Predicting hand function after hemispherotomy: TMS versus fMRI in hemispheric polymicrogyria

Authors

  • Andrea Zsoter,

    1. Department of Pediatric Neurology and Developmental Medicine, Children’s Hospital, University of Tübingen, Tübingen, Germany
    2. Experimental Pediatric Neuroimaging, Children’s Hospital and Department of Neuroradiology, University of Tübingen, Tübingen, Germany
    3. Clinic for Pediatric Neurology and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany
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  • Tom Pieper,

    1. Clinic for Pediatric Neurology and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany
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  • Manfred Kudernatsch,

    1. Clinic for Neurosurgery and Epilepsy Surgery, Schön Klinik Vogtareuth, Germany
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  • Martin Staudt

    1. Department of Pediatric Neurology and Developmental Medicine, Children’s Hospital, University of Tübingen, Tübingen, Germany
    2. Clinic for Pediatric Neurology and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany
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Address correspondence to Andrea Zsoter, Department of Pediatric Neurology and Developmental Medicine, Children’s Hospital, University of Tübingen, Hoppe Seyler Str. 1, 72076 Tübingen Germany. E-mail: andrea.zsoter@med.uni-tuebingen.de

Summary

Patients with hemispheric malformations of cortical development (such as polymicrogyria) often develop medically intractable epilepsies for which hemispherotomy can be an excellent treatment option. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are noninvasive methods used to evaluate the sensorimotor system in adults and children before surgery. Preoperative results of both methods and their predictive values regarding hand function after hemispherotomy are described in four boys with hemispheric polymicrogyria, pharmacoresistent epilepsy, and hemiparesis with preserved grasp function of the paretic hand. TMS showing ipsilateral projections from the contralesional hemisphere but no evidence of crossed corticospinal projections from the lesioned hemisphere correctly predicted preserved postoperative grasp function in all four patients. In contrast, the interpretation of sensorimotor fMRI in patients with congenital hemiparesis is more difficult, as ipsilesional activation can occur as it was the case in three of four patients in the current study. This activation might represent contralaterally preserved primary somatosensory (S1) and not primary motor (M1) representation and is apparently not necessary for the paretic hand to still perform grasp movements.

Hemispheric polymicrogyria (PMG) can cause congenital hemiparesis of variable severity. Frequently, this malformation is also associated with medically refractory epilepsies, and these patients may be excellent candidates for epilepsy surgery, especially disconnecting procedures such as hemispherotomy. Before surgery, the chances for seizure freedom or for relevant seizure reduction as well as the potential risks and functional consequences of the procedure have to be considered. Regarding hemispherotomy, a major concern in patients with residual motor function of the paretic hand is the risk of losing this function. Predicting postoperative motor function is difficult, since both the localization of sensorimotor function within polymicrogyric cortex as well as reorganization into the contralesional hemisphere have been reported (Staudt et al., 2004; Araujo et al., 2006; Gerloff et al., 2006). Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) have been used extensively as noninvasive methods in the evaluation of (re-)organization in patients with hemiparesis (Staudt, 2007). Results of both techniques have been described in case reports before hemispherotomy/functional hemispherectomy (Rutten et al., 2002; Kamida et al., 2003; Sun et al., 2009), but their different predictive validities in this setting have not yet been addressed. Herein we describe the results of both sensorimotor fMRI and TMS in four children with hemispheric polymicrogyria and their predictive values regarding hand function after hemispherotomy.

Patients and Methods

Four boys with hemispheric polymicrogyria, medically refractory epilepsy, and congenital hemiparesis were included; mean age at examination was 6.9 years (range 3–9 years), mean age at epilepsy onset was 3.7 years (range 2 months to 4 years). Note that preoperative findings of patients 1 and 2 have been described previously in Staudt et al. (2001) and Staudt et al. (2004). All four patients showed preserved grasp function of the paretic hand preoperatively, with significant mirror movements during unimanual movement of either hand. Because of the hemispheric pathologies and widespread epileptogenic zones, hemispherotomy was considered the best treatment option with respect to seizure outcome. Therefore, fMRI (active or passive movement of the paretic hand) and TMS were performed preoperatively to evaluate the functional organization of the sensorimotor system. Written informed consent and approval of the local ethics committee were obtained.

Transcranial magnetic stimulation

Single-pulse TMS was performed with a Magstim 200 Stimulator (Magstim Company Ltd, Whitland, United Kingdom) using a focal 2 × 70 mm figure-eight coil. Motor evoked potentials (MEPs) from both first dorsal interosseal (FDI) muscles were recorded simultaneously (Viking IV D EMG unit; Nicolet Biomedical Instruments, Madison, WI, U.S.A.) with muscle precontraction. A broad area of the presumptive motor cortex of each hemisphere was stimulated separately with increasing stimulator output up to 100% if no potentials could be evoked at lower output values.

Functional magnetic resonance imaging

Functional images were acquired on 1.5 T magnetic resonance scanners (Siemens Medical Systems, Erlangen, Germany) as described previously (Staudt et al., 2004), with slight modifications (patient 1: 2 × 2 × 5 mm3 voxel size, 27 slices, 40 scans; patients 2–4: 3 × 3 × 5 mm3 voxel size, 28 slices, 80 scans). High-resolution structural images were acquired with the patients under general anesthesia on a 1.5 T scanner (Siemens Medical Systems) before the functional diagnostics. fMRI paradigms were implemented in block designs (block length 40 s [patient 1] or 30 s [patients 2–4]) of alternating periods of silent rest and activation; activation was either active (squeezing the examiner’s index finger with the paretic hand) or passive (opening and closing of the paretic hand by the examiner), according to the patient’s cooperation. Sessions were repeated at least once to evaluate reproducibility of activation.

fMRI data processing

Preprocessing and statistical analysis were performed with the SPM8 software package (Welcome Trust Centre for NeuroImaging, University College London, United Kingdom) running on MATLAB (The MathWorks, Natick, MA, U.S.A.). It included motion correction, coregistration of functional and structural images, and smoothing the functional data with a Gaussian filter of 9 mm. Single-subject analyses were done for each session, employing a boxcar reference function convolved with the hemodynamic response, and appropriate contrasts (active > rest) resulted in statistical T-maps. T-Maps were overlaid on the individual T1-weighted image. Activation was assessed at different thresholds, especially with respect to lower thresholds, in order to increase sensitivity for contralateral activation.

Results

TMS of the lesioned hemisphere did not elicit MEPs in any patient. TMS of the contralesional hemisphere elicited bilateral MEPs with short latencies in all four patients (Table 1).

Table 1.   TMS and fMRI results
Patient no.fMRI task and activationTMS (latency, stimulator output)
Affected hemisphereContralesional hemisphere
Paretic and nonparetic hand (%)Nonparetic hand (%)Paretic hand (%)
  1. MEP, motor evoked potential; TMS, transcranial magnetic stimulation.

  2. aExact latency measure was not possible due to young age (3 years) and poor compliance of the patient. However, there was one clear bilateral evoked potential at 100% stimulator output, and superimposing and modulation of several curves supported this result.

1Paretic hand (active): ipsilateral rolandicNo MEP (100)18.9 ms (80)18.1 ms (80)
2Paretic hand (active): bilateral rolandicNo MEP (100)14.1 ms (70)14.2 ms (70)
3Paretic hand (active): bilateral rolandicNo MEP (100)16.2 ms (100)16.0 ms (100)
4Paretic hand (passive): contralateral rolandicNo MEP (100)15–18 msa (100)15–18 msa (100)

fMRI during active movement of the paretic hand showed activation of the ipsilateral (=contralesional) rolandic cortex in one of three patients and bilateral activation in two of three patients. In the youngest patient, who was not cooperative enough, passive movement of the paretic hand was performed and a purely contralateral (=lesional) activation was elicited (Table 1). Representative axial MRI slices demonstrating hemispheric polymicrogyria and suprathreshold fMRI activation of all four patients are displayed in Fig. 1; the hemisphere from which bilateral MEPs could be elicited is labeled with a TMS-coil symbol.

Figure 1.


Representative axial slices of structural MRI (T1-weighted) and results of functional MRI (activation overlaid in red (T ≥ 3); lower row) for all four patients of the study. Suprathreshold activation during active movement of the paretic hand was ipsilateral in patient 1 and bilateral in patients 2 and 3. Patient 4 showed purely contralateral activation during passive movement of the paretic hand. TMS-coil symbols mark the hemispheres from which bilateral MEPs could be elicited; PHA, paretic hand, active; PHP, paretic hand, passive.

After hemispherotomy, all patients showed a preserved grasp function in their paretic hands. Mirror movements did not change. All patients became seizure free (follow up 2–6 years).

Discussion

TMS with bilateral short-latency MEPs from the contralesional and no MEPs from the lesioned hemisphere predicted favorable hand motor outcome (preserved grasp function) after hemispherotomy in all four patients with hemispheric polymicrogyrias. These results are in line with those in previous TMS reports of altogether four patients with unilateral congenital brain lesions who also received hemispherotomies without losing distal muscle strength in the paretic hand (Rutten et al., 2002; Sun et al., 2009): in all four patients, TMS of the lesional hemisphere elicited no MEPs, and TMS of the contralesional hemisphere elicited bilateral MEPs of similar short latency. fMRI results in our patients, in contrast, are more difficult to interpret. Purely ipsilateral (=contralesional) activation, the desirable result regarding planned hemispherotomy, was seen in only one patient, whereas activation of the malformed hemisphere occurred in three patients. Despite the activation in the lesioned hemisphere in these patients, active hand function was preserved postoperatively.

This observation could be explained by the concept of hemispheric dissociations between ipsilateral motor (M1) and contralateral somatosensory (S1) representations. This phenomenon was described recently in patients with congenital hemiparesis due to prenatally acquired unilateral periventricular brain lesions (Staudt et al., 2006). These patients also showed bilateral MEPs after TMS of the contralesional hemisphere; fMRI activation patterns were similar with exclusively contralateral activation during passive and bilateral activation during active movement of the paretic hand.

This hemispheric dissociation between M1 and S1 is most likely a consequence of developmental differences between corticospinal and thalamocortical pathways (Eyre, 2007; Staudt, 2007). In the second trimester of gestation, outgrowing thalamocortical pathways have not yet reached the cortex. Therefore, they can bypass a periventricular lesion occurring during that time, and reach primary somatosensory cortex in its typical location (Staudt et al., 2006). At the same time, corticospinal pathways have already descended bilaterally from each primary motor cortex to the spinal cord. During normal development, most ipsilateral projections are withdrawn during the first 2 years of life. In case of a unilateral lesion, however, ipsilateral corticospinal projections from the contralesional hemisphere can persist (Eyre, 2007).

This hemispheric dissociation between M1 and S1 can also occur in patients with “malfunctioning lesions” such as polymicrogyria. In a patient with schizencephalic polymicrogyria (Patient 2 in Gerloff et al., 2006), ipsilesional somatosensory fields on magnetoencephalography demonstrated localization of S1 within the polymicrogyria, and TMS verified contralesional (=ipsilateral) M1 of the paretic hand.

In the four patients of the current study, we demonstrate that a resection or disconnection of such an isolated S1 is possible without the loss of grasp function. Because of the retrospective character of the study, however, detailed data regarding preoperative and postoperative sensorimotor function of the paretic hand were not available; in addition there was no detailed data available on quantified motor assessment.

The small number of patients is one limitation of this study. Furthermore, because we report only on patients with polymicrogyria, we do not know yet whether our results can be extrapolated to different pathologies. Finally, our patient cohort does not include any patients with contralateral MEPs who lost hand motor function after hemispherotomy. Therefore, up to now, we can only speculate that these would lose motor function after disconnection of the corticospinal tract. Therefore, future work is needed to evaluate patients with different etiologies and patients without ipsilateral corticospinal tracts to the paretic hand, who nevertheless receive hemispherotomies due to catastrophic epilepsies.

To conclude, TMS and fMRI are important tools in the evaluation of sensorimotor function before hemispherotomy. In all four patients, TMS showing bilateral short-latency MEPs from the contralesional hemisphere and no MEPs from the lesioned hemisphere correctly predicted favorable hand motor outcome. Ipsilesional fMRI activation in these patients does not exclude the possibility of performing hemispherotomy with the preservation of the existing (e.g., grasp) function of the paretic hand.

Disclosure

Andrea Zsoter, Tom Pieper, and Manfred Kudernatsch report no disclosures. Martin Staudt received funding during the study period by the University of Tuebingen (Fortuene 584-0 and 865-0) and the Deutsche Forschungsgemeinschaft (SFB 550-C4). We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

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