Abstract

Unilateral spastic cerebral palsy, caused by damage to the developing central nervous system, is characterized by motor impairments mainly lateralized to one side of the body, with hand impairments greatly contributing to functional limitations. The integrity of the motor areas and the corticospinal tract (CST) is often compromised. The specific etiology may drastically influence subsequent development of CST pathways. Here we describe the pathophysiology underlying impaired upper extremity function, with particular emphasis on the relation between CST damage and hand function. We also describe the resulting sensory and motor deficits, with an emphasis on studies of precision grip, which highlight impairments in motor execution, sensorimotor integration, motor planning, and bimanual coordination beyond dexterity impairments. We show that the type and extent of early brain damage and/or CST reorganization is highly predictive of the severity of these impairments. We discuss the clinical implications of these findings, including the intriguing possibility that the specific pathophysiology is predictive of treatment outcomes. We suggest that a ‘one‐treatment fits all approach’ may be insufficient, and that future rehabilitation efforts will be best guided by closely relating treatment efficacy with the specific pathophysiology.

Abbreviation

Abbreviation

  • CST
  • Corticospinal tract

What this paper adds

  • Type and extent of early brain damage and/ or CST reorganization is highly predictive of the severity of these upper extremity impairments.
  • Future rehabilitation efforts will be best guided by closely relating treatment efficacy with the specific pathophysiology.

Cerebral palsy (CP) is among the most common pediatric neurological disorders, and is caused by damage to the brain during early development. Unilateral spastic CP, characterized by motor impairments mainly lateralized to one body side, is among the most common subtypes.

Here we review the pathophysiology and mechanisms underlying impaired upper extremity function of unilateral spastic CP. We also relate the specific pathophysiology with the hand impairments, showing clear relations between the type and extent of early brain damage and/or reorganization with impairment severity. Finally we discuss clinical implications, including possible pathophysiological predictors of treatment outcome.

Neural Basis of Unilateral Spastic CP

During typical human development, corticospinal tract (CST) motor pathways from motor areas, notably primary motor cortex, develop in a corticofugal manner, approaching the spinal cord by the 20th week of gestation.1 Subsequently these projections undergo synaptogenesis, with target cells at the spinal‐segmental level. The motor cortices initially develop bilateral projections (i.e. projections to both contralateral and ipsilateral upper extremities). Continued development is characterized by gradual weakening of ipsilateral projections, and strengthening of contralateral projections through synaptic competition,1which is driven by primary motor cortex activity.2 This intricate process is susceptible to prenatal and perinatal brain damage. CST directly innervates hand motoneurons, which provide the capacity for selective upper extremity movement control.3 Thus, damage to this developing system can permanently impair manual dexterity.3

Unilateral spastic CP is typically the result of middle cerebral artery infarct, hemi‐brain atrophy, periventricular lesions, brain malformation, or posthemorrhagic porencephaly,4, 5and the integrity of the motor areas and CST is often compromised.6, 7 The specific etiology may drastically influence subsequent development of CST pathways.1 The severity of hand impairments largely depends on the extent of damage to the CST,7, 8 which can be estimated by using both conventional MRIs and diffusion tensor imaging, by measuring the asymmetry in the cross‐sectional area of the cerebral peduncles through which the CST passes (Fig. 1a),7 or by measuring the fractional anisotropy.8 The asymmetry in the CST innervating each hand (Fig. 1a) is highly correlated to severity of manual dexterity impairments, with higher asymmetry (values below 100) related to greater impairments. The timing of CST damage is also predictive of outcome. Generally speaking, cortical malformation in the first two trimesters results in less severe hand impairments than periventricular lesions early in the third trimester or middle cerebral artery damage later in the third trimester (Fig. 1b).6 Unilateral brain damage occurring during the intrauterine period can attenuate or prevent neuronal activity in CST projections originating in the affected hemisphere, with the result being that the ipsilateral projections are maintained and strengthened during further development, whereas the contralateral projections are partly or completely abolished, especially in individuals with large lesions.1, 6, 9 Even in individuals with small lesions, there can also be a reorganization whereby involvement of the ipsilateral hemisphere can show significant activation of ipsilateral premotor areas.1Generally, individuals who undergo such ipsilateral reorganization have more severely affected hand function (fewer blocks manipulated, Fig. 1c)10 and the persistence of mirror movements. However, that is not to say that this reorganization is dysfunctional; instead, it probably represents functional compensation of the affected hemisphere by the unaffected hemisphere. The extent to which this ipsilateral reorganization is able to compensate for the absent contralateral projects decreases with increasing age at the time of damage.6 It should also be pointed out that CST projections to spinal interneurons, which are also important for transmitting signals from cortex to muscle, are also impaired, further affecting coordination and reflex control.11

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Figure 1

 
(a) Cross‐sectional area of corticospinal tract (CST) estimated with diffusion tensor imaging (DTI) as it passes through the cerebral peduncles at the level of the mammillary bodies. Correlations between manual ability measured using box and blocks and DTI symmetry indexes of the CST in children with unilateral spastic cerebral palsy (filled circles) and controls (open circles). Modified from Bleyenheuft et al.7 (b) Comparison of hand motor dysfunction scores among patients with congenital lesions acquired during the three major timing periods (malformations of cortical development [MCD], first and second trimester of pregnancy; periventricular [PV] lesions, early third trimester of pregnancy; middle cerebral artery [MCA] infarctions, late third trimester of pregnancy). Open circles, patients with preserved crossed corticospinal projections from the affected hemispheres; filled circles, patients with reorganized ipsilateral projections from the contra‐lesional hemispheres; half‐filled circles, patients with both preserved contralateral and reorganized ipsilateral corticospinal projections to the more‐affected hand. Modified from Staudt et al.6 (c) Relation between box and blocks score using the more‐affected hand and the CST motor‐projection pattern to the hand, assessed using transcranial magnetic stimulation (TMS). Modified from Holstrom et al.10

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