WOW. Zero understanding of anything here. Have your doctor create a stroke protocol out of this and in 10 years and a couple more Ph.Ds and maybe this could be deciphered. Damn, lazy talk of biomarkers and patterns of recovery also. We don't need biomarkers, we need rehab protocols that deliver results.
The Association Between Reorganization of Bilateral M1 Topography and Function in Response to Early Intensive Hand Focused Upper Limb Rehabilitation Following Stroke Is Dependent on Ipsilesional Corticospinal Tract Integrity
Mathew Yarossi1,2*†, 
Jigna Patel3†, 
Qinyin Qiu3, 
Supriya Massood4, 
Gerard Fluet3, Alma Merians3, 
Sergei Adamovich3,5 and 
Eugene Tunik1,6,7- 1Movement Neuroscience Laboratory, Department of Physical Therapy, Movement and Rehabilitation Science, Bouve College of Health Sciences, Northeastern University, Boston, MA, United States
- 2SPIRAL Group, Department of Electrical and Computer Engineering, Northeastern University, Boston, MA, United States
- 3Department of Rehabilitation and Movement Sciences, School of Health Professions, Rutgers Biomedical and Health Sciences, Newark, NJ, United States
- 4Brookdale Rehabilitation – North Campus, Naples Community Hospital, Naples, FL, United States
- 5Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, United States
- 6Department of Bioengineering, College of Engineering, Northeastern University, Boston, MA, United States
- 7Department of Electrical and Computer Engineering, College of Engineering, Northeastern University, Boston, MA, United States
Introduction
Stroke is a leading cause of adult long-term disability
in the United States and the financial burden of related care is among
the fastest-growing expenses for Medicare (1).
Proportionally more stroke survivors are left with upper extremity
impairment and disability than that of the lower extremity (2).
At 6 months post-stroke, about 30–60% of affected individuals do not
regain functional use and only 5–20% achieve full return of arm function
(3, 4).
Recovery of hand function is notably impervious to intervention in part
due to the complexity of motor control required for dexterous function.
At six months post-stroke ~65% of affected persons continue to have
hand deficits that profoundly affect their ability to perform their
usual activities and affect their independence (2, 5); and only 5% of those with initial severe paresis will have full recovery (6). Importantly, impaired hand function is often the most disabling deficit for many post lesion (7).
Numerous investigations have provided evidence
indicating rehabilitation interventions must be initiated early after
stroke to maximize recovery (8, 9). Although the optimal time period is not clear, the first month post-stroke is a crucial time for plasticity (8).
Yet the vast majority of studies on emerging therapeutic interventions
have focused on individuals in the chronic phase after stroke with
limited work looking at interventions during acute and sub-acute phases (10–12).
In fact, as reported in a 2013 review, only 6% of all stroke motor
rehabilitation clinical trials have enrolled all patients within the
first 30 days after a stroke (9).
In light of recent evidence for the greater effectiveness of early
rehabilitation, this staggering statistic highlights the need for
investigation of intensive hand focused upper limb rehabilitation
initiated early after stroke.
Perhaps most important are investigations comparing
changes in impairments, function and neurophysiology early following
stroke to identify the biomarkers of recovery. Transcranial Magnetic
Stimulation (TMS) induced motor evoked potentials (MEPs) are an
established proxy of corticospinal excitability (13).
Numerous previous investigations have found that the presence (MEP+) or
absence (MEP-) of MEPs early after stroke is a robust indicator of
long-term recovery (14, 15). More recently, Stinear (16)
suggested that people without MEPs (MEP-) at 2 weeks post-stroke have
“limited or no predicted potential for upper extremity recovery” at 12
weeks after stroke.
Though numerous studies have indicated that the presence
or absence of MEPs may be a strong predictor of recovery, change in the
distribution of activation indicating reorganization of motor
topography may provide additional insight into patterns of recovery.
MEPs can be acquired over the sensorimotor cortex such that the
two-dimensional position of the coil over the scalp can be used to
generate a multivariate excitability map akin to those classically
acquired with invasive stimulation, albeit with lower resolution. Use of
TMS mapping to track ipsilesional motor reorganization over the first
months to 1 year following stroke has generally indicated that increased
excitable area in the ipsilesional hemisphere was associated with
recovery of the impaired hand (17–19), though other studies found no change in ipsilesional excitable area over the same period (20, 21).
Association of better outcomes with expansion of ipsilesional cortex
activation is in line with numerous findings in human and animal models
[see (22, 23)
for a review]. Two investigations using TMS mapping during this early
time period found increased excitable area in the contralesional
hemisphere was associated with poorer outcomes (17, 24).
This finding is in contrast with a number of studies which did not find
changes in contralesional hemisphere excitable area or associations
between changes in contralesional hemisphere topography and recovery of
function in the subacute period (18–20).
The association between contralesional topographic reorganization and
functional recovery is complex, with numerous conflicting findings in
both human and animal models, indicating beneficial or maladaptive
influence on function [see (22, 23)
for a review]. Although, these studies provide some indication of the
general pattern of recovery; it is equally important to investigate the
changes in functional-structural associations during focused
intervention.
Interventional studies in the chronic phase post-stroke
have used TMS based mapping of the ipsilesional hemisphere to quantify
the spatial patterns of recovery of the corticospinal system in MEP+
patients (25, 26);
all noting an increase in the peak MEP and area of MEPs representing
the hand in the ipsilesional sensorimotor cortex. To date, there have
been few studies that have investigated the association of functional
outcomes and TMS measures of cortical topography with intensive upper
limb intervention in the early stages following stroke (27–30). Findings from Ro et al. (30), Boake et al. (28) and Sawaki et al. (29) [in which patients were enrolled either in the first 14 days (28, 30), or at 3 to 9 months (29)]
indicate that increased area of excitation in the ipsilesional
hemisphere is associated with increased functional improvement in
individuals receiving Constraint Induced Movement Therapy (CIMT)
compared to controls receiving usual care. Contrary to this finding,
Platz et al. (27)
did not find any change in the number of active sites in their two
treatment groups (Bobath and BASIS training), though reduction in map
area was shown in the usual care group (27). Ludemann-Posdubecka and Nowak (31)
offer a comprehensive review of observation and interventional studies
assessing TMS mapping of cortical hand motor representation as a marker
for recovery of function after stroke. Overall, most studies have
compared changes in motor topography to a limited set of clinical
measures of function or impairment and no study to date has compared
contralesional changes between those individuals who do and do not have
ipsilesional MEPs.
In this investigation, we examined the relationship
between changes in function/motor recovery and cortical motor topography
in a group of patients undergoing early (<3 months) and intensive
hand focused upper limb rehabilitation using the NJIT-RAVR, an
integrated VR/Robotic platform that was shown to be effective at
reducing impairments in a chronic stroke population (32–34). With the exception of one small study from our group, no study has yet examined this relationship post VR/Robotic training (35).
Data was collected in preparation for a now ongoing randomized
controlled trial (RCT) to study the effects of timing and dosing of
VR/Robotic intervention, and results for the intervention group are
presented to show feasibility for use of TMS to measure
neurophysiological correlates of recovery. Because specific hand
therapy, by and large, is a small percentage of therapy received in the
subacute period in US rehabilitation practice, selection of subjects
from the intervention group only ensured that each individual did indeed
receive therapy and that the dosage, in actual movement repetitions,
was roughly equal among our sample. Specifically, we tested the degree
to which clinical, kinematic, and kinetic measures of functional
improvement correlated with changes in bilateral motor cortical
topography (assessed by TMS mapping) in individuals with and without
preserved ipsilesional corticospinal integrity (also assessed with TMS).
We hypothesized that functional improvements would be greater in MEP+
individuals and that an increase in ipsilesional cortical territory
would correlate to markers of functional improvement. In a secondary
analysis we compared functional and topographical changes in the
contralesional hemisphere between individuals who were positive for the
presence of MEPs in the ipsilesional hemisphere (MEP+) and those who
were not (MEP–). We predicted greater expansion of contralesional
cortical territory in MEP- individuals, and that the degree of expansion
would be associated with worse outcomes in this cohort of subjects. An
important and novel tertiary exploratory analysis of MEP “converters,”
individuals who were MEP- at baseline and later converted to MEP+, was
also carried out to understand how reinstatement of MEPs is related to
functional recovery.
More at link.
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