Seizure activity-induced changes in polyamine metabolism and neuronal pathology during the postnatal period in rat brain.

Systemic injection of kainic acid (KA) does not cause neuronal pathology in limbic structures in rat brain prior to postnatal day (PND) 21. The present study tested if the development of the pathogenic response is associated with the maturation of a link between seizure activity and polyamine metabolism. Pathology was assessed with histological techniques and with the binding of [3H]Ro5-4864, a ligand for the peripheral type benzodiazepine binding sites (PTBBS), a marker of glial cell proliferation. In agreement with previous results, peripherally administered kainate at doses sufficient to induce intense behavioral seizures produced a loss of Nissl staining in hippocampus after PND 21 but not at earlier ages. The pattern of neuronal damage observed after PND 21 resembled that found in adult animals: extensive losses of Nissl staining in area CA3 of hippocampus and in piriform cortex, more modest effects in CA1 and sparing of the granule cells of the dentate gyrus. Similarly, no increase in [3H]Ro5-4864 binding as a result of KA administration was observed in hippocampus and piriform cortex until PND 21. Ornithine decarboxylase (ODC) activity and putrescine levels were high in the neonatal brain and decreased to reach adult values by PND 21. KA-induced seizure activity did not significantly alter both variables until PND 21. After PND 21, ODC activity and putrescine levels markedly increased 16 h after KA-induced seizure activity in hippocampus and piriform cortex. The magnitude of the effects increased between PND 21 and PND 30, at which point the changes in both parameters were comparable to those found in adults. Polyamines stimulate the activity of the calcium-dependent proteases calpain in brain fractions and may increase calpain-mediated proteolysis in situ. In accord with this, kainate-induced breakdown of spectrin, a preferred substrate of calpain, measured 16 h after KA injection followed a developmental curve parallel to that for kainate-induced increases in putrescine levels. These results indicate that the onset of vulnerability to seizure activity triggered by kainic acid is correlated with the development of an ODC/polyamine response to the seizures and further support a critical role for the ODC/polyamine pathway in neuronal pathology following a variety of insults.

Primary intramedullary primitive neuroectodermal tumor of the spinal cord: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Primary intraspinal primitive neuroectodermal tumors (PNETs) are rare. We report a case and review the literature. CLINICAL PRESENTATION: A 22-year-old woman presented with rapidly progressive paraparesis and neurogenic bladder. INTERVENTION: Preoperative computed tomography myelograms revealed a complete block at T12-L1, consistent with an intramedullary lesion. An urgent operation was performed with gross total tumor removal. The pathological findings were consistent with a PNET. Recurrence was noted within 10 weeks of surgery and has been somewhat responsive to chemotherapy and radiotherapy thus far. A review of the English literature shows that only 13 cases of primary intraspinal PNETs have been reported to date, and the present case is the second one in which the tumor was purely intramedullary. Most of the reported patients survived less than 2 years. CONCLUSION: Primary intraspinal PNETs are rare tumors and carry a poor prognosis.

A review of the pathophysiology of cervical spondylotic myelopathy with insights for potential novel mechanisms drawn from traumatic spinal cord injury.

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction. Despite advances in diagnosis and surgical treatment, many patients still have severe permanent neurologic deficits caused by this condition. An improved understanding of the pathophysiology of cervical spondylotic myelopathy, particularly at a cellular and molecular level, may allow improved treatments in the future. A detailed review of articles in the literature pertaining to cervical spondylotic myelopathy was supplemented by an analysis of relevant mechanisms of spinal cord injury. The pathologic course of cervical spondylotic myelopathy is characterized by early involvement of the corticospinal tracts and later destruction of anterior horn cells, demyelination of lateral and dorsolateral tracts, and relative preservation of anterior columns. Static and mechanical factors and ischemia are critical to the development of cervical spondylotic myelopathy. Free radical-and cation-mediated cell injury, glutamatergic toxicity, and apoptosis may be of relevance to the pathophysiology of cervical spondylotic myelopathy. To date, research in cervical spondylotic myelopathy has focused exclusively on the role of mechanical factors and ischemia. Fundamental research at a cellular and molecular level, particularly in the areas of glutamatergic toxicity and apoptosis may result in clinically relevant treatments for this condition.

The optimal radiologic method for assessing spinal canal compromise and cord compression in patients with cervical spinal cord injury. Part II: Results of a multicenter study.

STUDY DESIGN: A multicenter, retrospective study using computed tomographic and magnetic resonance imaging data to establish quantitative, reliable criteria of canal compromise and cord compression in patients with cervical spinal cord injury. OBJECTIVES: To develop and validate a radiologic assessment tool of spinal canal compromise and cord compression in cervical spinal cord injury for use in clinical trials. SUMMARY OF BACKGROUND DATA: There are few quantitative, reliable criteria for radiologic measurement of cervical spinal canal compromise or cord compression after acute spinal cord injury. METHODS: The study included 71 patients (55 men, 16 women; mean age, 39.7 +/- 18.7 years) with acute cervical spinal cord injury. Causes of spinal cord injury included motor vehicle accidents (n = 36), falls (n = 20), water-related injuries (n = 8), sports (n = 5), assault (n = 1), and farm accidents (n = 1). Canal compromise was measured on computed tomographic scan and T1- and T2-weighted magnetic resonance imaging, and cord compression at the level of maximum injury was measured on T1- and T2-weighted magnetic resonance imaging. All films were assessed by two independent observers. RESULTS: There was a strong correlation of canal compromise and/or cord compression measurements between axial and midsagittal computed tomography, and between axial and midsagittal T2-weighted magnetic resonance imaging. Spinal canal compromise assessed by computed tomography showed a significant although moderate correlation with spinal cord compression assessed by T1- and T2-weighted magnetic resonance imaging. Virtually all patients with canal compromise of 25% or more on computed tomographic scan had evidence of some degree of cord compression on magnetic resonance imaging, but a large number of patients with less than 25% canal compromise on computed tomographic scan also had evidence on magnetic resonance imaging of cord compression. CONCLUSIONS: In patients with cervical spinal cord injury, the midsagittal T1- and T2-weighted magnetic resonance imaging provides an objective, quantifiable, and reliable assessment of spinal cord compression that cannot be adequately assessed by computed tomography alone.

Pyogenic spondylodiscitis: an overview.

Although uncommon, spontaneous and postoperative pyogenic spondylodiscitis entail major morbidity and may be associated with serious long-term sequelae. A review of the literature was done to advance our understanding of the diagnosis, treatment, and outcome of these infections. The principles of conservative treatment are to establish an accurate microbiological diagnosis, treat with appropriate antibiotics, immobilize the spine, and closely monitor for spinal instability and neurological deterioration. The purpose of surgical treatment is to obtain multiple intraoperative cultures of bone and soft tissue, perform a thorough debridement of infected tissue and decompression of neural structures, and reconstruct the unstable spinal column with bone graft with or without concomitant instrumentation. Appropriate management requires aggressive medical treatment and, at times, surgical interventions. If recognized early and treated appropriately, a full recovery can often be expected. Therefore, clinicians should be aware of the clinical presentation of such infections to improve patient outcome.

Solitary brain metastasis 13 years after removal of renal adenocarcinoma.

We report a case of a patient who developed a single brain metastasis to the cerebellum 13 years after removal of a renal adenocarcinoma. The cerebellar metastasis was removed twice due to local recurrence one year after the first operation. The patient is alive and doing well 18 months after the second neurosurgical procedure. The metastasis was not associated with any other evidence of disease. Brain metastasis may present many years after removal of kidney adenocarcinoma and when not associated with other evidence of disease their operative treatment may carry a good prognosis.

Changes in polyamine levels and spectrin degradation following kainate-induced seizure activity: effect of difluoromethylornithine.

The induction of ornithine decarboxylase (ODC) in adult CNS and the resulting changes in polyamine levels are often observed under conditions associated with activation of NMDA receptors, calpain stimulation and spectrin degradation. The present study was directed at evaluating the links between these two sets of events. We measured the effects of an acute treatment of adult rats with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, on biochemical alterations following kainate-induced seizure activity. Beside ODC activity and polyamine levels, we assayed the in situ spectrin degradation and the in vitro binding of 3H-Ro5-4864, a ligand for the peripheral benzodiazepine binding sites which is a good marker of glial proliferation, at various time intervals following systemic kainic acid (KA) injection. Kainate-induced seizure activity was followed by a transient increase in ODC activity, a long-lasting increase in putrescine levels and spectrin degradation, and a delayed increase in 3H-Ro5-4864 binding, mainly in hippocampus and piriform cortex. Treatment of the animals with DFMO markedly reduced the increase in putrescine levels up to 7 days after KA injection. It also reduced the increase in spectrin breakdown observed at 16 h but not at 4 and 7 days after KA injection. Finally, it did not modify the increase in 3H-Ro5-4864 binding measured 4 and 7 days after KA injection. The levels of putrescine were positively correlated with the extent of spectrin proteolysis in KA-treated animals whether or not they were treated with DFMO, at 16 h but not at 7 days after KA injection. The results indicate that the extent of spectrin breakdown observed shortly after KA-induced seizure activity is causally related to the changes in ODC activity and putrescine levels. Although the data are consistent with the idea that putrescine could be a marker for acute pathology, they do not support a role for polyamines in delayed neurotoxicity.