[Show abstract][Hide abstract] ABSTRACT: A variety of associated movements have been described in patients with pyramidal tract lesions. We report three patients in whom involuntary stretching of an otherwise plegic arm could be observed during yawning. These patients had radiologically verified lesions at different levels of the pyramidal tract. As yawning and stretching are an automatic behavioural pattern in animals, it is likely that stretches during yawning in man are also an automatic motor pattern, usually inhibited in the presence of an intact corticospinal tract. The physiological function of yawning is unclear at present. Yawning might be the somatomotor manifestation of a particular emotional state characterized by boredom and fatigue. Our observation that movements of an otherwise plegic arm occur in patients with pyramidal tract lesions supports therefore the concept of an emotional motor system which has an independent input to motoneurones in the brain stem and the spinal cord.
European Journal of Neurology 10/2003; 10(5):495-9. DOI:10.1046/j.1468-1331.2003.00599.x · 4.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Keratan sulphate proteoglycan (KSPG) is a developmentally regulated barrier molecule, directing axonal growth during central nervous system (CNS) formation. The possible re-expression and functional significance of KSPG in preventing axon regeneration following spinal cord injury (SCI) is poorly understood. In the present investigation, the spatio-temporal expression of KSPG was studied following experimental SCI. There was no indication of sparing of axons at the lesion epicentre following severe compression injury. By 7 days post operation (p.o.) a diffuse increase of KSPG immunoreactivity (KSPG-IR) was observed in the parenchyma surrounding the lesion. This was followed by a delayed (21-28 days p.o.) and largely heterogeneous increase of KSPG-IR in the lesion epicentre, which revealed both cellular and extracellular matrix-like distribution patterns. Although no re-growth of anterogradely labelled corticospinal axons was observed, many 200-kDa neurofilament (NF)-positive axons could be detected growing into the connective tissue scar. This phase of spontaneous axonal re-growth was closely associated with a framework of glial cells (including Schwann cells from damaged local spinal nerve roots) that had migrated into the lesion site. The spontaneous nerve fibre re-growth could be detected in both KSPG-rich and KSPG-poor territories. The present data suggest that the lesion-induced up-regulation of KSPG-IR may have contributed to the lack of corticospinal axon re-growth. However, the lack of any direct spatio-temporal correlation between the distribution of raised KSPG-IR and spontaneous NF-positive axonal regeneration suggests that at least some populations of axons can resist the putative inhibitory effects of this extracellular matrix molecule.
[Show abstract][Hide abstract] ABSTRACT: Acute hemorrhagic leukoencephalomyelitis is considered to be a rare autoimmune disorder. The present case, a 34-year-old male, developed non-specific symptoms 3 weeks after surgical removal of his meniscus and following an inconspicuous infection of the upper respiratory tract. The spinal cord was the first to be affected, followed by symptoms of headache, nausea and fever which reached 39.4 degrees C. Autopsy revealed acute hemorrhagic leukoencephalomyelitis with marked involvement of the spinal cord. Diagnosis was established by histopathological examination of the brain and spinal cord. This is the first description of the onset of this disease in the spinal cord.
[Show abstract][Hide abstract] ABSTRACT: Zusammenfassung Ausgeprägte Rückenmarktraumen führen regelmäßig zu einem persistierenden Querschnittsyndrom mit entsprechender lebenslanger Behinderung. Ursache ist eine funktionell unzureichende Regeneration durchtrennter Nervenfasern im zentralen Nervensystem. In den vergangenen 20 Jahren konnten eine Reihe zellulärer und molekularer Mechanismen der abortiven Nervenregeneration und der komplexen Reorganisation nach Rückenmarktrauma tierexperimentell identifiziert werden. Auf der Grundlage dieser Erkenntnisse konnten im Rahmen zahlreicher experimenteller Therapiestrategien partielle funktionelle Restitutionen erzielt werden. Eine klinische Anwendung dieser Behandlungskonzepte bei querschnittgelähmten Patienten ist jedoch noch nicht absehbar. Die folgende Übersicht fasst die wichtigsten neurobiologischen Aspekte der Regeneration nach Rückenmarktrauma zusammen und skizziert die Prinzipien der experimentellen Behandlungsstrategien. Abstract In recent years, our neurobiological knowledge of the various cellular mechanisms that mediate successful peripheral nerve regeneration, and also of those that prevent repair of damaged nerve fibre pathways following traumatic injury to the central nervous system (CNS), has become more precise. On the basis of this knowledge, a range of experimental therapies for promoting axonal regeneration and functional recovery after spinal cord injury have been developed in animal models. Such intervention strategies focus on the molecular inactivation of glial-associated growth-inhibitory factors and on the application of trophic molecules and cellular substrates that enhance the postlesional regenerative capacity of intrinsic CNS neurons. At present, these experimental therapies cannot be applied in the clinical situation for the treatment of spinal cord-injured patients. This overview briefly summarizes current progress in the neurobiology of spinal cord trauma.
Trauma und Berufskrankheit 01/2002; 4. DOI:10.1007/s10039-001-0529-z
[Show abstract][Hide abstract] ABSTRACT: This paper presents a system for computer-assisted quantification of axo-somatic boutons at motoneuron cell-surface membranes. Different immunohistochemical stains can be used to prepare tissue of the spinal cord. Based on micrographs displaying single neurons, a finite element balloon model has been applied to determine the exact location of the cell membrane. A synaptic profile is extracted next to the cell membrane and normalized with reference to the intracellular brightness. Furthermore, a manually selected reference cell is used to normalize settings of the microscope as well as variations in histochemical processing for each stain. Thereafter, staining, homogeneity, and allocation of boutons are determined automatically from the synaptic profiles. The system is evaluated by applying the coefficient of variation (Cv) to repeated measurements of a quantity. Based on 1856 motoneuronal images acquired from four animals with three stains, 93% of the images are analyzed correctly. The others were rejected, based on process protocols. Using only rabbit anti-synaptophysin as primary antibody, the correctness increases above 96%. Cv values are below 3%, 5%, and 6% for all measures with respect to stochastic optimization, cell positioning, and a large range of microscope settings, respectively. A sample size of about 100 is required to validate a significant reduction of staining in motoneurons below a hemi-section (Wilcoxon rank-sum test, alpha = 0.05, beta = 0.9). Our system yields statistically robust results from light micrographs. In future, it is hoped that this system will substitute for the expensive and time-consuming analysis of spinal cord injury at the ultra-structural level, such as by manual interpretation of nonoverlapping electron micrographs.
[Show abstract][Hide abstract] ABSTRACT: Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4-14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1-4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage.
[Show abstract][Hide abstract] ABSTRACT: It is widely accepted that the devastating consequences of spinal cord injury are due to the failure of lesioned CNS axons to regenerate. The current study of the spontaneous tissue repair processes following dorsal hemisection of the adult rat spinal cord demonstrates a phase of rapid and substantial nerve fibre in-growth into the lesion that was derived largely from both rostral and caudal spinal tissues. The response was characterized by increasing numbers of axons traversing the clearly defined interface between the lesion and the adjacent intact spinal cord, beginning by 5 days post operation (p.o.). Having penetrated the lesion, axons became associated with a framework of NGFr-positive non-neuronal cells (Schwann cells and leptomeningeal cells). Surprisingly few of these axons were derived from CGRP- or SP-immunoreactive dorsal root ganglion neurons. At the longest survival time (56 days p.o.), there was a marked shift in the overall orientation of fibres from a largely rostro-caudal to a dorso-ventral axis. Attempts to identify which recognition molecules may be important for these re-organizational processes during attempted tissue repair demonstrated the widespread and intense expression of the cell adhesion molecules (CAM) L1 and N-CAM. Double immunofluorescence suggested that both Schwann cells and leptomeningeal cells contributed to the pattern of CAM expression associated with the cellular framework within the lesion.
European Journal of Neuroscience 08/2000; 12(9):3224 - 3238. DOI:10.1046/j.1460-9568.2000.00228.x · 3.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nerve injury leads to the release of a number of cytokines which have been shown to play an important role in cellular activation after peripheral nerve injury. The members of the signal transducer and activator of transcription (STAT) gene family are the main mediators in the signal transduction pathway of cytokines. After phosphorylation, STAT proteins are transported into the nucleus and exhibit transcriptional activity. Following axotomy in rat regenerating facial and hypoglossal neurons, a transient increase of mRNA for JAK2, JAK3, STAT1, STAT3 and STAT5 was detected using in situ hybridization and semi-quantitative polymerase chain reaction (PCR). Of the investigated STAT molecules, only STAT3 protein was significantly increased. In addition, activation of STAT3 by phosphorylation on position Tyr705 and enhanced nuclear translocation was found within 3 h in neurons and after 1 day in astrocytes. Unexpectedly, STAT3 tyrosine phosphorylation was obvious for more than 3 months. In contrast, none of these changes was found in response to axotomy of non-regenerating Clarke's nucleus neurons, although all the investigated models express c-Jun and growth-associated protein-43 (GAP-43) in response to axonal injury. Increased expression of Janus kinase (JAK) and STAT molecules after peripheral nerve transection suggests changes in the responsiveness of the neurons to signalling molecules. STAT3 as a transcription factor, which is expressed early and is activated persistently until the time of reinnervation, might be involved in the switch from the physiological gene expression to an 'alternative program' activated only after peripheral nerve injury.
European Journal of Neuroscience 05/2000; 12(4):1165-76. DOI:10.1046/j.1460-9568.2000.00005.x · 3.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Capillary telangiectasia is a vascular abnormality primarily of the brainstem. The clinical relevance is unclear as is the association with clearly pathologic findings such as cavernous haemangioma. We report on four cases with capillary telangiectasia proven by follow-up and describe the imaging characteristics. T2 abnormality was only observed in half of the patients as was the presence of a discernable collecting vein. Whereas two cases were incidental findings in neurologically normal persons and one had symptoms clearly attributable to lacunar stroke, one patient may have had symptoms due to the vascular abnormality in the pons.
European Radiology 02/2000; 10(6):945-50. DOI:10.1007/s003300051043 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In recent years, a more precise neurobiological knowledge has been gained concerning the various cellular parameters which mediate successful peripheral nerve regeneration, and also those which prevent repair of damaged nerve fibre pathways following traumatic injury to the the central nervous system (CNS). On this basis, a range of experimental therapeutical approaches for promoting axonal regeneration and functional recovery after spinal cord injury have been developed in animal models. Such intervention strategies focus on the molecular inactivation of glial-associated growth-inhibitory factors and on the application of trophic molecules and cellular substrates which enhance the postlesional regenerative potential of intrinsic CNS neurons. At the present, these experimental therapies cannot be transferred to the clinical situation for the treatment of spinal cord injured patients. This overview briefly summarizes current progress in the neurobiology of spinal cord trauma, the main findings of which are discussed in the light of clinical expectations.
Der Nervenarzt 09/1999; 70(8):702-13. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Monoclonal antibody Py was developed as a useful tool for the identification of large diameter neurons of the adult rat central nervous system [Woodhams et al., J. Neurosci., 9 (1989) 2170-2181]. Here, we present a detailed light-microscopic study of the distribution of Py-immunoreactivity in the developing rat spinal cord. The first cells which demonstrated Py-immunoreactivity were the motoneurons in layer IX of the gray matter at embryonic day 15. These cells, including their axons and dendrites, remained Py-immunoreactive throughout subsequent developmental stages into adulthood and were the most intensely stained cells in the adult rat spinal cord. Other cell populations which became Py-immunoreactive during development were neurons in layers III-VIII, and large-to-medium diameter neurons of the dorsal root ganglion (DRG). Transient Py-immunoreactivity was observed in the distal portions of DRG axons as well as in the ascending fibers in the dorsal funiculus. Py-immunoreactive fibers could be detected in the ventral most part of the dorsal funiculus (corticospinal tract area), even at embryonic ages prior to the arrival of corticospinal fibers. The localization and transient expression of the antigen recognized by the Py-antibody in developing rat spinal cord strongly suggests an important role of this molecule in stabilization and/or plasticity of the neuronal cytoskeleton. The results presented here form the foundation for the use of Py-immunocytochemistry to study well-defined cell populations under a range of experimental and pathological conditions.
Developmental Brain Research 09/1999; 116(1):87-96. DOI:10.1016/S0165-3806(99)00079-6 · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Die klinische Relevanz von vaskulären Fehlbildungen des Hirnstamms soll mit den Befunden der bildgebenden Diagnostik verglichen
Acht Patienten mit vaskulären Fehlbildungen des Hirnstamms wurden magnetresonanztomographisch und teilweise angiographisch
untersucht. Zusätzlich wurden klinischneurologische und elektrophysiologische Untersuchungen durchgeführt.
In jeweils der Hälfte der Fälle wurden die vaskulären Veränderungen des Hirnstamms nach der MRT als venöse Dysplasie (DVA)
und kapilläre Teleangiektasie eingestuft. Begleitende Kavernome wurden bei zwei Patienten gefunden, Übergangsformen einmal.
Als Ursache klinischer Symptome wurden zweimal die Kavernome identifiziert, in einem Fall mit Trigeminusneuralgie die Drainagevene
der DVA. Einmal bestand ein möglicher Zusammenhang zwischen einer kapillären Teleangiektasie und einer latenten Hemiparese.
In den anderen Fällen bestand kein Zusammenhang.
Die erste Methode zur Diagnostik der Gefäßveränderungen des Hirnstamms ist die MRT. Die differentialdiagnostische Abgrenzung
zu pathologischen Hirnstammprozessen ist mittels Dünnschichtuntersuchung bei Kenntnis der Malformation fast immer möglich.
Die klinische Relevanz von Kavernomen ist gesichert, von DVA und kapillärer Teleangiektasie nur in Ausnahmefällen. Es gibt
Übergangsformen zwischen den venösen Veränderungen des Hirnstamms.
To compare the clinical findings in patients with venous anomalies of the brainstem with imaging findings.
Eight patients with venous anomalies of the brainstem were examined with magnetic resonance imaging. In addition, intraarterial
angiographies were obtained in 4 patients with developmental venous anomalies. All patients were evaluated clinically and
The lesions were classified as developmental venous anomalies (DVA) in 4 cases and as capillary telangiectasia in the other
4. Concomitant cavernomas were discovered in 2 patients, borderline lesions in 1. The clinical symptoms were attributable
to the cavernomas in 2 cases, to the draining vein of the DVA in 1 patient. A slight subclinical hemiparesis may have been
caused by a capillary telangiectasia in 1 patient. A causative link between the unspecific complains of the other patients
and a brainstem vascular dysplasia could not be established.
MRI is the imaging method of choice for the imaging of vascular brainstem anomalies. Safe diagnosis is nearly always possible
if the typical imaging appearance of vascular malformations is appreciated. The clinical relevance of cavernomas has long
been established. The clinical significance of DVA and capillary telangiectasia seems to be exceptional.
[Show abstract][Hide abstract] ABSTRACT: The term 'spinal shock' describes the sudden and transient suppression of neural functions below the level of acute spinal cord lesions, usually in the setting of trauma, ischemia, hemorrhage, or inflammatory diseases. The syndrome of spinal shock primarily refers to motor and autonomic disorders (see Young and Woolsey and Guttmann for reviews) mediated by the reduced excitability of spinal neurons following disconnection from descending input. During this state, a flaccid paralysis of skeletal muscles occurs, and all tendon, cutaneous, and autonomic reflexes integrated in the spinal cord below the lesion are abolished or greatly reduced. Following variable periods of time, from several days up to 4 to 6 weeks, spinal reflexes return and eventually become exaggerated as the syndrome of spasticity develops (see Noth for review).
[Show abstract][Hide abstract] ABSTRACT: Seit einigen Jahren präzisieren sich die Kenntnisse über die unterschiedlichen zellbiologischen Mechanismen, die eine funktionell
effiziente Regeneration im peripheren Nervensystem ermöglichen und im zentralen Nervensystem (ZNS) verhindern. Auf dieser
Grundlage wurden erfolgreich experimentelle therapeutische Strategien entwickelt, die auf eine axonale Regenerationsförderung
und eine entsprechende Funktionsrestitution nach Rückenmarkstrauma abzielen. Wichtige Therapieprinzipien sind neben einer
molekularen Inaktivierung wachstumshemmender glialer Faktoren, die Applikation trophischer Substanzen und zellulärer Transplantate
zur Intensivierung des neuronalen Regenerationsprogramms und der axonalen Aussprossung. Noch ist eine klinische Anwendung
dieser Interventionen bei querschnittverletzten Patienten aufgrund konzeptioneller und methodischer Probleme nicht möglich.
In der vorliegenden Übersicht werden die aktuellen Fortschritte auf dem Gebiet der Neurobiologie des Rückenmarkstraumas zusammengefaßt
und vor dem Hintergrund der damit verbundenen klinischen Hoffnungen kritisch diskutiert.
In recent years, a more precise neurobiological knowledge has been gained concerning the various cellular parameters which
mediate successful peripheral nerve regeneration, and also those which prevent repair of damaged nerve fibre pathways following
traumatic injury to the the central nervous system (CNS). On this basis, a range of experimental therapeutical approaches
for promoting axonal regeneration and functional recovery after spinal cord injury have been developed in animal models. Such
intervention strategies focus on the molecular inactivation of glial-associated growth-inhibitory factors and on the application
of trophic molecules and cellular substrates which enhance the postlesional regenerative potential of intrinsic CNS neurons.
At the present, these experimental therapies cannot be transferred to the clinical situation for the treatment of spinal cord
injured patients. This overview briefly summarizes current progress in the neurobiology of spinal cord trauma, the main findings
of which are discussed in the light of clinical expectations.
Der Nervenarzt 07/1999; 70(8):702-713. DOI:10.1007/s001150050499 · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a 72-year-old patient who developed an isolated bilateral hypoglossal nerve paralysis following head trauma with complete recovery after three months. Since the CT scan did not show any fractures of the posterior skull base, we discuss a traction nerve injury as a possible mechanism.
Der Nervenarzt 05/1999; 70(4):357-8. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Up-regulation of the intermediate filament protein, nestin, is a sensitive indicator for the extent of astrocytic activation in regions of CNS close to the point of injury. However, it remains unclear whether activated astrocytes in distant, deafferented CNS territories are also capable of nestin re-expression. Here, we demonstrate that traumatic injury to the dentate gyrus is followed by the rapid but transient expression of nestin in astrocytes located in the stratum lucidum of field CA3. Up-regulation of nestin was first detected at 1 day, was still visible at 14 days, and returned to close to control levels by 28 days post-injury. The present investigation clearly demonstrates the sensitivity of nestin expression as a indicator of astroglial activation in hippocampal target territories undergoing deafferentation-related changes.
[Show abstract][Hide abstract] ABSTRACT: The growth-associated protein GAP-43 (B-50) and the transcription factor C-Jun are involved in regeneration of the injured nervous system. In this study, we investigated the possibility of the induction of GAP-43 and C-Jun in axotomized neurons of Clarke's nucleus (CN) in adult rats, of which a large population undergoes degeneration several weeks after a low thoracic lateral funiculotomy of the spinal cord. In situ hybridization and immunohistochemistry revealed a transient up-regulation of GAP-43 mRNA, C-Jun protein, and its activated, phosphorylated form, peaking around 7 days after injury in preferentially large diameter CN-neurons ipsilateral and caudal to the lesion. Our results document that some populations of axotomized central nervous system neurons, similar to axotomized regenerating neurons of the peripheral nervous system, can up-regulate GAP-43 and C-Jun, even if they are destined to degenerate. This might reflect a transient regenerative capacity, which fails over time.
Neurobiology of Disease 05/1999; 6(2):122-30. DOI:10.1006/nbdi.1998.0231 · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Wir berichten über einen 72jährigen Patienten, bei dem nach einem mittelschweren Schädel-Hirn-Trauma eine bilaterale Hypoglossusparese
ohne sonstige neurologische Defizite auftrat, die sich klinisch innerhalb von 3 Monaten vollständig zurückbildete. Da sich
computertomographisch keine Schädelbasisfraktur im Bereich der hinteren Schädelgrube nachweisen ließ, diskutieren wir eine
beidseitige Zerrung des N. hypoglossus als einen möglichen pathogenetischen Mechanismus.
We report a 72-year-old patient who developed an isolated bilateral hypoglossal nerve paralysis following head trauma with
complete recovery after three months. Since the CT scan did not show any fractures of the posterior skull base, we discuss
a traction nerve injury as a possible mechanism.
Der Nervenarzt 03/1999; 70(4):357-358. DOI:10.1007/s001150050448 · 0.79 Impact Factor