NORTHWESTERN UNIVERSITY

Neural Mechanisms Underlying Altered Interlimb Coupling in

Pediatric and Adult-Onset Hemiplegia

A DISSERTATION

SUBMITTED TO THE GRADUATE SCHOOL

IN PARTIAL FULFILLMENT OF THE REQUIREMENTS

W
IE
for the degree
EV

DOCTOR OF PHILOSPHY
PR

Field of Biomedical Engineering

By

Rachel Lauren Hawe

EVANSTON, ILLINOIS

December 2016




ProQuest Number: 10194111




All rights reserved

INFORMATION TO ALL USERS
The quality of this reproduction is dependent upon the quality of the copy submitted.

In the unlikely event that the author did not send a complete manuscript
and there are missing pages, these will be noted. Also, if material had to be removed,
a note will indicate the deletion.



W

IE


EV
ProQuest 10194111

Published by ProQuest LLC (2016 ). Copyright of the Dissertation is held by the Author.


All rights reserved.
PR

This work is protected against unauthorized copying under Title 17, United States Code
Microform Edition © ProQuest LLC.


ProQuest LLC.
789 East Eisenhower Parkway
P.O. Box 1346
Ann Arbor, MI 48106 - 1346
 2

W
IE
EV
PR

© Copyright by Rachel Lauren Hawe 2016

All Rights Reserved

 3

ABSTRACT
Neural Mechanisms Underlying Altered Interlimb Coupling in
Pediatric and Adult-Onset Hemiplegia

Rachel Lauren Hawe

A stroke can occur at any point throughout the lifespan, including in utero. The timing of

the injury relative to neural development can have implications on the type of lesion, plasticity,

and motor deficits. However, associated reactions, which refer to involuntary movement in one

W
limb in response to voluntary activity at another, have been observed in children and adults

regardless of injury timing. The goal of this work was to quantify associated reactions in both
IE
pediatric and adult hemiplegia, as well as changes in neural structures, to understand how

damage from lesions at different points in development can result in abnormal interlimb
EV

coupling.

A novel method of measuring associated reactions was devised using a haptic robotic
PR

device. In adults with chronic stroke and children with prenatal and perinatal lesions, involuntary

upper extremity movements and EMG activity were quantified while participants performed

knee flexion and extension at varying effort levels with the instruction to relax their arm.

Additionally, diffusion tensor imaging was used to assess the corticospinal tracts and corpus

callosum.

All groups displayed involuntary interlimb coupling, however, the patterns of coupling

differed between groups. In adult stroke, upper extremity movements occurred in stereotyped

patterns based on the lower extremity task. This was seen to some extent in individuals with

perinatal lesions, but not with prenatal lesions. Additionally, participants with prenatal lesions
 4

displayed increased involuntary coupling in the non-paretic upper extremity. The coupling

patterns seen in adult stroke are indicative of the extensively branching brainstem pathways that

are upregulated after stroke. In earlier lesions, a direct ipsilateral corticospinal pathway may be

used instead, which may account for the differences in interlimb coupling. Imaging findings

show that the corticospinal tract is more impacted by perinatal lesions than prenatal lesions,

which may affect differences in reorganization and motor deficits. Lastly, the corpus callosum

was found to be affected more by earlier lesions, which may impact the bilateral nature of

W
associated reactions and other deficits. This work demonstrates the need to address interlimb

coupling in clinical practice rather than treat the upper and lower extremities in isolation.
IE
EV
PR
 5

ACKNOWLEDGEMENTS
The upside to an eight-year degree spanning multiple departments is the many people you

meet along the way who shape your research and life in countless ways. Finishing this degree

would not have been possible without my amazing support crew, for whom this

acknowledgements section cannot come close to giving them the praise and credit they deserve.

First, I would not be here if not for a phone call I got from Jules Dewald, inviting me to

start this adventure. Jules’ love for science is infectious, and support of his students never

W
ending. He has an unwavering vision of the marriage of physical therapy and engineering, and

has successfully instilled this in me. Jules, I have seen you stand up for me and support me
IE
through the highs and lows, and am fortunate to call you a mentor and friend. My committee

members have also served to keep me on track, and have witnessed my research direction
EV

changing over the years as I discovered my interests and matured as a scientist. Deb Gaebler has

a passion for pediatric rehabilitation that is relentless. Her clinical insights, enthusiasm, and
PR

assistance with recruitment made this all possible. Todd Parrish, Tim Carroll, and Carson Ingo

were all invaluable resources in imaging and their technical expertise ensures I have the tools

needed to answer the scientific question. Matt Tresch is never without insightful comments, and

is a master of all things neuroscience. And while not a committee member, Ana Maria Acosta

was a much sought after resource, whether it was planning experiments, figuring out Jacobians,

or just someone to vent to.

I have learned more from senior graduate students than books and papers could ever

teach. Dan Krainak held my hand through the start of imaging work and instilled in me a healthy

(and at times crippling!) skepticism. Laura Miller, Jeremy Eagles, Jacob McPherson, and Laila
 6

Alibiglou have all inspired me and provided me with sounding boards of scientific discussion

throughout the years. And most of all, a hearty thanks to Thersea Sukal Moulton, for paving the

way both in terms of the dual degree and in pediatric research. She has been a mentor and

friend, and I will always continue to seek her valuable opinions and advice.

Paul Krueger and Stuart “Friend” Traxel were both my knights in shining armor. The

experimental work would not have been possible without either one of them. Paul took on the

challenge of building a device that could work for the smallest 6 year old up to the tallest and

W
strongest adult. Thankfully, we never tested those boundaries! Stuart was the robot tamer, and

the first one I’d run to with robot failures or when I broke (another) load cell. He answered
IE
every dumb Matlab question without losing patience (at least outwardly), and even responded to

a few “emergency” emails after he left the department. Brad Holubar was also my superhero-
EV
whether it was getting grants in last minute, ordering supplies, or help with IRB, he always had a

“can-do!” attitude that made my life much easier! MRI data acquisition would not have been
PR

possible or gone as smoothly without the help of Marie Wasielewski and Azmi Banibaker.

Much of my experimental work was facilitated by a fantastic group of DPT students in

my synthesis group- Victoria Azzi, Tommy Chrusciel, Katie Lullo, Laura Schorfheide, and

Liesel von Gontard, who made my experiments a breeze and taught me so much about

mentoring. Additional thanks to all the grad students and staff I would bug for intermittent help

– you were all the extra hands I needed for successful experiments.

None of this work is possible without our research participants donating their time and

trust, and inspiring me with their stories and strength. To everyone who signed on even after

hearing they would receive no direct benefit but possibly advance science, your generosity and
 7

commitment to advancing medicine for the benefit of others is appreciated. The children and

adults alike have taught me, tested me, and made me laugh more times than I can count. I also

have possibly the most diverse Pandora and Netflix accounts thanks to everyone’s requests!

The camaraderie between my fellow graduate students has been a constant source of

strength- whether sharing idea or chocolate, it has been a joy to work with you all. Special

thanks to Meriel Owel, Nayo Hill, Emma Baillargeon, Rebecca Abbott, Christa Nelson, Lindsay

Garmirian, Natalia Sanchez- all of whom I frequently seek out their opinions and help, and seek

W
comfort in their candy stash.

The PTHMS faculty and staff have become a second family, and there is no group of
IE
people I would have rather spend these years with and learn from in so many ways. A special

thanks to Lois Hedman, for mentorship in teaching, friendship and shared almond flour orders
EV
that kept me going. Babette Sanders and Marjorie Hilliard are constant cheerleaders and sources

of support. Kristin Krosschell’s insights into all things pediatrics (and more) have been valuable
PR

throughout the years. Kathy Martinez was way too often my weekend friend, and watching her

finish her degree while carrying a heavy teaching load was inspiration for the final push. Daniel

Corcos and his endless supply of chocolate (and advice) that would magically appear was a

frequent lifesaver, and he was often responsible for keeping me out of trouble on weekends.

Carolina Carmona and Roberto Lopez have also been fantastic people to work with, always

willing to lend a hand and knowledge.

While my clinical education started with the PTHMS faculty, my clinical instructors

helped shape me into the therapist and researcher I am. Heather Rennie of Athletico provided an

excellent introduction to clinical practice and tried not to flinch when I told her I had taken none
 8

of my musculoskeletal courses! Caryn Harris and Melanie Farris of TerrioKIDS in Bakersfield,

CA confirmed my love of pediatrics, and taught me more than seemed possible in six weeks.

Special thanks to Leslie Kuhagen at Swedish Covenant Hospital and Tracy Alvarez at Weiss

Memorial Hospital, for their patience, second chances, and instilling confidence when mine was

buried. I have been grateful for the opportunity to continue to grow as a therapist at Weiss

Memorial Hospital, where I am amazed and humbled by my co-workers dedication to their

patients and profession. Thanks are due to my patients, who trusted me when I was a student and

W
new therapist, and whom I continue to learn from constantly.

While cliché, I’d be lost without my friends both within and outside this graduate school
IE
bubble. I embarked on this adventure with Camila Shirota and Jen Nichols, and together we were

victorious over Matlab and ice cream sundaes- neither stood a chance! Bethany (Vaughn)
EV
Rowson and Ali Anoff were always just a phone call away for good and bad news. Theresa

Murray, who started as a temporary roommate but after seeing me attempt to assemble Ikea
PR

furniture on my own, became a very dear friend and Skipbo partner. I may have self-combusted

without the triathlon community, for giving me an outlet and supporting me on my journey to

cross both athletic and academic finish lines. Even the sport itself deserves credit for all the

breakthroughs ideas and clarity gained during long swims, bikes, and runs.

Many thanks go out to Greg and Martha Gdowski, who took a chance on me as a

freshman and fostered my research development for four years. More importantly, you provided

me a second family and made sure I crossed the road safely (literally) to reach this chapter of my

adventure. Additional thanks to Amy Lerner and the rest of the Rochester BME faculty for more

than preparing me and instilling in me the notion of “Meliora- Ever Better”. Also thanks to
 9

Sandra Hunter and Marquette University’s REU program for showing me that BME and

physical therapy were a perfect match.

It is easy to get back up from the inevitable lows of graduate school when you have a

family that stands behind you 110%. My mom has loved me unconditionally, and been the

biggest cheerleader of my work. I only got my father for the first 14 years of my life, but the

work ethic and humor he instilled in me have been a source of constant strength. And last but

certainly not least, Lola and Olivia, for their unconditional love and understanding when days

W
were long, walks were short, and dinner was late.

Lastly, I was fortunate to be supported by various funding agencies over the years,
IE
including the National Science Foundation (Graduate Research Fellowship Program), National

Institutes of Health (NIH RO1 HD039343 and NIH T32 EB009406) and the American Heart
EV
Association (AHA 15PRE22990027).
PR
 10

LIST OF ABBREVIATIONS
AD axial diffusivity

BF biceps femoris

BIC biceps brachii

CP cerebral palsy

CSC cortical-subcortical

DTI diffusion tensor imaging

W
EEG electroencephalogram

EMG electromyography IE
EPSP excitatory post-synaptic potential

FA fractional anisotropy
EV

FMA Fugl-Meyer Assessment

fMRI functional magnetic resonance imaging

PR

GMFCS Gross Motor Function Classification System

GW gestational week

IDL intermediate deltoid

IPSP inhibitory post-synaptic potential

LE FM Lower Extremity Fugl-Meyer Assessment score

MACS Manual Ability Classification System

MCA middle cerebral artery

MD mean diffusivity

MRI magnetic resonance imaging

 11

npKE non-paretic knee extension

npKF non-paretic knee flexion

NT not tested

PCA post-conceptual age

PEC pectoralis major

PERI perinatal

pKE paretic knee extension

W
pKF paretic knee flexion

POST postnatal

PMRF
IE
pontomedullary reticular formation

PRE prenatal
EV
PVL periventricular leukomalacia

PWM periventricular white matter

PR

RD radial diffusivity

SCALE Selective Control Assessment of the Lower Extremity

STD standard deviation

TD typically developing

TMS transcranial magnetic stimulation

TRI triceps brachii (lateral head)

UE FM Upper Extremity Fugl-Meyer Assessment score

VM vastus medialis
 12

TABLE OF CONTENTS

Abstract .......................................................................................................................................... 3  

Acknowledgements ........................................................................................................................ 5  

List of Abbreviations ................................................................................................................... 10  

Table of Contents ......................................................................................................................... 12  

W
List of Figures .............................................................................................................................. 17  

List of Tables ................................................................................................................................ 19  

IE
1.   Introduction .......................................................................................................................... 20  
EV

2.   Background Information and Literature Review ............................................................. 23  

2.1.   Introduction to Adult Onset Stroke: ......................................................................................... 23  

PR

2.2.   Introduction to Pediatric Onset Stroke and Cerebral Palsy: ................................................. 24  

2.2.1.   Prenatal Etiology ................................................................................................................... 25  

2.2.2.   Perinatal Etiology .................................................................................................................. 27  

2.2.3.   Postnatal Etiology .................................................................................................................. 28  

2.3.   Overview of Neural Development: ............................................................................................ 29  

2.3.1.   Embryonic Period .................................................................................................................. 29  

2.3.2.   Fetal Period ............................................................................................................................ 30  

2.3.3.   Postnatal Period ..................................................................................................................... 31  

2.3.4.   Childhood .............................................................................................................................. 32  

2.3.5.   Corticospinal Tract Development .......................................................................................... 32  

 13

2.4.   Review of Motor Pathways: ....................................................................................................... 34  

2.4.1.   Corticospinal .......................................................................................................................... 34  

2.4.2.   Reticulospinal ........................................................................................................................ 37  

2.4.3.   Vestibulospinal Pathway ....................................................................................................... 38  

2.4.4.   Propriospinal Pathway ........................................................................................................... 39  

2.4.5.   Rubrospinal Pathway: ............................................................................................................ 39  

2.5.   Reorganization in Pediatric Hemiplegia: .................................................................................. 40  

2.6.   Reorganization in Adult Onset Hemiplegia .............................................................................. 44  

W
2.7.   Overview of Movement Impairments in Pediatric and Adult Onset Hemiparesis ............... 45  

2.8.   Associated Reactions in Pediatric and Adult Onset Hemiparesis .......................................... 46  

IE
2.8.1.   Associated Reactions in Adult Stroke ................................................................................... 47  

2.8.2.   Associated Reactions in Pediatric Hemiplegia ...................................................................... 49  

EV
2.9.   Introduction to Diffusion Tensor Imaging................................................................................ 51  

2.10.   Diffusion Tensor Imaging in Pediatric Hemiplegia: Review of Literature ......................... 55  

PR

3.   Development of a Method to Quantify Interlimb Coupling in Individuals with

Hemiparetic Stroke. .................................................................................................................... 58  
3.1.   Abstract ........................................................................................................................................ 58  

3.2.   Introduction ................................................................................................................................. 58  

3.3.   Methods ........................................................................................................................................ 60  

3.3.1.   Isometric Method ................................................................................................................... 60  

3.3.2.   Electromyography Method .................................................................................................... 61  

3.3.3.   Haptic Robotic Method.......................................................................................................... 62  

3.4.   Results .......................................................................................................................................... 63  

3.4.1.   Isometric Method Results ...................................................................................................... 63  

3.4.2.   Electromyography Method Results ....................................................................................... 64  

 14

3.4.3.   Haptic Robotic Method Results ............................................................................................. 65  

3.5.   Discussion ..................................................................................................................................... 66  

3.5.1.   Comparison of Methodologies .............................................................................................. 66  

3.5.2.   Interpretation of Underlying Neural Mechanisms ................................................................. 68  

3.6.   Conclusion.................................................................................................................................... 69  

4.   Altered Interlimb Coupling in Adult-Onset Hemiplegia .................................................. 70  

4.1.   Introduction ................................................................................................................................. 70  

4.2.   Materials and Methods ............................................................................................................... 72  

W
4.2.1.   Participants ............................................................................................................................ 72  

4.2.2.   Protocol .................................................................................................................................. 74  

IE
4.2.3.   Data Analysis ......................................................................................................................... 77  

4.2.4.   Statistical Analysis................................................................................................................. 78  

EV

4.3.   Results .......................................................................................................................................... 79  

4.3.1.   Magnitude of Fingertip Excursion ......................................................................................... 80  

PR

4.3.2.   Directionality of involuntary movement ............................................................................... 82  

4.3.3.   EMG Activity ........................................................................................................................ 84  

4.4.   Discussion ..................................................................................................................................... 85  

4.4.1.   Limitations ............................................................................................................................. 87  

4.4.2.   Clinical Relevance ................................................................................................................. 88  

5.   Interlimb Coupling in Pediatric Hemiplegia ..................................................................... 89  

5.1.   Introduction ................................................................................................................................. 89  

5.2.   Methods ........................................................................................................................................ 91  

5.2.1.   Participants ............................................................................................................................ 91  

5.2.2.   Clinical Measures .................................................................................................................. 92  

 15

5.2.3.   Protocol .................................................................................................................................. 93  

5.2.4.   Statistical Analysis................................................................................................................. 95  

5.3.   Results .......................................................................................................................................... 96  

5.3.1.   Participants ............................................................................................................................ 96  

5.3.2.   Associated Reactions in the Paretic Upper Extremity ........................................................... 96  

5.3.3.   EMG Activity ...................................................................................................................... 100  

5.3.4.   Non-Paretic Upper Extremity .............................................................................................. 100  

5.3.5.   Interlimb Coupling in Post-Natal Lesions ........................................................................... 101  

W
5.4.   DISCUSSION ............................................................................................................................ 102  

5.4.1.   Clinical Relevance ............................................................................................................... 105  

IE
6.   Comparison of the Impact of Prenatal and Perinatal Lesions on the Corticospinal

Tracts .......................................................................................................................................... 107  

EV

6.1.   Introduction ............................................................................................................................... 107  

6.2.   Methods ...................................................................................................................................... 110  

PR

6.2.1.   Participants .......................................................................................................................... 110  

6.2.2.   Clinical Measures ................................................................................................................ 111  

6.2.3.   Imaging Protocol ................................................................................................................. 112  

6.2.4.   Analysis ............................................................................................................................... 112  

6.2.5.   Statistical Analysis............................................................................................................... 115  

6.3.   Results ........................................................................................................................................ 115  

6.3.1.   Motor Impairments .............................................................................................................. 115  

6.3.2.   DTI Metrics ......................................................................................................................... 116  

6.3.3.   Cross-Sectional Area ........................................................................................................... 117  

6.3.4.   Correlations Between DTI Metrics of Lesioned and Non-Lesioned Tracts ........................ 118  
 16

6.3.5.   Cortical Projections ............................................................................................................. 118  

6.3.6.   Relationship to Motor Outcomes ......................................................................................... 119  

6.4.   Discussion ................................................................................................................................... 121  

7.   The Effect of Injury Timing on White Matter Changes in the Corpus Callosum

Following Unilateral Brain Injury ........................................................................................... 127  

7.1.   Abstract ...................................................................................................................................... 127  

7.2.   Introduction ............................................................................................................................... 128  

7.3.   Methods ...................................................................................................................................... 129  

W
7.4.   Results ........................................................................................................................................ 136  

7.5.   Discussion ................................................................................................................................... 140  

IE
8.   Conclusion ........................................................................................................................... 144  
EV
PR
 17

LIST OF FIGURES

Figure 2.1 Periventricular injuries. ................................................................................................ 26  

Figure 2.2 Example of perinatal MCA lesion in 10 year old. ....................................................... 28  

Figure 2.3 Embryonic neural development ................................................................................... 30  

Figure 2.4 Activity-dependent development of corticospinal system. .......................................... 34  

Figure 2.5 Course of lateral corticospinal tract. ............................................................................ 36  

W
Figure 2.6 Reorganization in prenatal lesions based on size of lesion. ......................................... 43  

Figure 2.7 Diffusion trajectories and ellipsoid models ................................................................. 52  

IE
Figure 2.8. FA-Weighted color maps. ........................................................................................... 53  

Figure 3.1 ACT-3D Robot. ............................................................................................................ 63  

EV

Figure 3.2 Example of isometric torques generated during lower extremity task ......................... 64  

Figure 3.3 Examples of interlimb coupling patterns. .................................................................... 65  

PR

Figure 3.4 Flexion and extension synergy patterns with robotic method...................................... 66  

Figure 4.1 Experimental set-up ..................................................................................................... 76  

Figure 4.2 Example of fingertip traces in the x-y plane. ............................................................... 80  

Figure 4.3 Magnitude of fingertip excursions. .............................................................................. 82  

Figure 4.4 Directionality of upper extremity movements. ............................................................ 83  

Figure 4.5 Normalized EMG activity. ........................................................................................... 84  

Figure 5.1 Magnitude of paretic fingertip excursions. .................................................................. 98  

Figure 5.2 Magnitude of fingertip excursions for different effort levels. ..................................... 98  

Figure 5.3 Directionality of excursions. ........................................................................................ 99  

 18

Figure 5.4 Magnitude of non-paretic upper extremity excursions .............................................. 101  

Figure 6.1 Seed placement and example tracts. .......................................................................... 114  

Figure 6.2 DTI Metrics for TD, PWM and CSC Lesions ........................................................... 117  

Figure 6.3 Cross-sectional area of corticospinal tracts. ............................................................... 118  

Figure 6.4 Full corticospinal tract reconstructions. ..................................................................... 119  

Figure 6.5 Relationship between Fugl-Meyer Assessment score and Imaging Measures. ......... 120  

Figure 7.1. Representative diffusion color maps ......................................................................... 137  

W
Figure 7.2 Fractional Anisotropy by region.. .............................................................................. 138  

Figure 7.3: Cross-sectional area by region. ................................................................................. 139  

IE
Figure 7.4 Involuntary coupling in the paretic arm ..................................................................... 140  
EV
PR
 19

LIST OF TABLES
Table 4-1 Characteristics of participants with chronic stroke. ...................................................... 73  

Table 5-1 Participant characteristics for PRE, PERI, and POST groups. ..................................... 93  

Table 6-1 Participant Characteristics........................................................................................... 111  

Table 7-1 Pediatric hemiplegia participant information .............................................................. 132  

Table 7-2 Adult hemiplegia participant information. .................................................................. 134  

W
IE
EV
PR
 20

1. INTRODUCTION

Hemiplegia can result from a lesion acquired at any point in development, including in

utero. It is often thought that lesions acquired earlier in development have better outcomes than

later lesions. This notion comes from the fact that brain plasticity may be greater earlier in life,

and the ability to recover or compensate from a lesion decreases with maturity. While some

aspects of this are true, the effects of lesion timing on motor outcomes are much more nuanced.

W
Rather than seeing one pattern of reorganization as superior to another, each comes with distinct

tradeoffs that can be seen in motor behaviors. For example, individuals with earlier lesions show
IE
deficits with mirror movements and bilateral coordination, while later lesions have greater

deficits in independent joint control and demonstrate increased spasticity.

EV

Despite the many differences in hemiplegia acquired at different timings, a deficit

clinically referred to as “associated reactions” has appeared to transcend the limits of injury
PR

timing and is seen in both children and adults with hemiplegia. Associated reactions refer to

involuntary movement in one limb in response to voluntary movement in another. For example,

when a child with hemiplegia runs, driving the legs with great effort, the paretic upper extremity

is observed moving into a flexed posture. Since many activities of daily living require

coordination of lower and upper extremities, associated reactions can pose challenges beyond the

deficits isolated to the upper and lower extremities individually. While most clinicians will

acknowledge the presence of associated reactions, they are rarely addressed, and some

interventions such as high intensity gait training may actually exacerbate them.
 21

Motor behavior is an outward sign of underlying neural function. Therefore, while

associated reactions are an important clinical problem that warrants further study, they can also

serve as a probe to examine reorganization of the motor system after a lesion. Certain patterns of

movement are known to be reflective of using specific motor pathways. By pairing quantitative

measures of motor behavior with measures of morphological changes from diffusion tensor

imaging, further insight is gained as to the underlying neural mechanisms individuals with

hemiplegia.

W
The goal of this dissertation was to quantify associated reactions in both pediatric and

adult hemiplegia, as well as changes in neural structures, to understand how damage from lesions
IE
at different points in development can result in abnormal interlimb coupling. In Chapter 2, the

necessary background information will be provided, including etiologies of lesions at varying

EV
time points, an overview of neural development, and review of the literature on associated

reactions in both pediatric and adult hemiplegia. Chapter 3 will detail the development of an
PR

appropriate methodology to investigating abnormal interlimb coupling between the lower and

upper extremities. Chapter 4 presents the study of associated reactions characterized in

individuals with hemiplegia from an adult-onset lesion, setting the groundwork for the pediatric

work by establishing the effect of a lesion to the fully developed nervous system. Next, in the

study presented in Chapter 5, associated reactions were examined in individuals with hemiplegia

from prenatal, perinatal, or postnatal lesions to determine how associated reactions manifest

when the lesion occurs at varying time points in early development. To further understand the

differences between early injury timing groups, Chapter 6 presents a diffusion tensor imaging

study to quantify differences in the corticospinal tracts in prenatal and perinatal injury groups to
 22

determine if differences in motor behaviors may be due to the amount of damage. Lastly,

while the focus of this dissertation is on coupling between the lower and upper extremities,

bilateral coupling is also problematic and may be due to changes in the corpus callosum.

Chapter 7 compares changes in the corpus callosum between pediatric and adult onset

hemiplegia to give insight into this motor behavior. Cohorts of age-matched control participants

are also included in each study.

W
IE
EV
PR
 23

2. BACKGROUND INFORMATION AND LITERATURE REVIEW

2.1. Introduction to Adult Onset Stroke:

A stroke occurs when blood flow in the brain is blocked due to a clot (ischemic stroke) or

burst vessel (hemorrhagic stroke), starving brain tissue of oxygen and nutrients resulting in death

of brain cells. Current statistics (Mozaffarian et al 2016) report approximately 795,000 people in

the United States have a new or recurrent stroke each year, 610,000 of those being first time

W
events. It is estimated that 6.6 million Americans over 20 years old have had a stroke. Risk

factors include high blood pressure, diabetes mellitus, arrhythmias, and smoking. Ischemic
IE
strokes are more common and account for 87% of strokes, with intracranial hemorrhages making
EV
up 10% and sub-arachnoid hemorrhages accounting for 3% (Mozaffarian et al 2016). The

recovery and deficits following a stroke are varied, and can depend on the location of the lesion.

The middle cerebral artery (MCA) is the most common vessel involved in stroke, and MCA
PR

strokes can result in weakness or paralysis on the opposite side of the body (hemiparesis),

sensory losses, and attention and language deficits. Fifty percent of all stroke survivors report

hemiparesis six months following the stroke, which has significant implications on mobility,

activities of daily living, and quality of life (Go et al 2014).

The Brunnstrom stages of recovery describe recovery from a stroke to occur in six stages,

however, an individual could plateau at any one stage, which could become their chronic status.

Stages progress from initial flaccidity and inability to move the limb at all, to the appearance and

strengthening of spasticity and flexor and extensor synergy patterns. Movement confined to

synergy patterns is followed by movement out of synergies, with decreasing spasticity. Nearing