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.     

Bilateral subthalamic nucleus stimulation in the treatment of advanced Parkinson's disease. Five years' personal experience

Background and purposeThe objective of the study was to assess bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with advanced Parkinson disease (PD).Material and methodsThe study population included 5 patients with bilateral STN DBS who completed a 5-year postoperative follow-up period. In all patients electrodes (Model 3387 or 3389) were stereotactically bilaterally inserted into the STN using a Leksell stereotactic G frame. The clinical rating tests included Unified Parkinson's Disease Rating Scale (UPDRS) and two motor-timed tests derived from CAPIT (rapid movements between two points and stand-walk-sit test). All patients were assessed in off and on condition before implantation and 1, 3 and 5 years in medication on and off condition and stimulation on condition and stimulation off condition. To compare preoperative to postoperative UPDRS scores, only mean values and standard deviations are presented because of the small study population.ResultsThe stimulation effect was noted in the off state, resulting in a 59% improvement in motor scores of UPDRS at 5-year follow-up, when compared to preoperative scores. In the on state the stimulation improved motor scores by 17%. At 5-year follow-up, reduction of daily levodopa dose was 50%.ConclusionsBilateral STN DBS is an effective and safe treatment for patients with advanced PD. Bilateral STN DBS contributes to improvement of parkinsonian symptoms in the off state and levodopa-induced dyskinesia. This can be correlated with a 50% reduction of daily levodopa dose 5 years postoperatively.     

Subthalamic deep brain stimulation in patients with a previous pallidotomy.

The safety and efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients who have had a previous unilateral pallidotomy is not clear. We identified 10 patients (9 male) at the Baylor College of Medicine Parkinson's Disease Center who underwent STN DBS after prior unilateral pallidotomy. Demographics, efficacy as determined by off Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, and levodopa equivalent dosing were analyzed. We then compared these to an age- and sex-matched group of 25 DBS patients who had no prior pallidotomy. After their initial pallidotomy (mean age, 51.8 +/- 10.8 years), the mean UPDRS motor off medicine scores improved from 51.3 +/- 14.3 to 34.9 +/- 12.8, and the UPDRS dyskinesia score improved from 1.8 +/- 1.0 to 0.8 +/- 0.7. Their STN DBS off UPDRS motor scores (mean age, 56.0 +/- 10.2 years) improved by 16.0% from 53.1 +/- 9.7 (range, 42-68) to 44.6 +/- 11.1 (range, 25-67). In contrast, the UPDRS off motor scores in a control group of 25 DBS patients improved by 49.9%, from 49.7 +/- 11.1 to 25.7 +/- 18.9, (16.0% vs. 49.9%; P < 0.001). Changes in UPDRS dyskinesia scores were similar in both groups. AE thought to be related to the STN DBS following pallidotomy included worse dysarthria (three) and worse balance (two). STN DBS patients with prior pallidotomy had less improvement in UPDRS off motor score compared to other STN DBS patients, despite relatively good outcomes immediately after their pallidotomy. This may be partially due to a selection bias, but it may also indicate that prior pallidotomy is a negative predictor of outcome of STN DBS and should be considered in patient selection.     

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.     

Subthalamic stimulation in a patient with multiple system atrophy: a clinicopathological report

INTRODUCTION: Efficacy of high frequency subthalamic nucleus (STN) stimulation has been demonstrated in idiopathic Parkinson's disease (IPD). However, since it may be difficult to differentiate IPD from multiple system atrophy with parkinsonian presentation (MSA-P), a few cases of MSA-P has been treated by deep brain stimulation (DBS) and showed no sustained improvement of clinical signs. We report a patient with a clinical misdiagnosed MSA-P, later confirmed by neuropathological study, who was improved by DBS for one year. CASE REPORT: A 63-year-old parkinsonian patient had been treated by levodopa for 6 years with a persistent good response. Over one year he progressively developed disabling fluctuations with severe axial syndrome and vegetative non motor symptoms in off periods. After checking usual contraindications, he was included in surgical procedure protocol (bilateral STN stimulation). During the first year after surgery, the clinical status improved with disappearance of non motor fluctuations, a 45 percent decrease of the OFF UPDRS III score, and a 39 percent reduction of the treatment. However after one year, axial symptoms reappeared with recurrent falls, as well as increasing dysarthry and swallowing difficulties which were only slightly improved by levodopa. He developed severe urinary disorders increased by a prostatic adenoma which led to surgical treatment. During the post operative period, 2 years after DBS, he died suddenly from an unexplained cause. A cerebral autopsy was performed and showed a good position of the two electrodes in the STN. Microscopic studies revealed severe neuronal depletion in the substantia nigra but no Lewy bodies. Immunohistochemical methods demonstrated numerous argyrophilic glial cytoplasmic inclusions positive for alpha-synuclein and ubiquitin in the STN, putamen, globus pallidus, pontine nuclei and cerebellar white matter, significant of MSA. CONCLUSION: This case shows that DBS can improve parkinsonian signs in MSA-P with persistent dopa sensitivity. However, probably because of striatal degeneration progression, this improvement is time limited and STN DBS cannot be recommended in MSA.     

Treatment of advanced Parkinson's disease by subthalamotomy: one-year results.

We studied effects on parkinsonian features at 6 and 12 months in 12 patients who underwent unilateral ablation of subthalamic nucleus (STN). Microelectrode mapping was used, and a lesion was created in the STN using thermal coagulation and confirmed with magnetic resonance imaging. At 6 months postoperatively, improvements were seen in several areas: 1) Unified Parkinson's Disease Rating Scales II and III (UPDRS II and III) scores, 30% in off period, 38% in on period; 2) Schwab and England Scale (S&E) score, 21%; and 3) on dyskinesia, 85%. Contralateral rigidity, bradykinesia, UPDRS II and III scores, and S&E scores remained improved at 12 months. Daily dosage of levodopa requirement was reduced by 42%. Axial motor features, gait, postural stability, off period tremor, and motor fluctuation improved at 6 and 12 months but showed a decline in benefits at 18 months. Complications include 3 cases of hemiballism, of whom 2 patients recovered spontaneously but 1 died from aspiration pneumonia. One patient had asymptomatic hematoma, and 2 suffered transient postural asymmetries. We conclude that unilateral subthalamotomy results in moderate improvement in all aspects of parkinsonian features, allows reduction in the dose of levodopa required, and ameliorates drug-induced complications throughout 12-month assessments.     

Effects of bilateral stimulation of the subthalamic nucleus in patients with severe Parkinson's disease and motor fluctuations.

We present the efficacy and side effects of bilateral deep brain stimulation (DBS) of the subthalamic nuclei (STN) performed with a more simplified surgical procedure than described by the Grenoble group. A consecutive series of 26 patients with advanced and levodopa-responsive Parkinson's disease and motor complications was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) part I-VI, timed tests, and a patient diary for 2 days concerning on-off phenomenon and dyskinesias. At 3 months, evaluation of stimulation by the UPDRS motor score was performed in a double-blind manner and a significant improvement of 57% was found. The results 12 months after surgery off medication showed significant improvement in both UPDRS motor score and activities of daily living of 64% and, on medication, a significant reduction of 86% in duration of dyskinesias and 83% in duration of off-periods. Reduction in medication was less than for other groups, probably because we used smaller doses of levodopa before the operation. No serious side effects were encountered. When the patients are carefully selected and followed up, bilateral DBS of STN is a significant progress in treatment of advanced idiopathic Parkinson's disease with levodopa-induced motor complications.     

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.     

Pallidal stimulation in advanced Parkinson's patients with contraindications for subthalamic stimulation

The aim of this study was to evaluate the efficacy and safety of bilateral pallidal (GPi) deep brain stimulation (DBS) 6 months after surgery in advanced parkinsonian patients whose dopa‐resistant axial motor signs or cognitive decline constituted contraindications for subthalamic nucleus (STN) DBS. Seventeen patients with a mean age of 59.3 ± 7.1 years (range, 45–70), mean disease duration of 12.5 ± 4.3 years (range, 7–20), and contraindications for STN DBS, underwent bilateral GPi DBS. They were evaluated before surgery and 6 months afterward, in accordance with Core Assessment Program for Intracerebral Transplantation recommendations. There were mean improvements of 41.1% in the UPDRS III motor score in the off‐dopa condition and 20.3% in the activities of daily living score. Motor fluctuations were reduced by 22.9% and dyskinesias by 68.6%. Axial motor signs improved in the off‐dopa condition by 34.2%. Neuropsychological performances remained unchanged at the 6‐month assessment. Bilateral GPi DBS is both safe and effective in advanced parkinsonian patients with untreatable motor fluctuations, for whom STN DBS is contraindicated due to dopa‐resistant axial motor signs or cognitive decline. As such, it should be regarded as a viable option for these patients. © 2010 Movement Disorder Society     

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.     

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     

Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease

CONTEXT: Subthalamic nucleus (STN) stimulation may be effective in ameliorating parkinsonian symptoms even to the extent to permit levodopa withdrawal. OBJECTIVES: To analyze the efficacy of STN stimulation in patients with Parkinson disease (PD) and to determine if levodopa may be withdrawn after surgery. DESIGN: Before-after trial. SETTING: Referral center, hospitalized care. PATIENTS: Fifteen patients with advanced PD. INTERVENTIONS: Microelectrode-guided bilateral STN high-frequency stimulation. OUTCOME MEASURES: Before surgery patients were evaluated in off-medication and on-medication conditions. Dopaminergic drug dosages were reduced after surgery, aiming for complete withdrawal. Six months after surgery, patients were reeavaluated in off- and on-medication conditions, with the stimulation turned on and off. RESULTS: Total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the off-medication condition improved by 65.9%; and axial symptoms, bradykinesia, rigidity, and tremor improved by 65.8%, 60.4%, 66.1%, and 81.1%, respectively. UPDRS part II scores were reduced by 71.8% and Schwab and England scores improved by 45.3%. Levodopa was withdrawn in 8 patients and the overall levodopa dose was reduced 80.4%. "Off" time was reduced 89.7% and the severity of dyskinesias decreased 80.6% after surgery. All results reached significance (P<.001). Stimulation of the STN achieved antiparkinsonian effect similar to that of treatment with levodopa. No life-threatening adverse effects occurred. CONCLUSIONS: Bilateral STN stimulation safely improves all parkinsonian symptoms, decreases or eliminates the need for levodopa, and ameliorates motor fluctuations and dyskinesias. Complete withdrawal of levodopa is feasible with this technique and the overall motor effect of STN stimulation is quantitatively comparable to that obtained with levodopa.     

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.     

Change in fatigue after bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease

BackgroundBilateral subthalamic nucleus (STN) deep brain stimulation (DBS) improves motor function in patients with medically intractable Parkinson’s disease (PD), but the effects of STN DBS on fatigue are unknown. The purpose of this study was to examine the effects of STN DBS on fatigue scores in patients with PD.MethodsTwenty PD patients underwent bilateral STN DBS surgery at our institution from 2007 to 2009. Only data from the 17 patients who completed the Parkinson Fatigue Scale (PFS) and Unified PD Rating Scale (UPDRS) before and approximately 6 months after surgery were analyzed. Other evaluations included the Geriatric Depression Scale (GDS), Apathy Evaluation Scale (AES), and Epworth Sleepiness Scale (ESS).ResultsWhen the cohort was analyzed as a whole, there was no significant change in the mean or binary PFS score from baseline to the 6 month evaluation. However, the fatigue response of individual subjects was variable. Six of 12 subjects with fatigue before surgery were not fatigued post-operatively, while 3/5 subjects without fatigue before surgery became fatigued after DBS surgery. Fatigue in 8 subjects remained unchanged. Change in fatigue scores correlated significantly with change in the motor UPDRS, GDS and AES. Improvement in PFS also correlated with a higher PFS baseline score and higher baseline UPDRS motor off score.ConclusionsChanges in fatigue severity were not observed in our cohort as a whole, but there were changes in fatigue on an individual level. These changes appear to be related to the effects of STN DBS on motor improvement and mood.     

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.     

Body weight gain rate in patients with Parkinson's disease and deep brain stimulation.

We evaluated body weight changes in patients with Parkinson's disease (PD) after electrode implantation for deep brain stimulation (DBS) in the subthalamic nucleus (STN) in relation to clinical improvement. Thirty PD patients who received STN DBS were included (22 men, 8 women; mean age, 60.0 +/- 7.1 years; mean PD duration, 13.5 +/- 3.7 years; mean body mass index [BMI], 21.6 +/- 3.0 kg/m2). Body weight, physical activity, and Unified Parkinson's Disease Rating Scale (UPDRS) scores were noted before and 3 and 12 months after the procedure. Significant weight gain occurred in 29 patients; the mean increase was 14.8 +/- 9.8% of initial body weight in 1 year. Of the patients, 46.5% reported weight gain in the first 3 months, 21.4% gradual weight gain in the first 6 months, and 32.1% a slow increase for 1 year. Mean BMI increased up to 24.7 +/- 3.7 kg/m2. After 1 year, mean UPDRS motor score improved significantly in off and in on; and therapy complications improved by 91.0 +/- 17.0%. BMI changes at 3 and 12 months were significantly correlated to dyskinesia score changes, and levodopa dosage was not. In PD, STN DBS produces not only symptom control, but also weight gain. DBS candidates should be given nutritional counseling before the intervention to prevent rapid and/or excessive weight gain.     

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.     

Reduced levodopa-induced complications after 5 years of subthalamic stimulation in Parkinson’s disease: a second honeymoon

The purpose of this paper is to describe the effect of 5 years of subthalamic nucleus deep brain stimulation (STN DBS) on levodopa-induced complications, both in everyday life and during an acute challenge with levodopa. Thirty three patients were evaluated during an acute levodopa challenge before surgery and then 1 and 5 years afterwards (both off stim and on stim), using the UPDRS III scale and the CAPSIT-PD scales for dystonia and peak-dose dyskinesia. The UPDRS IV scale was used to assess motor complications in everyday life. The levodopa daily dose and DBS parameters were also recorded. Levodopa-induced complications in everyday life (UPDRS IV) and during an acute levodopa challenge had improved markedly after 1 year (both on and off stim) and still further at 5 years. Peak-dose dyskinesia decreased between the 1- and 5-year measurements. STN DBS decreases levodopa-induced motor complications over the long term. This phenomenon may be explained by (a) overall stabilization of the basal ganglia network and (b) striatal synaptic changes. Our results suggest that DBS leads to both qualitative and quantitative modulations in the corticostriatal loops.     

STN vs. Pallidal Stimulation in Parkinson Disease: Improvement With Experience and Better Patient Selection

Objectives. This is a prospective study to determine the outcomes of subthalamic nucleus (STN) vs. globus pallidus internus (GPi) deep brain stimulation (DBS) at our institution. Materials and Methods. We studied a total of 39 patients — 29 with STN and 10 with GPi DBS over a period of up to 6 years. Mean ages in the two groups were similar (59 and 60 years, respectively) and disease duration prior to implantation was similar (9.6 and 11.7 years, respectively). Unified Parkinson Disease Rating Scale (UPDRS) was recorded preoperatively and at follow‐up (at least at 6‐month intervals). Medications also were recorded, and each patient's levodopa equivalent units (LEU) were calculated. Results were analyzed using a paired Student's t‐test. Results. LEU reduced significantly (p < 0.05) in the STN group (5.7 to 3.7) but not the GPi group. Both targets significantly improved part 3 and part 4 scores of the UPDRS but GPi DBS did not improve part 2 scores (activities of daily living). STN DBS had much better outcome on the motor “off” scores of the UPDRS, whereas GPi only improved tremor. A comparison of the “earliest 10” and “most recent 10” STN patients showed a significant improvement in outcome in the most recent cases. Conclusions. In our group, STN was more effective for alleviating the symptoms of Parkinson disease, even in older patients with significant dyskinesias. Better patient selection and greater experience have led to more improvement in the more recent patients.     

Temporal changes in movement time during the switch of the stimulators in Parkinson's disease patients treated by subthalamic nucleus stimulation

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a very effective therapy for the advanced phase of Parkinson's disease (PD). The functional inhibition of this nucleus is responsible for a significant improvement of cardinal motor symptoms of PD. The aim of the study was the assessment of the effectiveness of STN DBS on bradykinesia by the analysis of movement time (MT) in 2 conditions: with the stimulators turned on ('stim-on') or off ('stim-off'). METHODS: After pharmacological wash-out, 10 patients submitted to bilateral STN DBS were studied with an MT analyser in 3 phases: stim-on, stim-off and stim-on again, in order to establish the time course of MT lengthening, the posteffect duration and the latency of the effect of STN DBS. MT data were then compared with the UPDRS motor scores. RESULTS: After turning off the stimulators, MT progressively increases, reaching a plateau after about 30 min, which then lasts for the subsequent observation time (2 h). A significant elongation is achieved after the first 5 min. Upon pulse generator activation, MT shows a dramatic shortening, already significant after 2 min. Moreover, we observed a significant correlation between MT and the severity of PD, higher with bradykinesia than with rigidity or tremor. CONCLUSION: Our findings show a relevant effect of STN DBS on MT, a parameter strongly related to bradykinesia. This study confirms the effectiveness of STN inhibition on the whole parkinsonian triad, suggesting that this target can be considered a proper choice for the surgical treatment of advanced PD.