Telemedicine in deep brain stimulation

Despite optimal medical treatment, including epilepsy surgery, many epilepsy patients have uncontrolled seizures. In the last decades, interest has grown in invasive intracranial neurostimulation as a treatment for these patients. Intracranial stimulation includes both deep brain stimulation (DBS) (stimulation through depth electrodes) and cortical stimulation (subdural electrodes). To assess the efficacy, safety and tolerability of deep brain and cortical stimulation for refractory epilepsy based on randomized controlled trials. We searched PubMed (6 August 2013), the Cochrane Epilepsy Group Specialized Register (31 August 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7 of 12) and reference lists of retrieved articles. We also contacted device manufacturers and other researchers in the field. No language restrictions were imposed. Randomized controlled trials (RCTs) comparing deep brain or cortical stimulation to sham stimulation, resective surgery or further treatment with antiepileptic drugs. Four review authors independently selected trials for inclusion. Two review authors independently extracted the relevant data and assessed trial quality and overall quality of evidence. The outcomes investigated were seizure freedom, responder rate, percentage seizure frequency reduction, adverse events, neuropsychological outcome and quality of life. If additional data were needed, the study investigators were contacted. Results were analysed and reported separately for different intracranial targets for reasons of clinical heterogeneity. Ten RCTs comparing one to three months of intracranial neurostimulation to sham stimulation were identified. One trial was on anterior thalamic DBS (n = 109; 109 treatment periods); two trials on centromedian thalamic DBS (n = 20; 40 treatment periods), but only one of the trials (n = 7; 14 treatment periods) reported sufficient information for inclusion in the quantitative meta-analysis; three trials on cerebellar stimulation (n = 22; 39 treatment periods); three trials on hippocampal DBS (n = 15; 21 treatment periods); and one trial on responsive ictal onset zone stimulation (n = 191; 191 treatment periods). Evidence of selective reporting was present in four trials and the possibility of a carryover effect complicating interpretation of the results could not be excluded in 4 cross-over trials without any washout period. Moderate-quality evidence could not demonstrate statistically or clinically significant changes in the proportion of patients who were seizure-free or experienced a 50% or greater reduction in seizure frequency (primary outcome measures) after 1 to 3 months of anterior thalamic DBS in (multi)focal epilepsy, responsive ictal onset zone stimulation in (multi)focal epilepsy patients and hippocampal DBS in (medial) temporal lobe epilepsy. However, a statistically significant reduction in seizure frequency was found for anterior thalamic DBS (-17.4% compared to sham stimulation; 95% confidence interval (CI) -32.1 to -1.0; high-quality evidence), responsive ictal onset zone stimulation (-24.9%; 95% CI -40.1 to 6.0; high-quality evidence) ) and hippocampal DBS (-28.1%; 95% CI -34.1 to -22.2; moderate-quality evidence). Both anterior thalamic DBS and responsive ictal onset zone stimulation do not have a clinically meaningful impact on quality life after three months of stimulation (high-quality evidence). Electrode implantation resulted in asymptomatic intracranial haemorrhage in 3% to 4% of the patients included in the two largest trials and 5% to 13% had soft tissue infections; no patient reported permanent symptomatic sequelae. Anterior thalamic DBS was associated with fewer epilepsy-associated injuries (7.4 versus 25.5%; P = 0.01) but higher rates of self-reported depression (14.8 versus 1.8%; P = 0.02) and subjective memory impairment (13.8 versus 1.8%; P = 0.03); there were no significant differences in formal neuropsychological testing results between the groups. Responsive ictal-onset zone stimulation was well tolerated with few side effects but SUDEP rate should be closely monitored in the future (4 per 340 [= 11.8 per 1000] patient-years; literature: 2.2-10 per 1000 patient-years). The limited number of patients preclude firm statements on safety and tolerability of hippocampal DBS. With regards to centromedian thalamic DBS and cerebellar stimulation, no statistically significant effects could be demonstrated but evidence is of only low to very low quality. Only short term RCTs on intracranial neurostimulation for epilepsy are available. Compared to sham stimulation, one to three months of anterior thalamic DBS ((multi)focal epilepsy), responsive ictal onset zone stimulation ((multi)focal epilepsy) and hippocampal DBS (temporal lobe epilepsy) moderately reduce seizure frequency in refractory epilepsy patients. Anterior thalamic DBS is associated with higher rates of self-reported depression and subjective memory impairment. SUDEP rates require careful monitoring in patients undergoing responsive ictal onset zone stimulation. There is insufficient evidence to make firm conclusive statements on the efficacy and safety of hippocampal DBS, centromedian thalamic DBS and cerebellar stimulation. There is a need for more, large and well-designed RCTs to validate and optimize the efficacy and safety of invasive intracranial neurostimulation treatments.

Identifying and troubleshooting low-frequency artifacts mimicking atrial flutter caused by deep brain stimulator

Exploring magneto-electric nanoparticles (MENPs): a platform for implanted deep brain stimulation

Objective To assess the long-term outcome of globus pallidus intema (Gpi) deep brain stimulation (DBS) in adult patients with Tourette syndrome (TS). Methods Five adult drug-resistant TS patients, performed bilateral Gpi DBS in our hospital from May 2007 to May 2008,were chosen in our study; their symptoms before DBS and 3 and 6 months and 1 year after DBS,and over a year of DBS were evaluated by Yale global tic severity scale. Results The duration of follow-up ranged from 21 to 33 months.Scores of motor tic,phonic tic and social impairment in the last follow-up were significantly decreased as compared with those before DBS (P＜0.05); Scores of motor tic,phonic tic and social impairment 3 and 6 months and 1 year after DBS,and over a year of DBS were significantly decreased as compared with those before DBS (P＜0.05).The symptoms were gradually improved; in the first 6 months,the symptoms were obviously improved; 6 months after DBS,the symptoms were solid and can be mildly improved.3 and 6 months,1 year after DBS and till to the last follow-up (mean 26.4 months),the severity of symptom meanly improved 28.50％,52.35％,57.62％ and 62.88％,respectively;and till the last follow-up,the motor tic,phonic tic and social impairment was improved 51.38％,46.16％ and 71.00％,respectively; no serious adverse effects were noted. Conclusion Gpi DBS,improving the symptoms as motor tic,phonic tic and social impairment,is a useful and safe treatment method for adult patients with medically refractory TS; the long-term efficiency is solid. Key words: Tourette syndrome; Globus pallidus intema; Deep brain stimulation

IntroductionDepression continues to be a leading cause of disability worldwide. Despite the availability of several classes of antidepressants, a third of patients do not recover from their depression. Deep brain stimulation (DBS) is an invasive treatment approach that was found to be effective in the treatment of Parkinson’s Disease and presents as an alternative to standard antidepressant therapy for people with treatment-resistent depression (TRD).ObjectivesWe aimed to compare the use of DBS to standard antidepressant therapy and decipher whether DBS can be used for TRD. In addition, electroconvulsive therapy (ECT), a current brain stimulation method administered for TRD, was contrasted with DBS.MethodsA narrative review of the current literature concerning DBS application and TRD was conducted to evaluate whether standard antidepressant therapy was as effective as psychosurgical intervention. Emphasis on TRD-associated DBS was noted.ResultsThe studies discussed found that DBS was an effective treatment option for TRD, however, the results were limited due to the studies being conducted in small sample sizes and using DBS in combination with antidepressant therapy. Nonetheless, the concomitant use of DBS and antidepressants demonstrated to be an effective treatment for TRD, highlighting the potential benefit of DBS in inducing remission in TRD. DBS has a wider range of complications compared to ECT as it involves a more invasive neurosurgical approach to implant the device. On comparing the cost of the devices between the 2 studies, DBS costs approximately three times more than ECT.ConclusionsThe spectrum of depressive disorders is known to affect multiple regions of the brain. A more cohesive approach would be a comprehensive study using DBS in multiple brain regions while incorporating blinded controls. In summary, DBS could be a viable treatment addition for TRD, but more thorough studies are needed to deduce its true efficacy. Future collaborative studies investigating the efficacy of DBS over ECT in TRD may assess further therapeutic potential.Disclosure of InterestNone Declared

Deep Brain Stimulation and Movement Disorder Treatment

Deep brain stimulation (DBS) is an FDA-approved neurosurgical procedure for treating patients with movement disorders such as Parkinson’s disease. Patient-specific computational modeling and visualization play a key role for efficient surgical and therapeutic decision-making relevant to DBS. The computational models analyze DBS post-operative brain imaging, e.g., computed tomography (CT), to understand the DBS electrode positions within the patient’s brain. The DBS stimulation settings for optimal patient response depend upon a physician’s knowledge regarding precise electrode positions. The finite resolution of brain imaging, however, restricts our understanding regarding precise DBS electrode positions. In our contribution, we study the problem of the quantification of positional uncertainty in the DBS electrodes caused by the finite resolution of post-operative imaging. We propose a Monte Carlo statistical framework, which takes the advantage of our analytical characterization of the DBS electrode geometry to understand the spatial uncertainty in DBS electrodes. Our statistical framework quantifies the uncertainty in two positional parameters of the DBS electrodes, namely, the longitudinal axis direction and the positions at sub-voxel levels. We interactively visualize quantified uncertainties by employing volume rendering and isosurfaces. We show that the spatial variations in the DBS electrode positions are significant for finite resolution imaging, and interactive visualization can be instrumental for efficient interpretation of the positional variations in the DBS lead.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely performed for medically refractory Parkinson’s disease (PD). Several western studies have examined the long-term outcomes of STN DBS. However, the long-term outcomes in Japanese patients have not been reported. Methods: We studied the long-term outcomes of STN DBS in Japanese patients with PD. Fifty-five consecutive patients treated with bilateral STN DBS were followed for 5 years after surgery. Each patient underwent Unified Parkinson’s Disease Rating Scale assessments preoperatively and 1 and 5 years after surgery. Results: Twelve patients (22%) were lost to follow up within 5 years. Among them, 7 died and 5 became bed ridden because of PD deterioration. In the 43 patients followed for 5 years, STN DBS significantly improved motor function. The cardinal motor symptoms of tremor, rigidity, and bradykinesia in medication-on periods were significantly better than baseline 5 years after DBS. However, axial motor symptoms of speech, gait and postural stability gradually deteriorated and significantly worsened 5 years after DBS. Motor complications, including dyskinesia and motor fluctuations, significantly improved after DBS with a marked reduction in dopaminergic medication. These effects were maintained 5 years after DBS. Frequently, persisting adverse effects included apraxia of eyelid opening and dysarthria. Conclusions: STN DBS significantly improved motor symptoms in patients with advanced PD. These effects were maintained over 5 years in most patients. However, some showed rapid PD progression even after STN DBS. Other treatments for the axial symptoms and disease progression are needed in long-term PD treatment.

Background:Deep brain stimulation (DBS) of the ventralis intermedius (VIM) nucleus of the thalamus has been successful in mitigating upper limb tremor, but the effect on gait and balance performance is unclear. Here, we aim to examine the effectiveness of VIM DBS on stride length variability, sway path length, and task-relevant tremor of various body segments in essential tremor (ET).Methods:Seventeen ET individuals treated with DBS (ET DBS) and 17 age-and sex-matched healthy controls (HC) performed a postural balance and overground walking task. In separate and consecutive visits, ET DBS performed gait and balance tasks with DBS ON or OFF. The main outcome measures were sway path length, stride length variability, and tremor quantified from upper limb, lower limb, upper and lower trunk (axial) during the gait and balance tasks.Results:With DBS OFF, ET DBS exhibited significantly greater stride length variability, sway path length, and tremor during gait and balance task relative to HC. Relative to DBS OFF, DBS ON reduced stride length variability and sway path length in ET DBS. The DBS-induced reduction in stride length variability was associated with the reduction in both upper trunk tremor and upper limb tremor. The DBS-induced reduction in sway path length was associated with the reduction in upper trunk tremor.Discussion:The findings of this study revealed that VIM DBS was effective in improving gait and balance in ET DBS and that improvements in gait and postural balance were associated with a reduction of axial tremor during the tasks.Highlights:ET patients exhibit tremor in various body locations during gait and balance.DBS reduced stride length variability and sway path length.DBS-induced improvements in gait and balance were associated with reduction in axial tremor.

The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD). The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson's Disease Rating Scale-part III) and medication usage were also assessed pre- and postoperatively. Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group. The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.

Predictors of future deep brain stimulation surgery in de novo Parkinson’s disease: analysis of the PPMI cohort

BackgroundThe safety and efficacy of neuroablation (ABL) and deep brain stimulation (DBS) for treatment refractory obsessive-compulsive disorder (OCD) has not been examined. This study sought to generate a definitive comparative...

Back to table of contents Previous article Next article LettersFull AccessDBS, Parkinson's Disease, and SuicideChristian Saleh, M.D.Christian SalehSearch for more papers by this author, M.D.Published Online:1 Apr 2011AboutSectionsView articleView PDFView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View articleTo the Editor: I read with interest Dr. Mahgoub's and Dr. Kotbi's case report, “Acute depression and suicidal attempt following lowering the frequency of deep brain stimulation.”1 The authors report the case of a 66-year-old patient treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) of 20 years' duration, who suffered an acute depressive episode associated with a suicide attempt after the modification of his DBS stimulation parameters.In this patient, a reduction of the frequency of the stimulation from 185 Hz to 60 Hz was noted with the induction of an acute suicidal state. By increasing the frequency, the depressive state improved, and the suicidal ideations subsided. Dr. Mahgoub and Dr. Kotbi write that “Our case demonstrates the risk of suicide when lowering the frequency of the stimulation… Patients at high risk for suicide should be excluded from deep brain stimulation surgery.”Some differentiations and specifications here might be needed: The patient reported by the authors was treated with DBS of the subthalamic nucleus (STN). Although DBS STN for PD is known to be associated with a plethora of neuropsychiatric adverse effects, such as confusion, psychosis, depression, mania, and suicidal ideation,2 noteworthy within this context is that psychosis, depression, and suicidal ideation are known also in patients with PD not undergoing DBS treatment.3The authors write that DBS “has now also been extended to other neuropsychiatric conditions and has shown some promising results in patients suffering from profound depression.” It is advisable though to differentiate that while the main target for DBS for PD is the STN, DBS applied to treat depression has different targets, such as the nucleus accumbens, the subgenual cingulate (Cg25), and the ventral capsule and ventral striatum (VC/VS).4The relationship between stimulation settings of the DBS device and neuropsychiatric adverse effects is known; however it is important to note that the literature shows considerable contrasting findings in this matter.2Some authors reported that stimulation induced limbic effects, whereas termination of stimulation led to a resolution of the limbic symptoms;5 in contrast to the case reported by Dr. Mahgoub and Dr. Kotbi. Still other authors specified that limbic side effects were not affected by changing the stimulation parameters, but required the changing of the localization of the stimulating contacts or subsided solely after pharmacological treatment.2Although Dr. Mahgoub and Dr. Kotbi's report is important, the statement that “our case demonstrates the risk of suicide when lowering the frequency of the stimulation” cannot be made with such implicitness. The plethora of contrasting reports on this subject matter2 does not allow for generalization of findings, especially if they are based on a single case report. More research is yet needed to elucidate the polyhedral relation between STN DBS, PD, and suicide.Paris, France1. Mahgoub NA , Kotbi N : Acute depression and suicidal attempt following lowering the frequency of deep brain stimulation. J Neuropsychiatry Clin Neurosci 2009; 21:468Link, Google Scholar2. Saleh C , Okun MS : Clinical review of deep brain stimulation and its effects on limbic basal ganglia circuitry. Front Biosci 2008; 13:5708–5731Crossref, Medline, Google Scholar3. Nazem S , Siderowf AD , Duda JE , et al.: Suicidal and death ideation in Parkinson's disease. Mov Disord 2008; 23:1573–1579Crossref, Medline, Google Scholar4. Kuhn J , Grundler TO , Lenartz D , et al.: Deep brain stimulation for psychiatric disorders. Dtsch Arztebl Int 2010; 107:105–113Google Scholar5. Stefurak T , Mikulis D , Mayberg H , et al.: Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study. Mov Disord 2003; 18:1508–1516Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByBrain stimulation treatments in bipolar disorder: A review of the current literature4 December 2014 | The World Journal of Biological Psychiatry, Vol. 17, No. 7 Volume 23Issue 2 Spring 2011Pages E4-E4 Metrics History Published online 1 April 2011 Published in print 1 April 2011

The sleep gap in deep brain stimulation in psychiatry: A systematic review.

To the Editor: Modern deep brain stimulation (DBS) devices are often advertized as being “whole-body conditional,” and this label is an important consideration when assessing the suitability of DBS for a given patient (eg, a patient who would likely require spinal imaging in the future). However, we found that unforeseen contradictions between DBS vendor guidelines and MRI manufacturer manuals rendered diagnostic “whole-body” (eg, spine) imaging unfeasible at our center, leading to deleterious effects on patient care. As described previously,1 the main risk of MRI on deep DBS patients is heating at the DBS lead tips. To mitigate this risk, DBS vendor guidelines typically include 2 heating-related thresholds that scans must be acquired within: most commonly (1) specific absorption rate (SAR) or, if available, (2) B1 + rms. Of the 2, SAR thresholds are extremely restrictive while the more permissive B1 + rms metric is less established and not universally available. Although these factors have been useful in preventing adverse events, they also have limited MRI for DBS patients.2 At our institution, our previous MRI (1.5T GE-Signa; software: HDxT 23.0_V021406.a) did not offer B1 + rms, and the SAR thresholds specified in DBS vendor guidelines meant that it was only practical to acquire diagnostic quality imaging of the head. Given the demand for MRI in DBS patients—1 study estimating that up to 75% of patients require MRI within 10 years of DBS surgery, the majority (62%) of whom calling for body and/or spine scans3—we performed rigorous phantom testing to ensure the safety of off-label (ie, outside SAR threshold) spinal scans on our GE machine.4 Recently, we upgraded our MRI to the one enabling B1 + rms measurements (1.5T Siemens-Magnetom; software: XA20), theoretically allowing us to leverage a more permissive heating-related threshold and acquire diagnostic scans within DBS guidelines. However, we found that the Siemens system displayed a warning prohibiting scans based on B1 rms values: “The actual B1 rms value may be much higher than the value displayed. Do not scan patients with implants based on this value.” This is in conflict with the recommendations of DBS vendor guidelines, which even acknowledge potential discrepancies between real and predicted B1 + rms: “The actual B1 + rms value may differ slightly from the predicted value… The MRI Guidelines for Medtronic …requires only that the predicted B1 + rms value for the protocol is <2.0 µT.”5 Consequently, our MRI department was unable to perform clinically practical scans for extracranial pathology (eg, for the spine) without breaching DBS vendor guidelines or MRI manufacturer recommendations. The delays caused by this impasse have compromised patient care and ultimately led us back to square 1, in which we had to reproduce our phantom safety experiments using the Siemens MRI to facilitate off-label whole-body imaging. It is important that the DBS and radiology community are aware of the contradictory guidelines set by major MRI and DBS manufacturers, which we have not previously seen described in the literature and the considerable hurdles that they can impose.