DEEP BRAIN STIMULATION: BEST PRACTICE AND MORE Francesca Morgante - - PowerPoint PPT Presentation

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DEEP BRAIN STIMULATION: BEST PRACTICE AND MORE Francesca Morgante - - PowerPoint PPT Presentation

Feb 03, 2023 37 likes •348 views

Parkinson's research and the future of treatments DEEP BRAIN STIMULATION: BEST PRACTICE AND MORE Francesca Morgante Institute of Molecular and Clinical Sciences, St George's University of London, London, United Kingdom Disclosures Dr

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Parkinson's research and the future of treatments

DEEP BRAIN STIMULATION: BEST PRACTICE AND MORE

Francesca Morgante

Institute of Molecular and Clinical Sciences, St George's University of London, London, United Kingdom

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Disclosures

  • Dr Francesca Morgante has received honoraria as a Consultant &

Advisory Boards from Medtronic and Merz.

  • She has received honoraria for speaking from Merz, Bial, UCB

Pharma, Medtronic, Chiesi, Abbvie, Zambon.

  • She serves in the Editorial board of Movement Disorders, Movement

Disorders Clinical Practice and Frontiers in Movement Disorders.

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MILESTONES OF PARKINSON’S DISEASE

STARTING TREATMENT: how to start Advanced PD issues leading to non-oral treatments Psychiatric modifiers Late stage PD: Falls, psychosis, dementia Motor and non-motor fluctuations & dyskinesia

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OVERVIEW OF PD TREATMENT

Fluctuation and dyskinesia Stable phase Postural instability Falls

Stage I-II Stage II-III Stage III-IV Stage IV-V

50 55 60 65 70 75 80 years

Infusions Surgery Rehabilitation Complex therapies Medications

Education about disease phases Prevent auto-medication and addiction to DA medications

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WHAT IS BEST PRACTICE FOR DBS TREATMENT?

  • Recognition of the advanced phase at the right time
  • Correct Selection of surgical candidates
  • Concomitant management of medication and DBS with novel

programming strategies after surgery

  • Multidisciplinary care from selection to follow-up
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Symptoms mainly due to disease progression Symptoms due to DA treatment + disease progression Fluctuations and Dyskinesia

  • Motor fluctuations
  • Levodopa-induced dyskinesia
  • ICB, depression, anxiety
  • Psychosis
  • Dysautonomia
  • Sleep disorders
  • Cognitive Impairment

Non-motor symptoms modulate by DA treatment

  • Freezing of gait
  • Falls
  • Speech disturbance
  • Dysphagia
  • Postural abnormalities
  • Gastrointestinal
  • Fatigue and Apathy
  • Cognitive disturbances

PD CLINIC SPECTRUM OVER DISEASE COURSE

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SEVERE MOTOR FLUCTUATIONS (i.e. with gait impairment or need of assistance)

WHEN DOES THE ADVANCED PHASE START?

↑ ↑ ↑ DA Medication DYSKINESIA SLEEP DISTURBANCES FLUCTUATING PAIN AXIAL DISTURBANCES BEHAVIOURAL DISTURBANCES (i.e. DA abuse, disabling ICD) GASTROINTESTINAL DISTURBANCES

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COMPLEXITY OF PD TREATMENT OVER THE YEARS

Stage I-II Stage II-III

Dopamine - Agonists Dopamine - Agonists Levodopa Dopamine - Agonists Levodopa COMT-I MAO-I Dopamine - Agonists Levodopa COMT-I MAO-I Amantadine Antidepressants Benzodiazepines Dietary restrictions Botulinum toxin

Stage IV-V

Dopamine - Agonists Levodopa COMT-I MAO-I Levodopa Disp-Levodopa COMT-I Levodopa Amantadine

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ADVANCED PD TREATMENT: GOALS

  • Decrease motor fluctuations ( Off time;  On time)
  • Decrease dyskinesias
  • Avoid or treat psychiatric and behavioral complications
  • Management of non motor symptoms (NMS), especially Non-motor

fluctuations

  •  Dopaminergic daily dose

PRIMARY GOAL: IMPROVING QUALITY OF LIFE

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Schuepbach et al, Neurology 2019

Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in PD and early motor complications, fulfilling

  • bjective gold standard inclusion criteria

for STN-DBS. Our results prompt systematically including evaluation

  • f

disease-specific QOL when selecting patients with PD for STN-DBS.

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Apo Duo DBS Advanced age (<70 for DBS) +/- OK NO Mild cognitive impairment OK OK NO Dementia NO +/- NO Mild psychosis (drug-induced, visual hallucinations) +/- OK +/- Severe psychosis NO NO NO Brain MRI: atrophy OK OK NO Lack of MDT Team OK NO NO

ADVANCED THERAPIES

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THE IMPORTANCE OF A PATHWAY FOR ADVANCED PD AND A MDT TEAM FOR ADVANCED PD TRIAGING TO DIFFERENT ADVANCED THERAPIES – St GEORGE’S MODEL

ADVANCED THERAPY CLINIC Advanced PD with poor QoL

Extensive Motor and Non-motor assessment Discussion of Expectations Review from Neuropsychiatric symptoms including ICD Neuropsychological assessment Neuroimaging MDT MEETING for ADVANCED THERAPIES MDT CLINIC

Discussion of the:

  • treatment selected
  • expectations
  • complications
  • Follow-up organization

ADVANCED TREATMENT

WORSHOPS TO PREPARE PD AND CAREGIVERS TO DBS

ADVT - TEAM Neurologists PD nurses Neuropsychologist Neurosurgeon

Follow-up MDT Pathway

Thalamotomy Best Medical treatment

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THE IMPORTANCE OF SELECTION FOR DBS

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Absolute selection criteria

Disease Duration > 5 years (> 4 years by Early Stim) Age < 70 years Severe motor complications despite optimal medical treatment Severe disability, poor quality of life Response to Levodopa Absence of major depression Absence of active psychosis Absence of cognitive disturbances

Relative Exclusion criteria

Gait disturbances resistant to levodopa Severe postural instablity (in ON) Single Mild Cognitive impairment

GOOD SELECTION = GOOD OUTCOME!!!

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1999 2019

How inclusion criteria were changed by recent acquisition on PD progression and management?

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TOO FAR IN THE DISEASE MIGHT BE TOO LATE!

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DBS vs. BMT Favoring UPDRS-III off

  • 16.4

DBS UPDRS-III on

  • 4.5

DBS UPDRS-II off

  • 6.2

DBS UPDRS-IV

  • 4.1

DBS On w/o dysk +1.9h DBS SCOPA-PS

  • 2.1

DBS LEDD

  • 609.1

DBS BPRS

  • 2.2

DBS Montgomery -2.4 DBS BDI

  • 1.9

DBS All statistically different

Neurostimulation for Parkinson’s Disease with Early Motor Complications

Schuepbach et al., EARLYSTIM SG, NEJM 2013

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WHAT PATIENT-RELATED FACTORS MAY INFLUENCE THE CHOICE OF THERAPY?

  • Age and duration of disease
  • Cognitive and neuropsychiatric status
  • Medical co-morbidities
  • Non-motor symptoms
  • Presence of dysarthria
  • Presence of gait and balance problems

Few data are available on these issues for all the 3 treatments, mainly for DBS

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WHAT MAKES DBS SURGERY UNIQUE?

Reduce dopaminergic daily dose (LEDD) (STN DBS in PD) Treatment may be regulated ASYMMETRICALLY Different targets for different symptoms

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REDUCTION OF LEDD BY STN DBS BUT NOT BY INFUSIONAL THERAPIES

Romito et al, MDJ 2008 Antonini et al, MDJ 2007 De Gaspari et al, JNNP 2006

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CONSEQUENCES OF ↓ LEDD AFTER DBS

DYSKINESIA BEHAVIOURAL COMPLICATIONS AND HYPERACTIVE BEHAVIOUR NON-MOTOR CONSEQUENCES OF OVERMEDICATION WITH DA DRUGS

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Lhommè et al, Brain 2012

After surgery, the OFF medication motor score improved (45.2%), allowing for a 73% reduction in dopaminergic treatment

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Ricciardi, et al, MDJ 2018

Effect of DBS on NMS in Young-onset PD

T0 T6 T12 T24 p-value Post-hoc tests

NMSS total score

58.2 ± 25.6 38.3 ± 28.03 32.9 ± 18.8 45.7 ± 31.1 0.004 T0-T6=0.04 T0-T12=0.01* T0-T24=0.07

Cardiovascular

1.36 ± 2.77 0.42 ± 0.78 0.58 ± 1.83 1.16 ± 2.30 0.1

Sleep/fatigue

16.6 ± 8.6 5.9 ± 6.3 3.7 ± 3.3 4.4 ± 4.6 <0.0001 T0-T6=0.0004* T0-T12=0.0004* T0-T24=0.0004*

Mood/Cognition

9.4 ± 16.1 13.9 ± 17.0 10.4 ± 14.9 14.6 ± 18.0 0.2

Perception/ hallucinations

0.1 ± 0.3 0.7 ± 1.4 0.3 ± 0.6 1.0 ± 3.2 0.4

Attention/Memory

1.4 ± 3.4 3.2 ± 5.7 1.8 ± 2.8 2.5 ± 3.4 0.7

Gastrointestinal

5.6 ± 5.7 3.6 ± 7.0 3.8 ± 5.4 6.2 ± 7.6 0.09

Urinary

8.0 ± 8.0 7.0 ± 9.7 8.1 ± 7.1 11.0 ± 12.3 0.8

Sexual function

2.4 ± 4.7 1.2 ± 3.3 0.6 ± 2.7 1.4 ± 3.2 0.3

Miscellaneous

12.4 ± 6.9 4.5 ± 5.9 8.2 ± 8.9 7.5 ± 5.1 0.01 T0-T6=0.01* T0-T12=0.08 T0-T24=0.03

PDSS-2

22.9 ± 10.6 12.5 ± 10.5 10.8 ± 7.8 11.1 ± 9.2 <0.0001 T0-T6=0.003* T0-T12=0.0009* T0-T24=0.0005*

Significant positive correlation at T6 between the relative change of PDSS-2 and dopamine-agonists LEDD (PMX in 10 pts) (rho=-0.49, p=0.04).

N=18

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GAIT DISTURBANCES AND DBS

WHY PD PEOPLE FALL OFF?

  • Freezing of gait in OFF, asymmetry in gait and posture
  • On-Phase dyskinesia
  • Orthostatic syncope
  • Loss of postural reflexes
  • Severe Executive Dysfunction
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Bakker et al, MDS 2004

DBS IMPROVE GAIT DISTURBANCES OF THE OFF PHASE

Moreau et al, Neurology 2008

60 Hz 130 Hz

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Effect of STN-DBS on FOG in PD

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NOVEL DBS TECHNOLOGIES TO MANAGE ADVANCED SYMPTOMS

  • Short pulse width
  • Current steering
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AIMING TO BEST PRACTICE IN ADVANCED PD MANAGEMENT WITH DBS

  • Redefining Advanced phase: not delaying treatment
  • Need of better predictors of disease progression at the time of

selection: better selection

  • Need to work on PD people expectations before and after DBS
  • Need to have clear guidelines on how to program DBS based on

prominent symptoms.

  • Need of a pathway for Neurophysiotherapy and SLT for late stage

PD treated with DBS.

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ACKNOWLEDGEMENTS

  • St. George’s University of London – MDS group
  • Neurologists: Dominic Paviour, Lucia Ricciardi, Jan Coebergh, Mark Edwards
  • PD nurses: Alison Leake, Catherine Parry, Lucy Kerogoi
  • Clinical Research Fellows: Marianna Sarchioto, Andrea De Angelis
  • Neurosurgeon: Erlick Pereira
  • Neuropsychologist: Priyanka Pradhan
  • DBS group coordinator: Donna Nottage

Collaborators:

  • Alfonso Fasano, University of Toronto
  • Alberto Espay, University of Cincinnati
  • Davide Martino, University of Calgary
  • Giovanni Cossu, AOU Brotzu, Cagliari
  • Maria Chiara Sensi, University Hospital Ferrara
  • Enza Maria Valente, University of Pavia
  • Maurizio Zibetti, Leonardo Lopiano, University of Turin
  • Michele Tinazzi, University of Verona
  • Chiara Sorbera, IRCCS Neurolesi, Messina

St George’s DBS Team