Effect of high‐frequency subthalamic neurostimulation on gait and freezing of gait in Parkinson's disease: a systematic review and meta‐analysis

The aim of this meta‐analysis was to summarize the short‐ and long‐term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN‐DBS) on gait and freezing of gait (FOG) in Parkinson's disease and to detect predictors of post‐stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN‐DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinson's Disease Rating Scale (UPDRS) and six studies with the FOG item (no. 14) were included. Data were summarized for the following follow‐up periods: 6–15, 24–48 and >48 months. For the medication (Med)‐Off/stimulation(Stim)‐On condition compared with baseline Med‐Off, STN‐DBS significantly improved gait on average from 2.43 to 0.96, 2.53 to 1.31 and 2.56 to 1.40 points at 6–15, 24–48 and >48 months, respectively (P < 0.05). Pre‐operative levodopa responsiveness of UPDRS‐III and Med‐Off severity of gait were the predictors of this beneficial effect. STN‐DBS significantly improved FOG for the Med‐Off/Stim‐On condition compared with baseline on average from 2.26 to 0.82, 2.43 to 1.13 and 2.48 to 1.38 points at 6–15, 24–48 and >48 months, respectively (P < 0.05). There was no significant effect in the Med‐On/Stim‐On condition. This meta‐analysis showed a robust improvement of gait and FOG by STN‐DBS for more than 4 years in the Med‐Off/Stim‐On condition. No beneficial effect was found for the On state of medication. Pre‐operative levodopa responsiveness of global motor performance (UPDRS‐III) is the strongest predictor of the effect of deep brain stimulation on gait.     

Effects of contact location and voltage amplitude on speech and movement in bilateral subthalamic nucleus deep brain stimulation

Subthalamic nucleus deep brain stimulation (STN‐DBS) is particularly effective in improving limb symptoms in Parkinson's disease. However, speech shows a variable response. Contact site and amplitude of stimulation have been suggested as possible factors influencing speech. In this double blind study, we assessed 14 patients post bilateral STN‐DBS, without medication. Six conditions were studied in random order as follows: stimulation inside the STN at low voltage (2 V) and at high voltage (4 V); above the STN at 2 V and at 4 V, at usual clinical parameters, and off‐stimulation. The site of stimulation was defined on the postoperative stereotactic MRI data. Speech protocol consisted of the assessment of intelligibility of the dysarthric speech, maximum sustained phonation, and a 1‐minute monologue. Movement was assessed using the UPDRS‐III. Stimulation at 4 V significantly reduced the speech intelligibility (P = 0.004) independently from the site of stimulation. Stimulation at 4 V significantly improved the motor function. Stimulation inside the nucleus was significantly more effective than outside the nucleus (P = 0.0006). The significant improvement in movement coupled with significant deterioration in speech intelligibility when patients are stimulated inside the nucleus at high voltage indicates a critical role for electrical stimulation parameters in speech motor control. © 2008 Movement Disorder Society     

Deep brain stimulation effects on gait variability in Parkinson's disease

The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on fall risk in patients with Parkinson's disease (PD) currently remain unclear. Although several gait parameters, such as gait speed, have shown improvement with DBS, some studies have reported an increased fall risk following DBS. The purpose of this study was to examine the effect of bilateral DBS on gait variability, a marker of fall risk. The gait of 13 patients with idiopathic PD was analyzed to determine the influence of DBS, levodopa and both therapies together. Following treatment with both levodopa and STN DBS, subjects displayed improved gait speed, reduced gait variability (enhanced stability), and lower Unified Parkinson's Disease Rating Scale (UPDRS) scores. Although UPDRS scores improved with STN DBS alone, parallel improvements were not seen for gait variability. These findings suggest that different mechanisms may contribute to performance on UPDRS motor testing and gait stability in response to DBS. © 2009 Movement Disorder Society     

Long‐term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease

We report the 5 to 6 year follow‐up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty‐five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross‐over double‐blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off‐ and on‐medication states with and without stimulation, activities of daily living (ADL), anti‐PD medications, and dyskinesias. In double‐blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off‐stimulation, regardless of the sequence of stimulation. In open assessment, both STN‐ and GPi‐DBS significantly improved the off‐medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti‐PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long‐term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN‐DBS patients and fewer adverse events in the GPi‐DBS group. © 2010 Movement Disorder Society     

Gait analysis in patients with advanced Parkinson disease: different or additive effects on gait induced by levodopa and chronic STN stimulation

Summary. The aim of our study was to observe the effects on gait parameters induced by STN stimulation and levodopa medication in patients with advanced Parkinson’s disease in order to determine different or additive effects. Therefore we examined 12 patients with advanced Parkinson disease after bilateral implantation of DBS into the STN. We assessed the motor score of the UPDRS and quantitative gait analysis under 4 treatment conditions: with and without stimulation as well as with and without levodopa. The mean improvement of the UPDRS motor score was almost the same with levodopa and DBS. Combining both therapies we saw a further improvement of the motor score. Gait parameters of patients with PD treated either with levodopa or STN stimulation were greatly improved. A significant difference between levodopa and STN stimulation could only be shown for the parameters velocity and step length. These parameters improved more with levodopa than with stimulation. The combination of both therapeutic methods showed the best results on the UPDRS motor score and gait parameters.     

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.     

The effects of subthalamic nucleus deep brain stimulation on parkinsonian tremor

Deep brain stimulation (DBS) of the ventral intermediate (Vim) nucleus of the thalamus has been the target of choice for patients with disabling essential tremor or medication refractory parkinsonian tremor. Recently there is evidence that the subthalamic nucleus (STN) should be the targets for patients with tremor associated with Parkinson's disease (PD). To assess the effects of STN DBS on parkinsonian tremor, eight consecutive patients with PD and disabling tremor were videotaped using a standardized tremor protocol. Evaluations were performed at least 12 h after last dose of medication with the DBS turned off followed by optimal DBS on state. A rater blinded to DBS status evaluated randomized video segments with the tremor components of the Unified Parkinson Disease Rating Scale (UPDRS) and Tremor Rating Scale (TRS). Compared with DBS off state there were significant improvements in mean UPDRS tremor score 79.4% (p = 0.008), total TRS score 69.9% (p = 0.008) and upper extremity 92.5% (p = 0.008) TRS subscore. Functional improvement was noted with pouring liquids. Our findings provide support that STN DBS is an effective treatment of tremor associated with PD.     

Effects of chronic subthalamic stimulation on nonmotor fluctuations in Parkinson's disease.

The aim of this study was to assess the outcome of nonmotor fluctuations (NMF) after chronic Subthalamic nucleus (STN) Deep Brain Stimulation (DBS) in Parkinson's disease(PD). Chronic stimulation of the STN has proved to be an effective treatment for advanced PD with motor complications. The outcome of NMF, which are also disabling, remains unknown. Forty-patients underwent bilateral STN stimulation. Each patient was interviewed before and after 1 yr of STN DBS with a structured questionnaire about their NMF. After 1 yr of chronic stimulation, the improvement in the motor score (UPDRS III) and dyskinesia amounted respectively to 67.4 and 76.3%. The decrease in motor fluctuations (MF) was 59% and 13 patients reported that their MF had disappeared. Comparatively, a reduction of the total number of NMF was also observed (mean number preoperatively: 15.6 per patient, postoperatively: 6.6). Most of the nonmotor fluctuating symptoms occurred in the "off" state preoperatively and no longer depended on the patient's motor state after surgery. The improvement in NMF was not identical for the different categories: pain/sensory fluctuations showed the best response to STN DBS (84.2%). Dysautonomic and cognitive fluctuations were also markedly improved (>60%) while psychic fluctuations remained the most frequent postoperative NMF observed. Some incapacitating manifestations such as drenching sweats and akathisia showed a remarkably good response to STN stimulation. In conclusion STN DBS alleviates NMF. It has strikingly successful effects on sensory, dysautonomic and cognitive fluctuations. However, psychic fluctuations respond less consistently to this treatment.     

Different cerebral cortical areas influence the effect of subthalamic nucleus stimulation on parkinsonian motor deficits and freezing of gait.

Inconsistent response in freezing of gait (FOG) with levodopa treatment or STN DBS makes the pathogenesis difficult to understand. We studied brain areas associated with the expression of STN DBS effect on parkinsonian motor deficits and FOG. Ten Parkinson's disease patients with typical FOG were included. One month before STN DBS, we performed [(18)F]-deoxyglucose PET scans and measured the UPDRS motor and modified FOG (mFOG) scores during levodopa off and on periods. At two months after STN DBS, same rating scores were measured. The percentage improvement of mFOG and UPDRS motor scores by STN DBS during levodopa off period was calculated. We searched for brain areas in which glucose metabolism correlated with the improvement of mFOG and UPDRS motor scores by DBS. During levodopa off period, STN DBS improved the UPDRS motor scores by 32.3% and the mFOG scores by 56.6%. There was no correlation between the improvements of both scores. The improvement of UPDRS motor score by DBS correlated with the metabolic activities of rostral supplementary motor area (Brodmann's area 8; BA8), anterior cingulate cortex (BA32), and prefrontal cortex (BA9). On the other hand, there was a positive correlation between the improvement of mFOG score by DBS and the metabolic activity of the parietal, occipital, and temporal sensory association cortices. In conclusion, dysfunction of different cerebral cortical areas limits the beneficial effects of DBS on parkinsonian motor deficits and FOG.     

Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF.MethodsAn atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales.ResultsSites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal).ConclusionThis study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.     

Could ZI have a role in DBS for Parkinson’s Disease? An observational study to optimize DBS target localization

Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a well-recognized intervention for Parkinson’s Disease (PD). We used LEAD-DBS, a toolbox facilitating DBS electrode reconstructions and computer simulations based on postoperative MRI and CT imaging, to investigate the interaction and followed benefits of electrical field generated by STN-DBS and surrounding areas, such as caudal Zona Incerta (cZI). Thirty-two PD patients, treated with directional STN-DBS in the period 2016–2018 at the Walton Center NHS Foundation Trust, were retrospectively recruited. Their MRI and CT imaging were analyzed with LEAD-DBS to measure the volume of tissue activated (VTA). Considering the clinical outcome based on the UPDRS III score improvement of 62.65% at 6 months follow up, we found a VTA intersection of 21.5% with motor STN and 61.7% with cZI. These observations may support the contribution of cZI deep stimulation to improve clinical outcome of PD patients treated with DBS, promoting the intriguing path of dual targeting.     

Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson's disease

Evidente VGH, Premkumar AP, Adler CH, Caviness JN, Driver‐Dunckley E, Lyons MK. Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson’s disease.
Acta Neurol Scand: 2011: 124: 211–214.
© 2010 John Wiley & Sons A/S. Objective – To compare the medication dose reduction between deep brain stimulation (DBS) of the globus pallidus interna (GPi) vs subthalamic nucleus (STN) in matched patients with Parkinson’s disease (PD). Materials and methods – Records of 12 patients with PD who underwent GPi‐DBS at our institution from 2002 to 2008 were matched by pre‐operative PD medication doses and pre‐operative motor Unified Parkinson’s Disease Rating Scale (UPDRS) scores to 12 cases of STN‐DBS. PD medication doses were converted to levodopa equivalent doses (LEDs). Results – GPi and STN groups had similar mean pre‐operative LEDs and motor UPDRS scores. At 6 months post‐DBS, there was no significant difference in percent reduction in LEDs between the GPi (47.95%) and STN (37.47%) groups (P = 0.52). The mean post‐operative ‘medication off/stimulation on’ motor UPDRS scores did not differ significantly between GPi (15.33) and STN (16.25) groups (P = 0.74). The mean percent reduction in motor UPDRS scores was also similar between GPi (58.44%) and STN (58.98%) patients (P = 0.94). Conclusions – We conclude that in disease‐matched patients with PD undergoing DBS, both GPi and STN may result in similar reduction in PD medication doses.     

Deep Brain Stimulation of the Subthalamic and Pedunculopontine Nucleus in a Patient with Parkinson's Disease

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel therapy developed to treat Parkinson''s disease. We report a patient who underwent bilateral DBS of the PPN and subthalamic nucleus (STN). He suffered from freezing of gait (FOG), bradykinesia, rigidity and mild tremors. The patient underwent bilateral DBS of the PPN and STN. We compared the benefits of PPN-DBS and STN-DBS using motor and gait subscores. The PPN-DBS provided modest improvements in the gait disorder and freezing episodes, while the STN-DBS failed to improve the dominant problems. This special case suggests that PPN-DBS may have a unique role in ameliorating the locomotor symptoms and has the potential to provide improvement in FOG.     

Mood response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease

Deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) improves motor functioning but has variable effects on mood. Little is known about the relationship between electrode contact location and mood response. The authors identified the anatomical location of electrode contacts and measured mood response to stimulation with the Visual Analog Scale in 24 STN DBS PD patients. Participants reported greater positive mood and decreased anxiety and apathy with bilateral and unilateral stimulation. Left DBS improved mood more than right DBS. Right DBS-induced increase in positive mood was related to more medial and dorsal contact locations. These results highlight the functional heterogeneity of the STN.     

Combination targeting of subthalamic nucleus and ventral intermediate thalamic nucleus with a single trajectory in deep brain stimulation for tremor-dominant Parkinson’s disease

Deep brain stimulation (DBS) has traditionally been used to target the subthalamic nucleus (STN) or globus pallidus internus (GPi) to treat Parkinson’s disease (PD) and the ventral intermediate thalamic nucleus (VIM) to treat essential tremor (ET). Recent case reports have described targeting both the STN and VIM with a single trajectory and electrode to treat patients with tremor-dominant PD, yet outcome data for this procedure remains sparse. Our objective is to determine the safety and efficacy of combination STN-VIM DBS. We conducted a single-center retrospective case series of all patients who underwent combined STN-VIM DBS. Demographic, perioperative, and outcome data, including Unified Parkinson Disease Rating Scale-III (UPDRS) and tremor scores (OFF-medication), and levodopa equivalent daily dose (LEDD), were collected and analyzed. Nineteen patients underwent this procedure. Patients were 89% male and 11% female, with a mean age of 63.6 years. Mean preoperative UPDRS was 24.1, and LEDD was 811.8. At a mean follow-up of 33.8 months, UPDRS and LEDD decreased by an average of 9.2 (38.2%) and 326.3 (40.2%), respectively. Tremor scores decreased by 4.9 (59.0%), and 58% were able to decrease total medication burden. One patient developed transient left-sided weakness, yielding a complication rate of 5.3%. Combined targeting of STN and VIM thalamus via a single frontal trajectory for tremor-dominant Parkinson’s Disease results in similar UPDRS outcomes to STN DBS and improved control of tremor symptoms. Larger multicenter studies are necessary to validate this as the optimal DBS target for tremor-dominant PD.     

Freezing of gait after bilateral subthalamic nucleus stimulation for Parkinson's disease

OBJECTIVE: To determine the long-term effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on freezing of gait in Parkinson's disease patients. PATIENTS AND METHODS: Sixty-seven patients were followed 12 months after bilateral STN DBS and 32 patients were followed 24 months post-surgery. Patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) with medications on and off at baseline and again in both conditions with stimulation on at follow-up. Specific attention was paid to the freezing item of the ADL section. RESULTS: Freezing scores in the medication off state improved significantly with stimulation at 1 and 2 years. In the medication on state there were no significant improvements in freezing. CONCLUSION: Off period freezing of gait is significantly improved with STN DBS up to 24 months; however, on period freezing is not affected by STN DBS.     

A Comparison of LEDD and Motor Scores Following STN‐DBS Treatment in Patient with Young Onset vs. Late Onset Parkinson's Disease

Introduction: We compared the role of subthalamic nucleus deep brain stimulation (STN‐DBS) in the management of medically refractory idiopathic Parkinson's disease in patients with relatively young onset (<40 years of age) Parkinson's disease (YOPD) and patients with relatively late onset Parkinson's disease (≥56 years of age, rLOPD). Methods: A total of 33 patients with YOPD (18 patients, median age 32.5 years, range, 20–40 years) and rLOPD (15 patients, median age 58.0 years, range, 56.0–67.0 years) underwent STN‐DBS between May 2000 and May 2008. We divided the patients into YOPD and rLOPD as the age of disease onset. The median follow‐up period was 43 months (range, 12–95 months). We assessed Hoehn and Yahr stages, activities of daily living, and Unified Parkinson's Disease Rating Scale (UPDRS) motor scales (III) for all patients preoperatively and at six months postoperatively. We measured levodopa equivalent doses (LEDD) and stimulation parameters preoperatively, six months postoperatively, and 12 months postoperatively. Results: There were no significant differences in UPDRS motor scales between two groups at preoperative and six‐month postoperative drug off/stim on, but UPDRS III was lower in rLOPD at six‐month postoperative drug on/stim on state. A significant difference was noted in the improvement of UPDRS III between two groups for preoperative drug off and drug on conditions, but no difference was seen between two groups in a comparison of drug off/stim on vs. drug on/stim on conditions. Stimulation parameters and postoperative LEDD were not different between the two groups. Preoperative dyskinesia was more common in YOPD patients and, psychotic problems were more common in rLOPD patients. Conclusions: Patients with YOPD and rLOPD exhibited comparable UPDRS motor scores and LEDD six months postoperatively. Levodopa could be prescribed at optimum doses following STN‐DBS in patients with YOPD as abnormal movements are better controlled following STN‐DBS implantation. Stimulation parameters were not different between the two groups. Our results suggest the age of onset does not influence response to STN‐DBS Parkinson's disease patients.     

Modulation of metabolic brain function by bilateral subthalamic nucleus stimulation in the treatment of Parkinson’s disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) was proposed as an effective way to improve the symptoms of Parkinson’s disease (PD). We studied metabolic modulation in the brain by bilateral STN stimulation using FDG PET. Five PD patients (age 61.6 ± 3.9 years) at advanced stage were scanned under OFF and ON conditions of stimulation. Network analysis was used to evaluate the effect of stimulation on the expression of an abnormal Parkinson’s disease-related spatial covariance pattern (PDRP). In addition, statistical parametric mapping was used to assess the effect of this intervention on regional glucose metabolism. We found that bilateral STN DBS led to a significant reduction (P < 0.02) in the PDRP network activity on an individual subject basis between OFF and ON conditions, parallel to significant improvement (P < 0.002) of clinical symptoms in these patients. The treatment also decreased glucose metabolism in the right lentiform nucleus and cerebellum, and in the bilateral ventral thalamus and precuneus, but increased metabolism in the left midbrain and pons. This was consistent with the notion that clinical benefit in a PD patient was associated with the suppression of hyperactive motor circuitry following STN stimulation. These findings suggest that DBS is more likely to function by regulating the entire neural network rather than merely exciting or inhibiting certain nuclei.     

Subthalamic deep brain stimulation for Parkinson's disease: Correlation between locations of oscillatory activity and optimal site of stimulation

Subthalamic nucleus deep brain stimulation (STN DBS) is an effective surgical treatment for Parkinson's disease (PD). Recent studies demonstrated that pathological oscillations are seen largely within the dorsolateral portion of the STN, which is the same location that predicts optimal therapeutic benefit with DBS; however, the precise nature of the relationship between these two phenomena remains unclear. The purpose of this study was to explore localization of oscillatory activity in relation to the optimal contacts of DBS which results in the best motor improvement. We studied 23 PD patients who underwent electrode implantation into the STN for motor symptoms.Microelectrode recordings were taken from the STN during surgery and neuronal activity was analyzed offline. Spectral characteristics were calculated. Clinical outcomes were evaluated pre- and post-STN DBS implantation using the Unified Parkinson's Disease Rating Scale (UPDRS III). The position of optimal electrode contacts was assessed by postoperative magnetic resonance imaging (MRI) and was compared to the location of oscillatory activity within the STN as well as its dorsal margin (where STN neuronal activity was first detected). Of the total 188 neurons obtained, 51 (27.1%) neurons showed significant oscillatory activity. Of those, 47 (92.2%) were localized in the dorsal portion of the STN. Furthermore, there was no significant difference between the averaged coordinates of the position of 40 optimal contacts and the coordinates of the dorsal margin of the STN. The data indicate that the positions of the best contacts correlate with the locations of the oscillatory neurons supporting the prediction that stimulation of the dorsolateral oscillatory region leads to an effective clinical outcome for STN DBS surgery.     

Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation.

OBJECTIVE: To compare the effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) with bilateral STN DBS in advanced PD. METHODS: Our initial 10 consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic bilateral STN DBS underwent a standardized evaluation of unilateral and bilateral STN DBS in the medication-off state 6 to 18 months after electrode implantation. RESULTS: Bilateral STN DBS improved the mean total Unified Parkinson's Disease Rating Scale motor score by 54%, whereas unilateral stimulation improved motor scores only 23%. Unilateral STN DBS improved postural stability and gait 14%, other axial motor features 19%, and overall parkinsonism in limbs contralateral to stimulation by 46%, including an 86% improvement in contralateral tremor. However, bilateral STN DBS resulted in greater improvement in each of these domains, including limb function, i.e., the reduction in scores from the limbs on one side was greater with bilateral than with unilateral stimulation of the contralateral STN. CONCLUSIONS: Bilateral STN DBS improves parkinsonism considerably more than unilateral STN DBS; bilateral simultaneous electrode implantation may be the most appropriate surgical option for patients with significant bilateral disability. Unilateral STN DBS results in moderate improvement in all aspects of off-period parkinsonism and improves tremor as much as is typically reported with DBS of the ventral intermedius nucleus of the thalamus (Vim). For this reason, STN DBS may be a more appropriate choice than Vim DBS or thalamotomy for parkinsonian tremor. Some patients with highly asymmetric tremor-dominant PD might be appropriately treated with unilateral instead of bilateral STN DBS.