Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow-up of patients.

Bilateral subthalamic nucleus stimulation (STN-DBS) is used to improve parkinsonian symptoms and attenuate levodopa-induced motor complications. In some patients, such clinical improvement allows antiparkinsonian medication (ApMed) withdrawal. We show the clinical outcome at the long-term follow-up of patients with advanced Parkinson's disease (PD) in which STN-DBS was used in monotherapy, and compare the clinical results of patients without medication with those obtained in parkinsonian patients in which ApMed were reduced but could not be totally displaced after surgery. We analyzed clinical outcome of ten patients with PD in which all ApMed was withdrawn after bilateral subthalamic stimulation and 16 parkinsonian patients still taking antiparkinsonian medication after surgery. After 1.5 years, STN-DBS monotherapy produced UPDRS motor scores similar to those observed in the on-drug condition before surgery without the inconvenience of motor fluctuations and dyskinesias. No significant differences were seen in most of clinical outcome measures when comparing patients still taking ApMed with patients in STN-DBS monotherapy but a few patients still taking ApMed presented mild dyskinesias and motor fluctuations and patients with STN-DBS monotherapy did not. STN-DBS is useful in the treatment of advanced PD and in some patients it is possible to maintain this therapy alone in the long term. The therapeutic effect of STN-DBS on motor signs can be equipotent to that of levodopa with the additional benefit of avoiding motor fluctuations and dyskinesias.     

Variance in effects of subthalamic nucleus stimulation]

Chronic stimulation of subthalamus nucleus (STN) is effective in treating severe motor fluctuation and levodopa induced dyskinesia as well as parkinsonian motor symptoms. The improvement of peak-dose/diphasic dyskinesias of STN stimulation is considered to be due to the decrease in the daily dosage of antiparkinsonian drugs. However one report pointed out that STN stimulation improved directly levodopa induced dyskinesia. Moreover the timing of the improvement for levodopa induced dyskinesia is not yet obvious. In the present study, we have assessed variance in the latency of improvement of levodopa induced dyskinesia due to STN stimulation. In addition, we would clarify an issue which cite of STN stimulation improved parkinsonian symptoms and motor complication (motor dyskinesias and motor fluctuation). We have studied seven patients diagnosed with advanced idiopathic Parkinson's disease with motor fluctuations and levodopa induced dyskinesias. Before and after the implantation of stimulating electrode, patients were assessed by the Unified Parkinson's Disease Rating Scale and % 'OFF' motor state. The dosage of the antiparkinsonian medication was not modified for one month prior to implantation. Following implantation, dosage of the medication and strength of stimulation was adjusted, if necessary. Symptoms of motor fluctuation and dyskinesia improved in all patients six month after surgery. The mean off-time duration and dyskinesia disability improved compared with presurgical conditions. However, the time course of the improvement of dyskinesias was not the same among patients. Contralateral limb dyskinesias in three patients improved immediately after the stimulation without modification of medication. In contrast, the stimulation worsened contralateral limb dyskinesias in other three patients immediately following the surgery. In two of the three patients, dyskinesias gradually improved within one month after surgery without reducing the dosage of medication. Dyskinesias of the other patient improved following a reduction in the dosage of medication one month after the surgery. Improvement of parkinsonian symptoms of the patients with longer latency of stimulation effect for dyskinesias was better than that of the patients with shorter latency. Stimulation cite of the former group appeared to locate more central than that of the latter group. Latency and strength of the effects of STN stimulation are variable.     

Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow up

BACKGROUND: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease (PD) are well documented, but long term benefits are still uncertain. OBJECTIVES: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. METHODS: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and 60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. CONCLUSIONS: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.     

Bilateral subthalamic nucleus stimulation in advanced Parkinson’s disease

Objective To assess the long-term efficacy and safety of chronic bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced Parkinson’s disease (PD). Methods 36 consecutive patients with idiopathic Parkinson’s disease treated with bilateral stimulation of the STN were studied. Parkinsonian status was assessed preoperatively and at 1 and 3 years postoperatively using the Unified Parkinson’s Disease Rating Scale (UPDRS) and neuropsychological evaluation in on and off-medication / on and off stimulation conditions. Results At 3 years follow-up, STN stimulation reduced the UPDRS motor score by 54.2 % compared to baseline in the off-medication conditions. Tremor, rigidity, bradykinesia, postural stability, and gait improved by 72.2 %, 62.4 %, 56.8 %, 40.5 % and 45.3 %, respectively. UPDRS part II scores were reduced by 41.4 %. The overall dopaminergic drugs dose was reduced by 48.6 % after surgery and four patients were no longer taking antiparkinsonian medication at three years. However, axial dopa-unresponsive signs worsened in some patients. The most frequent transient adverse event consisted in mood disorders in 23 patients. Conclusions Our data demonstrate that: 1) bilateral STN stimulation is relatively safe, improves the motor symptoms and drug-related motor complications of PD, and reduces the daily dosage of medication; 2) this benefit is sustained over time despite the occurrence of axial doparesistant signs in some patients.     

Clinical and economic results of bilateral subthalamic nucleus stimulation in Parkinson's disease

BACKGROUND: High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications. OBJECTIVE: To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation. METHODS: We conducted a prospective multicentre study in 95 consecutive Parkinson's disease (PD) patients receiving bilateral STN stimulation and assessed its effects over 12 months. A double blind randomised motor evaluation was carried out at 3 month follow up, and quality of life, self care ability, and predictive factors of outcome following surgery were assessed. The cost of PD was estimated over 6 months before and after surgery. RESULTS: The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p<0.0001) and activities of daily living improved by 48% (p<0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p<0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p<0.001). The better the preoperative motor score after a levodopa challenge, the better the outcome after STN stimulation. Five patients developed an intracerebral haematoma during electrode implantation with permanent after effects in two. The 6 month costs of PD decreased from 10,087 euros before surgery to 1673 euros after surgery (p<0.0001) mainly because of the decrease in medication. These savings allowed a return on the procedure investment, estimated at 36,904 euros over 2.2 years. CONCLUSIONS: STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications.     

Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson's disease.

OBJECTIVE: To reduce antiparkinsonian medication in parkinsonian patients with bilateral high frequency subthalamic nucleus (STN) stimulation. BACKGROUND: Parkinsonian syndromes are characterized by hyperactivity of the STN. Preliminary data indicate that functional inactivation of the STN may reduce the requirement for dopaminergic therapy in PD. METHODS: Bilateral quadripolar leads were implanted stereotactically in the STN of seven patients with advanced PD (mean age, 57.4 years; mean disease duration, 15.4 years). High-frequency stimulation was applied for 24 hours a day. Following implantation, antiparkinsonian medication was reduced to the minimum possible and stimulation was gradually increased. The patients were evaluated in the practically defined "off" and "on" conditions using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab & England scale. The average follow-up was 16.3+/-7.6 months. A battery of neuropsychological tests was applied before and 9 months after the implant. RESULTS: Parkinsonian features improved in all patients--the greatest change seen in rigidity, then tremor, followed by bradykinesia. Compared with the presurgical condition, off-drug UPDRS motor scores improved by 41.9% on the last visit (p = 0.0002), UPDRS activities of daily living (ADL) scores improved by 52.2% (p = 0.0002), and the Schwab & England scale score improved by 213% (p = 0.0002). The levodopa-equivalent daily dose was reduced by 65%. Night sleep improved in all patients due to increased mobility at night, and in five patients insomnia was resolved. All patients gained weight after surgery and their appetite increased. The mean weight gain at the last follow-up was 13% compared with before surgery. During the last visit, the stimulation amplitude was 2.9+/-0.5 V and the total energy delivered per patient averaged 2.7+/-1.4 W x10(-6). The results of patient self-assessment scales indicated a marked improvement in five patients and a moderate improvement in the other two. The neuropsychological data showed no changes. Side effects were mild and tolerable. In all cases, a tradeoff between the optimal voltage and the severity of side effects made it possible to control parkinsonian signs effectively. The most marked side effects directly related to STN stimulation consisted of ballistic or choreic dyskinesias of the neck and the limbs elicited by contralateral STN stimulation above a given threshold voltage, which varied depending on the individual. CONCLUSIONS: Parkinsonian signs can be controlled by bilateral high-frequency STN stimulation. The procedure is well tolerated. On-state dyskinesias were greatly reduced, probably due to the reduction of total antiparkinsonian medication. Bilateral high-frequency STN stimulation compensated for drug reduction and elicited dyskinesias, which differ from those observed following dopaminergic medication. ADL improved significantly, suggesting that some motor tasks performed during everyday chores, and that are not taken into account in the UPDRS motor score, also improved.     

Effects of bilateral subthalamic nucleus deep brain stimulation on motor symptoms in Parkinson’s disease: a retrospective cohort study

Deep brain stimulation of the bilateral subthalamic nucleus (STN) is a therapeutic option for patients with Parkinson’s disease (PD) in whom medical therapies have been ineffective. This retrospective cohort study analyzed the motor function of 27 patients with advanced PD, from the First Affiliated Hospital of Guangzhou Medical University, China, who received deep brain stimulation of the bilateral subthalamic nucleus and evaluated its therapeutic effects. The 10-year follow-up data of patients was analyzed in Qingyuan People’s Hospital, Sixth Affiliated Hospital of Guangzhou Medical University, China. The follow-up data were divided into two categories based on patients during levodopa treatment (on-medication) and without levodopa treatment (off-medication). Compared with baseline, the motor function of on-medication PD patients improved after deep brain stimulation of the bilateral subthalamic nucleus. Even 2 years later, the motor function of off-medication PD patients had improved. On-medication PD patients exhibited better therapeutic effects over the 5 years than off-medication PD patients. On-medication patients’ akinesia, speech, postural stability, gait, and cognitive function worsened only after 5 years. These results suggest that the motor function of patients with advanced PD benefitted from treatment with deep brain stimulation of the bilateral subthalamic nucleus over a period up to 5 years. The overall therapeutic effects were more pronounced when levodopa treatment was combined with deep brain stimulation of the bilateral subthalamic nucleus. This study was approved by Institutional Review Board of Qingyuan People’s Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, China (approval No. QPH-IRB-A0140) on January 11, 2018.

Chinese Library Classification No. R454.1; R741; R338.2+4     

Subthalamic nucleus stimulation in tremor dominant parkinsonian patients with previous thalamic surgery

Before the introduction of high frequency stimulation of the subthalamic nucleus (STN), many disabled tremor dominant parkinsonian patients underwent lesioning or chronic electrical stimulation of the thalamus. We studied the effects of STN stimulation in patients with previous ventral intermediate nucleus (VIM) surgery whose motor state worsened. Fifteen parkinsonian patients were included in this study: nine with unilateral and two with bilateral VIM stimulation, three with unilateral thalamotomy, and one with both unilateral thalamotomy and contralateral VIM stimulation. The clinical evaluation consisted of a formal motor assessment using the Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests encompassing a 50 point frontal scale, the Mattis Dementia Rating Scale, and the Beck Depression Inventory. The first surgical procedure was performed a mean (SD) of 8 (5) years after the onset of disease. STN implantation was carried out 10 (4) years later, and duration of follow up after beginning STN stimulation was 24 (20) months. The UPDRS motor score, tremor score, difficulties in performance of activities of daily living, and levodopa equivalent daily dose significantly decreased after STN stimulation. Neither axial symptoms nor neuropsychological status significantly worsened after the implantation of the STN electrodes. The parkinsonian motor state is greatly improved by bilateral STN stimulation even in patients with previous thalamic surgery, and STN stimulation is more effective than VIM stimulation in tremor dominant parkinsonian patients.     

Motor features and response to oral levodopa in patients with Parkinson’s disease under continuous dopaminergic infusion or deep brain stimulation

Background: Subthalamic nucleus deep brain stimulation (STN DBS) and continuous dopaminergic infusions (jejunal levodopa or subcutaneous apomorphine) are indicated in complicated Parkinson’s disease (PD), although it remains unsettled how they compare to each other. Methods: We investigated the daytime motor condition in patients with advanced PD under monotherapy with jejunal levodopa, subcutaneous apomorphine, or STN DBS and also measured the motor changes produced by an additional standard morning dose of levodopa. Motor performance was assessed with the UPDRS‐III, hand taps, the AIMS dyskinesia score and patients’ diaries. Outcome measures were time to best motor ‘on’ after start of morning treatment, daytime variability of motor condition, motor scores. Results: The time to ‘on’ was longest in the jejunal levodopa group. DBS and jejunal levodopa treatments produced stable motor conditions without appreciable ‘off’ episodes. Continuous apomorphine infusion was associated with the worst motor scores (UPDRS‐III and taps) and the most frequent off‐states. Jejunal levodopa infusion was associated with the highest AIMS scores. Addition of a levodopa dose produced shortening of time to ‘on’ and a transient motor improvement in the jejunal levodopa group without increase in dyskinesias; in the DBS and apomorphine groups, there was an increase in dyskinesias without changes in UPDRS‐III or taps. Conclusions: STN DBS provided adequate trade‐off between motor improvement and dyskinesia control, although dyskinesias could be elicited by adding oral levodopa. Jejunal levodopa infusion produced adequate motor improvement with slow time to ‘on’ and moderate dyskinesias. Apomorphine infusion produced insufficient motor control and negligible dyskinesias.     

Subthalamic DBS replaces levodopa in Parkinson's disease: two-year follow-up

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) of patients with PD allows reduction of antiparkinsonian medication but has only a mild direct effect on dyskinesia. Since antiparkinsonian medication has short- and long-term effects that may prevent an estimate of the maximal possible impact of STN DBS, such medication was used at the lowest possible dosage after DBS implantation. OBJECTIVE: To study the maximal and long-term effects of STN DBS using the lowest dose of medication. METHODS: Twenty consecutive patients with PD with motor fluctuations and dyskinesia underwent bilateral implantation under stereotactic guidance, microrecording, and clinical control. All medications were stopped before implantation and reintroduced, at the lowest dosage needed, only if the postoperative motor score did not reach the baseline level. Unified PD Rating Scale (UPDRS) motor (subscale III) scores were measured at baseline and after 3, 6, 12, and 24 months. RESULTS: After 21 plus minus 8 months, the UPDRS III "off-medication" score was decreased by 45% and was similar to the preoperative UPDRS III "on" score. Overall, medication was reduced by 79%, being completely withdrawn in 10 patients. Fluctuations and dyskinesia showed an overall reduction of >90%, disappearing completely in patients without medication. These improvements were maintained for 2 years. CONCLUSIONS: These results show that STN DBS could replace levodopa and allowed all antiparkinsonian medication to be discontinued in 50% of patients with PD. Fluctuations and dyskinesia disappeared completely in these patients but persisted in those still on medication. These improvements were maintained for 2 years.     

Effect of bilateral subthalamic nucleus stimulation on parkinsonian gait

Clinical reports show that bilateral subthalamic nucleus (STN) stimulation is effective in improving parkinsonian gait. Quantitative analysis of the efficacy of STN stimulation on gait is of interest and can be carried out using a commercially available stride analyser. Ten parkinsonian patients (5 men, 5 women) with a mean age of 55.8, SD 9.6 years were included in our study. They had a mean duration of Parkinson's disease (PD) of 13.3, SD 4.5 years and a motor examination score (part III of the Unified Parkinson's Disease Rating Scale) (UPDRS) of 43, SD 13 in off-stimulation off-drug condition. All the patients had bilateral chronic STN stimulation which had started from 3 to 36 months before the study. Patients were evaluated in off-drug and on-drug conditions both with and without stimulation. We analysed the principal gait measures: velocity, cadence, stride length, gait cycle, duration of single and double limb support. The clinical parkinsonian signs were evaluated with the part III of the UPDRS. In the off-drug condition, STN stimulation significantly (p < 0.05) improved velocity and stride length. The effect was similar to that of levodopa. When STN stimulation was switched on at the best of the levodopa induced effect, no further improvement was observed. The UPDRS motor score was significantly (p < 0.001) decreased after both stimulation and levodopa. In conclusion, STN stimulation is effective on parkinsonian gait.     

Staged unilateral versus bilateral subthalamic nucleus stimulator implantation in Parkinson disease.

In 17 consecutive patients with Parkinson disease (PD), bilateral subthalamic nucleus (STN) stimulators were implanted during staged surgeries. The Unified Parkinson Disease Rating Scale (UPDRS) and the Dyskinesia Disability Scale were completed both off and on medication prior to any surgery and also OFF and ON stimulation after each surgery. On-medication UPDRS activities of daily living (ADL) and motor examination scores changed little with unilateral or bilateral stimulation. Off-medication UPDRS motor examination scores improved to similar degrees after each staged STN electrode implantation. Most of the improvements in off-medication ADL scores, dyskinesia scores, complications of therapy, and medication dose reduction occurred after unilateral STN stimulation with smaller improvements after the second operation.     

Effective long-term subthalamic stimulation in PARK8 positive Parkinson’s disease

Whether patients with genetically defined Parkinson’s disease (PD) may be particularly eligible to benefit from deep brain stimulation of the nucleus subthalamicus (STN-DBS) is currently the subject of debate. We report on a patient with advanced PD due to R793M missense mutation in the LRRK2 gene successfully treated by STN-DBS. Disease onset was at age 42 with bradykinesia, rigidity and rest tremor. During the course of the disease he developed severe motor fluctuations, dyskinesias, postural instability with falls, but preserved levodopa responsiveness. At age 60 the patient was treated by bilateral DBS of the STN. At one year after surgery a 66% improvement of the UPDRS motor score in the off-medication state was determined. During the long-term follow-up there was sustained benefit with 56% improvement of motor score after 8 years. Our report adds evidence that patients with LRRK2 monogenetic Parkinsonism are well suited candidates for DBS treatment and may indicate a potential genetic predictor for positive long-term effect of STN-DBS treatment.     

Impact of Subthalamic Nucleus Stimulation on Young‐Onset Parkinson's Disease

Objective. To clarify the efficacy of subthalamic nucleus (STN) stimulation in young‐onset Parkinson's disease (PD), we compared the effects of STN stimulation on the motor symptoms between young‐onset PD (YOPD) and late‐onset PD (LOPD). Methods. We analyzed the effects of STN stimulation on motor function and motor fluctuations in 15 patients with YOPD, and 113 patients with LOPD who underwent STN stimulation during the same period. The Unified Parkinson's Disease Rating Scale (UPDRS) was evaluated during the on‐period and off‐period, which are defined as the times at which the motor symptoms are the best and worst during the daily active time with sustaining anti‐parkinsonian drugs. The dyskinesia severity rating scale (DSRS) also was employed to assess the severity of peak‐dose dyskinesia. We analyzed the changes in levodopa equivalent daily dose (LED), motor fluctuations, DSRS, and UPDRS part 3 score after STN stimulation, and compared the changes in each score between the two groups (YOPD vs. LOPD). Results. The LED was reduced, and the on‐off motor fluctuation index, dyskinesia rating scale score (on‐period), and UPDRS part 3 score (on‐ and off‐periods) were improved in both the YOPD and LOPD groups. The improvement rates of the UPDRS part 3 scores in both the on‐ and off‐periods in the YOPD group were superior to those in the LOPD group. The results of multivariate logistic regression analysis demonstrated that YOPD itself is the best responder to STN stimulation. Conclusions. STN stimulation can reduce the LED and improve motor fluctuations in patients with YOPD. The effects of STN stimulation on the motor symptoms of YOPD patients are superior to those in LOPD. The present findings suggest that YOPD patients suffering from several problems related to pharmacological therapy are probably good candidates for STN stimulation.     

Effects of gabapentin on the motor response to levodopa: a double-blind, placebo-controlled, crossover study in patients with complicated Parkinson disease

BACKGROUND: Motor fluctuations and dyskinesias affect many parkinsonian patients chronically treated with levodopa. Imbalance between gabaergic direct and indirect striatopallidal pathways may originate them. Manipulating GABA neurotransmission may be effective in the treatment of these patients. Gabapentin is an antiepileptic drug that increases the synthesis and release of GABA. Previous studies suggest that gabapentin may be useful in Parkinson disease (PD). OBJECTIVE: To know the effects of gabapentin on the motor response to levodopa in PD patients with motor complications. DESIGN: A randomized double-blind, placebo-controlled, cross-over trial with four weeks of treatment. SETTING: A tertiary referral center. PARTICIPANTS: Twenty subjects with PD and motor fluctuations and dyskinesias on stable antiparkinsonian treatment, took gabapentin up to a maximum dose of 2.400 mg/d in three doses and placebo. METHODS: Three levodopa challenges were performed: at the beginning of the study and at the end of each period of treatment (4 weeks). Basal (off) and best (on) motor status were assessed by the UPDRS III. Latency to peak effect, magnitude of motor response (difference between "on" and "off" scores in the UPDRS III), duration of motor response and severity and duration of dyskinesias after each levodopa challenge were assessed. Patients' diaries were administered. RESULTS:: Fifteen patients completed the study. A significant improvement in the basal UPDRS III resulting in a significant reduction in the magnitude of the motor response after gabapentin was obtained (P < 0.001). No other changes were observed, either on pharmacological parameters or in levodopa-induced dyskinesias. Number of daily hours spent in "on," "on with dyskinesias" and "off" also remained unchanged. Tolerance was good, dizziness being the most common side effect. CONCLUSION: Gabapentin improved parkinsonian symptoms (basal UPDRS III and magnitude of the motor response) following levodopa. This improvement was not reflected in the daily motor situation of patients. Dyskinesias remained unchanged. Gabapentin was well tolerated. Further studies are needed to know the impact of these results in the long-term.     

Effects of bilateral subthalamic nucleus deep brain stimulation on motor symptoms in Parkinson's disease:a retrospective cohort study

Deep brain stimulation of the bilateral subthalamic nucleus(STN) is a therapeutic option for patients with Parkinson's disease(PD) in whom medical therapies have been ineffective. This retrospective cohort study analyzed the motor function of 27 patients with advanced PD, from the First Affiliated Hospital of Guangzhou Medical University, China, who received deep brain stimulation of the bilateral subthalamic nucleus and evaluated its therapeutic effects. The 10-year follow-up data of patients was analyzed in Qingyuan People's Hospital, Sixth Affiliated Hospital of Guangzhou Medical University, China. The follow-up data were divided into two categories based on patients during levodopa treatment(on-medication) and without levodopa treatment(off-medication). Compared with baseline, the motor function of onmedication PD patients improved after deep brain stimulation of the bilateral subthalamic nucleus. Even 2 years later, the motor function of off-medication PD patients had improved. On-medication PD patients exhibited better therapeutic effects over the 5 years than offmedication PD patients. On-medication patients' akinesia, speech, postural stability, gait, and cognitive function worsened only after 5 years. These results suggest that the motor function of patients with advanced PD benefitted from treatment with deep brain stimulation of the bilateral subthalamic nucleus over a period up to 5 years. The overall therapeutic effects were more pronounced when levodopa treatment was combined with deep brain stimulation of the bilateral subthalamic nucleus. This study was approved by Institutional Review Board of Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, China(approval No. QPH-IRB-A0140) on January 11, 2018.     

Chronic bilateral electrical stimulation of the subthalamic nucleus for the treatment of advanced Parkinson's disease

Preliminary reports in patients with Parkinson's disease (PD) showed that subthalamic nucleus (STN) stimulation was able to reverse parkinsoniam state. Since 1998 we evaluated the safety and the efficacy of STN stimulation in 7 patients affected by advanced PD. All patients were included using CAPIT protocol. Motor functions and quality of life were evaluated, before and after surgery, with UPDRS and PDQ38, respectively. At the 6-month follow-up, the off medication/on stimulation UPDRS motor score improved by 50.6% and the on medication/on stimulation by 20.3%. Motor fluctuations were reduced by 57.2% and dyskinesias by 73.5%. The total D-dopa equivalent daily dose was reduced by 40.7%. PDQ38 ameliorated by 49.9%. We did not observe any perioperatory complication and only mild and tolerable side effects after stimulation.     

Effects of subthalamic nucleus stimulation on parkinsonian dysarthria and speech intelligibility

Subthalamic stimulation is known to improve tremor, akinesia and rigidity in Parkinson's disease. However, other signs such as hypophonia and swallowing disorders can be relatively resistant to this technique. The effect on dysarthria remains unclear. The aim of this study was to investigate the effects of implantation of electrode and stimulation of the subthalamic nucleus (STN) on parkinsonian dysarthria. Seven patients were prospectively included. Electrodes (Medtronic) were implanted in both STN. The electrode contacts and stimulation parameters were adjusted to provide best relief of symptoms with fewest side effects. Assessment used global scales (Unified Parkinson Disease Rating Scale, UPDRS II and III), dyskinesia scale, exhaustive dysarthria assessment (bucco-facial movements, voice, articulation, intelligibility) and the 'dysarthria' item from the UPDRS III. Evaluations were performed in six conditions: before and three months after surgery (pre-op, post-op) stimulation turned off or on (off-stim, onstim), and without or with a suprathreshold levodopa dose (offdrug, on-drug). Performance level on the UPDRS III significantly improved following electrode implantation and stimulation. For dysarthria, modest beneficial effects were observed on several motor parameters, especially lip movements. Voice mildly improved, especially for the modulation in loudness and pitch. Articulation was not affected. Furthermore, intelligibility was slightly reduced in the on-stimulation condition, especially when patients received levodopa. At an individual level, negative effects on intelligibility were observed in two patients, and this was associated with a discrete increase in facial and trunk dyskinesias, but not with the electrode position or stimulation parameters. In conclusion, surgery had weak effects on dysarthria. Intelligibility can be worsened, especially in the on-drug condition. Thus, adaptation of the stimulation parameters can be difficult.     

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.     

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