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Presurgical Prediction

of Motor Functional
Loss Using
Tractography
Rajkumar Munian Govindan, MD*,
Harry T. Chugani, MD*, Aimee F. Luat, MD*,
and Sandeep Sood, MD
The usefulness of magnetic resonance imaging tractography is demonstrated in the presurgical planning of an
8-year-old girl with intractable epilepsy. Imaging and intracranial electrode monitoring suggested a left hemispherectomy for complete control of her seizures.
Although this child was hemiplegic, she retained considerable motor function in her right hand, and her parents
and the epilepsy team voiced significant concern that she
would lose right-hand function after a hemispherectomy.
Tractography indicated near-complete absence of her
left corticospinal tract and a more robust than normal
corticospinal tract in the right hemisphere. This finding
suggested that her right motor function had reorganized
to the right hemisphere and the ipsilateral corticospinal
tract. After surgery, her seizures were completely controlled, and no change in right motor activity was evident
compared with her presurgical status. Tractography
helped determine the extent of cortical resection and predict the extent of motor functional loss. 2010 by
Elsevier Inc. All rights reserved.
Govindan RM, Chugani HT, Luat AF, Sood S. Presurgical
prediction of motor functional loss using tractography. Pediatr Neurol 2010;43:70-72.

Introduction
The accurate localization of cerebral cortical regions serving crucial neurologic functions is important in neurosurgical
practice for the preservation of vital motor, sensory, lan-

guage, and other neurologic functions. In pediatric epilepsy


surgery, this information about localization is essential, but
often difficult to acquire, because ambiguities often arise
concerning the extent and localization of the epileptogenic
zone, in addition to the huge variation in the cortical location
of neurologic functions attributable to malformations or dysplasia, often leading to reorganization. For such localizations
of neurologic functions in the human brain, many investigative techniques, such as functional magnetic resonance imaging [1,2] and magnetoencephography [3], have been used.
However, these methods contain some limitations because
they require active subject participation during the test,
which is especially difficult in children and neurologically
impaired patients.
Diffusion magnetic resonance imaging and tractography
provide an advantage in this respect, i.e., they can provide
valuable functional localization noninvasively, without active patient participation. This technique was used to identify the normal course of the corticospinal tract in normal,
healthy children [4]. In one clinical application, this technique helped identify the optic radiation and predict contralateral superior quadrantanopsia loss after temporal lobe
resections [5]. In other studies, tractography was used as
a navigational tool in neurosurgical procedures [6,7].
Here, we demonstrate the usefulness of tractography in
planning the extent of cortical resection and in predicting
motor functional loss in a child with intractable epilepsy.

Case Report
An 8-year-old girl, born at 38 weeks of gestation, was diagnosed with
hemiplegic cerebral palsy at age 1 year, and she had manifested complex
partial seizures since age 2 years. Her seizures were poorly controlled despite the use of multiple antiepileptic medications. Her seizure semiology
generally consisted of an aura, staring episodes, and occasional jerking of
the right limbs, followed by vomiting. Her partial status epilepticus occasionally lasted up to 2 hours. Scalp electroencephalography revealed slow
background activity in the left hemisphere, with spike-and-wave activity in
the left posterior quadrant. She had right hemiparesis, bilateral spasticity,
and cognitive delay. Right peripheral visual-field loss was suspected but
was difficult to evaluate formally during her examination. Facial movements were symmetric, with no weakness. Her magnetic resonance imaging scan at age 6 years suggested in utero vascular injury with decreased
white matter volume in the left centrum semiovale and peritrigonal areas,
and an increased signal consistent with gliosis. The corpus callosum was
thin in the posterior segment. A glucose metabolism positron emission tomography scan indicated decreased metabolism in the left parietal and temporal cortices. The left basal ganglia and thalamus also exhibited severe
hypometabolism. The right hemisphere appeared normal.

From the *Department of Pediatrics and Neurology, and Department of


Neurosurgery, Childrens Hospital of Michigan, Wayne State University,
Detroit, Michigan.

Communications should be addressed to:


Dr. Chugani; Department of Pediatrics and Neurology; Childrens Hospital
of Michigan; School of Medicine, Wayne State University;
3901 Beaubien Boulevard; Detroit, MI 48201.
E-mail: hchugani@pet.wayne.edu
Received September 4, 2009; accepted February 22, 2010.

70 PEDIATRIC NEUROLOGY Vol. 43 No. 1

2010 by Elsevier Inc. All rights reserved.


doi:10.1016/j.pediatrneurol.2010.02.004  0887-8994/$see front matter

Figure 1. (A, C) Right and left corticospinal tracts (CST) of child with intractable epilepsy. (B, D) An age-matched, left-handed healthy child. In the right
hemisphere, on visual evaluation, the isolated corticospinal tract (A) was thicker compared with its appearance in an age-matched, left-handed normal control subject (B). In the left hemisphere, no significant fiber bundle connecting the brainstem to the sensorimotor cortex was evident, except for a single, small
tractographic fiber bundle that failed to reach the sensorimotor cortex (C).
Based on these clinical and imaging data, two-stage epilepsy surgery
was proposed, with the placement of intracranial cortical surface electrodes
for seizure localization and cortical mapping. Intracranial electrodes covered most of her left occipital, parietal, temporal, and frontal lobes, with
additional electrodes in the subtemporal regions and interhemisphere electrodes in the parietal region. Intracranial monitoring indicated very frequent interictal epileptic activity in the left occipital, frontal, and parietal
regions, including the precentral and postcentral gyri. These activities
were frequent enough to resemble electrographic seizures, suggesting
a multiple epileptogenesis involving the entire left hemisphere, including
the primary motor cortex.
Furthermore, using these electrodes, cortical motor and somatosensory
functional mapping was performed via repeated electrical stimulation of
the intracranial electrodes over the precentral sulcus and right tibial nerve, respectively. Both these methods failed to elicit any motor or somatosensory
response in the left cortical hemisphere covered by the intracranial electrodes.
We performed tractography of the corticospinal tract, using diffusion
tensor imaging. The diffusion tensor imaging scan was acquired using
a General Electric (General Electric Company, Fairfield, CT) system
with a 3 T magnet. Diffusion tensor images were acquired in the axial
planes, using six diffusion-sensitized gradients in six noncollinear directions, each with a b-value of 1000 second/mm2, along with a T2-weighted
reference image with a b-value of zero. Each image volume was acquired
using six repetitions to increase image quality (i.e., to reduce geometric distortion and eddy current artifacts) and the signal-to-noise ratio in a matrix
(size, 128  128  41 axial slices), and the images were reconstructed into
a 256  256 matrix. Tensor calculation and tractography were performed
using DTI-Studio software, version 2.40 [8]. Tractography was performed
according to the fiber assignment by continuous tracking algorithm
(deterministic) [9], with fiber propagation starting at a fractional anisotropy
threshold value of 0.2, and with fiber propagation discontinued if the
fractional anisotropy value was <0.2 or the angle threshold was >60 .
To isolate the corticospinal tract on the contralateral right side, an initial
wide-seed region-of-interest with an OR operator was drawn on the posterior limb of the internal capsule on the transaxial slice. A second region of
interest with an AND operator was drawn on a transaxial slice at the
anterior aspect of the brainstem, just below the level of cerebellar efferent
fiber decussation. Afterward, multiple small regions of interest with

a NOT function were drawn, to exclude fibers going to other nonsomatosensory cortical regions. This procedure yielded a long corticospinal
tract, descending from the right precentral and postcentral cortex, and passing through the posterior limb of the internal capsule and anterior part of the
brainstem (Fig 1A). On visual evaluation, this tract was thicker compared
with its appearance in an age-matched, left-handed, normal control subject
(Fig 1B). On the ipsilateral (surgical) left side, an exhaustive search for the
corticospinal tract was performed by placing large-seed OR regions of
interest at several locations, i.e., the subcortical white matter underlying
the sensory motor cortex, the posterior limb of the internal capsule, and
the brainstem. Despite three different seed regions of interest placed along
the expected course of the corticospinal tract, no significant fiber bundle
connecting the brainstem to the sensorimotor cortex was evident, except
for a single, small tractographic fiber bundle that failed to reach the sensorimotor cortex (Fig 1C).

Discussion
In this child, based on intracranial electrode recordings,
a left hemispherectomy was indicated to achieve seizure
control. Although this child was hemiplegic, she exhibited
considerable motor function in her right hand, and could
hold and drink from a cup. Therefore, her parents and the
epilepsy team expressed significant concern that she would
lose right-hand function after a hemispherectomy.
Because this child had manifested in utero injury, we
considered the possibility that right motor function had
reorganized in the opposite hemisphere. Such motor reorganization from an ipsilateral corticospinal tract had been
demonstrated in a number of studies, using various techniques [10-12]. If such reorganization had occurred, this
child had the potential to achieve a seizure-free outcome
after hemispherectomy, without any worsening of her right
hemiparesis.

Govindan et al: Tractography in Presurgical Planning 71

Although functional motor cortical mapping, performed


using repetitive electrical stimulation of the intracranial
electrodes on the left precentral gyrus, failed to elicit any
right motor activity, this test was not sufficiently conclusive
to exclude an absence of motor activity in the precentral
cortex (and other electrode-covered areas) because of
a lack of confidence about the accurate placement of intracranial electrodes on the corresponding cortex, and also
because of variations in the stimulus threshold required to
elicit a motor response. Similarly, somatosensory cortical
mapping failed to produce a conclusive sensory functional
localization in the left hemisphere. Under these circumstances, a robust motor mapping method such as functional
magnetic resonance imaging would have been useful for
a precise localization of the right sensory motor cortex.
However, this procedure requires a level of patient cooperation that the child could not provide. Therefore, the nearcomplete absence of a tractographic corticospinal tract in
the left hemisphere and a normal, if not more robust, corticospinal tract in the right hemisphere reinforced our confidence that motor function in the left hemisphere was
probably absent, suggesting that right motor function had
reorganized to the right hemisphere. Thus, tractography
exerted an impact on our clinical decision, and allowed us
to extend the surgical resection to involve the entire left
hemisphere, including the primary motor and sensory cortex, with the presumption that the child would not undergo
any further right motor functional loss. Indeed, after surgery, the seizures were completely controlled, and no
change in the strength and tone of the right upper and lower
extremities were evident compared with her presurgical
status.
The limitations of diffusion tensor tractography should
be mentioned. Tractography alone is unreliable in terms
of suggesting the presence or absence of the corticospinal
or any other white matter tract. This unreliability is inevitable because diffusion magnetic resonance imaging is inherently low in spatial resolution. Diffusion values were
measured in a range of millimeters, whereas the actual
size of white matter axons are in a range of micrometers
or even less. To overcome this issue, at least partly,
higher-resolution prolonged image-acquisition protocols
are needed, but these protocols are very time-consuming
and difficult to apply in clinical practice. Moreover, our
tractographic method (deterministic) only involved corticospinal tract segments mostly arising from the superior part
of the precentral gyrus. Fibers arising from the lateral and

72 PEDIATRIC NEUROLOGY Vol. 43 No. 1

medial precentral regions were not visualized. This limitation was based on the presence of a large corona radiata
and corpus callosum in the lateral and medial aspects of
the corticospinal tract, acting as a huge diffusion barrier impeding fiber propagation. Complex multiple-fiber model
tractographic methods may overcome this limitation, but
these methods are still in developmental stages. Furthermore, in many disease conditions, functionally active axons
often traverse the edematous and gliotic tissue regions, and
these axons may be difficult to isolate even with the most
robust imaging or tractographic techniques. Therefore, for
present clinical use, tractography must be applied with
some caution. Nevertheless, in selected cases, it can provide
important clinical information that affects patient management.

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