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Ingeborg Krägeloh-Mann

Publications and source records attributed to Ingeborg Krägeloh-Mann.

At least 19 recordsLinked to original sources
PubMed2006

European consensus table 2006 on botulinum toxin for children with cerebral palsy.

An interdisciplinary group of experienced botulinum toxin users and experts in the field of movement disorders was assembled, to develop a consensus on best practice for the treatment of cerebral palsy using a problem-orientated approach to integrate theories and methods. The authors tabulated the supporting evidence to produce a condensed but comprehensive information base, pooling data and experience from nine European countries, 13 institutions and more than 5500 patients. The consensus table summarises the current understanding regarding botulinum toxin treatment options in children with CP.

Anti-Dyskinesia Agents↗
PubMed2006

Global and local development of gray and white matter volume in normal children and adolescents.

Over the last decade, non-invasive, high-resolution magnetic resonance imaging has allowed investigating normal brain development. However, much is still not known in this context, especially with regard to regional differences in brain morphology between genders. We conducted a large-scale study utilizing fully automated analysis-approaches, using high-resolution MR-imaging data from 200 normal children and aimed at providing reference data for future neuroimaging studies. Global and local aspects of normal development of gray and white matter volume were investigated as a function of age and gender while covarying for known nuisance variables. Global developmental patterns were apparent in both gray and white matter, with gray matter decreasing and white matter increasing significantly with age. Gray matter loss was most pronounced in the parietal lobes and least in the cingulate and in posterior temporal regions. White matter volume gains with age were almost uniform, with an accentuation of the pyramidal tract. Gender influences were detectable for both gray and white matter. Voxel-based analyses confirmed significant differences in brain morphology between genders, like a larger amygdala in boys or a larger caudate in girls. We could demonstrate profound influences of both age and gender on normal brain morphology, confirming and extending earlier studies. The knowledge of such influence allows for the consideration of age- and gender-effects in future pediatric neuroimaging studies and advances our understanding of normal and abnormal brain development.

Adolescent↗
PubMed2006

Language lateralization in magnetoencephalography: two tasks to investigate hemispheric dominance.

Hemispheric specialization for language has been the focus of many studies, mainly using functional magnetic resonance imaging. Here, we used magnetoencephalography to investigate hemispheric dominance and time-dependent aspects of cortical language processing. We implemented a verb generation task and a newly designed vowel identification task. Eleven healthy adults were investigated. By using oscillatory magnetoencephalography spectral analysis, significant hemispheric differences were found for both tasks in cerebral language areas. Robust left-lateralization in frontal brain regions was observed with the verb generation task, confirming previous functional magnetic resonance imaging and magnetoencephalography studies. Our new vowel identification task yields significant left-lateralization in posterior language regions, making this silent and child-friendly task a valuable alternative for non-invasive language assessment in difficult populations.

Brain↗
PubMed2006

An fMRI task battery for assessing hemispheric language dominance in children.

Hemispheric dominance for language is an important issue in functional neuroimaging, particularly driven by efforts to overcome the need for the invasive Wada test, which is all the more pressing in children. Here, we aimed at developing new paradigms for functional magnetic resonance imaging (fMRI) for assessment of language dominance that can be used in younger children and allow for performance monitoring. Two new tasks (letter and animal task) were developed and compared to two reference tasks (synonyms and verb generation task) from the literature. Overall, 23 healthy children participated (13 boys, 10 girls, 10.2 +/- 2.5 years, range 6.1-15.3 years). Analysis was done using statistical nonparametrical mapping (SnPM2) on SPM2. Both reference tasks show activation in a number of left-frontal brain regions. The letter task induced a very localized activation in the left hemisphere's Broca's region, while not activating other frontal brain regions. Lateralization (as assessed in different anatomically and functionally defined regions) was consistent and strong. The animal task failed to activate frontal brain regions and was not suitable for assessing language dominance in children in this form. We conclude that while both reference tasks are useful for determining language dominance, they coactivate a number of task-related frontal areas not directly involved in language processing. Additionally, one task is not applicable in young children while the other does not allow performance monitoring. The letter task allows to selectively activate language areas in the dominant hemisphere and is applicable even in the very lowest age group amenable to fMRI investigations while still allowing performance monitoring. It may thus be a useful tool in assessing normal and pathological language organization.

Animals↗
PubMed2006

Visual navigation in adolescents with early periventricular lesions: knowing where, but not getting there.

Visual navigation in familiar and unfamiliar surroundings is an essential ingredient of adaptive daily life behavior. Recent brain imaging work helps to recognize that establishing connectivity between brain regions is of importance for successful navigation. Here, we ask whether the ability to navigate is impaired in adolescents who were born premature and suffer congenital bilateral periventricular brain damage that might affect the pathways interconnecting subcortical structures with cortex. Performance on a set of visual labyrinth tasks was significantly worse in patients with periventricular leukomalacia (PVL) as compared with premature-born controls without lesions and term-born adolescents. The ability for visual navigation inversely relates to the severity of motor disability, leg-dominated bilateral spastic cerebral palsy. This agrees with the view that navigation ability substantially improves with practice and might be compromised in individuals with restrictions in active spatial exploration. Visual navigation is negatively linked to the volumetric extent of lesions over the right parietal and frontal periventricular regions. Whereas impairments of visual processing of point-light biological motion are associated in patients with PVL with bilateral parietal periventricular lesions, navigation ability is specifically linked to the frontal lesions in the right hemisphere. We suggest that more anterior periventricular lesions impair the interrelations between the right hippocampus and cortical areas leading to disintegration of neural networks engaged in visual navigation. For the first time, we show that the severity of right frontal periventricular damage and leg-dominated motor disorders can serve as independent predictors of the visual navigation disability.

Adolescent↗
PubMed2006

Periventricular leukomalacia specifically affects cortical MEG response to biological motion.

OBJECTIVE: Periventricular leukomalacia (PVL) underlies most of the neurological morbidity including visual-perceptual deficits in survivors of premature birth. However, it is unknown whether and, if so, how PVL affects functional cortical activity. METHODS: Here, we assessed changes in the magnetoencephalographic (MEG) response to visual displays depicting human locomotion in adolescents who were born premature with magnetic resonance imaging signs of PVL. RESULTS: Dynamics of MEG activity parallel behavioral deficits. Early (140-170 milliseconds) brain activation over the right parietal cortex was weaker in patients compared with term-born controls. INTERPRETATION: This is the first evidence for stimulus-specific modulation of cortical activity by periventricular lesions providing new insights into the functional pathology of PVL.

Adolescent↗
PubMed2006

Coherent corticomuscular oscillations originate from primary motor cortex: evidence from patients with early brain lesions.

Coherent oscillations of neurons in the primary motor cortex (M1) have been shown to be involved in the corticospinal control of muscle activity. This interaction between M1 and muscle can be measured by the analysis of corticomuscular coherence in the beta-frequency range (beta-CMCoh; 14-30 Hz). Largely based on magnetoencephalographic (MEG) source-modeling data, it is widely assumed that beta-CMCoh reflects direct coupling between M1 and muscle. Deafferentation is capable of modulating beta-CMCoh, however, and therefore the influence of reafferent somatosensory signaling and corresponding neuronal activity in the somatosensory cortex (S1) has been unclear. We present transcranial magnetic stimulation (TMS) and MEG data from three adult patients suffering from congenital hemiparesis due to pre- and perinatally acquired lesions of the pyramidal tract. In these patients, interhemispheric reorganization had resulted in relocation of M1 to the contralesional hemisphere, ipsilateral to the paretic hand, whereas S1 had remained in the lesioned hemisphere. This topographic dichotomy allowed for an unequivocal topographic differentiation of M1 and S1 with MEG (which is not possible if M1 and S1 are directly adjacent within one hemisphere). In all patients, beta-CMCoh originated from the contralesional M1, in accordance with the TMS-evoked motor responses, and in contrast to the somatosensory evoked fields (SEFs) for which the sources (N20m) were localized in S1 of the lesioned hemisphere. These data provide direct evidence for the concept that beta-CMCoh reflects the motorcortical efferent drive from M1 to the spinal motoneuron pool and muscle. No evidence was found for a relevant contribution of neuronal activity in S1 to beta-CMCoh.

Adult↗
PubMed2006

In vitro analysis of multipotent mesenchymal stromal cells as potential cellular therapeutics in neurometabolic diseases in pediatric patients.

Multipotent mesenchymal stromal cells (MSCs) play an important role in stromal support for hematopoietic stem cells, immune modulation, and tissue regeneration. We investigated their potential as cellular therapeutic tools in neurometabolic diseases as a growing number of affected children undergo to bone marrow transplantation. MSCs were isolated from bone marrow aspirates and expanded ex vivo under various culture conditions. MSCs under optimal good medical practice (GMP)-conform culture conditions showed the typical morphology, immunophenotype, and plasticity. Biochemically, the activities of beta-hexosaminidase A, total beta-hexosaminidase, arylsulfatase A (ASA), and beta-galactosidase measured in MSCs were comparable to those in fibroblasts of healthy donors. These four enzymes were interesting for their expression in MSCs, as each of them is defective, respectively, in well-known neurometabolic diseases. We found that MSCs released significant amounts of ASA into the media. In coculture experiments, fibroblasts from patients with metachromatic leukodystrophy, who are deficient for ASA, took up a substantial amount of ASA that was released into the media from MSCs. Mannose-6-phosphate (M6P) inhibited this uptake, which was in accordance with the M6P receptor-mediated uptake of lysosomal enzymes. Taken together, we show that MSCs produce appreciable amounts of lysosomal enzyme activities, making these cells first-choice candidates for providing metabolic correction when given to enzyme-deficient patients. With the example of ASA, it was also shown that an enzyme secreted from MSCs is taken up by enzyme-deficient patient fibroblasts. Given the plasticity of MSCs, these cells represent an interesting add-on option for cellular therapy in children undergoing bone marrow transplantation for lysosomal storage diseases and other neurometabolic diseases.

Bone Marrow Transplantation↗
PubMed2005

Visuospatial deficits in patients with early left-hemispheric lesions and functional reorganization of language: consequence of lesion or reorganization?

INTRODUCTION: Patients with early left-hemispheric lesions have repeatedly been reported to show spared language functions (which are then mediated by the right hemisphere), but exhibit deficits in visuospatial functions. The "crowding hypothesis" explains these deficits by a neuronal scarcity in the right hemisphere for the original right hemispheric functions. An alternative hypothesis suggests direct lesion effects as the sole reason for the visuospatial impairments. The scope of this study was to examine the relations between visuospatial skills and hemispheric preference for language, and between visuospatial skills and cerebral lesion size. METHODS: In a sample of young adults with pre- or perinatally acquired focal lesions of the left hemisphere and unilateral spastic cerebral palsy on the right side, we assessed intelligence and neuropsychological functions in the verbal and visuospatial domains. The behavioural data was correlated with structural MRI information and language preference as assessed using fMRI. RESULTS: Patients with right hemispheric language production were impaired in visuospatial functions, compared not only to normal controls, but also to patients without right hemispheric language preference. Additionally, the degree of right hemispheric language correlated negatively with performance in visuospatial tasks. Lesion size correlated negatively only with performance IQ, which again correlated negatively with motor impairment of the patients and thus does not seem to reflect true cognitive deficits. CONCLUSION: Visuospatial deficits in patients with early left-hemispheric lesions are a consequence of lesion-induced right hemispheric language organization, thus lending further support to the "crowding hypothesis".

Adolescent↗
PubMed2005

Biological motion processing in adolescents with early periventricular brain damage.

The developing brain is traditionally viewed to possess a great compensatory potential. Here we ask whether visual processing of point-light displays depicting human walking is compromised in adolescents who were born premature (between 27 and 33 gestation weeks) and suffer early bilateral damage to periventricular brain regions. Combining psychophysics with volumetric analysis of structural magnetic resonance imaging (MRI), we found that even relatively small periventricular parieto-occipital lesions may result in long-lasting breakdown of visual processing of point-light displays. Analysis of receiver operating characteristic (ROC) curves revealed higher susceptibility of the patients' perceptual system to camouflage of a point-light figure. The lack of difference in sensitivity between former preterms with normal MRI scan and term-born controls indicates that perceptual deficiencies in patients with periventricular leukomalacia (PVL) are not simply due to premature birth. Most importantly, sensitivity in patients even with mild PVL was lower than in both control groups. Display 180 degrees inversion in the image plane, which is known to impair processing of point-light displays, resulted in a substantial reduction of sensitivity so that it no longer differed between the groups. Despite the social and ecological significance of human locomotion, the capacity of the brain to detect biological motion is substantially modulated by periventricular lesions even if they occur very early in life. The findings point to specific restrictions on the brain's spontaneous compensatory plasticity in perceptual development.

Adolescent↗
PubMed2005

Comprehensive language mapping in children, using functional magnetic resonance imaging: what's missing counts.

Noninvasive language mapping is a frequently used application of functional magnetic resonance imaging. The examination of children, however, poses both practical and technical challenges. To this effect, we have developed two new paradigms mainly requiring passive listening to stories from which several key words were removed. Results were compared with a standard active verb-generation task, particularly with regard to hemispheric dominance in frontal brain areas. Fifteen healthy children (seven boys, eight girls, 6-14 years) were scanned. Distinct frontal activation was seen in our new tasks, which was stronger when the tasks were analyzed specifically with regard to the missing words. This confirms the hypothesis that the removal of these words is the key in inducing frontal activation. Frontal lateralization was consistent and strong in all three paradigms. Additionally, receptive language areas are also mapped by our new tasks. We conclude that our two new, child-friendly functional magnetic resonance imaging paradigms are useful in determining hemispheric dominance for language in children too young or too impaired to execute an active task. They also allow robust mapping of receptive language areas.

Adolescent↗
PubMed2005

Ipsilateral corticospinal pathways in congenital hemiparesis on routine magnetic resonance imaging.

Several transcranial magnetic stimulation studies have demonstrated that patients with congenital hemiparesis can possess ipsilateral corticospinal pathways projecting from the contralesional hemisphere to the paretic hand. This study reports on signal abnormalities in the pons (focal areas of hyperintensity on T(2)-weighted magnetic resonance imaging), which were observed in the course of the corticospinal tract of the contralesional hemisphere in 6 of 10 patients with evidence for ipsilateral corticospinal projections on transcranial magnetic stimulation, but in none of 13 patients without such projections. Thus this magnetic resonance imaging abnormality seems to be related to the presence of ipsilateral corticospinal projections from the contralesional hemisphere in congenital hemiparesis.

Adolescent↗
PubMed2005

Development and lateralization of language in the presence of early brain lesions.

There is a broad consensus that language is, in most right-handers and in a substantial part of left-handers, controlled by the left hemisphere. This seems to be, at least in part, genetically determined, as neuroanatomical asymmetries have been observed already prenatally (e.g. a larger left planum temporale). Left hemisphere lesions in adolescents and adults accordingly lead to persistent language deficits. However, this is not the case in lesions acquired prenatally or in early childhood.

Adolescent↗
PubMed2004

Recruitment of periventricular parietal regions in processing cluttered point-light biological motion.

Recent findings point to the existence of a cortical-subcortical parietal network that drives attention-related integration of features and elements. Here we ask whether the functioning of this network might be modulated by early periventricular lesions. To this end, a cohort of adolescents who were born premature with different severity of bilateral periventricular leukomalacia (PVL) and two groups of matched peers (term-born adolescents and former preterms with normal MRI scan) were shown a set of impoverished point-light stimuli. Observers had to detect a point-light walker embedded in an array of distracters mimicking the motion of the target's dots. Patients exhibited higher susceptibility to distortions caused by distracters. In patients only, sensitivity to the point-light figure highly correlates not just with performance on additionally administered feature integration tasks but also on visual attention-demanding IQ tasks. Moreover, the sensitivity index, as well as the values of both IQ factors, decreases with an increase in the volumetric PVL extent in the parieto-occipital region. No relationship was found between these variables and the lesion extent in the frontal or temporal periventricular regions. The data suggest that visual integration and attention in processing cluttered point-light displays are intimately connected. Most importantly, periventricular parieto-occipital regions might be part of a distributed network recruited in deployment of the posterior attentional system. The functioning of this system seems to be vulnerable to bilateral periventricular damage even if it occurs very early in brain development.

Adolescent↗
PubMed2004

Reorganization in congenital hemiparesis acquired at different gestational ages.

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.

Adolescent↗
PubMed2004

Imaging of early brain injury and cortical plasticity.

The human brain undergoes complex organizational changes during development in and ex utero. Pathogenic events affecting the developing brain cause abnormalities or lesions, the patterns of which depend on the stage of brain development. During the first and second trimester, cortical neurogenesis predominantly takes place, characterized by proliferation, migration, and organization of neuronal cells. Brain pathology is characterized by maldevelopments. During the third trimester, growth and differentiation events are predominant, which persist into postnatal life. Disturbances of brain development during this period mainly cause lesions. During the early third trimester, periventricular white matter is especially affected, whereas toward the end of the third trimester, gray matter, either cortical or deep gray matter, appears to be more vulnerable. These patterns of brain maldevelopments or lesions offer excellent models to study mechanisms of organization and reorganization in the developing brain. Evidence for superior brain plasticity is well established for language function after early left-sided lesions. Some evidence exists for higher compensatory potential within in the motor system; maintenance of ipsilateral tracts seems to play a certain, but only incomplete functional role after unilateral lesions in early and mid gestation. The visual system seems to have limited compensatory potential.

Adolescent↗
PubMed2004

Searching for motor functions in dysgenic cortex: a clinical transcranial magnetic stimulation and functional magnetic resonance imaging study.

OBJECT: Cortical motor organization/reorganization was studied in patients with malformation of cortical development (MCD) by applying two noninvasive motor mapping techniques: transcranial magnetic stimulation (TMS) and functional magnetic resonance (fMR) imaging. METHODS: Eight patients (age range 6-22 years), all suffering from congenital hemiparesis of similar severity, were included. Underlying lesions were schizencephalies in four cases, nonschizencephalic polymicrogyria in one, and complex hemispheric malformations in three. All MCDs involved rolandic cortex of the hemisphere contralateral to the hemiparesis. Transcranial magnetic stimulation was used to search, in both hemispheres, for brain regions with corticospinal projections to the paretic hand, and cortical activation during simple repetitive movements of the paretic hand was monitored using fMR imaging. Transcranial magnetic stimulation identified abnormal ipsilateral corticospinal projections from the contralesional hemisphere to the paretic hand in six of eight patients, in all of whom fMR imaging activation of the contralesional hand area was demonstrated during paretic hand movement. In two patients with schizencephaly in this subgroup, additional activation was shown in the affected hemisphere, located in dysgenic cortex lining the schizencephalic clefts but without TMS evidence for corticospinal projections originating from these sites. Corticospinal projections to the paretic hand originating in the MCD were identified in the remaining two patients, one with (nonschizencephalic) polymicrogyria and one with a complex hemispheric malformation. CONCLUSIONS: Malformations of cortical development can show various degrees of participation in motor functions, ranging from corticospinal ("primary") motor control, to putative participation as "nonprimary" motor areas, to absence of evidence for any functional participation. This information can be obtained, noninvasively, using a combination of TMS and fMR imaging.

Adolescent↗