Low frequency subthalamic stimulation and event-related potentials in Parkinson disease

BackgroundHigh frequency (130 Hz) subthalamic Deep-Brain-Stimulation (STN-DBS) optimally improves cardinal motor symptoms in Parkinson disease (PD). Low stimulation frequencies (60–80 Hz) improve axial symptoms in some patients and, according to preliminary evidences, may also have a beneficial effect on the cognitive component of motor planning.ObjectiveTo analyze the configuration of the P300 component of cortical event-related auditory potentials (ERPs), a reliable index of attentive cognitive functions, at different stimulation frequencies in STN-DBS in PD patients.Methods12 PD patients underwent ERPs recordings using a standard oddball auditory paradigm with STN-DBS at 60 Hz, 80 Hz, 130 Hz, and OFF-stimulation, applied in a randomized double-blind sequence. ERPs analysis considered the peak amplitude and latency of the P300 components at midline electrode positions (Fz, Cz, Pz).ResultsP300 latency over Cz and Pz electrodes significantly increased with STN-DBS at 130 Hz compared to OFF-stimulation. P300 latency was also significantly increased, though to a lesser degree, over Pz electrode with stimulation at 80 Hz. No significant P300 latency modifications were detected at 60 Hz stimulation compared to OFF-stimulation condition. P300 amplitude did not change significantly for any of the stimulation conditions tested.ConclusionsLow frequency STN-DBS is associated with minor modifications of P300 latency compared to conventional stimulation at 130 Hz, possibly suggesting that 60 and 80 Hz may have less interference with attentive and cognitive processes in PD patients.     

Subthalamic stimulation and levodopa modulate cortical reactivity in Parkinson's patients

BackgroundThe effects of deep brain stimulation of the subthalamic nucleus (DBS-STN) and L-dopa (LD) on cortical activity in Parkinson's disease (PD) are poorly understood.ObjectivesBy combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) we explored the effects of STN-DBS, either alone or in combination with L-Dopa (LD), on TMS-evoked cortical activity in a sample of implanted PD patients.MethodsPD patients were tested in three clinical conditions: i) LD therapy with STN-DBS turned on (ON/ON condition); ii) without LD therapy with STN-DBS turned on (OFF/ON condition); iii) without LD therapy with STN-DBS turned off (OFF/OFF condition). TMS pulses were delivered over left M1 while simultaneously acquiring EEG. Eight age-matched healthy volunteers (HC) were tested as a control group.ResultsSTN-DBS enhanced early global TMS-evoked activity (∼45–80ms) and high-alpha TMS-evoked oscillations (11–13 Hz) as compared to OFF/OFF condition, independently from concomitant LD therapy. LD intake (ON/ON condition) produced a further increase of late TMS-evoked activity (∼80–130ms) and beta TMS-evoked oscillations (13–30 Hz), as compared to OFF/OFF and OFF/ON conditions, that normalized reactivity as compared to HC range of values.ConclusionsOur data reveal that bilateral STN-DBS and LD therapy induce a modulation of specific cortical components and specific ranges of frequency. These findings demonstrate that STN-DBS and LD therapy may have synergistic effects on motor cortical activity.     

Deep brain stimulation outcomes in the malignant end of Parkinson's disease spectrum

BackgroundHeterogeneity of Parkinson's Disease (PD) phenotype may influence deep brain stimulation (DBS) outcome. However, DBS response in the malignant end of the PD spectrum has been poorly investigated.ObjectiveTo evaluate and compare DBS outcomes in malignant and benign PD patients, defined according to motor and non-motor symptom presentation at the presurgical selection.MethodsWe categorized a cohort of 154 parkinsonian patients fulfilling criteria for subthalamic nucleus (STN)-DBS into malignant, benign, and intermediate subtypes, according to a recently validated clinical PD classification. DBS efficacy on daily living independence (Schwab and England –S&E-score ≥70%), motor symptoms, and motor fluctuations (Unified Parkinson's Disease Rating Scale -UPDRS- part-III and -IV, and Ambulatory Capacity Measure) were compared between malignant and benign patients, using corrected binary logistic regressions and repeated measure general linear model.ResultsOne year after surgery, the probability of losing daily life independence was 16-fold higher in malignant patients, even after adjusting for age at PD onset, PD duration, and percentage of motor improvement after STN-DBS (OR: 16.233; p: 0.035). Conversely, malignant and benign patients showed a similar extent of improvement after STN-DBS (p > 0.05) in motor symptoms, motor fluctuations, and ambulatory capacity, both in medication-ON and medication-OFF conditions.ConclusionDBS candidates in the malignant end of the PD spectrum may profit from a similar improvement of motor symptoms and fluctuations after STN-DBS when compared to benign PD. However, patients of the malignant group have a lower probability of maintaining independence in daily life early after surgery.     

Does subthalamic nucleus deep brain stimulation affect the static balance at different frequencies?

PurposeTo investigate the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) with different stimulation frequencies on static balance.Materials and methodsTwenty patients (15 males and 5 females), aged between 43 and 81 (mean: 60.05 ± 7.4) years, who had been diagnosed with idiopathic Parkinson's disease (PD) and undergone STN-DBS surgery were included in the study. Static balance was assessed with TecnoBody Rehabilitation System at four different frequencies: 230, 130, 90 and 60 Hz and off-stimulation. Static balance tests were ‘stabilometric test, stabilometric compared bipedal closed/opened eye, stabilometric compared mono pedal (right/left foot)’. These tests reported the centre of pressure data ‘ellipse area, perimeter, front/back and mediolateral standard deviations’.ResultsThere were no statically differences between the static balance test results at any frequency (p > 0.05), but results were found better at 90 Hz. Stabilometric compared bipedal opened eye forward–backward standard deviation result was significant between off-stimulation and 130 Hz (p = 0.04). Different frequency stimulation affected the static balance categories percentage with no statistical significance between off-stimulation and others (all p > 0.05).ConclusionThis study showed that STN-DBS did not affect the static balance negatively. Low-frequency (LF) stimulation improved the static equilibrium. Posturography systems will give more precise and quantitative results in similar studies with wide frequency ranges.     

Clinical patterns of gait freezing in Parkinson's disease and their response to interventions: An observer-blinded study

BackgroundFreezing of gait (FOG) in Parkinson's disease (PD) is provoked by specific situations. The sensitivity of these situations to detect FOG and the relative FOG response to l-dopa and subthalamic nucleus deep brain stimulation (STN-DBS) is unknown.MethodsTwo blinded reviewers analyzed the video recordings of a standardized patient assessment before and 10 months after DBS-implantation of 124 PD patients with positive FOG according to the Unified Parkinson Rating Scale part II item 14. Baseline evaluations were done under 2 conditions (OFF- and ON-drug states). Postoperatively, the patients were evaluated under 4 conditions (OFF-drug/OFF-stim, OFF-drug/ON-stim, ON-drug/OFF-stim, and ON-drug/ON-stim). FOG frequency and its severity was rated during different provoking situations (start, turning, reaching a destination and open space hesitations) during a standardized walking task. Cumulative link mixed models were calculated to investigate the immediate and carry-over effect of medication and stimulation.ResultsEighty-one percent of patients presented FOG at least in one provoking situation on video assessment. During turning, the FOG severity was significantly worse than for the other subtypes (p < 0.0001). Both interventions improve all FOG subtypes similarly. The effect size of l-dopa and STN-DBS on subtypes were similar (p > 0.05), but the combined intervention had a stronger effect on FOG severity (p < 0.0001) compared to each intervention separately. FOG severity was lower at follow-up OFF compared to baseline OFF condition (p < 0.02) demonstrating a carry-over effect of STN-DBS.ConclusionTurning is the most sensitive provoking situation for gait freezing. STN-DBS and l-dopa improve all FOG subtypes similarly, their effect is stronger in combination.     

Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease

BackgroundIn Parkinson's disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD.MethodsWe investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson's disease Questionnaire 39 and the Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17.ResultsAll pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or l-Dopa reduction.ConclusionsSTN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients.     

Deep brain stimulation fine-tuning in Parkinson's disease: Short pulse width effect on speech

Backgroundsubthalamic nucleus deep brain stimulation (STN-DBS) may have a detrimental effect on speech in Parkinson's disease (PD) patients and new stimulation technologies may help in addressing this issue.Objectiveto evaluate the STN-DBS acute effect of 30 μs pulse width (30PW) versus conventional 60 μs PW (60PW) on speech and identify the core features of voice modified by 30PW.Methodsseven STN-DBS treated PD patients participated into a pilot cross-sectional study. Motor and speech performances were tested by means of both automatic analysis and blinded clinical evaluations in four stimulation conditions: 30PW and 60PW both at the usual amplitude and at an amplitude just below the threshold for stimulation-related side effects.Resultsat the threshold amplitude, 30PW stimulation improved speech intelligibility for both words (p = 0.02) and sentences (p = 0.04), without worsening motor performance. A lower but not statistically significant voice variability and instability and percentage of stuttering disfluencies was also observed. The beneficial effect of 30PW detected by automatic analysis, was confirmed by patients’ perception.ConclusionsSTN-DBS treated patients experiencing low speech intelligibility may benefit from a 30PW stimulation trial at a higher amplitude. Deep characterization of PD speech profiles may help in a better application of recent DBS hardware advances.     

Effect of frequency on subthalamic nucleus deep brain stimulation in primary dystonia

BackgroundSubthalamic nucleus deep brain stimulation (DBS) is an alternative target choice for treating primary dystonia, but little is known about the most effective programming parameters.ObjectiveHere we prospectively evaluate the effect of low versus high frequency subthalamic nucleus DBS in patients with predominantly cervical or upper extremity primary dystonia.MethodsSeven patients were stimulated at low frequency stimulation (60 Hz) for the first three months and then switched to high frequency stimulation (130 Hz) until month six. Severity of dystonia was determined by a blinded rater (unaware of the patient's pre or post-operative status) who scored the Burke Fahn Marsden dystonia rating scale movement score (BFMDRS-M) and the Toronto Western Spasmodic Torticollis Rating Scale severity score (TWSTRS-S) preoperatively, three, six, and twelve months post-surgery.ResultsPatients had a lower mean improvement of 16.6% in BFMDRS-M and 9.5% in TWSTRS-S at three months using low frequency stimulation compared to a 52.3% (p = 0.018) and 45.2% (p = 0.028), respectively, noted at six months using high frequency stimulation. At 12 months (using 130 Hz), the BFMDRS-M and TWSTRS-S improved by 51.8% (p = 0.022) and 56% (p = 0.034). Patients developed transient dyskinesia (during low and high frequency stimulation) which improved with programming adjustments.ConclusionThis study offers further support of the effectiveness of subthalamic nucleus DBS in the treatment of primary dystonia and finds that high frequency stimulation was more effective than low frequency stimulation.     

Anti-cholinergics for axial symptoms in Parkinson's disease after subthalamic stimulation

Objective

We studied the effect of anti-cholinergic therapy on axial symptoms that show a tendency to worsen over time after deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson's disease (PD).

Patients and methods

We conducted a prospective study of 20 consecutive patients treated with the anti-cholinergic agent trihexyphenidyl after bilateral STN-DBS and assessed the effect of anti-cholinergic therapy on parkinsonism 1 month after its initiation using the Unified Parkinson's Disease Rating Scale (UPDRS).

Results

After a mean post-operative follow-up period of 22.3 months, the scores of axial symptoms on UPDRS part II (ADL score) and part III (motor score) deteriorated by 87% and 54% (baseline), respectively, compared with the pre-operative scores (P < 0.001 for both comparisons). After adding trihexyphenidyl to dopaminergic medication with stimulation, the scores of axial symptoms on UPDRS part II and part III improved from baseline by 33% and 39%, respectively (P < 0.001 for both comparisons).

Conclusions

Our findings demonstrated that the anti-cholinergic agent trihexyphenidyl shows positive effect for a patient population developing deterioration of axial symptoms after STN-DBS. The results in the present study may provide insights into the mechanism of emergence or progression of axial symptoms in patients with PD after STN-DBS.     

Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease?

BackgroundDeep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD), but only few studies investigated its long-term efficacy. Furthermore, little is known about the role of PD-subtype on STN-DBS long-term outcome.ObjectiveTo report the results of a long-term follow-up (mean 11 years, range 10–13) on 26 patients bilaterally implanted in two centres.MethodsPatients were assessed preoperatively and 1, 5 and 11 years after the implant by the Unified Parkinson's Disease Rating Scale (UPDRS) and a battery of neuropsychological tests. Stimulation parameters, drugs dosages, non-motor symptoms and adverse events were also recorded.ResultsAt 11 years, stimulation significantly improved the motor symptoms by 35.8%, as compared to the preoperative off-state. Motor complications were well controlled, with a 84.6% improvement of dyskinesias and a 65.8% improvement of motor fluctuations. Despite this, the UPDRS-II-on score worsened by 88.5%, mainly for the worsening of poorly levodopa-responsive symptoms. More than 70% of the patients performed in the normal range in most of the neuropsychological tests, despite the development of dementia in 22.7%. Age at disease onset, axial subscore in off-condition and presence of REM behaviour disorder at baseline were found to be associated with a higher risk of developing disability over time.ConclusionsOur study confirms the long-term safety and efficacy of STN-DBS in PD. Nevertheless, the functionality of patients worsens over time, mainly for the onset and progression of levodopa-resistant and non-motor symptoms. The role of PD-subtype seems to be relevant in the long-term outcome.     

Probable REM sleep behaviour disorder and STN-DBS outcome in Parkinson's Disease

ObjectiveTo assess whether the presence of probable REM sleep behaviour disorder (pRBD) influences the long-term outcome of Parkinson's Disease (PD) patients undergoing Subthalamic Nucleus Deep Brain Stimulation (STN-DBS).BackgroundRBD is a parasomnia characterized by loss of muscular atonia and complex motor behaviours during REM sleep, frequently reported in PD patients. Recent evidence suggests that RBD is associated with akinetic rigid disease type and increased frequency of falls. We wondered whether the presence of RBD would also influence the long-term outcome of STN-DBS.MethodsForty-one consecutive PD patients treated with bilateral STN-DBS were assessed. The diagnosis of pRBD was based on a clinical interview investigating the occurrence of diagnostic criteria for RBD. The Unified Parkinson's Disease Rating Scale was used to compare the on- and off-medication conditions preoperatively and the on-stimulation/on- and off-medication conditions 1 and 3 years postoperatively. The general linear model for multivariate measures was used to analyse the interaction of pRBD with STN-DBS outcome measures.ResultspRBD was present in 12 out of 41 patients (29%) undergoing STN-DBS. Patients with pRBD had a significantly poorer outcome three years after STN-DBS compared to patients without pRBD, in particular for axial symptoms.ConclusionsOur findings suggest that the presence of pRBD in PD patients undergoing STN-DBS may be associated with a less favourable outcome and a more prominent development of axial symptoms over time.     

Effect of deep brain stimulation of the subthalamic nucleus on non-motor fluctuations in Parkinson's disease: Two-year' follow-up

BackgroundDeep brain stimulation of the subthalamic nucleus (STN-DBS) reduces motor fluctuations in Parkinson's disease (PD) but its effect on non-motor fluctuations (NMF) is not well known. In this study we assess the efficacy of STN-DBS on NMF two years after surgery.MethodsAutonomic, cognitive, psychiatric and sensory NMF in 20 patients were evaluated using a questionnaire designed to assess the frequency and severity of the NMF preoperatively and after two years of follow-up. The UPDRS scale was used for assessing the motor state.ResultsCompared with the preoperative situation, STN-DBS at 2 years of follow-up was associated with a significant reduction in the number and severity of autonomic and psychiatric NMF in the “off” state (without medication), and in the severity of sensory NMF, which were not observed in the “on” state (with medication). A cross-sectional analysis at the two-year time-point of the four possible motor conditions (combining medication and stimulation) showed a reduction in the total number of NMF and in the severity of autonomic and sensory NMF after switching on the stimulation in the “on” state. Improvement of the UPDRS-motor score was correlated with a reduction in the severity but not in the frequency of NMF. A worsening of motor function after suppressing stimulation in the “off” state was not paralleled by a worsening of NMF.ConclusionAfter two years of follow-up, STN-DBS in the “off” medication was associated with a reduction in the frequency and severity of NMF. These results will need to be confirmed in controlled studies.     

Two discrete components of the 20 Hz steady-state response are distinguished through the modulation of activation level

ObjectiveTo investigate the modulation of amplitude and phase precision of the auditory steady-state response (SSR) to 20 Hz stimulation in two conditions varying in the level of activation.MethodsClick stimuli (20 Hz) were applied while subjects were sitting upright silently reading a book of interest (high activation level) and while subjects were sitting in a reclined position with eyes closed and the lights turned off (low activation level). Sixty-one channel EEG data was wavelet transformed, the amplitude and phase precision measures extracted and decomposed by the multi-subject non-negative multi-way factorization (NMWF).ResultsThe NMWF decomposition of amplitude and phase precision measures resulted in the observation of two distinct components: a component at the frequency of stimulation – 20 Hz SSR and a component emerging at 40 Hz – 20 Hz SSR-related 40 Hz activity. Modulation by the activation level was observed only for 20 Hz SSR-related 40 Hz activity as increased amplitude and phase precision during low activation level. No such effects were observed for 20 Hz SSR.ConclusionThe discrete components of the 20 Hz SSR are distinguished through modulation of activation level, 20 Hz SSR- related 40 Hz being higher in low activation state.SignificanceThe biological modulation of 20 Hz SSR-related 40 Hz activity by the level of activation points to a physiological nature of this activity beyond a mere periodic effect in relation to the 20 Hz activity.     

Long-term outcome of young onset Parkinson's disease after subthalamic stimulation—A cross-sectional study

Objective

Age of onset is considered a poor prognostic factor for subthalamic deep brain stimulation (STN-DBS) outcome in the case of Parkinson's disease (PD). The goal of current study is to identify the long-term impact of STN-DBS for young onset PD (YOPD) patients.

Methods

17 YOPD patients with a mean disease onset at 32.3 years were prospectively followed up at 1, 2, 5 and 7 years after STN-DBS. Unified Parkinson's disease rating scale (UPDRS) was evaluated in 4 combinations of Med/DBS on/off.

Results

UPDRS part II–IV improved significantly 7 years after operation. While a slowly progressive worsening of levodopa response on part III, synergistic effect of medication and stimulation consistently improves motor disabilities. STN-DBS could remarkably reduce levodopa equivalent daily dose at 7 years. The morbidity rates were low. However, these patients seem to have more transient stimulation dyskinesia (47.1%) and dopamine dysregulation syndrome (11.8%) after surgery.

Conclusions

STN-DBS remains effective to improve motor disabilities over 7 years for YOPD and is a safe procedure concerning cognitive outcome and morbidity. However, stimulation dyskinesia and dopamine dysregulation syndrome deserve attention for the causal relationship between DBS surgery and behavioral outcomes.     

Effects of ramped-frequency thalamic deep brain stimulation on tremor and activity of modeled neurons

ObjectiveWe conducted intraoperative measurements of tremor to quantify the effects of temporally patterned ramped-frequency DBS trains on tremor.MethodsSeven patterns of stimulation were tested in nine subjects with thalamic DBS for essential tremor: stimulation ‘off’, three ramped-frequency stimulation (RFS) trains from 130 → 50 Hz, 130 → 60 Hz, and 235 → 90 Hz, and three constant frequency stimulation (CFS) trains at 72, 82, and 130 Hz. The same patterns were applied to a computational model of the thalamic neural network.ResultsTemporally patterned 130 → 60 Hz ramped-frequency trains suppressed tremor relative to stimulation ‘off,’ but 130 → 50 Hz, 130 → 60 Hz, and 235 → 90 Hz ramped-frequency trains were no more effective than constant frequency stimulation with the same mean interpulse interval (IPI). Computational modeling revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but long IPIs, concurrent with pauses in afferent cerebellar and cortical firing, allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions.ConclusionFrequency-ramped DBS produced equivalent tremor suppression as constant frequency thalamic DBS. Tremor-related thalamic burst activity may result from burst-driver input, rather than by an intrinsic rebound mechanism.SignificanceRamping stimulation frequency may exacerbate thalamic burst firing by introducing consecutive pauses of increasing duration to the stimulation pattern.     

Neuro-psychiatric therapy during chronic subthalamic stimulation in Parkinson's disease

BackgroundNeuro-psychiatric (NP) disturbances are highly prevalent in patients with Parkinson's disease (PD) and contribute to worsen quality of life. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is commonly utilized as surgical treatment for advanced PD with motor complications. The effectiveness of the procedure on motor symptoms is well established whereas the effects of STN-DBS on NP symptoms are less clear. The aim of our study was to analyze the postoperative pharmacological therapy for NP symptoms in a group of STN-DBS treated PD patients. Such therapy provides indirect information about the evolution of underlying NP disturbances during the follow-up in this group of PD patients.MethodsNP therapy (benzodiazepines, antidepressants, antipsychotics) was assessed in 48 consecutive PD patients treated by STN-DBS, preoperatively and postoperatively after 4 months, 1 year and 3 years. Motor symptoms were evaluated by the Unified PD Rating Scale (UPDRS) and levodopa equivalence daily dose (LEDD) was calculated. Cognitive, mood and anxiety assessments were performed with appropriate rating scales.ResultsThe number of patients treated with antidepressant drugs gradually increased during the follow-up. The use of antipsychotic drugs was stable until 1 year, with a subsequent increase at 3 years. Benzodiazepines were given to fewer patients immediately after surgery.ConclusionsPharmacological treatment supplies further information about NP symptoms in the follow-up of PD patients undergoing STN stimulation.     

Acute response of non-motor symptoms to subthalamic deep brain stimulation in Parkinson's disease

BackgroundSubthalamic deep brain stimulation (STN-DBS) is an established treatment for the motor complications of Parkinson's disease (PD) and may have beneficial effects on non-motor symptoms (NMS). However, the acute effect of STN stimulation on NMS has only been explored in small PD cohorts with short post-surgical follow-up.ObjectiveTo study NMS response to an acute stimulation challenge in an STN-DBS PD population with a medium/long-term post-surgical follow-up.Methods32 STN-DBS PD patients were tested twice (MED OFF/STIM OFF and MED OFF/STIM ON). MDS-UPDRS-III, blood pressure (BP) assessment, a visual analogue scale for pain and fatigue and State Trait Anxiety Scale score were evaluated during both stimulation conditions. NMS were assessed with MDS-UPDRS-I, Non-Motor Symptoms Scale, Geriatric Depression Scale and the Neuropsychiatric Inventory scale.ResultsMean (SD) age was 62.5 (±13.3) years, mean disease duration 18.7 (±5.1) years, mean post-surgical follow-up 4.6 (±1.3) years, and the mean reduction of levodopa equivalent daily dose after surgery was 58.9% (±25.4%). Mean (SD) motor response to stimulation was 40% (15%). STN stimulation significantly improved anxiety (mean 18% ± 19%, P < 0.005) and fatigue (mean 25% ± 51%; P < 0.05), while pain, although improved did not reach statistical significance. With stimulation ON, BP significantly decreased during orthostatism (P < 0.05) and there was a significant increase in asymptomatic orthostatic hypotension (P < 0.05).ConclusionsAcute STN stimulation improves anxiety and fatigue but decreases orthostatic BP in PD, several years after surgery. These effects should be considered when assessing long-term effect of DBS.     

Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial.MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients.ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I² = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I² = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I² = 53%, P < 0.001).ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.     

Acute low frequency dorsal subthalamic nucleus stimulation improves verbal fluency in Parkinson's disease

BackgroundParkinson's disease (PD) is a common neurodegenerative disorder that results in movement-related dysfunction and has variable cognitive impairment. Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) has been shown to be effective in improving motor symptoms; however, cognitive impairment is often unchanged, and in some cases, worsened particularly on tasks of verbal fluency. Traditional DBS strategies use high frequency gamma stimulation for motor symptoms (∼130 Hz), but there is evidence that low frequency theta oscillations (5–12 Hz) are important in cognition.MethodsWe tested the effects of stimulation frequency and location on verbal fluency among patients who underwent STN DBS implantation with externalized leads. During baseline cognitive testing, STN field potentials were recorded and the individual patients’ peak theta frequency power was identified during each cognitive task. Patients repeated cognitive testing at five different stimulation settings: no stimulation, dorsal contact gamma (130 Hz), ventral contact gamma, dorsal theta (peak baseline theta) and ventral theta (peak baseline theta) frequency stimulation.ResultsAcute left dorsal peak theta frequency STN stimulation improves overall verbal fluency compared to no stimulation and to either dorsal or ventral gamma stimulation. Stratifying by type of verbal fluency probes, verbal fluency in episodic categories was improved with dorsal theta stimulation compared to all other conditions, while there were no differences between stimulation conditions in non-episodic probe conditions.ConclusionHere, we provide evidence that dorsal STN theta stimulation may improve verbal fluency, suggesting a potential possibility of integrating theta stimulation into current DBS paradigms to improve cognitive outcomes.     

Eleven-Year Outcomes of Deep Brain Stimulation in Early-Stage Parkinson Disease

ObjectiveThe deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) pilot clinical trial randomized 30 patients (Hoehn & Yahr II off; medication duration 0.5–4 years; without dyskinesia/motor fluctuations) to optimal drug therapy (ODT) (early ODT) or bilateral subthalamic nucleus (STN) DBS plus ODT (early DBS+ODT). This study aims to report the 11-year outcomes of patients who completed the DBS in early-stage PD pilot clinical trial.Materials and MethodsAttempts were made to contact all 29 subjects who completed the two-year trial to participate in an 11-year follow-up study. Mixed-effects models compared overall trend in outcomes for randomization groups (fixed-effects: assigned treatment, year, their interaction; random-effect: subject) to account for repeated measures.ResultsTwelve subjects participated in this 11-year follow-up study (n = 8 early ODT, n = 4 early DBS+ODT). Participating subjects were 70.0 ± 4.8 years old with a PD medication duration of 13.7 ± 1.7 years (early DBS duration 11.5 ± 1.3 years, n = 4). Three early ODT subjects received STN-DBS as standard of care (DBS duration 6.5 ± 2.0 years). Early ODT subjects had worse motor complications (Unified Parkinson’s Disease Rating Scale [UPDRS]–IV) than early DBS+ODT subjects over the 11-year follow-up period (between-group difference = 3.5 points; p_interaction = 0.03). Early DBS+ODT was well-tolerated after 11 years and showed comparable outcomes to early ODT for other UPDRS domains, Parkinson Disease Questionnaire–39 (PDQ-39), and levodopa equivalent daily dose (LEDD).ConclusionsEleven years after randomization, early DBS+ODT subjects had fewer motor complications than early ODT subjects. These results should be interpreted with caution because only 40% of pilot trial subjects participated in this 11-year follow-up study. The Food and Drug Administration has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016).Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT00282152.