It is well established that the reorganizational potential of the developing human brain is superior to that of the adult brain, but whether age-dependent differences exist already in the prenatal and perinatal period is not known. We have studied sensorimotor reorganization in 34 patients with congenital hemiparesis (age range, 5-27 years), using transcranial magnetic stimulation and functional magnetic resonance imaging during simple hand movements. Underlying pathologies were brain malformations (first and second trimester lesions; n = 10), periventricular brain lesions (early third trimester lesions; n = 12), and middle cerebral artery infarctions (late third trimester lesions; n = 12). Of this cohort, eight patients with malformations and all patients with periventricular lesions have been published previously. In all three groups of pathologies, transcranial magnetic stimulation identified patients in whom the paretic hand was controlled via ipsilateral corticospinal projections from the contralesional hemisphere (n = 16). In these patients, the motor dysfunction of the paretic hand correlated significantly with the timing period of the underlying brain lesion. This demonstrates that the efficacy of reorganization with ipsilateral corticospinal tracts indeed decreases during pregnancy.

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.

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This study investigates whether the type of corticospinal reorganization (identified by transcranial magnetic stimulation) influences the efficacy of constraint-induced movement therapy (CIMT). Nine patients (five males, four females; mean age 16y [SD 6y 5mo], range 11-30y) controlling their paretic hand via ipsilateral corticospinal projections from the contralesional hemisphere and seven patients (three males, four females; mean age 17y [SD 7y], range 10-30y) with preserved crossed corticospinal projections from the affected hemisphere to the paretic hand underwent 12 consecutive days of CIMT. A Wolf motor function test applied before and after CIMT revealed a significant improvement in the quality of upper extremity movements in both groups. Only in patients with preserved crossed projections, however, was this amelioration accompanied by a significant gain in speed, whereas patients with ipsilateral projections tended to show speed reduction. These data, although preliminary, suggest that patients with congenital hemiparesis and ipsilateral corticospinal projections respond differently to CIMT.Constraint-induced movement therapy (CIMT) is a relatively new therapeutic approach focused on ameliorating upper extremity function in hemiparetic patients. It consists of immobilization of the nonparetic hand combined with individualized, intensive repetitive training of the paretic hand. CIMT has its origins in earlier basic research with rhesus monkeys that underwent deafferentation (surgical abolition of sensation by dorsal rhizotomy) of a single forelimb, followed by intensive training of the deafferented limb combined with constraint of the other, intact limb.

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AIM This study aimed to systematically map the severity of mirror movements in both hands in a prospective cohort of children with unilateral cerebral palsy, and to explore the relationship with hand function and brain lesion type.METHOD Seventy-eight children were included (41 males, 37 females; age 9y 4mo, SD 3y 1mo, range 5-15y). Mirror movements were scored during three repetitive tasks following Woods and Teuber criteria. Strength, tone, Melbourne Assessment, Jebsen-Taylor test, and Assisting Hand Assessment were evaluated. Lesions were classified into malformations (n=5), periventricular (n=43), cortico-subcortical (n=22), and postnatally acquired lesions (n=8).RESULTS Significantly more mirror movements were observed in the non-paretic versus the paretic hand (p≤0.003). Higher mirror movement scores in the non-paretic hand significantly correlated with lower distal strength and lower scores on unimanual and bimanual assessments (r=0.29-0.41). In the paretic hand, significant differences were found between lesion types (p=0.03). INTERPRETATIONThe occurrence of mirror movements in the non-paretic hand seems related to hand function while mirror movements in the paretic hand seem more related to the lesion timing, whereby children with earlier lesions present with more mirror movements.Children with unilateral cerebral palsy (CP) often experience difficulties in bimanual coordination which affects daily life activities. Apart from spasticity, muscle weakness, and sensory deficits the occurrence of mirror movements has also been suggested as a possible contributing factor that interferes with bimanual performance. 1 Mirror movements are described as 'involuntary movements of one body part that mirror the voluntary movement of the contralateral homologous body part'.2,3 They are mainly observed in the upper limbs, are symmetrical by nature, and their intensity increases with increasing task complexity or fatigue. 4,5 Physiological mirror movements are present in newborn infants, show a steep decrease between 5 years and 8 years of age, and disappear after 10 years of age. 4,6 These mirror movements are most likely to be caused by incomplete maturation of the corpus callosum and concurrent less effective interhemispheric inhibition. Unilateral tasks thereby invoke activation of bilateral motor cortices. [6][7][8] Further maturation of the transcallosal pathways with age ensures increasing inhibition of the motor cortex ipsilateral to the task hand, thus reducing the occurrence of mirror movements. 7Mirror movements have frequently been described in unilateral CP, 3,8,9 mostly in the non-paretic hand, albeit with large variability. 1,3,[8][9][10] The pathogenesis for their occurrence is not yet fully understood. One potential hypothesis could be the activation of bilateral primary motor cortices due to deficient interhemispheric inhibition caused by the underlying brain lesion. 2,6 Conversely, the persistence of ipsilateral corticospinal projections between the non-lesioned motor cortex and the paretic hand has ...

Right-hemispheric organization of speech has been observed following early left-sided brain lesions involving the language cortex. The authors studied speech organization in hemiparetic patients with pre- and perinatally acquired lesions in the left periventricular white matter using fMRI, and found that right-hemisphere activation correlated with left facial motor tract involvement. This suggests that the impairment of speech motor output from the left hemisphere plays an important role in this alteration of language representation.

The developing human brain can compensate for pre-and perinatally acquired focal lesions more effectively than the adult brain. The mechanisms by which this effective reorganization is achieved vary considerably between different functional systems, reflecting differences in the normal maturation of these systems. In the motor system, descending cortico-spinal motor projections have already reached their spinal target zones at the beginning of the third trimester of pregnancy, with initially bilateral projections from each hemisphere. During normal development, the ipsilateral projections are gradually withdrawn, whereas the contralateral projections persist. When, during this period, a unilateral brain lesion disrupts the cortico-spinal projections of one hemisphere, the ipsilateral projections from the contralesional hemisphere will persist. This allows the contralesional hemisphere to take over motor control over the paretic extremities. Although this mechanism of reorganization is available throughout the pre-and perinatal period, the efficacy of this ipsilateral takeover of motor functions decreases with increasing age at the time of the insult. In the somatosensory system, ascending thalamo-cortical somatosensory projections have not yet reached their cortical target zones at the beginning of the third trimester of pregnancy. Therefore, these projections can still 'react' to brain lesions acquired during this period, and can form 'axonal bypasses' around periventricular white matter lesions to reach their original cortical target areas in the postcentral gyrus. Thus, somatosensory functions can be well preserved even in cases of large periventricular lesions. In contrast, when the postcentral gyrus itself is affected, no signs for reorganization have been observed. Accordingly, somatosensory functions are often poor in these patients. Language functions can be normal even in patients with extensive early left-hemispheric brain lesions. This is achieved by language organization in the right hemisphere, which takes place in brain regions homotopic to the classical left-hemispheric language areas in normal subjects. In patients with periventricular lesions, the degree of right-hemispheric takeover of language functions correlates with the severity of structural damage to facial (and, thus, articulatory) motor projections.