authors compared T2*-weighted images obtained using 7-T MR imaging with those obtained using 1.5- and 3-T MR imaging to ascertain whether 7-T imaging enables better visualization of targets for DBS in PD.
The authors compared 1.5-, 3-, and 7-T MR images obtained in 11 healthy volunteers and 1 patient with PD.
With 7-T imaging, distinct images of the brain were obtained, including the subthalamic nucleus (STN) and internal globus pallidus (GPi). Compared with the 1.5- and 3-T MR images of the STN and GPi, the 7-T MR images showed marked improvements in spatial resolution, tissue contrast, and signal-to-noise ratio.
Data in this study reveal the superiority of 7-T MR imaging for visualizing structures targeted for DBS in the management of PD. This finding suggests that by enabling the direct visualization of neural structures of interest, 7-T MR imaging could be a valuable aid in neurosurgical procedures.
Nicolas Kon Kam King, Vibhor Krishna, Diellor Basha, Gavin Elias, Francesco Sammartino, Mojgan Hodaie, Andres M. Lozano and William D. Hutchison
The ventral intermediate nucleus (VIM) of the thalamus is not visible on structural MRI. Therefore, direct VIM targeting methods for stereotactic tremor surgery are desirable. The authors previously described a direct targeting method for visualizing the VIM and its structural connectivity using deterministic tractography. In this combined electrophysiology and imaging study, the authors investigated the electrophysiology within this tractography-defined VIM (T-VIM).
Thalamic neurons were classified based on their relative location to the T-VIM: dorsal, within, and ventral to the T-VIM. The authors identified the movement-responsive cells (kinesthetic and tremor cells), performed spike analysis (firing rate and burst index), and local field potential analysis (area under the curve for 13–30 Hz). Tremor efficacy in response to microstimulation along the electrode trajectory was also assessed in relation to the T-VIM.
Seventy-three cells from a total of 9 microelectrode tracks were included for this analysis. Movement-responsive cells (20 kinesthetic cells and 26 tremor cells) were identified throughout the electrode trajectories. The mean firing rate and burst index of cells (n = 27) within the T-VIM are 18.8 ± 9.8 Hz and 4.5 ± 5.4, respectively. Significant local field potential beta power was identified within the T-VIM (area under the curve for 13–30 Hz = 6.6 ± 7.7) with a trend toward higher beta power in the dorsal T-VIM. The most significant reduction in tremor was also observed in the dorsal T-VIM.
The electrophysiological findings within the VIM thalamus defined by tractography, or T-VIM, correspond with the known microelectrode recording characteristics of the VIM in patients with tremor.
Michael L. Schwartz, Robert Yeung, Yuexi Huang, Nir Lipsman, Vibhor Krishna, Jennifer D. Jain, Martin G. Chapman, Andres M. Lozano and Kullervo Hynynen
One patient for whom an MR-guided focused ultrasound (MRgFUS) pallidotomy was attempted was discovered to have multiple new skull lesions with the appearance of infarcts on the MRI scan 3 months after his attempted treatment. The authors conducted a retrospective review of the first 30 patients treated with MRgFUS to determine the incidence of skull lesions in patients undergoing these procedures and to consider possible causes.
A retrospective review of the MRI scans of the first 30 patients, 1 attempted pallidotomy and 29 ventral intermediate nucleus thalamotomies, was conducted. The correlation of the mean skull density ratio (SDR) and the maximum energy applied in the production or attempted production of a brain lesion was examined.
Of 30 patients treated with MRgFUS for movement disorders, 7 were found to have new skull lesions that were not present prior to treatment and not visible on the posttreatment day 1 MRI scan. Discomfort was reported at the time of treatment by some patients with and without skull lesions. All patients with skull lesions were completely asymptomatic. There was no correlation between the mean SDR and the presence or absence of skull lesions, but the maximum energy applied with the Exablate system was significantly greater in patients with skull lesions than in those without.
It is known that local skull density, thickness, and SDR vary from location to location. Sufficient energy transfer resulting in local heating sufficient to produce a bone lesion may occur in regions of low SDR. A correlation of lesion location and local skull properties should be made in future studies.
Francesco Sammartino, Vibhor Krishna, Tejas Sankar, Jason Fisico, Suneil K. Kalia, Mojgan Hodaie, Walter Kucharczyk, David J. Mikulis, Adrian Crawley and Andres M. Lozano
The aim of this study was to evaluate the safety of 3-T MRI in patients with implanted deep brain stimulation (DBS) systems.
This study was performed in 2 phases. In an initial phantom study, a Lucite phantom filled with tissue-mimicking gel was assembled. The system was equipped with a single DBS electrode connected to an internal pulse generator. The tip of the electrode was coupled to a fiber optic thermometer with a temperature resolution of 0.1°C. Both anatomical (T1- and T2-weighted) and functional MRI sequences were tested. A temperature change within 2°C from baseline was considered safe. After findings from the phantom study suggested safety, 10 patients with implanted DBS systems targeting various brain areas provided informed consent and underwent 3-T MRI using the same imaging sequences. Detailed neurological evaluations and internal pulse generator interrogations were performed before and after imaging.
During phantom testing, the maximum temperature increase was registered using the T2-weighted sequence. The maximal temperature changes at the tip of the DBS electrode were < 1°C for all sequences tested. In all patients, adequate images were obtained with structural imaging, although a significant artifact from lead connectors interfered with functional imaging quality. No heating, warmth, or adverse neurological effects were observed.
To the authors' knowledge, this was the first study to assess the clinical safety of 3-T MRI in patients with a fully implanted DBS system (electrodes, extensions, and pulse generator). It provided preliminary data that will allow further examination and assessment of the safety of 3-T imaging studies in patients with implanted DBS systems. The authors cannot advocate widespread use of this type of imaging in patients with DBS implants until more safety data are obtained.
Alexandre Boutet, Ileana Hancu, Utpal Saha, Adrian Crawley, David S. Xu, Manish Ranjan, Eugen Hlasny, Robert Chen, Warren Foltz, Francesco Sammartino, Ailish Coblentz, Walter Kucharczyk and Andres M. Lozano
Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients’ accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research.
A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from “the worst” to “the most common.”
In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed.
In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event.
Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.
Rosa Q. So, Vibhor Krishna, Nicolas Kon Kam King, Huijuan Yang, Zhuo Zhang, Francesco Sammartino, Andres M. Lozano, Richard A. Wennberg and Cuntai Guan
The authors explored the feasibility of seizure detection and prediction using signals recorded from the anterior thalamic nucleus, a major target for deep brain stimulation (DBS) in the treatment of epilepsy.
Using data from 5 patients (13 seizures in total), the authors performed a feasibility study and analyzed the performance of a seizure prediction and detection algorithm applied to simultaneously acquired scalp and thalamic electroencephalography (EEG). The thalamic signal was obtained from DBS electrodes. The applied algorithm used the similarity index as a nonlinear measure for seizure identification, with patient-specific channel and threshold selection. Receiver operating characteristic (ROC) curves were calculated using data from all patients and channels to compare the performance between DBS and EEG recordings.
Thalamic DBS recordings were associated with a mean prediction rate of 84%, detection rate of 97%, and false-alarm rate of 0.79/hr. In comparison, scalp EEG recordings were associated with a mean prediction rate of 71%, detection rate of 100%, and false-alarm rate of 1.01/hr. From the ROC curves, when considering all channels, DBS outperformed EEG for both detection and prediction of seizures.
This is the first study to compare automated seizure detection and prediction from simultaneous thalamic and scalp EEG recordings. The authors have demonstrated that signals recorded from DBS leads are more robust than EEG recordings and can be used to predict and detect seizures. These results indicate feasibility for future designs of closed-loop anterior nucleus DBS systems for the treatment of epilepsy.
Diellor Basha, Jonathan O. Dostrovsky, Suneil K. Kalia, Mojgan Hodaie, Andres M. Lozano and William D. Hutchison
The amputation of an extremity is commonly followed by phantom sensations that are perceived to originate from the missing limb. The mechanism underlying the generation of these sensations is still not clear although the development of abnormal oscillatory bursting in thalamic neurons may be involved. The theory of thalamocortical dysrhythmia implicates gamma oscillations in phantom pathophysiology although this rhythm has not been previously observed in the phantom limb thalamus. In this study, the authors report the novel observation of widespread 38-Hz gamma oscillatory activity in spike and local field potential recordings obtained from the ventral caudal somatosensory nucleus of the thalamus (Vc) of a phantom limb patient undergoing deep brain stimulation (DBS) surgery. Interestingly, microstimulation near tonically firing cells in the Vc resulted in high-frequency, gamma oscillatory discharges coincident with phantom sensations reported by the patient. Recordings from the somatosensory thalamus of comparator groups (essential tremor and pain) did not reveal the presence of gamma oscillatory activity.
Robert E. Gross, Wendy J. Lombardi, William D. Hutchison, Soni Narula, Jean A. Saint-Cyr, Jonathan O. Dostrovsky, Ronald R. Tasker, Anthony E. Lang and Andres M. Lozano
Object. To understand the factors that determine the distribution of lesions after microelectrode-guided pallidotomy for Parkinson's disease, the authors quantitatively characterized lesion location in a cohort of patients who were prospectively followed to determine the effects of pallidotomy on clinical outcome.
Methods. Thirty-three patients underwent volumetric magnetic resonance (MR) imaging after surgery to allow quantitative lesion localization in relation to conventional intraventricular landmarks and, alternatively, more anatomically relevant landmarks. The validity of the method was verified in a cohort of postpallidotomy patients who underwent concurrent volumetric and stereotactic MR imaging in an external head frame. Lesions were distributed over a considerable distance in the anteroposterior (8.8 mm) and mediolateral (8.7 mm) dimensions in relation to the anterior commissure and wall of the third ventricle, respectively. Less variation was seen in lesion location in the dorsoventral dimension (4.8 mm) in relation to the intercommissural plane.
Conclusions. Lesion distribution was not random: lesion locations in the anteroposterior and mediolateral dimensions were highly correlated, such that lesions were distributed from anteromedial to posterolateral, parallel to the border of the globus pallidus internus with the obliquely oriented internal capsule. The factors that led to variability in lesion location were variation in third ventricle width and the oblique anteromedial-to-posterolateral course of the internal capsule. This demonstration of variability of lesion location in a cohort of patients who experienced excellent clinical benefits and minimal postoperative complications emphasizes the importance of anatomical variations in determining lesion position and the need for physiological corroboration for correct lesion placement.