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Balance and gait are differentially affected by deep brain stimulation in Parkinson’s disease
Katherine LadwigWashington State UniversityUndergraduate Summer Fellow, 2015Balance Disorders LaboratoryDepartment of Neurology
Parkinson’s Disease (PD) Cause: Lack of dopamine in the brain Symptoms:
Tremor, bradykinesia, rigidity Balance and gait interference Cognitive deficits
Treatments: Physical therapy Medication Lesions Deep brain stimulation
Deep Brain Stimulation (DBS)in Parkinson’s Disease Two sites commonly
used to treat PD Subthalamic Nucleus
(STN) Globus Pallidus interna
(GPi) Reversible Improves cardinal
symptoms Effects on balance and
gait are less certain http://www.neurosurgery.uthscsa.edu/images/pages/dbs_parkinsons/dbs_brain.jpg
What are we looking for? Balance
Speed of sway Sway area Smoothness
Gait Initiation Postural preparation Delay
Gait Speed Range of motion Symmetry
Turning Steps Speed Smoothness
Relevant to risk of falling and quality of life
Hypotheses GPi stimulation will have a greater
benefit on balance and gait.
https://apackofneurons.files.wordpress.com/2012/06/basal-ganglia-scheme.png
Clinical Scores
Scoring done by trained clinicians Estimation of symptom severity UPDRSIII
Unified Parkinson’s Disease Rating Scale, section 3 (motor symptoms)
Standard scale for assessing PD symptoms
Mini-BESTest More focus on balance and gait Developed by Dr. Fay Horak and
collaborators
Population Demographics
DBS
SiteN Age %
FemaleUPDRSII
I OFFUPDRSII
I ONMini-
BESTest OFF
Mini-BESTes
t ON
GPi 27
62.33(8.70
)51.9 42.58
(13.89)31.94
(14.35)15.35(7.82)
20.00(5.39)
STN 15
65.60(7.17
)20.0 48.69
(6.51)34.62(7.60)
14.00(7.11)
19.38(5.38)
Values are reported as mean (standard deviation)
Quantitative Data Collection
Advantages of quantitative measurements High resolution Sensitive to small changes Unbiased
Opal inertial sensors (APDM) are worn on various points of the body Triaxial accelerometers Triaxial gyroscopes Data streaming to laptop Does not require specialized lab
http://www.apdm.com/wp-content/uploads/2014/07/opals-with-quarter.jpg
Data Collection: ISAW Instrumented Stand and Walk
Curtze C, Nutt JG, Carlson-Kuhta P, Mancini M, Horak FB. Levodopa Is a Double-Edged Sword for Balance and Gait in People With Parkinson's Disease. Mov Disord. 2015;12(10):26269.
Timeline
Study Enrollment (n = 80)
BaselineClinical & QuantitativePre Surgery (n =57)• Off medication (n =
35)• On medication (n =
37)
30 Days Post Surgery (n = 23)Clinical & Quantitative• Off medication off DBS (n =
18)• Off medication on DBS (n =
17)• On medication on DBS (n =
15)
SurgeryGPi (n = 31)STN (n = 15)
60, 90, and >90 Days Post Surgery (n = 5, 19, 12)Clinical & Quantitative• Off medication on DBS (n = 2, 16, 9)• On medication on DBS (n = 3, 15,
12)
Note: analysis n values were usually lower due to data not matching.
Data Analysis
Organized and grouped data Statistical analysis: Repeated
measures ANOVA and t-tests Examined 17 balance and gait metrics Pre surgery vs. post surgery On and off medication Site differences (GPi vs. STN)
Results: Clinical Improvement in Both DBS Sites, More for STN
0
5
10
15
20
25
30
35
40
45
50GPi
OFF
DOPA
DBS DOPA & DBS
Pre Surgery
Post Surgery
.0083
.0173
0
5
10
15
20
25
30
35
40
45
50STN
OFF
DOPA
DBS
DOPA & DBS
Pre Surgery
Post Surgery
.0043
.0424
.0448
UPDRSIII Score
Results: GPi Increases Postural Stability, STN Does Not
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
GPi
DOPA & DBS
Pre Surgery Post Surgery
OFF DOPA
DBS
.0045
.0053
0.044
0.046
0.048
0.05
0.052
0.054
0.056
STN
DOPA & DBS
Pre Surgery Post Surgery
OFF DOPA
DBS
Sway Dispersion (medio-lateral), m/s^2
Results: GPi Improved and STN Worsened Stride Length
0
10
20
30
40
50
60
70
80
90
100
GPi
DOPA & DBS
Pre Surgery Post Surgery
OFF DOPA DBS
.0179.0340
.0024.0088
0
10
20
30
40
50
60
70
80
90
100
STN
DOPA & DBS
Pre Surgery Post Surgery
OFF DOPA DBS
.0477
.0137
Stride Length, %height
Results: Turn Duration Improves with GPi DBS
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
GPi
DOPA & DBS
Pre Surgery Post Surgery
OFF DOPA DBS
.0116
.0258
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
STN
DOPA & DBS
Pre Surgery Post Surgery
OFF DOPA DBS
Turn Duration, seconds
Results: GPi vs. STNMetric GP
iSTN
Smoothness (AP)Smoothness (ML)Sway dispersion (AP)Sway dispersion (ML)Sway velocity (AP)Sway velocity (ML)Centroidal f (AP)Centroidal f (ML)
Metric GPi STN
Stride length XStride velocity XDouble support timeArm swing velocity X XArm range of motion
X
Peak weight shift (ML)Peak weight shift (AP)Turn durationTurn peak velocity
AP = Anterior-posterior ML = Medio-lateral
Bala
nce
Gai
t
Gait
Initi
atio
nTu
rnAr
ms
Summary GPi stimulation induced more
improvements in gait and balance than STN, with STN actually worsening stride length and velocity.
Both sites caused a worsening in arm parameters.
Inertial sensors have the potential to allow clinicians to quickly quantify changes in their patients over time.
Thank You Dr. Nancy Haigwood, ONPRC Director NSI Endowment Dr. Fay Horak and everyone working in
her lab A special thanks to my mentors Dr.
Martina Mancini and Dr. Patty Carlson-Kuhta