Two types of ipsilateral reorganization in congenital hemiparesis: A TMS and fMRI study

Abstract

Reorganization after early brain injuries is not only determined by the maturational stage of the CNS at the time of the insult (timing), but also by the structural properties, location and extent of the lesion. This study addresses the impact of different lesion extents on the type of reorganization induced in a cohort of patients with lesions of uniform structure and location (unilateral periventricular defects) and similar timing (early third trimester of pregnancy). Twelve young adult patients with congenital hemiparesis and 10 age-matched controls were studied. The severity of structural damage to hand motor projections of the cortico-spinal tract was assessed on semi-coronal MRI reconstructions along anatomical landmarks of cortico-spinal tract somatotopy. The functional integrity of these crossed cortico-spinal projections in the affected hemisphere, as well as the presence of any abnormal ipsilateral projections to the paretic hand, was examined by transcranial magnetic stimulation (TMS). Cortical activation during simple voluntary hand movements was studied by functional MRI (fMRI). Patients with small lesions (SL; n = 4) and only mild hand motor impairment possessed intact crossed cortico-spinal projections to the paretic hand, whereas no motor response could be elicited by TMS of the affected hemisphere in those with large lesions (LL; n = 6) and more severe hand motor impairment. Evidence for compensatory recruitment of the unaffected hemisphere was found in both subgroups. In the SL group, fMRI demonstrated ipsilateral activation of premotor areas, without any abnormal projections to the paretic hand originating from these sites. In the LL group, such abnormal ipsilateral projections to the paretic hand were indeed found, and fMRI confirmed cortical activation of an abnormal ipsilateral hand motor representation in the primary sensorimotor region of the unaffected hemisphere. Two patients with intermediate-sized lesions presented combined features of both groups (SL, LL). In conclusion, this study provides evidence that the type of cortico-spinal reorganization depends on the extent of the brain lesion. We propose that involvement of the ipsilateral hemisphere can be (i) of the premotor type, i.e. without ipsilateral motor projections but with significant activation of ipsilateral premotor areas, or (ii) of the primary motor type, i.e. with abnormal ipsilateral cortico-spinal projections to the paretic hand.

Transcranial magnetic stimulation in children

“…When used in conjunction with each other, TMS, cross-correlation analysis, and distal long-latency reflexes help to elucidate the origin of the projections by which the contra-lesional hemisphere participates in the motor control of paretic hand muscles. Thus, TMS-evoked ipsilateral projections which appear to originate from branched pyramidal tract neurons in the primary motor cortex of the contra-lesional hemisphere are associated with prominent mirror movements while those projections which appear to arise from areas other than the primary motor cortex are not associated with mirror movements (Carr et al, 1993;Eyre et al, 2001;Staudt et al, 2002).…”

“…This iMEP indicates the presence of an ipsilateral corticofugal motor projection that may be the means by which the motor cortex controls ipsilateral movements in healthy subjects (Ziemann et al, 1999). It may also mediate the enhanced participation of the less affected hemisphere after injury to the developing brain (see below) (Carr et al, 1993;Staudt et al, 2002). It is possible to identify different types of TMSevoked ipsilateral projections by comparing the characteristics of the iMEP with those of the contralateral MEP.…”

“…It is possible to identify different types of TMSevoked ipsilateral projections by comparing the characteristics of the iMEP with those of the contralateral MEP. Cross-correlation analysis of electromyographic (EMG) activity or, in distal muscles, the long latency reflex, can provide information regarding the origin of the ipsilateral projections (Carr et al, 1993;Eyre et al, 2001;Mayston et al, 1997;Staudt et al, 2002).…”

“…The presence of these mirror movements suggests that the contralesional hemisphere plays an important role in the motor control of the paretic hand. Neurophysiologic tools, including TMS, have shown that there may be enhanced participation of the contra-lesional hemisphere in motor control of the paretic hand in the absence of prominent mirror movements (Carr et al, 1993;Eyre et al, 2001;Staudt et al, 2002). When used in conjunction with each other, TMS, cross-correlation analysis, and distal long-latency reflexes help to elucidate the origin of the projections by which the contra-lesional hemisphere participates in the motor control of paretic hand muscles.…”

Prolonged coexistence of transient and permanent circuitry elements in the developing cerebral cortex of fetuses and preterm infants

“…It should be noted that the rearrangement of cortical pathways and its role in cortical plasticity have been well documented in experiments on fetal monkeys 51 and is consistent with structural plasticity of efferent cortical pathways in humans. 52 In preterm infants, major determinants of structural reorganization and plasticity of cortical connections after periventricular lesions are specific periventricular arrangement and sequential growth of subcortical afferents, cortical efferents, and corticocortical fibres, as well as the developmentally regulated expression of extracellular matrix growth substrates and axonal guidance molecules. The disturbance in the distribution of the extracellular matrix and axonal guidance molecules within periventricular crossroads of growing pathways and the 'waiting' compartment of the subplate zone may be a hitherto neglected pathogenetic mechanism in the damage of the fetal white matter after periventricular lesions.…”