Surgical management: DBS and effects on gait, posture and falls

overview

Miguel Coelho, MD

Neurology Department, Hospital Santa Maria

Clinical Pharmacology Unit, IMM, Lisbon

Portugal

25 September 2014 2nd Annual Allied Health Professional Summer School

Financial Disclosure• Nothing to declare.

Outline

• Indications for DBS in PD.

• Overall efficacy of DBS for advanced PD.

• Safety of DBS for advanced PD .

• DBS effects on gait, posture and falls.

Levodopa-induced motor complications

• Levodopa-induced motor complications (MC): high incidence in PD patients treated with L-dopa.

• General rule: ~ 40-50% after 5 yrs of L-dopa.

• Consist of motor fluctuations & dyskinesias.

• High impact on disability and QoL.

• Difficult to manage and complex drug regimens.

Ahlskog & Muenter 01; Schrag & Quinn 00; Marras 04

Indications for DBS in PD

• PD with disabling MC refractory to best medical treatment.

• Disabling tremor refractory to medical treatment.• Off dystonia.

• Neither curative nor disease-modifying.

• Benefit on QoL (mostly motor sub-domains; in those ≤ 65 yrs-old)

Bronstein 11; Lang 06; Deuschl 06; Hilker R et al 05; Kleiner-Fisman et al 06; Pahwa et al 06; Derost et al 07

Candidates for DBS in PD

• 70-75 years.

• Good response to L-dopa (best predictor).

• Indepedent on ADL during ON.

• No or few axial non-LD-responsive motor signs.

Bronstein 11; Lang 06

Candidates for DBS in PD

• No Dementia.

• No severe treatment-resistant depression or other severe psychiatric disorder.

• Psychosis should be carefully assessed (drug-induced ?).

• Realistic expectations & good social support.

Bronstein 11; Lang 06

Efficacy of DBS

• Superior to best medical therapy (BMT).

• Overall efficacious and safe on long-term (10 years), except axial signs.

• Improves QoL.

• STN or GPi.

Schuepbach 13; Odekerken 13; Castrioto 11; Deuschl 06; Williams 10; Weaver 09; Follett 10;

Efficacy of DBS

• Motor Benefit:

– Off periods in 30-60%.

– “On without dyskinesias” in 45%.

– Disability of dyskinesias in 50-60%.

– in parkinsonism severity (UPDRS motor off) in 40- 50%.

Odekerken 13; Castrioto 11; Deuschl 06; Williams 10; Weaver 09; Follett 10; Shupbach 07; Anderson 05; Parkinson Study Group 01; Limousin 96;

Efficacy of DBS

• Motor Benefit:

– ADL (UPDRS II off) in 20-40%.

– Levodopa Equivalent Dose (LED) in 40-50%.

– STN > GPi

Odekerken 13; Castrioto 11; Deuschl 06; Williams 10; Weaver 09; ; Follett 10; Krack 03; Kleiner-Fisman et al 06; Pahwa et al 06; Derost et al 07; Shupbach et al 07; Anderson et al 05; Parkinson Study Group 01; Limousin 96;

Krack 03

Rodriguez-Oroz 05

Safety of DBS• Safety:

– High frequency of clinical relevant AEs (11%).

– Increase concern with safety.

– Neuropsychiatric side effects.

– Axial side effects (gait \ balance \ speech)

Videnovic 08; Kleiner-Fisman et al 06; Pahwa et al 06;

Procedure and hardware-related AEs

Videnovic 08

Stimulation independent \ disease progression AEs

Videnovic 08

DBS on gait, posture and falls

The effects of DBS on balance and gait are difficult to interpret because they are complex behaviors that may or may not be sensitive to LD or DBS, and many postoperative observations are anecdotal.

Aspects of gait and speech that improve with LD therapy improve with DBS; however, these may later worsen with disease progression. There was consensus that STN DBS can worsen speech and gait in some patients whose symptoms may be improved by altering stimulation parameters.

Bronstein 11

DBS on gait, posture and falls

• Does DBS improve gait, posture and falls?– Short-term– Long-term– Compare to what? dopa-sensitive signs?

• Can DBS deteriorate axial symptoms in the short term?

• STN vs Gpi?

Does DBS improve gait, posture and falls?

Rodriguez-Oroz 05

Stim ON

Krack 03

Stim on +Med off

Follett 10

Odekerken 13

Stim on

med off

med on

Castrioto 11

Can DBS deteriorate axial symptoms in the short term?

Castrioto 11

Med off

Schuepbach, Earlystim 13

24 months

Weaver 09

Williams 10, PD SURG UK

12 months

Rodriguez-Oroz 05

Okun, 12

STN; control with no stimulation till 3 months

Adams 11

Ferraye 08

Umemura 10

Is there a difference between STN and GPi?

St. George 10

Meta-regression of 11 studies

Follett 10

Moro 10

Multicentre study with blinded and unblided assessments at 5-6 yrs FU

N = 51

Odekerken 13

Stim on

med off

med on

AEs

Rodriguez-Oroz 05

Stim ON

STN

GPI

Gait & Posture & Falls

• DBS improves gait and balance comparing on\off stimulation in the short and medium-term.

• DBS effect on these signs < apendicular.

• But DBS seems to worsen falls compared to baseline in a subset of patients.

• But DBS seems to worsen gait compared to baseline in a subset of patients.

Gait & Posture & Falls

• STN might be worse than GPi.

• Different test conditions (i.e med on\dbs off)

• Diverse clinical & laboratory outcomes among “axial symptoms umbrella”: different results.