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TROUBLESHOOTING ALGORITHMS FOR COMMON DBS RELATED PROBLEMS IN
PARKINSON’S DISEASE
Anna Castrioto, MD, PhDUnité trouble du mouvement
CHU Grenoble
INSERM U1216, GIN
Grenoble, July 6 - 8 20171st Summer School on Neuromodulation for Movement Disorders
OUTLINE
• Motor issues:– Dysarthria
– Freezing of gait
– Balance problems
• Behavioral issues:– Impulsivity, mania
– Apathy
– Depression
OUTLINE
• Motor issues:– Dysarthria
– Freezing of gait
– Balance problems
• Behavioral issues:– Impulsivity, mania
– Apathy
– Depression
DYSARTHRIA
• A complex & frequent problem in PD with STN DBS (variable frequency 9,3%)
• Several factors :
– dopaminergic medication
– surgical procedure
– stimulation & diffusion
– disease progression
Castrioto et al. 2013,Tripoliti et al. 2011, Moreau et al. 2011
DYSARTHRIA
ms5000 10000 15000 20000 25000
0.2
0.4
0
- 0.2
0
0.2
0.4
- 0.2
- 0.4
- 0.4
0.2
0.4
0
- 0.2- 0.4
Long-term effectPinto 2005
OFF med, OFF stim
R 3.3 V/185 Hz/60 µs
L 3.6 V/170 Hz /60 µs
R 3.3 V/185 Hz/90 µs
L 3.6 V/170 Hz/90 µs
Effectsof subthalamic stimulation onspeech of consecutivepatientswithParkinson disease
E. Tripoliti, MPhil
L. Zrinzo, MD, MSc
I. Martinez-Torres, MD
E. Frost, MSc
S. Pinto, PhD
T. Foltynie, MRCP, PhD
E. Holl, MD
E. Petersen, MD
M. Roughton, MSc
M.I. Hariz, MD, PhD
P. Limousin, MD, PhD
ABSTRACT
Objective: Subthalamic nucleus deep brain st imulat ion (STN-DBS) is an ef fect ive t reatment for
advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limit -
ing its benef icial ef fect . Here we prospect ively examined the short - and long-term speech re-
sponse to STN-DBS in a consecut ive series of pat ients to ident ify clinical and surgical factors
associated with speech change.
Methods: Thirt y-two consecut ive pat ients were assessed before surgery, then 1 month, 6
months, and 1 year af ter STN-DBS in 4 condit ions on- and of f -medicat ion with on- and of f -
st imulat ion using established and validated speech and movement scales. Fif t een of these
pat ients were followed up for 3 years. A cont rol group of 1 2 pat ients with PD were followed
up for 1 year.
Results: Within the surgical group, speech intelligibility signif icant ly deteriorated by an average of
14 .2% 20 .15% off -medicat ion and 16 .9% 21 .8% on-medicat ion 1 year af ter STN-DBS.
The medical group deteriorated by 3 .6% 5 .5% and 4 .5% 8 .8% , respect ively. Seven pa-
t ients showed speech ameliorat ion af ter surgery. Loudness increased signif icant ly in all tasks
with st imulat ion. A less severe preoperat ive on-medicat ion motor score was associated with a
more favorable speech response to STN-DBS after 1 year. Medially located elect rodes on the lef t
STN were associated with a signif icant ly higher risk of speech deteriorat ion than elect rodes
within the nucleus. There was a st rong relat ionship between high voltage in the lef t elect rode and
poor speech outcome at 1 year.
Conclusion: The ef fect of STN-DBS on speech is variable and mult ifactorial, with most pat ients
exhibit ing decline of speech intelligibility. Both medical and surgical issues cont ribute to deterio-
rat ion of speech in STN-DBS pat ients.
Classification of evidence: This study provides Class III evidence that STN-DBS for PD results in
deteriorat ion in speech intelligibility in all combinat ions of medicat ion and st imulat ion states at 1
month, 6 months, and 1 year compared to baseline and to cont rol subjects t reated with best
medical therapy. Neurology® 2011 ;76 :80–86
GLOSSARY
CI conf idence interval; LEDD levodopa equivalent daily dose; LTAS long-term average spectrum; PD Parkinson
disease; SPL sound pressure level; STN-DBS subthalamic nucleus deep brain st imulat ion; UPDRS-III Unif ied Parkin-
son’s Disease Rat ing Scale.
Speech isaffected in themajority of patientswith Parkinson disease(PD) at somestageof the
disease1 with a variable presentation of weak voice, monotony of pitch and loudness, short
rushesof speech, and impreciseconsonants. Deep brain stimulation in thesubthalamic nucleus
(STN-DBS) isan effective treatment for patientswith advanced PD who develop motor fluc-
e-Pub ahead of print on November 10, 2010, at www.neurology.org.
From theUCL (E.T., L.Z., E.F., T.F., M.I.H., P.L.), Institute of Neurology, Sobell Department, Unit of Functional Neurosurgery, Queen Square,
London, UK; Neurological Department (I.M.-T.), University Hospital LaFe, Valencia, Spain; Laboratoire Paroleet Langage (S.P.), CNRS/Aix-
Marseille Universite, France; Medical University Graz (E.H.), Austria; Department of Neurosurgery (E.P.), University of TexasSouthwestern Medical
Center, Dallas; and Cancer Research UK & UCL Cancer TrialsCentre (M.R.), UCL, London, UK.
Study funding: Supported by theParkinson’sDiseaseSociety UK (grant 4070), Parkinson’sAppeal, Brain Research Trust, Medtronic, and theNIH
(R01-NS40902). Thiswork wasundertaken at UCLH/UCL, which received aproportion of funding from theUK Department of Health’sNIHR
Biomedical Research Centres funding scheme.
Disclosure: Author disclosuresareprovided at theend of thearticle.
Supplemental data atwww.neurology.org
Addresscorrespondence and
reprint requests to Dr. Elina
Tripoliti, Unit of Functional
Neurosurgery, UCL Instituteof
Neurology, Box 146, Queen
Square, London, WC1N 3BG, UK
8 0 Copyright © 2 0 1 0 by AAN Enterprises, Inc.
Effectsof subthalamic stimulation onspeech of consecutivepatientswithParkinson disease
E. Tripoliti, MPhil
L. Zrinzo, MD, MSc
I. Martinez-Torres, MD
E. Frost, MSc
S. Pinto, PhD
T.Foltynie, MRCP,PhD
E. Holl, MD
E. Petersen, MD
M. Roughton, MSc
M.I. Hariz, MD, PhD
P. Limousin, MD, PhD
ABSTRACT
Objective: Subthalamic nucleus deep brain st imulat ion (STN-DBS) is an effect ive treatment for
advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limit-
ing its beneficial effect. Here we prospect ively examined the short- and long-term speech re-
sponse to STN-DBS in a consecut ive series of pat ients to ident ify clinical and surgical factors
associated with speech change.
Methods: Thirty-two consecut ive pat ients were assessed before surgery, then 1 month, 6
months, and 1 year af ter STN-DBS in 4 condit ions on- and of f -medicat ion with on- and of f -
st imulat ion using established and validated speech and movement scales. Fif teen of these
pat ients were followed up for 3 years. A cont rol group of 12 pat ients with PD were followed
up for 1 year.
Results: Within the surgical group, speech intelligibility signif icant ly deteriorated by an average of
14.2% 20.15% off-medicat ion and 16.9% 21.8% on-medicat ion 1 year after STN-DBS.
The medical group deteriorated by 3.6% 5.5% and 4.5% 8.8%, respect ively. Seven pa-
t ients showed speech ameliorat ion after surgery. Loudness increased signif icant ly in all tasks
with st imulat ion. A less severe preoperat ive on-medicat ion motor score was associated with a
more favorable speech response to STN-DBS after 1 year. Medially located electrodes on the left
STN were associated with a signif icant ly higher risk of speech deteriorat ion than electrodes
within the nucleus. There was a strong relat ionship between high voltage in the left electrode and
poor speech outcome at 1 year.
Conclusion: The effect of STN-DBS on speech is variable and mult ifactorial, with most pat ients
exhibit ing decline of speech intelligibility. Both medical and surgical issues contribute to deterio-
rat ion of speech in STN-DBS patients.
Classification of evidence: This study provides Class III evidence that STN-DBS for PD results in
deteriorat ion in speech intelligibility in all combinat ions of medicat ion and st imulat ion states at 1
month, 6 months, and 1 year compared to baseline and to control subjects treated with best
medical therapy. Neurology® 2011;76:80–86
GLOSSARY
CI confidence interval; LEDD levodopa equivalent daily dose; LTAS long-term average spectrum; PD Parkinson
disease; SPL sound pressure level; STN-DBS subthalamic nucleus deep brain stimulat ion; UPDRS-III Unified Parkin-
son’s Disease Rating Scale.
Speech isaffected in themajority of patientswith Parkinson disease(PD) at somestageof the
disease1 with a variable presentation of weak voice, monotony of pitch and loudness, short
rushesof speech, and impreciseconsonants. Deep brain stimulation in thesubthalamicnucleus
(STN-DBS) isan effectivetreatment for patientswith advanced PD who develop motor fluc-
e-Pub ahead of print on November 10, 2010, at www.neurology.org.
From theUCL (E.T., L.Z., E.F., T.F., M.I.H., P.L.), Instituteof Neurology, Sobell Department, Unit of Functional Neurosurgery, Queen Square,
London, UK; Neurological Department (I.M.-T.), University Hospital LaFe, Valencia, Spain; Laboratoire Paroleet Langage(S.P.), CNRS/Aix-
MarseilleUniversite, France; Medical University Graz (E.H.), Austria; Department of Neurosurgery (E.P.), University of TexasSouthwestern Medical
Center, Dallas; and Cancer Research UK & UCL Cancer TrialsCentre(M.R.), UCL, London, UK.
Studyfunding: Supported by theParkinson’sDiseaseSociety UK (grant 4070), Parkinson’sAppeal, Brain Research Trust, Medtronic, and theNIH
(R01-NS40902). Thiswork wasundertaken at UCLH/UCL, which received aproportion of funding from theUK Department of Health’sNIHR
Biomedical Research Centresfunding scheme.
Disclosure: Author disclosuresareprovided at theend of thearticle.
Supplemental data atwww.neurology.org
Addresscorrespondence and
reprint requeststo Dr. Elina
Tripoliti, Unit of Functional
Neurosurgery, UCL Instituteof
Neurology, Box 146, Queen
Square, London, WC1N 3BG, UK
80 Copyright © 2010 by AAN Enterprises, Inc.
POSTOPERATIVE DYSARTHRIA
TEST OFF - ON UNILATERAL STIMULATION
↑ STIM A
IMPROVEMENT NO EFFECT OR WORSENING
REPROGRAMMING:• try another contact• ↓ stim A or Fr• Bipolar stim• Interleaving stim
Long-term effect
NO EFFECT
LEVODOPA RESPONSIVE?
↑ DA TXLEAD
REPOSITIONING
NO EFFECT
FREEZING OF GAIT
Key-points:
• Levodopa responsiveness
• Effect of stimulation
Fleury et al. Mov Disord 2016
FREEZING OF GAIT
L-DOPA RESPONSIVE ?
↑ STIM
↑ DA tx
POSTOPERATIVE FOG
STIMULATION
Improvement No-effect or worsening
Reprogramming more ventral contact, ↓A, ↓Fr, bipolar stim
repositioning No-effect
Physiotherapy
No Yes
BALANCE PROBLEMS
• Timing (acutely after programming) ?
• Levodopa responsive ?
Acute after programming
Dyskinesias?
BALANCE PROBLEMS
Progressive worsening
Hypotonia & cerebellar syndrome
Levodopa responsive?
↓ STIM or DA txReprogramming:Try a more dorsal contact↓ STIM
Adjust DA txPhysiotherapy
OUTLINE
• Motor issues:– Dysarthria
– Freezing of gait
– Balance problems
• Behavioral issues:– Impulsivity, mania
– Apathy
– Depression
BEHAVIORAL EFFECTS
• ACUTE
– Lesion-like effect
– Synergistic effect of medication & stimulation
• CHRONIC
– Chronic medication changes
– Plastic changes induced by stimulation
ACUTE EFFECTS OF STIMULATION MIMICS PSYCHOSTIMULANT EFFECTS OF LEVODOPA
0
2
4
6
8
10
12
14
16
* *
* ** *
STN DBS
levodopa
off / off
on / on
Funkiewiz et al. 2003
ARCI euphoria subscale: Amphetamine-like motivational effects↑ well being, ↓ fatigue and anxiety
ACUTE BEHAVIORAL EFFECTS
• Transient euphoria
• Hypomania, mania
• Aggressive behavior
• Impulsivity
• Pathological crying, laughing
Castrioto et al. Lancet Neurol 2014Mallet et al. PNAS 2007
ACUTE BEHAVIORAL CHANGES
If time-locked to stimulation:• ↓stimulation• Try a more dorsal contact
↓ DA medication (Dopamine Agonists as first)
CLOZAPINE
Not effective
Apathie Depression
Brain 2010
Apathetic pt
placebopiribedil
12
wee
ks
Brain 2013
CHRONIC BEHAVIORAL ISSUES
Lhommée et al. 2012, Castrioto et al. 2014
CHRONIC BEHAVIORAL ISSUES
• Hypodopaminergic behaviors
– ↑ dopamine agonists
• Hyperdopaminergic behaviors
– ↓ dopamine agonists
– Change parameters (if time-locked to stimulation)
THANK YOU FOR YOUR ATTENTION