Evidence Table SURG 1What is the effectiveness and safety of any deep brain stimulation procedure vs. standard medical therapy in the treatment of motor fluctuations and complications in patients with Parkinson’s disease?

Bibliographic referenceRussmann H, Ghika J, Villemure JG, Robert B, Bogousslavsky J, Burkhard PR et al. Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age 70 years. Neurology 2004;63:1952–4.
Study type48 month follow-up before and after study
Evidence level3
Study objectiveTo better delineate the potential risk-to-benefit ratio of STN DBS in older patients (compared the effects of STN DBS in patients above and below age 70 in a cohort of 53 patients).
Number of patientsN=52 Parkinson’s disease (PD) patients

Location: Switzerland
sites: single
Patient characteristics52 consecutive PD patients. All had a dopa-responsive PD, without atypical signs and witout dementia and depression. Age was not a selection criterion. Pre-operatively (pre-op) all patients showed at least 25% improvement in UPDRS motor score in response to levodopa tests.
< 60 years60–70 years>70 years
N=152413
Sex (M:F)11: 413: 117: 6
Age, years55 ± 465 ± 2.574 ± 3
Duration of disease, y14 ± 515 ± 514 ± 5
Follow-up duration22.4 ± 11.217.5 ± 8.515.5 ± 9.63
InterventionBilateral STN DBS implantation (surgical protocol cited to other study by same authors)
ComparisonPre-operative assessment
Length of follow-up6 to 48 months
Outcome measuresUPDRS, medication changes, adverse events
Effect size➢ 13 patients older than 70 years of age were compared with 15 patients under the age of 60 and 24 patients aged 60 to 70 years
➢ Medication was reintroduced if patients did not reach pre-op ‘on’ score despite optimal stimulation
UPDRS I to IV and Hoehn and Yahr scores were assessed at 3,6,12,18,24,36 and 48 months after operation
➢ 42 patients (12 <60 years, 21 60–70 years, and 9 > 70 years) accepted to have the stimulation turned off in the practically defined ‘off’ medication state after 8.3 ± 4.1 months
> 70 years
➢ Differed from other subgroups only by lower daily levodopa equivalent dose (p<0.03)
➢ Medication reduction of 49% at last follow-up
➢ 5 had no anti-PD medication, 8 had levodopa (three in association with dopamine agonists)
< 70 years
➢ Medication reduction of 74% (p<0.01)

➢ In all groups dyskinesia and fluctuations were significantly (p<0.001) and similarly reduced (p=0.3 to 0.7)
➢ All UPDRS motor scores off medication were improved (p<0.001 to 0.02) but less in patients over 70 than other two groups (p<0.02)
➢ Changes in UPDRS motor scores on medication worsened in patients over 70 and improved in patients under 70 (p<0.05)
➢ Pre-operative activities of daily living (ADL) scores on medication were similar between 3 groups (p=0.3 to 0.9)
➢ The two younger groups had unchanged postoperative ADL (p>0.9) whereas the oldest group had a 40% worsening (p<0.001)

Correlations
➢ The STN DBS were linearly correlated with those of the pre-operative levodopa challenge (p<0.02)
➢ After correction by linear regression for the pre-op levodopa results all differences above were still significant
➢ Pre-op major signs subscores were the similar in all groups In ‘on’ and ‘off’ conditions (p=0.2 to 0.9)
➢ Post-op, off medication, bradykinesia and rigidity subscores were improved in all subgroups
Tremor subscores were improved in the two younger subgroups, whereas axial signed were unchanged
➢ On medication, bradykinesia, rigidity and tremor subscores had not significantly changed
➢ Axial signs only worsened in patients over age of 70 (inversely correlated to drug reduction, p<0.01)
Drug dosage
➢ Post-op 5 patients over 70 did not require antiparkinsonian medication
➢ Their pre-op scores were similar to other patients over 70- except trend toward lower pre-op axial scores (p=0.036) with scores for gait medication of ≤ 2 (no help to walk) contrasting with scores of 3 or 4 in five of the eight others (p<0.03)

Adverse perioperative events
➢ > 70 years: leads repositioning (1), transient confusional states (3), connection wound dehiscence (1), delayed infection (1)
➢ < 70 years leads reposition (1), air embolus (1), seizure (1), panic attack (1), transient confusional states (4), connect wound dehiscence
➢ There was neither haemorrhage nor any permanent neurologic deficit
➢ Three patients over age 70 and 4 younger patients developed post-op neuropsychological deficit impairing daily life
Source of fundingNon-profit foundations
Additional comments➢ Unblinded
➢ Uncontrolled
➢ Details of protocol in separate publication
➢ No inclusion criterion stated
Follow-up of 6–48 months – no numbers of drop-outs per time period mentioned
NCC CC ID (Ref Man)19727
Bibliographic referenceCharles PD, Van Blercom N, Krack P, Lee SL, Xie J, Besson G et al. Predictors of effective bilateral subthalamic nucleus stimulation for PD. Neurology 2002;59:932–4.
Study type5-year follow-up before and after study
Evidence level3
Study objectiveTo identify factors predictive of effective bilateral subthalamic nucleus (STN) stimulation for PD with severe motor complications.
Number of patientsN=56 PD patients

Location: France
Sites: 1
Patient characteristics56 consecutive PD patients, 29 men and 27 women, with a mean age of 56.0 ± 7.7 years at time of surgery. Mean disease duration at time of surgery was 15.7 ± 4.9 years. Average pre-op daily dose of levodopa 1102 ± 576 mg).
Inclusion criteria: clinically diagnosed idiopathic PD, disabling motor fluctuations despite all drug strategies, good general health, brain MRI within normal range, and no severe dementia.
InterventionBilateral STN stimulator implantation (see paper for details)
ComparisonPre-operative assessment
Length of follow-up5 years
Outcome measuresUPDRS, predictive formulae, adverse events
Effect sizeProtocol
➢ Patients were evaluated pre-op and 3 months post-op
➢ At 3 months post-op most patients demonstrated a chronic stable condition that was sustained for up to 3 years and required very little electrical adjustment
UPDRS was assessed pre-op in both on and off drug states
➢ Post-op UPDRS was evaluated in 4 conditions: off-drug/off stimulation (stim); off-drug/on-stim; on- drug/off-stim; on-drug/on-stim
Levodopa challenge was calculated as 120% of regular morning dose plus additional levodopa dose equivalent to the dopamine agonist dose that would usually have been taken in the morning
Efficacy
➢ Improvement from levodopa, as measured by change in the UPDRS-III score, correlated positively with post-op improvement from stimulation (p<0.00001)
➢ The R2 value indicating that this factor accounts for 32% of post-op improvement
➢ Age correlated negatively with post-op improvement from stimulation (p<0.01)
➢ A pre-op levodopa response in an individual symptom correlated with a post-op stimulation response for that same symptom: akinesia (p<0.001), tremor (p<0.001), rigidity (p<0.001), composite score for postural instability gait disorder (p<0.001), gait (p<0.001) and pull test (p<0.001)
➢ Improvement from levodopa in Hoehn and Yahr and Schwab and England global ratings was predictive of a similar improvement from stimulation in the same rating (both p<0.001)

➢ To predict the post-op improvement from pre-op levodopa response (multiple regression analysis) the following formula was obtained (after discarding factors with low predictive power):

➢ Predicted post-op improvement relative to pre-op UPDRS III off score= 38 − (age x 0.36 )+ (duration of illness x 0.33) + (rigidity response to levodopa x 1.3) + (pull test response to levodopa x 3.9) − (freezing response to levodopa x 2.4)

➢ This was simplified by retaining only the 3 most powerful factors:

➢ Predicted post-op improvement relative to pre-op UPDRS III off score= 34 − (age x 0.29) + (rigidity response to levodopa x 1.3) + (pull test response to levodopa x 3.8)

Withdrawals
➢ Two patients were not available for the 3-month assessment (one suffered from a severe frontal haematoma at time of surgery the other living far away reported great benefit but refused to return for formal assessments)
Source of fundingNone stated
Additional comments➢ Uncontrolled
➢ Unblinded
➢ No intention-to-treat
➢ Young patient population
NCC CC ID (Ref Man)19726

From: Evidence Tables

Cover of Parkinson's Disease
Parkinson's Disease: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care.
NICE Clinical Guidelines, No. 35.
National Collaborating Centre for Chronic Conditions (UK).
Copyright © 2006, Royal College of Physicians of London.

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