Pyramidal tract activation due to subthalamic deep brain stimulation in Parkinson's disease.

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract. OBJECTIVES: To assess the relevance of pyramidal tract activation with STN-DBS in PD. METHODS: In a multimodal, blinded study in 20 STN-DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography. RESULTS: Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 ± 1.0 mA) compared with ipsilaterally (4.1 ± 1.1 mA) and with the contralateral first dorsal interosseous (4.0 ± 1.2 mA). The modeled volumes of corticobulbar and corticospinal tract activated correlated inversely with the resting motor threshold of the contralateral orbicularis oris and first dorsal interosseous, respectively. Active motor thresholds were significantly lower compared with resting motor thresholds by around 30% to 35% and correlated with the clinically used stimulation amplitude. Backward multiple regression in 12 individuals with a "lateral-type" speech showed that stimulation amplitude, levodopa equivalent dose reduction postsurgery, preoperative speech intelligibility, and first dorsal interosseous resting motor thresholds explained 79.9% of the variance in postoperative speech intelligibility. CONCLUSIONS: Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. © 2017 International Parkinson and Movement Disorder Society.

Long-term outcome of subthalamic nucleus deep brain stimulation for Parkinson's disease using an MRI-guided and MRI-verified approach.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) represents a well-established treatment for patients with advanced Parkinson's disease (PD) insufficiently controlled with medical therapies. This study presents the long-term outcomes of patients with PD treated with STN-DBS using an MRI-guided/MRI-verified approach without microelectrode recording. METHODS: A cohort of 41 patients who underwent STN-DBS were followed for a minimum period of 5 years, with a subgroup of 12 patients being followed for 8-11 years. Motor status was evaluated using part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III), in on- and off-medication/on-stimulation conditions. Preoperative and postoperative assessments further included activities of daily living (UPDRS-II), motor complications (UPDRS-IV), neuropsychological and speech assessments, as well as evaluation of quality of life. Active contacts localisation was calculated and compared with clinical outcomes. RESULTS: STN-DBS significantly improved the off-medication UPDRS-III scores, compared with baseline. However, UPDRS scores increased over time after DBS. Dyskinesias, motor fluctuations and demands in dopaminergic medication remained significantly reduced in the long term. Conversely, UPDRS-III on-medication scores deteriorated at 5 and 8 years, mostly driven by axial and bradykinesia subscores. Quality of life, as well as depression and anxiety scores, did not significantly change at long-term follow-up compared with baseline. In our series, severe cognitive decline was observed in 17.1% and 16.7% of the patients at 5 and 8 years respectively. CONCLUSIONS: Our data confirm that STN-DBS, using an MRI-guided/MRI-verified technique, remains an effective treatment for motor 'off' symptoms of PD in the long term with low morbidity.

Predictive factors of speech intelligibility following subthalamic nucleus stimulation in consecutive patients with Parkinson's disease.

Speech changes after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) can be variable, with the majority of patients experiencing speech deterioration over time. The aim of this study was to describe the perceptual characteristics of speech following chronic STN-DBS and to analyze clinical and surgical factors that could predict speech change. Fifty-four consecutive patients (34 men; mean age ± standard deviation (SD), 58.8 ± 6.3 years; mean ± SD disease duration, 12.5 ± 4.7 years; mean ± SD levodopa equivalent, 1556 ± 671 mg/day; mean ± SD Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) off-medication score, 48.1 ± 17.9 [range, 20-89]; and mean ± SD UPDRS-III on-medication score, 12.4 ± 7.8 [range, 2-31]) participated in this study. They were assessed before and at 1 year after surgery using the Assessment of Intelligibility for the Dysarthric Speech, the perceptual scale from Darley et al., and the UPDRS-III. Speech intelligibility deteriorated on average by 14.4% (P = 0.0006) after 1 year of STN-DBS when off-medication and by 12.3% (P = 0.001) when on-medication. The effect on speech was not linked to age at surgery, unlike the effect on motor outcome. The most significant predictive factors for deterioration of speech intelligibility when patients were off-medication/on-stimulation were lower preoperative speech intelligibility on-medication, longer disease duration, and medially placed left hemisphere active electrode contact. Speech change after STN-DBS is variable and multifactorial. Consistent preoperative speech evaluation would help inform patients about the possible effects of surgery. Appropriate consideration of speech deficits might assist surgical targeting, particularly of the left electrode.

Genotype and phenotype in Parkinson's disease: lessons in heterogeneity from deep brain stimulation.

Variation in the genetic risk(s) of developing Parkinson's disease (PD) undoubtedly contributes to the subsequent phenotypic heterogeneity. Although patients with PD who undergo deep brain stimulation (DBS) are a skewed population, they represent a valuable resource for exploring the relationships between heterogeneous phenotypes and PD genetics. In this series, 94 patients who underwent DBS were screened for mutations in the most common genes associated with PD. The consequent genetic subgroups of patients were compared with respect to phenotype, levodopa (l-dopa), and DBS responsiveness. An unprecedented number (29%) of patients tested positive for at least 1 of the currently known PD genes. Patients with Parkin mutations presented at the youngest age but had many years of disease before needing DBS, whereas glucocerebrosidase (GBA) mutation carriers reached the threshold of needing DBS earlier, and developed earlier cognitive impairment after DBS. DBS cohorts include large numbers of gene positive PD patients and can be clinically instructive in the exploration of genotype-phenotype relationships.

Salem VAMC-U.S. Army Fort Bragg Warrior Transition Clinic telepsychiatry collaboration: 12-month operation clinical perspective.

OBJECTIVE: To describe the clinical experience in the first Veterans Affairs (VA)-U.S. Army Warrior Transition Clinic (WTC) telepsychiatry operation (September 2008-August 2009). MATERIALS: Joint VA and U.S. Army records. METHODS: Analysis of intake, follow-up, and last visit records. RESULTS: One hundred twenty active-duty U.S. Army soldiers were seen (394 clinic visits). Ninety-eight soldiers had one or more combat tours, principally in Iraq and Afghanistan. Posttraumatic stress disorder was diagnosed in 50.0% of the cases by the WTC telepsychiatrists. The majority of the soldiers had medical comorbidities, especially chronic pain (75.0%), in addition to mental health problems. Several of the soldiers were recovering from trauma (20.8%) and/or surgery (23.3%), 11.7% exhibited traumatic brain injuries, and 17.5% had headaches. Disrupted relationships (74.2%) were notable for non-family members, especially military cohorts such as other persons in the same WTC squad or platoon. CONCLUSION: The observations in this report come from a cross-section of soldiers who were triaged to meet WTC admission criteria. As this is the prototype VA-U.S. Army telepsychiatry collaboration, there are no comparative data at this time. The nature of the medical and psychiatric problems treated in the military WTC represents an index of the more severe combat trauma treated on military bases from ongoing combat operations and may predict future VA-U.S. Army collaborative telepsychiatry clinic experiences.

An Evaluation of KELVIN, an Artificial Intelligence Platform, as an Objective Assessment of the MDS UPDRS Part III.

BACKGROUND: Parkinson's disease severity is typically measured using the Movement Disorder Society Unified Parkinson's disease rating scale (MDS-UPDRS). While training for this scale exists, users may vary in how they score a patient with the consequence of intra-rater and inter-rater variability. OBJECTIVE: In this study we explored the consistency of an artificial intelligence platform compared with traditional clinical scoring in the assessment of motor severity in PD. METHODS: Twenty-two PD patients underwent simultaneous MDS-UPDRS scoring by two experienced MDS-UPDRS raters and the two sets of accompanying video footage were also scored by an artificial intelligence video analysis platform known as KELVIN. RESULTS: KELVIN was able to produce a summary score for 7 MDS-UPDRS part 3 items with good inter-rater reliability (Intraclass Correlation Coefficient (ICC) 0.80 in the OFF-medication state, ICC 0.73 in the ON-medication state). Clinician scores had exceptionally high levels of inter-rater reliability in both the OFF (0.99) and ON (0.94) medication conditions (possibly reflecting the highly experienced team). There was an ICC of 0.84 in the OFF-medication state and 0.31 in the ON-medication state between the mean Clinician and mean Kelvin scores for the equivalent 7 motor items, possibly due to dyskinesia impacting on the KELVIN scores. CONCLUSION: We conclude that KELVIN may prove useful in the capture and scoring of multiple items of MDS-UPDRS part 3 with levels of consistency not far short of that achieved by experienced MDS-UPDRS clinical raters, and is worthy of further investigation.

Treatment of dysarthria following subthalamic nucleus deep brain stimulation for Parkinson's disease.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment for patients with Parkinson's disease (PD). Speech impairment is a frequent side effect of the surgery. This study examined the efficacy of an intensive speech treatment, the Lee Silverman Voice Treatment (LSVT) on dysarthria after STN-DBS. METHODS: The LSVT was administered to 10 patients with STN-DBS (surgical group) and 10 patients without (medical group). Patients were assessed before, immediately after, and 6 months following the speech treatment using sustained phonation, a speech intelligibility scale, and monologue. Vocal loudness, speech intelligibility, and perceptual ratings were the primary outcome measures. RESULTS: Vocal loudness and perceptual scores improved significantly across tasks for the medical group only. Speech intelligibility did not significantly change for either group. Results in the surgical group were variable, with some patients deteriorating. CONCLUSIONS: Treatment of dysarthria following STN-DBS needs further investigation because of the variable response to LSVT.

Telemental health for our soldiers: a brief review and a new pilot program.

This small but significant telemental health clinical pilot could easily serve as a "best practice" model for resource utilization between the nation's VHA/DOD institutions that wish to form partnerships and capitalize on resources. It demonstrates several potential areas of collaboration for TMH projects. For example, this study also points out requisite preparation needs, e.g., an information technology (IT) needs assessment, and gap analysis between neighboring VHA/DOD installations should be considered beforehand. This would address equipment compatibility and address protected health information privacy concerns. This preparation would also lead to savings by avoiding equipment redundancy and minimize infrastructure (space) investment. While in this instance the equipment proved compatible, that may not always be the case. Second, regional strategic mapping of staff and services between institutions could help in specialty service utilization. This would improve recourse allocation, trim numerous costs, and avoid service duplication. A third area of collaboration would be the creation of a DOD/VHA electronic credentialing packet. This would simplify the preparation phase for TMH delivery and expand the availability of scarce medical specialty consultants for both the VHA and DOD. This would serve to streamline medical care and expedite the deployment of "virtual" practitioners in the event of a national disaster or emergency. To date there have not been any technical difficulties at either site and PC-PTSD-positive soldiers continue to be evaluated at the SVMAC. Anecdotal reports from both clinicians and patients are that they are highly satisfied with TMH delivery services.

Effect of Low versus High Frequency Subthalamic Deep Brain Stimulation on Speech Intelligibility and Verbal Fluency in Parkinson's Disease: A Double-Blind Study.

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) is an established treatment for late stage Parkinson's disease (PD). Speech intelligibility (SI) and verbal fluency (VF) have been shown to deteriorate following chronic STN-DBS. It has been suggested that speech might respond favourably to low frequency stimulation (LFS). OBJECTIVE: We examined how SI, perceptual speech characteristics, phonemic and semantic VF and processes underlying it (clustering and switching) respond to LFS of 60 and 80 Hz in comparison to high frequency stimulation (HFS) (110, 130 and 200 Hz). METHODS: In this double-blind study, 15 STN-DBS PD patients (mean age 65, SD = 5.8, 14 right handed, three females), were assessed at five stimulation frequencies: 60 Hz, 80 Hz, 110 Hz, 130 Hz and 200 Hz. In addition to the clinical neurological assessment of speech, VF and SI were assessed. RESULTS: SI and in particular articulation, respiration, phonation and prosody improved with LFS (all p < 0.05). Phonemic VF switching improved with LFS (p = 0.005) but this did not translate to an improved phonemic VF score. A trend for improved semantic VF was found. A negative correlation was found between perceptual characteristics of speech and duration of chronic stimulation (all p < 0.05). CONCLUSIONS: These findings highlight the need for meticulous programming of frequency to maximise SI in chronic STN-DBS. The findings further implicate stimulation frequency in changes to specific processes underlying VF, namely phonemic switching and demonstrate the potential to address such deficits through advanced adjustment of stimulation parameters.

Globus pallidal deep brain stimulation for Tourette syndrome: Effects on cognitive function.

INTRODUCTION: In a double-blind randomized crossover trial, we previously established that bilateral deep brain stimulation of the anteromedial globus pallidus internus (GPiam-DBS) is effective in significantly reducing tic severity in patients with refractory Tourette syndrome (TS). Here, we report the effects of bilateral GPiam-DBS on cognitive function in 11 of the 13 patients who had participated in our double-blind cross-over trial of GPi-DBS. METHODS: Patients were assessed at baseline (4 weeks prior to surgery) and at the end of each of the three-month blinded periods, with stimulation either ON or OFF. The patients were evaluated on tests of memory (California Verbal Learning Test-II (CVLT-II); Corsi blocks; Short Recognition Memory for Faces), executive function (D-KEFS Stroop color-word interference, verbal fluency, Trail-making test, Hayling Sentence Completion test), and attention (Paced Auditory Serial Addition Test, Numbers and Letters Test). RESULTS: GPiam-DBS did not produce any significant change in global cognition. Relative to pre-operative baseline assessment verbal episodic memory on the CVLT-II and set-shifting on the Trail-making Test were improved with DBS OFF. Performance on the cognitive tests were not different with DBS ON versus DBS OFF. GPiam-DBS did not alter aspects of cognition that are impaired in TS such as inhibition on the Stroop interference task or the Hayling Sentence Completion test. CONCLUSIONS: This study extends previous findings providing data showing that GPiam-DBS does not adversely affect cognitive domains such as memory, executive function, verbal fluency, attention, psychomotor speed, and information processing. These results indicate that GPiam-DBS does not produce any cognitive deficits in TS.

The Effect of Short Pulse Width Settings on the Therapeutic Window in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for selected Parkinson's disease (PD) patients, but therapy is often limited by side effects. Previous studies indicate an inverse relationship of the therapeutic window (TW) to pulse width (PW) settings down to 60µs, but there is limited data available on the effect of shorter PWs. OBJECTIVE: To define the TW of STN-DBS in PD at PW of 30µs (PW30) relative to standard PW settings at 60µs (PW60), and to compare speed of gait and speech intelligibility on the two PW conditions. METHODS: Monopolar review data of 15 consecutive PD patients who had screening of contacts performed at PW60 and PW30 was used to calculate the TW at each contact. We compared the TWs of the most efficacious contact per STN, and a secondary analysis was performed comparing all contacts. Speed of gait with a timed 10 metre walk test, speech intelligibility, and perceptual characteristics of speech were also compared at the efficacy thresholds for PW60 and PW30. RESULTS: The TW was significantly greater at PW30 [3.8±1.6mA] than at PW60 [1.7±1.1mA]. In the secondary analysis, 110 TWs could be calculated and these remained significantly higher at PW30. The timed 10 metre walk at PW30 was faster than at PW60, and perceptual rating scores of speech were significantly improved at PW30. CONCLUSIONS: STN-DBS in PD patients using a PW of 30µs significantly increases the TW compared to standard PW settings, and this effect is consistent across all contacts of an electrode. Speed of gait and perceptual speech scores are also improved at 30µs settings.

Changing of the guard: reducing infection when replacing neural pacemakers.

OBJECTIVE Infection of deep brain stimulation (DBS) hardware has a significant impact on patient morbidity. Previous experience suggests that infection rates appear to be higher after implantable pulse generator (IPG) replacement surgery than after the de novo DBS procedure. In this study the authors examine the effect of a change in practice during DBS IPG replacements at their institution. METHODS Starting in January 2012, patient screening for methicillin-resistant Staphylococcus aureus (MRSA) and, and where necessary, eradication was performed prior to elective DBS IPG change. Moreover, topical vancomycin was placed in the IPG pocket during surgery. The authors then prospectively examined the infection rate in patients undergoing DBS IPG replacement at their center over a 3-year period with at least 9 months of follow-up. RESULTS The total incidence of infection in this prospective consecutive series of 101 IPG replacement procedures was 0%, with a mean follow-up duration of 24 ± 11 months. This was significantly lower than the authors' previously published historical control group, prior to implementing the change in practice, where the infection rate for IPG replacement was 8.5% (8/94 procedures; p = 0.003). CONCLUSIONS This study suggests that a change in clinical practice can significantly lower infection rates in patients undergoing DBS IPG replacement. These simple measures can minimize unnecessary surgery, loss of benefit from chronic stimulation, and costly hardware replacement, further improving the cost efficacy of DBS therapies.

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center.

The effectiveness of medications for PTSD in general has been well studied, but the effectiveness of medicatio.ns prescribed specifically for post-traumatic stress disorder (PTSD) nightmares is less well known. This retrospective chart review examined the efficacy of various medications used in actual treatment of PTSD nightmares at one Veteran Affairs Hospital. Records at the Salem, VA Veterans Affairs Medical Center (VAMC) were examined from 2009 to 2013 to check for the efficacy of actual treatments used in comparis.on with treatments suggested in three main review articles. The final sample consisted of 327 patients and 478 separate medication trials involving 21 individual medications plus 13 different medication combinations. The three most frequently utilized medications were prazosin (107 trials), risperidone (81 trials), and quetiapine (72 trials). Five medications had 20 or more trials with successful results (partial to full nightmare cessation) in >50% of trials: risperidone (77%, 1.0-6.0 mg), clonidine (63%, 0.1-2.0 mg), quetiapine (50%, 12.5-800.0 mg), mirtazapine (50%; 7.5-30.0 mg), and terazosin (64%, 50.0-300.0 mg). Notably, olanzapine (2.5-10.0) was successful (full remission) in all five prescription trials in five separate patients. Based on the clinical results, the use of risperidone, clonidine, terazosin, and olanzapine warrants additional investigation in clinically controlled trials as medications prescribed specifically for PTSD nightmares.

Bilateral globus pallidus stimulation for severe Tourette's syndrome: a double-blind, randomised crossover trial.

BACKGROUND: Deep brain stimulation (DBS) has been proposed as a treatment option for severe Tourette's syndrome on the basis of findings from open-label series and small double-blind trials. We aimed to further assess the safety and efficacy of bilateral globus pallidus internus (GPi) DBS in patient's with severe Tourette's syndrome. METHODS: In a randomised, double-blind, crossover trial, we recruited eligible patients (severe medically refractory Tourette's syndrome, age ≥20 years) from two clinics for tertiary movement disorders in the UK. Enrolled patients received surgery for GPi DBS and then were randomly assigned in a 1:1 ratio (computer-generated pairwise randomisation according to order of enrolment) to receive either stimulation on-first or stimulation off-first for 3 months, followed by a switch to the opposite condition for a further 3 month period. Patients and rating clinicians were masked to treatment allocation; an unmasked clinician was responsible for programming the stimulation. The primary endpoint was difference in Yale Global Tic Severity Scale (YGTSS) total score between the two blinded conditions, assessed with repeated measures ANOVA, in all patients who completed assessments during both blinded periods. After the end of the blinded crossover phase, all patients were offered continued DBS and continued to have open-label stimulation adjustments and objective assessments of tic severity until database lock 1 month after the final patient's final trial-related visit. This trial is registered with ClinicalTrials.gov, number NCT01647269. FINDINGS: Between Nov 5, 2009, and Oct 16, 2013, we enrolled 15 patients (11 men, four women; mean age 34·7 years [SD 10·0]). 14 patients were randomly assigned and 13 completed assessments in both blinded periods (seven in the on-first group, six in the off-first group). Mean YGTSS total score in these 13 patients was 87·9 (SD 9·2) at baseline, 80·7 (SD 12·0) for the off-stimulation period, and 68·3 (SD 18·6) for the on-stimulation period. Pairwise comparisons in YGTSS total scores after Bonferroni correction were significantly lower at the end of the on-stimulation period compared with the off-stimulation period, with a mean improvement of 12·4 points (95% CI 0·1-24·7, p=0·048), equivalent to a difference of 15·3% (95% CI 5·3-25·3). All 15 patients received stimulation in the open-label phase. Overall, three serious adverse events occurred (two infections in DBS hardware at 2 and 7 weeks postoperatively, and one episode of deep-brain-stimulation-induced hypomania during the blinded on-stimulation period); all three resolved with treatment. INTERPRETATION: GPi stimulation led to a significant improvement in tic severity, with an overall acceptable safety profile. Future research should concentrate on identifying the most effective target for DBS to control both tics and associated comorbidities, and further clarify factors that predict individual patient response. FUNDING: UK National Health Service.

A telepsychiatry transition clinic: the first 12 months experience.

To improve the management of soldiers with combat-related mental health problems, an interdisciplinary telepsychiatry service was established between a clinic at the Fort Bragg army base and the Veterans Affairs (VA) Medical Center in Salem. In the first 12 months of operation, 120 soldiers (105 males) were seen in a total of 394 telepsychiatry sessions. The time spent on telepsychiatry by the six VA psychiatrists increased from 13 hours in the first month to 41 hours in the twelfth month. The number of telepsychiatry sessions increased from nine in the first month to 56 in the twelfth month. The mean global assessment of function score (GAF) in the soldiers increased significantly (P < 0.001) from 58.0 at intake to 62.3 at the last visit. Soldiers received VA telepsychiatry on average 22 days after the initial consultation with a primary care provider, a reduction of at least eight days compared to the previous delay. The majority of soldiers (89%) who were treated by VA psychiatrists enrolled in the VA within about six months of discharge. Similar VA-US Military collaborations may prove beneficial for other military bases that have returning combat soldiers.