Review(Re-)organization of the developing human brain following periventricular white matter lesions
Introduction
The developing central nervous system (CNS) possesses greater capacities of post-lesional compensation than the mature adult brain. This observation is known as the “Kennard principle”, referring to a study of motor outcome following experimental lesions to the motor cortex of monkeys at different ages (Kennard, 1936).
In the human brain, this principle has first been confirmed clinically, concerning both motor and language functions: Gardner et al., 1955 reported that hemispherectomies in patients suffering from a hemiparesis due to a brain lesion acquired before or around birth (“congenital hemiparesis”) seldomly led to a deterioration in hand motor functions, whereas hemispherectomies performed in patients without such pre-existing early lesions (e.g. for brain tumors) abolished active motor functions of the contra-lateral hand almost completely. This difference indicates that, in the patients with congenital hemiparesis, the initial “developmental” lesion had induced a (re-)organization of hand motor functions into the contra-lesional hemisphere, whereas this was no longer possible in the adult brain. In the language domain, the reorganizational potential of the developing brain is even more obvious. Children with pre- or perinatally acquired left-hemispheric lesions can reach normal levels of language abilities even in cases with extensive brain damage (Muter et al., 1997).
With the advent of modern neurophysiological and neuroimaging techniques, it has become possible to study the mechanisms by which this compensation is achieved. In the language domain, patients with early left-hemispheric lesions have repeatedly been reported to show an increased participation of brain areas in the contra-lesional right hemisphere during various language tasks (Booth et al., 1999; Hertz-Pannier et al., 1997; Lehéricy et al., 2000; Liegeois et al., 2004). In the sensorimotor domain, children with extensive unilateral early brain lesions but relatively preserved hand functions consistently showed evidence for ipsilateral, fast-conducting cortico-spinal pathways allowing the contra-lesional hemisphere to exert motor control over the paretic hand (Benecke et al., 1991; Carr et al., 1993; Eyre et al., 2001; Farmer et al., 1991; Jang et al., 2001; Kastrup et al., 2000; Macdonell et al., 1999; Maegaki et al., 1997; Nezu et al., 1999; Nirkko et al., 1997; Shimizu et al., 2000; Staudt et al., 2002a, Staudt et al., 2002b, Staudt et al., 2004a, Staudt et al., 2004b; Thickbroom et al., 2001; Vandermeeren et al., 2003). This type of cortico-spinal reorganization is possible throughout the pre- and perinatal period, and even during the first months of life; it has, however, never been reported for lesions acquired after the age of 2 years (Maegaki et al., 1997), or for adult hemiparetic stroke (Cramer and Bastings, 2000; Turton et al., 1996). Such pathways, however, do not develop in all patients with congenital hemiparesis, and even those in which such pathways had developed still show a broad range of residual hand functions (Staudt et al., 2004a).
This variability in the types and efficacies of CNS (re-)organization following early lesions has been attributed to several factors influencing the process of (re-)organization. Important factors are the extent and location of the lesion, the presence or absence of epilepsy, and the maturational stage of the CNS at the time when the insult occurred (Carr et al., 1993; Maegaki et al., 1997; Müller et al., 1997; Nezu et al., 1999; Thickbroom et al., 2001; Woods and Teuber, 1978). In addition to its likely influence on (re-)organization, the maturational stage of the brain at the time of the insult also determines the type of structural pathology, with a certain but not prominent overlap between the lesion types and the timing periods (Evrard, 2001; Krägeloh-Mann, 2004; Uvebrant, 1988; Volpe, 1995; Fig. 1):
Adverse events occurring during the period of cerebral morphogenesis and neuronal migration (i.e., the 1st and 2nd trimester of pregnancy) typically result in brain malformations, whereas insults acquired beyond this period (i.e., during the 3rd trimester of pregnancy) typically lead to gliotic and/or cystic defects. Such defects can be further subdivided into those affecting the periventricular white matter (e.g., periventricular leukomalacia or periventricular hemorrhages), which originate mainly during the “early” 3rd trimester, and those affecting mostly gray matter structures (e.g., cortico-subcortical infarctions, parasagittal “watershed” lesions, or basal ganglia/thalamic lesions), which originate mainly during the “late” 3rd trimester of pregnancy or perinatally.
For a number of reasons, periventricular lesions are an ideal model for a systematic investigation of the mechanisms of CNS (re-)organization in the developing human brain. First, periventricular lesions are known to arise during a narrowly defined period of brain development of 24–36 weeks of gestation. Second, these lesions do not cause direct cortical damage. This facilitates the data analysis during functional imaging experiments; in addition, absence of cortical damage often also means absence of epilepsy. And third, due to the vulnerability of long descending projections, especially of cortico-spinal motor tracts, in the periventricular white matter, such lesions often imply a well-defined structural damage to these fiber tracts. This facilitates the investigation of relationships between their structural properties and their consequences, both in terms of impairment and of the (re-)organization induced.
The purpose of this article is to review and summarize our previous publications on (re-)organization after periventricular brain lesions, with studies covering the sensorimotor system (Staudt et al., 2000, Staudt et al., 2002a, Staudt et al., 2003, Staudt et al., 2006) as well as the language system (Staudt et al., 2001a, Staudt et al., 2001b, Staudt et al., 2002b), and to compare the obtained results between the two domains.
Note: Whether lesions to a developing CNS induce actual “reorganization” (i.e., changes of an already existing organization), or whether they primarily cause abnormalities of organization can often not be decided. Therefore, the term “reorganization” might often be inappropriate in patients with developmental lesions. In order to express this uncertainty, the term (re-)organization is used.
Section snippets
(Re-)organization in the sensorimotor system
The first topic we addressed in the sensorimotor system was the relationship between the topography (e.g., location and extent) of periventricular lesions and the resulting impairment of motor functions.
We hypothesized that motor impairment in patients with periventricular lesions is caused, at least in part, by compromizing descending cortico-spinal motor tracts in the periventricular white matter (Banker and Larroche, 1962). To test this hypothesis, a technique was developed to quantify the
(Re-)organization of language
The (re-)organization of language functions was studied only in patients with left-sided lesions, since in patients with right-sided lesions, no interhemispheric shift of language functions was to be expected.
During fMRI of speech production (silent generation of word chains), all patients showed an increased participation of their contra-lesional (right) hemisphere, as compared with healthy right-handed controls. This indicated that, despite the absence of structural damage to cortical
Discussion
Unilateral periventricular brain lesions served as a model for the investigation of cortical and cortico-spinal (re-)organization following insults to the developing human brain. Since both sensorimotor and language functions were studied, we can now look at the similarities of and the differences between these two domains, concerning the potential and limitations of (re-)organization after early lesions.
The limitations of (re-)organization after early lesions are quite apparent in the motor
Acknowledgments
This work was supported by the German Research Council (DFG SFB 550—C4) and by the University of Tübingen (Fortüne 584-0, 865-0).
References (43)
- et al.
Functional organization of activation patterns in children: whole brain fMRI imaging during three different cognitive tasks
Progress in Neuropsychopharmacology and Biological Psychiatry
(1999) - et al.
Mapping clinically relevant plasticity after stroke
Neuropharmacology
(2000) - et al.
Multisubject fMRI studies and conjunction analyses
NeuroImage
(1999) - et al.
Combined functional magnetic resonance imaging and transcranial magnetic stimulation evidence of ipsilateral motor pathway with congenital brain disorder: a case report
Archives of Physical Medicine and Rehabiliation
(2001) - et al.
Cortical motor reorganization following early brain damage and hemispherectomy demonstrated by transcranial magnetic stimulation
Clinical Neurophysiology
(2000) - et al.
A longitudinal study of early intellectual development in hemiplegic children
Neuropsychologia
(1997) - et al.
Functional recovery in hemiplegic cerebral palsy: ipsilateral electromyographic responses to focal transcranial magnetic stimulation
Brain Deveopment
(1999) - et al.
Right hemispheric organization of language following early left-sided brain lesions: functional MRI topography
NeuroImage
(2002) - et al.
Contralateral and ipsilateral EMG responses to transcranial magnetic stimulation during recovery of arm and hand function after stroke
Electroencephalography and Clinical Neurophysiology
(1996) - et al.
Functional reorganization of brain in children affected with congenital hemiplegia: fMRI study
NeuroImage
(2003)
Periventricular leukomalacia of infancy
Archives of Neurology
Reorganisation of descending motor pathways in patients after hemispherectomy and severe hemispheric lesions demonstrated by magnetic brain stimulation
Experimental Brain Research
Patterns of central motor reorganization in hemiplegic cerebral palsy
Brain
MRI and clinical characteristics of children with hemiplegic cerebral palsy
Neuropediatrics
Pathophysiology of developmental brain damage
Developmental Neuroscience
Functional corticospinal projections are established prenatally in the human foetus permitting involvement in the development of spinal motor centres
Brain
Evidence of activity-dependent withdrawal of corticospinal projections during human development
Neurology
Plasticity of central motor pathways in children with hemiplegic cerebral palsy
Neurology
Residual function following hemispherectomy for tumour and for infantile hemiplegia
Brain
Noninvasive assessment of language dominance in children and adolescents with functional MRI: a preliminary study
Neurology
Age and other factors in motor recovery from precentral lesions in monkeys
American Journal of Physiology
Cited by (79)
Safety and feasibility of transcranial direct current stimulation stratified by corticospinal organization in children with hemiparesis
2023, European Journal of Paediatric NeurologyDevelopmental Remodelling of the Motor Cortex in Hemiparetic Children With Perinatal Stroke
2020, Pediatric Neurology