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