A case of anaplastic pleomorphic xanthoastrocytoma presenting with tumor bleeding and cerebrospinal fluid dissemination.

Pleomorphic xanthoastrocytoma (PXA) has been considered an astrocytic tumor with a relatively favorable prognosis. However, PXA cases having several recurrent patterns with poor prognosis have been reported in recent years, and a new concept of anaplastic PXA has been proposed. The present case was a 59-year-old woman who presented with tumor bleeding onset and cerebrospinal fluid dissemination. The patient had sudden-onset right hemiparesis, aphasia, and consciousness disturbance and was admitted to a local area hospital. After emergency surgery had removed the hematoma, postoperative contrast-enhanced CT scan revealed a left temporal tumor. A second surgery was therefore performed for initial tumor removal 2 months later. Histopathological findings showed that the tumor was typical PXA with strong pleomorphism and xanthomatous changes and contained an ependymoma-like component in the center area. However, endothelial proliferation and mitosis were more remarkable compared to ordinary PXA. The MIB-1 labeling index was 9.8% high. From these findings, the histopathological diagnosis was anaplastic PXA. The patient underwent surgery to remove recurrent tumors 5 and 16 months later. The patient died 36 months after the first onset, and CT revealed glioblastoma-like findings and cerebrospinal fluid dissemination. This case report is the first case in which PXA presented with tumor bleeding onset. Histopathological findings suggested anaplastic PXA from the first surgical specimens, and PXA recurred many times. We thus believe that the patient displayed primary anaplastic PXA rather than secondary anaplastic PXA that results in malignant transformation.

Macrophage colony stimulating factor (M-CSF) protects spiral ganglion neurons following auditory nerve injury: morphological and functional evidence.

Because hearing disturbance due to auditory nerve dysfunction imposes a formidable burden on human beings, intense efforts have been expended in experimental and clinical studies to discover ways to restore normal hearing. However, the great majority of these investigations have focused on the peripheral process side of bipolar auditory neurons, and very few trials have focused on ways to halt degenerative processes in auditory neurons from the central process side (in the cerebellopontine angle). In the present study, we investigated whether administration of macrophage colony-stimulating factor (M-CSF) could protect auditory neurons in a rat model of nerve injury. The electrophysiological and morphological results of our study indicated that M-CSF could ameliorate both anterograde (Wallerian) and retrograde degeneration in both the CNS and PNS portions of the auditory nerve. We attribute the success of M-CSF therapy to the reported functional dichotomy (having the potential to cause both neuroprotective and neurotoxic effects) of microglia and macrophages. Whether the activities of microglia/macrophages are neuroprotective or neurotoxic may depend upon the nature of the stimulus that activates the cells. In the present study, the neuroprotective effects of M-CSF that were observed could have been due to M-CSF we administered and to M-CSF released from endothelial cells, resident cells of the CNS parenchyma, or infiltrating macrophages. Another possibility is that M-CSF ameliorated apoptotic auditory neuronal death, although this hypothesis remains to be proved in future studies.

A case of definitely congenital glioblastoma manifested by intratumoral hemorrhage.

BACKGROUND: A female infant was born with a left-sided glioblastoma that manifested clinically with weakened crying and feeding on day 1 of life, fever and bulging anterior fontanel on day 4, and right hemiparesis by day 10. METHODS: Preoperative magnetic resonance imaging showed hemosiderin intensity indicating that hemorrhage had occurred during the prenatal period. Radical surgical removal of the tumor was performed on the 22nd postnatal day. RESULTS: Postoperatively, the right hemiparesis did not worsen and the patient did not have any new neurological deficits. The right hemiparesis gradually improved after her initial surgery, and she was able to stand by herself at 18 months of age. Adjuvant chemotherapy and radiation were administered. This patient survived for 27 months following birth, which is a relatively long time for glioblastoma cases. Radical removal at the first operation with reliance on the plasticity of infant cerebral function was the key point in the long survival.

Effect of topically applied basic fibroblast growth factor on injured cochlear nerve.

OBJECTIVE: Trauma-induced hearing loss after cerebellopontine angle manipulation has been regarded as having a hopeless natural course once it occurs. To challenge such a pessimistic view, we investigated whether pharmacological interventions with basic fibroblast growth factor (bFGF) could ameliorate trauma-induced cochlear nerve degeneration. METHODS: The cerebellopontine angle portion of the cochlear nerve of rats was quantitatively compressed, and bFGF was topically administered for 2 weeks with a bFGF-soaked absorbable sponge and an osmotic minipump. The animals were killed 2 weeks after the compression procedure. The effect of bFGF in ameliorating cochlear neuronal death was evaluated from the residual number of spiral ganglion cells. RESULTS: Cerebellopontine angle cisternal application of bFGF ameliorated cochlear nerve degeneration after the compression. Immunocytochemical studies of FGF receptors indicated that topically administered bFGF was internalized by a receptor-mediated mechanism through FGF receptor-1 and/or FGF receptor-2. CONCLUSION: This report demonstrated that therapeutic application of bFGF was feasible to ameliorate trauma-induced cochlear nerve degeneration. Recent technological advances for deafened ears, such as cochlear implants and auditory brainstem implants, in combination with neurotrophic and/or growth factor therapeutic intervention, would be of great potential benefit for patients with hearing loss.

Apoptosis of auditory neurons following central process injury.

Although apoptotic changes in auditory neurons induced by injury to peripheral processes (dendrites) have been intensively studied, apoptotic changes in auditory neurons induced by injury to central processes (axons of spiral ganglion cells, SGCs) have not been reported previously, probably due to lack of an experimental model. The present study reports for the first time the appearance, extent, and time course of SGC apoptosis following injury to the central processes. Apoptosis was studied in a rat model that consisted of compression of the auditory nerve in the cerebellopontine (CP) angle cistern with intraoperative recordings of auditory nerve compound action potentials (CAPs) to ensure highly reproducible results. Rats were killed between day 0 and day 14 after compression and apoptosis of SGCs was evaluated quantitatively as well as qualitatively by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, anti-activated caspase-3 immunostaining, Hoechst 33342 staining, and electron microscopy. The average number of TUNEL-positive apoptotic SGCs in each cochlear turn increased from day 1 to day 5 and then decreased gradually to an undetectable level on day 14 after compression. The average proportion of apoptotic SGCs identified in any cochlear turn on any day was always lower than 10%. The results of our present study should be useful in determining the therapeutic time window for rescuing auditory neurons undergoing apoptosis due to injury during surgery in the CP angle.

Nimodipine ameliorates trauma-induced cochlear neuronal death.

Excessive entry of Ca2+ into injured cochlear neurons activates various Ca(2+)-activated enzymes and subsequent spiral ganglion cell death. Therefore, preventing intracellular calcium overload by using Ca2+ channel antagonists may become an important countermeasure to spiral ganglion cell death. We experimentally investigated whether an L-type Ca2+ channel blocker (nimodipine) can rescue traumatized cochlear neurons from degeneration. A group of rats (n = 6) was pre-operatively treated with nimodipine for one week and compression injury was applied to the cerebellopontine angle portion of the cochlear nerve in a highly quantitative fashion. The rats from the compression with nimodipine treatment groups were post-operatively treated with nimodipine for 10 days and killed for histological examination. The histological analysis of the temporal bones revealed that the spiral ganglion cells in the basal turn of the cochlea where the magnitude of traumatic impact had been the least in our experimental condition were rescued in a statistically significant fashion in the compression with nimodipine treatment group. The results of the present study indicate that nimodipine may become an intra- and post-operative important adjunct to raise the rate of hearing preservation in vestibular schwannoma excision or other cerebellopontine angle surgical interventions.

Axonal injury in auditory nerve observed in reversible latency changes of brainstem auditory evoked potentials (BAEP) during cerebellopontine angle manipulations in rats.

Intraoperative monitoring of brainstem auditory evoked potentials (BAEP) has been widely utilized to reduce the incidence of postoperative hearing disturbance due to cerebellopontine angle manipulations. The prolongation of wave V of BAEP is usually used as a criterion to warn the surgeons to modify their surgical maneuvers. However, it is not known whether all neuropathological changes are avoided if BAEP latency intraoperatively returns to the baseline level or some neuropathological changes 'silently' occur even if BAEP normalizes. The aim of this study was to experimentally clarify this point that would be important for the long-term prognosis of patients' hearing. The cerebellopontine angle portion of the auditory nerve was quantitatively compressed in the rats and reversible prolongation of BAEP latency was reproduced just as it occurs during surgery in humans. Twenty-four hours after the compression, the auditory nerve was removed for beta-APP immunostaining to investigate the degree of axonal injury. The results of the present study disclosed that axonal injury occurred even in the cases where the intraoperative normalization of prolonged wave IV (equivalent to wave V in humans) latency had been obtained. Therefore, the interpretation of BAEP changes based only on the prolongation of the latency of BAEP was not enough to prevent the auditory nerve from developing morphological changes. Changes in the amplitude of wave V of BAEP appears to be more sensitive than its latency change as an intraoperative indicator for axonal injury in the auditory nerve.

Temporal pattern of cochlear nerve degeneration following compression injury: a quantitative experimental observation.

OBJECT: It has been empirically recognized that the cochlear nerve is highly vulnerable to traumatic stress resulting from surgical procedures; therefore, careful manipulation of the cochlear nerve is mandatory in preventing trauma-induced hearing loss during cerebellopontine angle (CPA) surgery. There is, however, no precise knowledge about the temporal pattern of cochlear nerve degeneration following trauma. This study was performed to determine the temporal pattern of injury that occurs after cochlear nerve trauma, knowledge of which is indispensable not only to neurosurgeons but also to all those who manage lesions involving the cochlear nerve. METHODS: Right suboccipital craniectomies were performed in groups of rats with the aid of a surgical microscope, and the seventh and eighth cranial nerve trunks were identified at the internal auditory meatus. The cochlear nerve was quantifiably compressed while compound action potentials of the cochlear nerve were monitored and recorded. Following injury, one group of rats was killed for histological examination at the end of each week for 4 weeks. Data from this study disclosed that the degeneration of the compressed cochlear nerve progressed in a relatively rapid manner and was complete within 1 week after the insult. The main pathophysiological mechanisms responsible for cochlear neuronal death in this experimental setting appeared to be necrosis, and an apoptotic mechanism seemed to play a subsidiary role. CONCLUSIONS: Accurate knowledge about the temporal profile of trauma-induced cochlear nerve degeneration is closely linked with the problem of the therapeutic time window. The results of the present study indicated that any measures to ameliorate cochlear nerve degeneration following trauma should be started as early as possible (within 1 week) after an injury.