Spinal neurinomas and meningiomas in children

Summary The literature on spinal neurinomas (N) and meningiomas (M) in children is reviewed, and five personal cases of N are added (one in the context of Recklinghausen's disease). The cases of N totalled 151, and of M 69, accounting respectively for 10.9% and 4.3% of childhood spinal tumours and 2.6% and 1.3% of spinal N and M of all ages. Sixty-one cases of N (16 in the context of Recklinghausen's disease) and 26 cases of M (5 in the context of Recklinghausen's disease) are analyzed in detail. N occurs chiefly between ages 9 and 15 years, the sex ratio is 3 2, all levels of the spinal canal are equally affected, and extradural N or conditions with an extradural component (48%) are more frequent than in adults (26.9%). M occurs chiefly between 12 and 15 years, the sex ratio is 3 2, the prevalence of the thoracic segment (47.8%) is less marked than in adults (81%), and the frequency of the extradural site (10.6%) is close to the sum of the extradural and dumb-bell lesions in adults (11.1%). In children vertebral signs,i.e., spinal rigidity and tenderness, and spasm of paravertebral muscles, are more intense, earlier, and more frequent than in adults, and the clinical history is shorter. The chances of recovery from neurological deficits are greater, as are those of malignant degeneration.     

Altered Topography in the Geniculo-cortical Projection of the Golden Hamster Following Neonatal Monocular Enucleation

The consequence of neonatal eye removal on the adult organization of the geniculo-cortical pathway was studied anatomically in hamsters. Separate discrete injections of rhodamine- and green-fluorescent latex microspheres were made into the primary visual cortex of adult hamsters. The distribution of labelling in the dorsal lateral geniculate nucleus (dLGN) of normal animals was compared with that seen in animals monocularly enucleated at birth. In the normal animals, as expected, the projection has a precise topographic order. This is also true of the projection contralateral to the remaining eye in the enucleated animals. However, on the side ipsilateral to the remaining eye, the visual cortex appears to receive two convergent projections from the deafferented dLGN, one mirroring the other. A single injection made in very lateral cortex labels cells in two discrete regions of the dLGN. As the injection is made progressively more medial, the two patches of labelled cells converge. Eventually, the two patches are no longer discrete so that injections into central area 17 produce just one, extended patch of labelling. These results suggest that the altered retinal input to the dLGN may affect the subsequent development of ordered geniculo-cortical projections.     

Intraoperative ultrasonography of extramedullary spinal tumours

Summary Intraoperative spinal sonography (IOSS) was performed in 28 patients with extramedullary spinal tumours. Images were obtained of 31 tumours, because 2 patients had multiple tumours. There were 17 neurilemmomas, 9 meningiomas and 2 dermoid, cysts. All tumours appeared well-defined and highly echogenic. There was no difficulty differentiating extramedullary spinal tumours from intramedullary nasses excepting case, a big neurilemmoma at the conus medullaris. All images were assessed with reference to the surface of the lesions, the existence of cysts, and movement. Neurilemmomas had smooth surfaces, some cysts, and exhibited a floating movement. Meningiomas had irregular surfaces, were more highly echogenic than neurilemmomas, and adhered tightly to the dura mater. However, some neurilemmomas and meningiomas did not have these, and it was not always possible to differentiate them. Although, IOSS has limitations of resolution, it gave useful information about the size of the tumours, the degree of displacement of the spinal cord, and even about the type of tumour in some cases. It was extremely helpful to the surgeon.     

Cell Type-specific Effects of the Neural Adhesion Molecules L1 and N-CAM on Diverse Second Messenger Systems

We have previously shown that the neural adhesion molecules L1 and N-CAM influence second messenger systems when triggered with specific antibodies at the surface of the phaeochromocytoma PC12 cell line (Schuch et al., Neuron, 3, 13 - 20, 1989). To determine whether the two molecules are linked to the same intracellular signalling cascades, independent of the cell type expressing them, or whether different neural cell types respond with different signal transduction mechanisms, we have investigated the effects of antibodies to L1 and N-CAM, and the isolated molecules themselves, on second messenger systems in different neural cell types. We have investigated cultures of cerebellar and dorsal root ganglion neurons and transformed Schwann cells and related these results to those obtained with the PC12 cell line. Here we show that addition of L1 and N-CAM antibodies and the isolated molecules themselves elicit cell type-specific responses that can be modulated by the substrate on which the cells are maintained. Depending on the cell type, cells respond to the triggering of L1 and N-CAM with antibodies, or addition of the purified molecules, by either up-regulation or down-regulation of inositol phosphate turnover, by a rise in intracellular Ca2+ levels dependent on or independent of the opening of voltage-gated Ca2+ channels, or by an increase or decrease in intracellular pH. Moreover, cerebellar neurons expressing N-CAM respond to addition N-CAM, but not to N-CAM antibodies, in contrast to the other neural cell types studied, which respond to both triggers. Furthermore, cerebellar neurons were the only cells to show a rise in cAMP levels in response to any of the ligands tested. This stimulation of cAMP production by L1 antibodies depended on the cross-linking of L1 molecules at the cell surface, whereas the other responses did not depend on clustering of L1. Simultaneous addition of L1 and N-CAM antibodies either elicited an additive or more than additive effect on the intracellular responses which, for cerebellar neurons, depends on the substrate on which the cells are maintained. These observations indicate that L1 and N-CAM or their antibodies activate cell type-specific intracellular signalling systems and that the two molecules can act interdependently or independently of each other.     

Developmentally Regulated Expression of HDNF/NT-3 mRNA in Rat Spinal Cord Motoneurons and Expression of BDNF mRNA in Embryonic Dorsal Root Ganglion

Northern blot analysis was used to demonstrate high levels of hippocampus-derived neurotrophic factor/neurotrophin-3 (HDNF/NT-3) mRNA in the embryonic day (E) 13 - 14 and 15 - 16 spinal cord. The level decreased at E18 - 19 and remained the same until postnatal day (P) 1, after which it decreased further to a level below the detection limit in the adult. In situ hybridization revealed that the NT-3 mRNA detected in the developing spinal cord was derived from motoneurons and the decrease seen at E18 - 19 was caused by a reduction in the number of motoneurons expressing NT-3 mRNA. The distribution of NT-3 mRNA-expressing cells in the E15 spinal cord was very similar to the distribution of cells expressing choline acetyltransferase or nerve growth factor receptor (NGFR) mRNA. Moreover, a striking similarity between the developmentally regulated expression of NT-3 and NGFR mRNA was noted in spinal cord motoneurons. A subpopulation of all neurons in the dorsal root ganglia expressed brain-derived neurotrophic factor (BDNF) mRNA from E13, the earliest time examined, to adulthood. These results are consistent with a trophic role of NT-3 for proprioceptive sensory neurons innervating the ventral horn, and imply a local action of BDNF for developing sensory neurons within the dorsal root ganglia.     

The rotational component in the dynamics of the C2–3 spinal segment

Summary The technique of the PA axial projection of the arches of the upper cervical vertebrae into the occipital foramen and the normal findings, are described. The influence of maximum forced anteflexion at the craniocervical junction and rotation of the head on the relations of atlas and axis is demonstrated. It seems that in this position rotation at atlasaxis level is restricted and partly transmitted to the C_2–3 segment. Thus, selective clinical examination of the rotational component of the dynamics at C_2–3 can be achieved and the pathological restrictions of movement can be assessed.     

Spastic paraplegia associated with addison's disease: Adult variant of adreno-leukodystrophy

Summary Clinical and pathological features of an adult variant of adreno-leukodystrophy (ALD) are presented. A male with clinical and laboratory signs of Addison's disease (AD) developed at age 22 a slowly progressing paraplegia with slight sensory deficits in both legs and bladder and sphincter dysfunctions; he died at age 24 in an AD crisis. Autopsy revealed hyperplasia of lymphatic tissues, lymphocytic infiltrates in various organs including the CNS and adrenocortical atrophy with prominence of large ballooned, sometimes bizarre and occasionally striated cortical cells. CNS lesions consisted in incomplete demyelination of long tracts of brain stem and spinal cord with accentuation in the pyramical tracts; in these areas, perivascular cuffs of epitheloid histiocytic cells contained a strongly PAS-positive non-sudanophilic material. Electron microscopy demonstrated massive storage of leaflet structures in perivascular histiocytes identical to the lamellar profiles previously described as specific for ALD. Some leaflets were found in close contact with compact lamellar arrays and with an electron-dense fingerprint material within astrocytes.In our case, the spastic paraplegia-AD syndrome which has been described previously in several clinical observations could be neuropathologically classified as an adult variant of ALD. Several differences to classical ALD occurring in young boys are stressed: the predominance of the endocrine disorder probably accounting for some of the perivascular lymphocytic infiltrates within the CNS; the absence of both clinical and pathological signs of diffuse cerebral involvement and the peculiar topistic pattern of CNS lesions and the very slow evolution of neurological signs paralleled by the absence of active sudanophilic demyelinating lesions. The possible mechanism of demyelination and the nature of the suggested metabolic defect in ALD are discussed. The ultrastructurally prominent leaflet structures may originate from myelin remnants, thus relating ALD to pathological storage of a myelin degradation product.

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Zusammenfassung Klinische und pathologische Befunde einer adulten Form der Adrenoleukodystrophie (ALD) werden dargestellt. Ein Patient mit klinischem Bild und Laboratoriumsbefunden der Addison-Krankheit (AD) entwickelte im Alter von 22 Jahren eine sehr langsam zunehmende Paraspastik mit geringer Hypaesthesie in beiden Beinen und Blasenund Mastdarmstörungen; er verstarb im Alter von 24 Jahren in einer AD-Krise. Bei der Autopsie fanden sich eine Hyperplasie des lymphatischen Apparats und lymphocytäre Infiltrate in verschiedenen Organen einschließlich des ZNS; beide Nebennieren waren atroph mit Hervortreten großer ballonierter, etwas bizarrer Rindenzellen mit gelegentlicher cytoplasmatischer Streifung. Im ZNS fanden sich pseudosystematische inkomplette Entmarkungen der langen Bahnen in Hirnstamm und Rückenmark mit Betonung der Pyramidenbahn, charakterisiert durch perivasale Manschetten epitheloider histiocytärer Zellen, die ein stark PAS-positives sudannegatives Material enthielten. Elektronenoptisch wurde eine massive Speicherung eines lamellären Materials in perivasalen Histiocyten nachgewiesen, welches mit den als spezifisch für die ALD angesehenen Einschlüssen übereinstimmte. Einige derartige Strukturen zeigten einen engen Zusammenhang mit kompakten Lamellenaggregaten und mit einem elektronendichten fingerprint-Material innerhalb von Astrocyten.In diesem Fall konnte das Paraplegie-AD-Syndrom, welches mehrfach bereits klinisch beschrieben worden war, aufgrund neuropathologischer Befunde als adulte Variante der ALD klassifiziert werden. Die Unterschiede dieser Form zur klassischen ALD, welche üblicherweise Knaben betrifft, werden hervorgehoben: das Überwiegen der endokrinen Symptomatik, was das Auftreten perivasaler Lymphocytensäume im ZNS zum Teil bedingen dürfte; das Fehlen klinischer und pathologischer Hinweise auf diffuse Beteiligung des Großhirns und die spezielle Topik der ZNS-Läsionen und die geringe Progredienz der neurologischen Symptomatik, welche im Einklang mit dem Fehlen florider sudanophiler Entmarkungsvorgänge steht. Der Mechanismus der Entmarkung und die Art der vermuteten metabolischen Störung bei der ALD werden diskutiert. Die elektronenoptisch charakteristischen lamellären Strukturen könnten aus dem Myelinabbau stammen, und damit könnte bei der ALD eine pathologische Speicherung eines Myelinabbauprodukts vorliegen.

     

Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury

Spinal cord injuries (SCI) result in a devastating loss of function and chronic central pain syndromes frequently develop in the majority of these patients. The present study uses a rodent spinal hemisection model of SCI in which mechanical and thermal allodynia develops by 24 days after injury. Post-operative paw withdrawal responses to low threshold and high threshold mechanical stimuli compared to pre-operative responses (4.78, 9.96, and 49.9 mN) were increased and were statistically significant (p<0.05) for both forelimbs and hindlimbs indicating the development of mechanical allodynia. By contrast, post-operatively, the temperature at which paw withdrawal accompanied by paw lick occurred was significantly decreased (p<0.05), indicating the development of thermal allodynia. The intrathecal application of either D-AP5, a competitive NMDA receptor antagonist, or NBQX-disodium salt, a competitive non-NMDA AMPA/kainate receptor antagonist, alleviated the mechanical allodynia and lowered the threshold of response for the high threshold mechanical stimuli in a dose-dependent manner, and these decreases were statistically significant (p<0.05). By contrast, neither the D-AP5 nor the NBQX produced a statistically significant change in the thermal allodynia behavior in either forelimbs or hindlimbs in the hemisected group. No significant changes in locomotion scores, and thus no sedation, were demonstrated by the hemisected group for the doses tested. These data support the potential efficacy of competitive excitatory amino acid receptor antagonists in the treatment of chronic central pain, particularly where input from low threshold mechanical afferents trigger the onset of the painful sensation. Furthermore, these data suggest a role for both NMDA and non-NMDA receptors in the development of plastic changes in the spinal cord that provide the underlying mechanisms for central neuropathic pain.     

Co-induction of HSP70 and heme oxygenase-1 in macrophages and glia after spinal cord contusion in the rat

HSP70 and heme oxygenase-1 (HO-1) are thought to be markers of cell injury and oxidative stress, respectively. We have immunolocalized these proteins in the spinal cord at 1-14 days after contusion. HSP70 and HO-1 were co-induced in glia and macrophages within the injured segment at all time points. This co-induction may reflect complementary functions that serve to protect these cells as they respond to the postcontusional environment.     

Surgical Treatment of Spinal Hemangioblastomas

Summary  Background. The routine use of magnetic resonance imaging (MRI) in recent years for the diagnostic assessment of the spinal column and especially for screening patients with von Hippel-Lindau (vHL) disease has shown that spinal hemangioblastomas (sHBs) are more common than assumed so far. Since most sHBs are thus discovered while they are still asymptomatic, especially in vHL disease, the question arises whether and when these tumors should be treated. The present article reports the results of the surgical treatment of sHBs using the protocol described below and compares them to the course in a control group of patients with conservatively treated sHBs.  Patients and Methods. A total of 30 sHBs were treated microsurgically in 15 patients. Hemangioblastoma-associated cysts were merely opened in 14 cases, drained with the help of Teflon cotton in 2 of these cases, and not opened in 4 instances. Laminoplasties were performed with insertion of absorbable, MRI-compatible micro-osteosynthesis plates. Perioperatively, all patients were administered methylprednisolone according to the NASCIS (National Acute Spinal Cord Injury Study) scheme, and sensory evoked potentials were monitored intra-operatively in all cases. Nine patients in whom the course of primarily conservative treatment of a total of 17 asymptomatic sHBs was documented served as controls. The follow-up time was 7 to 51 months (mean 20) after surgery and 10 to 51 months (mean 21) in the control group.  Findings. Preoperative HB-associated pareses showed transient postoperative deterioration (n=5). The other accompanying neurological deficits improved in 6 HBs and remained unchanged in all other HBs (n=19), of which 16 had been asymptomatic before surgery. In the control group, 6 HBs (in 6 different patients) became permanently symptomatic despite subsequent surgical treatment according to the study protocol.  Interpretations. With the new diagnostic tools now available, microsurgical removal of spinal hemangioblastomas has a low morbidity rate, suggesting that surgical treatment should be considered even for asymptomatic sHBs in certain circumstances.