Saman Hazany, MD¹², Daljit Mann (co-first author

advertisement
Changes in Neuroimaging as Result
of Robotic Rehabilitation in
Patients with Hemispherectomy
Abstract #: EP-126
SAMAN HAZANY, MD¹², DALJIT MANN (CO-FIRST
AUTHOR), BS²³; MINDY AISEN, MD¹²; STELLA DE BODE,
PHD4; SUSAN SHAW, MD¹²; KRISTI CLARK, PHD³
1. RANCHO LOS AMIGOS NATIONAL REHABILITATION CENTER. DOWNEY,
CA.
2. UNIVERSITY OF SOUTHERN CALIFORNIA (USC). LOS ANGELES, CA.
3. INSTITUTE FOR NEUROIMAGING AND INFORMATICS (INI) – USC. LOS
ANGELES, CA.
4. UNIVERSITY OF CALIFORNIA LOS ANGELES. LOS ANGELES, CA.
Disclosure statement
 The authors of this electronic poster have no relevant
financial relationships to disclose.
Purpose
To investigate anatomic changes in the brain
(specifically cortical thickness changes) as a result of
robotic rehabilitation in patients with
hemispherectomy, by using structural MRI.
Introduction
 Hemispherectomy is generally performed in patients with intractable –
drug-resistant epilepsy secondary to conditions including perinatal
stroke, hemimegalencephaly, multilobar cortical dysplasia, Rasmussen
encephalitis, and Sturge-Weber syndrome. This procedure improves
seizure control, however leads to sensorimotor deficits, visual, language
and behavioral impairments[1, 2].
 Many studies have shown residual motor function in the contralateral
extremities after hemispherectomy [3, 4].
 Areas of increased FDG uptake have been seen in posthemispherectomy subjects while performing a motor task in multiple
places: premotor area, SMA, Secondary sensory area, and lingual
gyrus[5].
Introduction
 Task-oriented training increases gray matter and white matter in
healthy human brains [6, 7, 8]. Functional MRI study has shown
functional sensorimotor cortex reorganization in the contralateral
hemisphere with subjective improvements in behavior in setting of
task-oriented locomotor rehabilitation [9].
 Other studies have shown that motor skill learning is associated with
structural brain plasticity, and that practice time and performance
modulate the extent of structural brain changes evoked by long term
training [10]. No other studies have looked at different methods of
rehabilitation.
 The aim of this study is to investigate the efficacy of a 2 week high
intensity rehabilitation program with help of robotics, by correlating
changes in cortical thickness to fugl-meyer scores.
Materials and Methods
Patients
 5 female patients with right-sided hemispherectomy; all
right-handed (except one subject who was too young at
time of surgery to determine handedness) with an
average age of 10.8 years (Range: 10-12 years) at the time
of therapy.
 The average age at first hemispherectomy surgery was
5.05 years (range: .25 – 9 years).
 List of diagnoses that led to hemispherectomy:




Rasmussen’s Encephalitis
Sturge-Weber Syndrome
brain trauma secondary to prior neurosurgery
Taylors Type 2 Cortical Dysplasia.
Materials and Methods
Training
 All subjects were enrolled in a high-intensity task-oriented robotic rehabilitation
program for two weeks with four consecutive days each week. Subjects received
three hours per day of robot-assisted therapy, consisting of one hour of Hocoma
Lokomat, one hour of Interactive Motion Technologies (IMT) ARM, and one hour
of IMT Anklebot training. All subjects also participated in value-added activities
consisting of one hour per day of recreational therapy, one hour per day of adaptive
yoga, one hour per day of virtual reality occupational therapy, and one hour per day
of miscellaneous fun activities which included ice cream social, dance, making
slime, and movies.
 Two subjects (1 and 2) also received an additional one hour of training with wrist
robot, focusing on wrist flexion, wrist extension, ulnar deviation and radial
deviation. The wrist training occurred on the same days as the other robotic
training, however HW participated in the wrist training for 7 days while AM
participated all 8 days.
 Fugl-Meyer assessment of physical performance (used in previous studies[1–3]) was
also applied in this study to assess behavioral changes in upper extremity motor
function before and after the therapy.
Materials and Methods
MRI scan:
 3D FSPGR (fast spoiled gradient echo) magnetic resonance imaging of each
subject was performed 1 day before and 1 day after period of two weeks training
on a General Electric (GE) Signa HDx 1.5 Tesla MRI scanner at Rancho Los
Amigos National Rehabilitation Center located in Downey, California, United
States with the following parameters:








TR: 9.3 msec
TE: 3.7 msec
Flip Angle: 13
NEX: 1
Field of view: 24 x 26.8 cm
Matrix: 256 x 256
Slice thickness: 1 mm with no space
Number of slices in sagittal direction : variable (about 200)
Materials and Methods
Image post-processing and analysis:
 Image post processing was performed at Institute for Neuroimaging and Informatics (INI); University
of Southern California (USC) located in Los Angeles, California, United States.
 Each subject had different amounts of their right hemisphere removed during surgery . In order to
process images with the analysis software, the whole hemisphere was duplicated and flipped and final
analyses were run focusing on the intact left hemisphere.
 Free-surfer was used to estimate a two-timepoint change in brain volume by aligning the two brain
images and performing tissue-type segmentation to find brain/non-brain edge points. Next,
perpendicular edge displacement between the two timepoints was calculated and the mean
displacement was converted into an estimated cortical thickness change. Finally, a group paired t-test
was used to calculate an average change in cortical thickness across all five patients.
Figure1: Example subject before and after hemisphere duplication.
Results
 Upper extremity fugl-meyer score changes following
training
Subject
number
Before training
After training
Difference
1
31
38
+7
2
22
22
0
3
21
24
+3
4
21
23
+2
5
20
21
+1
Results
 Figure 2 demonstrates average
results of all 5 subjects with red color
representing areas of increased
cortical thickness, and blue color
representing areas of decreased
cortical thickness when comparing
pre-training to post-training 3D
FSPGR MRI sequences.
 Images are inflated to expand the
sulci. Gyri appear light gray and
inflated sulci appear dark gray.
 The clusters indicated by the arrows
are in locations including the
Supplementary Motor Area and PreMotor Area (16, 35, 42), central
sulcus near hand knob (33) and
Sensory Associative Zones (26).
Figure 2.
Subject 1
Figure 3: Increased cortical thickness
is observed in the sensory associative
areas (a) with biggest contribution to
cluster 42 (b).
Figure 3a.
Figure 3b.
Subject 2
Figure 4: Increased cortical thickness is
observed in the sensory cortex and
sensory associative areas (a) with
biggest contribution to clusters 33 and
26 (b).
Figure 4b.
Figure 4a.
Subject 3
Figure 5: Increased cortical
thickness is observed in the motor
cortex, sensory cortex and sensory
associative areas (a) with biggest
contribution to clusters 26 and 42
(b).
Figure 5a.
Figure 5b.
Subject 4
Figure 6: Increased cortical thickness is
observed in the motor cortex including
the hand knob, sensory cortex and
sensory associative areas (a) with biggest
contribution to clusters 26, 33, and 42
(b).
Figure 6a.
Figure 6b.
Subject 5
Figure 7: Minimal increased cortical
thickness is observed in the sensory
associative areas (a) with small
contribution to clusters 26, 33, 42 (b).
Figure 7b.
Figure 7a.
Limitations
 Small number of subjects makes drawing statistical
conclusions unreliable.
 We do not have an explanation for areas of decrease
in cortical thickness.
 Motor outcomes of hemispherectomy patients after
therapy is highly variable, and the recovery
mechanisms and results will depend on factors like
structural properties of the lesion itself, the age at
which it was acquired, the exact pre-operateive level
of functioning, and the effects of the intractable
seizures on the remaining hemisphere [9].
Discussion and conclusions
 Our average results show increase in cortical thickness in
supplementary motor area, pre-motor area, and sensory
associative zones which is in agreement with previous
studies [5, 9, 11]
 These older studies have shown only functional
reorganization using fMRI BOLD or PET imaging and
our findings support older studies with physical increases
in cortical thickness underlying the same areas.
 Prior view that higher order cortical areas have an
increased capacity for sensorimotor reorganization than
primary motor areas [5] is supported by our findings.
Discussion and conclusions
 This study shows an objective physical increase in
cortical thickness that coincides with behavioral
improvements proven with increases in upper
extremity fugl-meyer score.
 These findings support the notion that intensive
training, for as little as two weeks, may induce
cortical changes years after hemispherectomy.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Liégeois F1, Connelly A, Baldeweg T, Vargha-Khadem F. Speaking with a single cerebral hemisphere: fMRI language
organization after hemispherectomy in childhood. Brain Lang. 2008 Sep;106(3):195-203. doi: 10.1016/j.bandl.2008.01.010.
Epub 2008 Mar 7.
Moosa AN, Jehi L, Marashly A, Cosmo G, Lachhwani D, Wyllie E, Kotagal P, Bingaman W, Gupta A. Long-term functional
outcomes and their predictors after hemispherectomy in 115 children. Epilepsia. 2013 Oct;54(10):1771-9. doi:
10.1111/epi.12342. Epub 2013 Aug 23.)
De Bode S1, Firestine A, Mathern GW, Dobkin B. Residual motor control and cortical representations of function following
hemispherectomy: effects of etiology. J Child Neurol. 2005 Jan;20(1):64-75.
Zhang J, Mei S, Liu Q, Liu W, Chen H, Xia H, Zhou Z, Wang L, Li Y. fMRI and DTI assessment of patients undergoing
radical epilepsy surgery. Epilepsy Res. 2013 May;104(3):253-63. doi: 10.1016/j.eplepsyres.2012.10.015. Epub 2013 Jan 20.
Bernasconi A, Bernasconi N, Lassonde M, Toussaint PJ, Meyer E, Reutens DC, Gotman J, Andermann F, Villemure JG.
Sensorimotor organization in patients who have undergone hemispherectomy: a study with (15)O-water PET and
somatosensory evoked potentials. Neuroreport. 2000 Sep 28;11(14):3085-90.
Bezzola L1, Mérillat S, Gaser C, Jäncke L.Training-induced neural plasticity in golf novices. J Neurosci. 2011 Aug
31;31(35):12444-8. doi: 10.1523/JNEUROSCI.1996-11.2011.
Boyke J, Driemeyer J, Gaser C, Büchel C, May A. Training-induced brain structure changes in the elderly. J Neurosci. 2008 Jul
9;28(28):7031-5. doi: 10.1523/JNEUROSCI.0742-08.2008.
Hofstetter S1, Tavor I, Tzur Moryosef S, Assaf Y. Short-term learning induces white matter plasticity in the fornix. J Neurosci.
2013 Jul 31;33(31):12844-50. doi: 10.1523/JNEUROSCI.4520-12.2013.
de Bode S, Mathern GW, Bookheimer S, Dobkin B. Locomotor training remodels fMRI sensorimotor cortical activations in
children after cerebral hemispherectomy. Neurorehabil Neural Repair. 2007 Nov-Dec;21(6):497-508. Epub 2007 Mar 16.
Sampaio-Baptista C, Scholz J, Jenkinson M, Thomas AG, Filippini N, Smit G, Douaud G, Johansen-Berg H. Gray matter
volume is associated with rate of subsequent skill learning after a long term training intervention. Neuroimage. 2014 Aug
1;96:158-66. doi: 10.1016/j.neuroimage.2014.03.056. Epub 2014 Mar 26.
Graveline CJ, Mikulis DJ, Crawley AP, Hwang PA (1998) Regionalized sensorimotor plasticity after hemispherectomy fMRI
evaluation. Pediatr Neurol 19:337–342. doi: 10.1016/S0887-8994(98)00082-4
Download