Implantable Subdural Cortical Stimulation for Chronic Intractable Pain Treatment-The Mayo Experience and Review of Literature.

OBJECTIVES: Motor cortex stimulation (MCS) is an effective technique in treating chronic intractable pain for some patients. However, most studies are small case series (n < 20). Heterogeneity in technique and patient selection makes it difficult to draw consistent conclusions. In this study, we present one of the largest case series of subdural MCS. MATERIALS AND METHODS: Medical records of patients who underwent MCS at our institute between 2007 and 2020 were reviewed. Studies with at least 15 patients were summarized for comparison. RESULTS: The study included 46 patients. Mean age was 56.2 ± 12.5 years (SD). Mean follow-up was 57.2 ± 41.9 months. Male-to-female ratio was 13:33. Of the 46 patients, 29 had neuropathic pain in trigeminal nerve territory/anesthesia dolorosa; nine had postsurgical/posttraumatic pain; three had phantom limb pain; two had postherpetic pain, and the rest had pain secondary to stroke, chronic regional pain syndrome, and tumor. The baseline numeric rating pain scale (NRS) was 8.2 ± 1.8 of 10, and the latest follow-up score was 3.5 ± 2.9 (mean improvement of 57.3%). Responders comprised 67% (31/46)(NRS ≥ 40% improvement). Analysis showed no correlation between percentage of improvement and age (p = 0.352) but favored male patients (75.3% vs 48.7%, p = 0.006). Seizures occurred in 47.8% of patients (22/46) at some point but were all self-limiting, with no lasting sequelae. Other complications included subdural/epidural hematoma requiring evacuation (3/46), infection (5/46), and cerebrospinal fluid leak (1/46). These complications resolved with no long-term sequelae after further interventions. CONCLUSION: Our study further supports the use of MCS as an effective treatment modality for several chronic intractable pain conditions and provides a benchmark to the current literature.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

Variability Between Direct and Indirect Targeting of the Anterior Nucleus of the Thalamus.

BACKGROUND: Preoperative thalamic targeting methods have historically relied on indirect targeting techniques that do not fully account for variances in anatomy or for thalamic atrophy in epilepsy. We aimed to address variability noted between traditional indirect targeting and direct targeting methods for the anterior nucleus of the thalamus (ANT). METHODS: Fifteen consecutive patients undergoing ANT deep brain stimulator placement were evaluated (30 thalamic nuclei). Direct ANT targeting was performed using a fast gray matter acquisition T1 inversion recovery sequence and compared with standard stereotactic coordinates. Thalamic volumes were calculated for each patient, and degree of thalamic volume loss was assessed compared with matched control subjects. Vertex analysis was performed to assess shape changes in the thalamus compared with age- and sex-matched subjects. RESULTS: There was significant variation between direct and indirect targets in the y-axis and z-axis on both sides. On the left, the direct target was located at y = 2 ± 1.3 mm and z = 9.3 ± 1.8 mm (both P = 0.02). On the right, the direct target was located at y = 2.9 ± 1.8 mm and z = 9.2 ± 2 mm (both P ≤ 0.0003). There was no significant difference in the x-coordinate on either side (P > 0.5). Additionally, there was a correlation between thalamic volume and difference between direct and indirect targets in the y-axis and the z-axis. CONCLUSIONS: We showed a significant difference in direct and indirect targeting in the y-axis and z-axis when targeting the ANT for deep brain stimulation for epilepsy. This difference is correlated to thalamic volume, with a larger difference noted in patients with thalamic atrophy.

Left Radiofrequency Thalamotomy for Drug-Refractory Essential Tremor.

Essential tremor is an idiopathic movement disorder characterized by bilateral action tremor of the upper limbs with or without other neurologic symptoms.1 Pharmacologic management is the first-line treatment for this condition. Surgical treatment includes deep brain stimulation and thalamotomy procedures.2 Furthermore, thalamotomy can be achieved by magnetic resonance imaging-guided focused ultrasound, stereotactic radiosurgery, or radiofrequency.3 Advantages of modulation therapies include bilateral implementation, adjustability, and reversibility of the effect.2 Disadvantages include delayed response, increased infection risk, and cost. Within ablation therapies, focused ultrasound is costly and not available widely, while stereotactic radiosurgery has a delayed symptomatic relief. Radiofrequency represents a cost-effective, widely available option with immediate results.3 We present the case of a 91-year-old right-handed man with essential tremor refractory to medical management (Video 1). He was offered all available treatment modalities and opted for a radiofrequency thalamotomy. Preoperative planning included stereotactic head frame placement and computed tomography scan. A left thalamic target with coordinates 11.5 mm lateral to the wall of the third ventricle, 8 mm anterior to the posterior commissure, and at the rostrocaudal level of the anterior commissure-posterior commissure plane was chosen. A 1.1-mm diameter, 10-mm tip RF electrode was advanced to the target. A lateral radiograph was taken to verify the position of the electrode. After trial stimulation, 2 RF lesions were performed. No intraoperative complications occurred. Immediate postoperative MRI showed an enhancing focus in the left thalamic lobe corresponding to the left thalamotomy lesion. The patient had excellent relief of tremor during his last follow-up, 5 months postoperatively.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

OBJECTIVE: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. METHODS: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. RESULTS: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Thalamic DBS with a constant-current device in essential tremor: A controlled clinical trial.

INTRODUCTION: This study of thalamic deep brain stimulation (DBS) investigated whether a novel constant-current device improves tremor and activities of daily living (ADL) in patients with essential tremor (ET). METHODS: A prospective, controlled, multicenter study was conducted at 12 academic centers. We investigated the safety and efficacy of unilateral and bilateral constant-current DBS of the ventralis intermedius (VIM) nucleus of the thalamus in patients with essential tremor whose tremor was inadequately controlled by medications. The primary outcome measure was a rater-blinded assessment of the change in the target limb tremor score in the stimulation-on versus stimulation-off state six months following surgery. Multiple secondary outcomes were assessed at one-year follow-up, including motor, mood, and quality-of-life measures. RESULTS: 127 patients were implanted with VIM DBS. The blinded, primary outcome variable (n = 76) revealed a mean improvement of 1.25 ± 1.26 points in the target limb tremor rating scale (TRS) score in the arm contralateral to DBS (p < 0.001). Secondary outcome variables at one year revealed significant improvements (p ≤ 0.001) in quality of life, depression symptoms, and ADL scores. Forty-seven patients had a second contralateral VIM-DBS, and this group demonstrated reduction in second-sided tremor at 180 days (p < 0.001). Serious adverse events related to the surgery included infection (n = 3), intracranial hemorrhage (n = 3), and device explantation (n = 3). CONCLUSION: Unilateral and bilateral constant-current VIM DBS significantly improves upper extremity tremor, ADL, quality of life, and depression in patients with severe ET.

Deep brain stimulation for levodopa-refractory benign tremulous parkinsonism.

Benign tremulous parkinsonism (BTP) is characterized by prominent resting tremor combined with action and postural components, and with only subtle rigidity and bradykinesia. This tremor is frequently disabling and poorly responsive to therapy with levodopa. Thus, BTP could be considered either as a distinct clinical disorder or a variant of PD. We present a case of a 57-year-old man who had a 3-year history of severe and functionally disabling resting tremor with action and postural features bilaterally but with left dominant hand predominance. There was only very mild rigidity and bradykinesia and no postural instability. His tremor was refractory to dopaminergic therapy, including carbidopa/levodopa. The dopamine transporter (DAT) imaging showed reduced tracer uptake in the putamen bilaterally, more so on the right side. He was treated with deep brain stimulation (DBS) targeting the right ventral intermediate nucleus of the thalamus. His tremor resolved immediately after procedure. The DAT imaging abnormalities indicate the presynaptic dopamine deficiency. In some autopsied BTP cases classic alpha-synuclein pathology of PD was observed. Thus, despite the lack of levodopa responsiveness BTP likely represents a variant of PD and not a distinct neurodegenerative disorder. DBS should be considered for patients with BTP PD variant despite their poor responsiveness to levodopa treatment.

Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial.

OBJECTIVE: To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. METHODS: Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up. RESULTS: All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was -37.9% in the active and -17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. SIGNIFICANCE: Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures.

Unilateral deep brain stimulation of the subthalamic nucleus for Parkinson disease.

OBJECT: The object of this study was to assess the results of unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for management of advanced Parkinson disease (PD). METHODS: A clinical series of 24 patients (mean age 71 years, range 56-80 years) with medically intractable PD, who were undergoing unilateral magnetic resonance imaging-targeted, electrophysiologically guided STN DBS, completed a battery of qualitative and quantitative outcome measures preoperatively (baseline) and postoperatively, using a modified Core Assessment Program for Intracerebral Transplantations protocol. The mean follow-up period was 9 months. Statistically significant improvement was observed in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score (18%), the total UPDRS PART III score (31%), the contralateral UPDRS Part III score (63%), and scores for axial motor features (19%), contralateral tremor (88%), rigidity (60%), bradykinesia (54%), and dyskinesia (69%), as well as the Parkinson's Disease Quality of Life questionnaire score (15%) in the on-stimulation state compared with baseline. Ipsilateral symptoms improved by approximately 15% or less. Performance on the Purdue pegboard test improved in the contralateral hand in the on-stimulation state compared with the off-stimulation state (38%, p < 0.05). The daily levodopa-equivalent dose was reduced by 21% (p = 0.018). Neuropsychological tests revealed an improvement in mental flexibility and a trend toward reduced letter fluency. There were no permanent surgical complications. Of the 16 participants with symmetrical disease, five required implantation of the DBS unit on the second side. CONCLUSIONS: Unilateral STN DBS is an effective and safe treatment for selected patients with advanced PD. Unilateral STN DBS provides improvement of contralateral motor symptoms of PD as well as quality of life, reduces requirements for medication, and possibly enhances mental flexibility. This method of surgical treatment may be associated with a reduced risk and may provide an alternative to bilateral STN DBS for PD, especially in older patients or patients with asymmetry of parkinsonism.

[Current therapies for parkinson's disease. Part II: surgical treatment]. / Wspólczesne leczenie choroby Parkinsona. Czesc II: Leczenie chirurgiczne.

Surgical treatment of Parkinson's disease (PD) is indicated in patients with severe neurological symptoms (tremor, bradykinesia, rigidity)--who do not benefit from nor tolerate pharmacological therapy. Surgery for PD modifies the motor system function by lesioning or electrostimulation of thalamic, pallidal or subthalamic nuclei. The technological progress together with refined CNS monitoring enabled wider application of deep brain stimulation (DBS). The efficacy of DBS is comparable with lesioning techniques (thalamotomy or pallidotomy) however bears less adverse effects. Both lesioning and DBS are generally well tolerated by patients. The side effects are mostly transient and neurological complications, if occur, usually do not affect quality of patient's life. Unfortunately, the modern surgery for PD is still very expensive and demanding for a large team of specialists and high technology.

Magnetic resonance imaging and deep brain stimulation.

OBJECTIVE: To determine whether cranial magnetic resonance imaging (MRI) is associated with deep brain stimulation (DBS) lead displacement or program interference. METHODS: In vitro and in vivo studies were performed with the Itrel II implantable pulse generator (IPG) (Model 7424; Medtronic, Minneapolis, MN), Medtronic 3387 and 3389 leads, and a 1.5-T GE Horizon LX scanner (General Electric, Milwaukee, WI). In the in vivo study, two MRI volumetric data sets were compared for each of five patients undergoing staged, bilateral, DBS electrode placement in the thalamic or subthalamic nucleus. The data sets were acquired shortly after the initial implantation and during stereotactic planning for the second implantation (1-8 mo between acquisitions). An additional thalamotomy-treated patient was included as a control patient. Volumetric data were analyzed in a blinded manner, using AnalyzeAVW 3.0 software (Biomedical Imaging Resource, Mayo Clinic, Rochester, MN), to determine lead movement. In the in vitro study, the IPG and leads were positioned in the magnetic field in various configurations and were systematically assessed for movement. RESULTS: In vivo, the majority of measured deviations (88%) were within the standard error of measurement (1.4 mm). The maximal measured deviation was 3 mm (2% occurrence). Excellent tremor control with stimulation was demonstrated, which did not change after MRI. In vitro, the DBS leads demonstrated no deflection when introduced into the magnetic field. Similarly, no changes in IPG battery strength, lead impedance, or program settings were observed. CONCLUSION: MRI was not associated with significant DBS electrode movement or changes in clinical responses. Other IPG models and components and MRI scanners should be evaluated, to develop specific guidelines for MRI among individuals with implanted DBS systems.