Jesús Vaquero

Functional recovery in chronic paraplegia after bone marrow stromal cells transplantation.

Previous reports showed the therapeutic effect of transplants of bone marrow stromal cells (BMSC) after incomplete traumatic spinal cord lesions. We studied the effect of this form of therapy in chronically paraplegic Wistar rats due to severe spinal cord injury (SCI). Rats were subjected to weight-drop impact causing paraplegia, and BMSC or phosphate buffered saline (PBS) was injected into spinal cord 3 months after injury. Functional outcome was measured using the Basso–Beattie–Bresnehan score until sacrifice of the animals, 4 weeks after transplantation. At this time, samples of spinal cord tissue were studied histologically. The results showed a clear and progressive functional recovery of the animals treated with BMSC transplantation, compared to controls. Grafted BMSC survived into spinal cord tissue, forming cell bridges within the traumatic centromedullary cavity. In this tissue, cells expressing neuronal and astroglial markers can be seen, together with a marked ependymal proliferation, showing nestin-positivity. These findings suggest the utility of BMSC transplantation in chronically established paraplegia.

Cavernomas of the central nervous system: Clinical syndromes, CT scan diagnosis, and prognosis after surgical treatment in 25 cases

SummaryWe present our clinical experience and the results of surgical management with 25 cavernomas of the CNS, treated in our hospital in the last 10 years. The location of the lesion assessed by clinical and CT scan examinations, proved to be the most significative factor determining the prognosis of cavernomas of the CNS, after surgical removal.The symptoms started in most of the cases in the third decade of life. 19 cases were located in the cerebral hemispheres and produced three well defined clinical syndromes:1)Irritative syndrome (seizures) present in 70% of the cases.2)Space-occupying lesion syndrome (20%) and3)haemorrhagic syndrome (10%). The remaining six cases were located within the basal ganglia, brainstem, pineal region, cerebellum and spinal cord, showing a progressive course.CT scan studies were performed on 24 cases. The characteristic image of a cavernoma is represented by a moderately hyperdense nodule with discreet contrast uptake. Calcification was observed in and around the lesions in 33% of the cases. Perilesional hypodensities suggestive of brain tissue atrophy were noted in 22% of the CT scans. On the other hand, 12% of cerebral hemisphere cavernomas showed atypical CT scan images that suggested an erroneous diagnosis of cystic gliomas.Radical surgical removal was performed in all cases. The postoperative results varied according to the location of the lesions. Complete recovery was obtained with cerebral hemisphere cavernomas presenting with a progressive history suggesting tumour or a haemorrhagic syndrome. 85% of the cases presenting with seizures, were symptom-free and taking no anticonvulsants 1 year after surgery. In deeply placed cavernomas (basal ganglia and brainstem) the surgical results were poor. In the latter cases surgery has to be carefully evaluated when a mode of treatment is to be considered in patients whose CT scan data strongly suggest a diagnosis of cavernoma.

Bone marrow stromal cells can achieve cure of chronic paraplegic rats: functional and morphological outcome one year after transplantation.

Chronic paraplegia resulting from severe spinal cord injury (SCI) is considered to be an irreversible condition. Nevertheless, recent studies utilizing adult stem cells appear to offer promise in the treatment of this and other neurological diseases. Here, we show that progressive functional motor recovery is achieved over the course of the year following the administration of bone marrow stromal cells (BMSC) in traumatic central spinal cord cavities of adult rats with chronic paraplegia. At this time, functional recovery is almost complete and associated with evident nervous tissue regeneration in the previously injured spinal cord.

Cell therapy using bone marrow stromal cells in chronic paraplegic rats: Systemic or local administration?

Recent studies showed the therapeutic effect of bone marrow stromal cells (BMSC) after spinal cord injury (SCI). In the present study, we compared the effect of systemic and local administration of BMSC in adult Wistar rats suffering chronic paraplegia as consequence of severe SCI. Adult Wistar rats were subjected to a weight-drop impact causing complete paraplegia, and 3 months later, all the animals remained without signs of functional recovery. At this moment, 3 x 10(6) BMSC were injected intravenously (n: 20) or into traumatic spinal cord cavity (n: 20). Outcome was evaluated until sacrifice of the animals, 6 months later, using the Basso-Beattie-Bresnehan (BBB) score, the cold spray test, and measuring the thigh perimeter. After sacrifice, samples of spinal cord tissue were studied histologically. The results showed that intravenous administration of BMSC achieves some degree of functional recovery when compared to controls. Nevertheless, administration of BMSC into postraumatic spinal cord cavity promotes a clear and progressive functional recovery, significantly superior to the recovery obtained by means of the intravenous administration. This effect is associated to long-term presence of BMSC in the injured spinal cord tissue, with images suggesting neuronal differentiation and spinal cord reconstruction.

Cavernomas of the Brain

Our clinical and surgical experience with 16 cases of cavernous hemangioma (cavernoma) of the brain is presented. In 50% of the cases, symptoms appeared during the 3rd decade of life. The clinical picture included seizures in 50% of the cases and a brain tumor-like syndrome in 37.5%, and 12.5% of the cases began with an intracerebral hemorrhage. In our series females predominated over males by 2:1. Computed tomographic (CT) scanning is the best procedure for the diagnosis of cavernomas. However, exact preoperative diagnosis of these lesions is infrequent because cavernomas are generally accepted to be very rare. A slightly hyperdense nodule, poorly enhanced after contrast administration, is the prominent feature on the CT scan. A small, hypodense zone surrounding the lesion and calcifications within the nodule are also found. An excellent result after operation was obtained in all cases of cavernoma located in the brain hemispheres. In deeply placed cavernomas (basal ganglia or brain stem), the surgical prognosis is doubtful, and features such as the size of the lesion and its anatomical location are important.

Neurocytoma of spinal cord

We report a case of spinal cord neurocytoma in a 67-year-old man who had experienced a progressive numbness of the left foot during the previous 4 years. Magnetic resonance imaging showed a well-defined intramedullary tumor located at the T10–T11 level. The pathological examination revealed histological characteristics described in neurocytomas. The tumor cells showed a uniform small nucleus and clear or slightly eosinophilic cytoplasm with frequent perinuclear halos, resembling the picture of oligodendroglioma. Some tumor cells exhibited mature ganglion cell appearance. Electron microscopy showed cells with microtubules and dense-core vesicles in their cytoplasm and cytoplasmic process. Immunohistochemically, the majority of tumor cells expressed synaptophysin and neuronspecific enolase. We conclude that this tumor is an exceptional case of neurocytoma located in the spinal cord, and consider that the term neurocytoma can be applied to tumors with neuronal differentiation intermediate between neuroblastoma and ganglioneuroma, even if arising in CNS outside of the intracranial ventricular system.

Functional recovery of chronic paraplegic pigs after autologous transplantation of bone marrow stromal cells.

Background. Bone marrow stromal cells (BMSC) transplantation offers promise in the treatment of chronic paraplegia in rodents. Here, we report the effect of this cell therapy in adult pigs suffering chronic paraplegia. Methods. Three months after spinal cord injury, autologous BMSC in autologous plasma was injected into lesion zone and adjacent subarachnoid space in seven paraplegic pigs. On the contrary, three paraplegic pigs only received autologous plasma. Functional outcome was measured weekly until the end of the follow-up, 3 months later. Results. Our present study showed progressive functional recovery in transplanted pigs. At this time, intramedullary postraumatic cavities were filled by a neoformed tissue containing several axons, together with BMSC that expressed neuronal or glial markers. Furthermore, in the treated animals, electrophysiological studies showed recovery of the previously abolished somatosensory-evoked potentials. Conclusions. These findings confirm previous observations in rodents and support the possible utility of BMSC transplantation in humans suffering chronic paraplegia.

Posterior fossa epidermoid cysts

SummaryThe authors present their clinical and surgical experience with 18 posterior fossa cholesteatomas, including three cases with atypical CT scan appearances that corresponded to calcification, haemorrhage or malignant change into an epidermoid carcinoma, respectively.

Genetic and epigenetic alteration of the NF2 gene in sporadic meningiomas

The role of the NF2 gene in the development of meningiomas has recently been documented; inactivating mutations plus allelic loss at 22q, the site of this gene (at 22q12), have been identified in both sporadic and neurofibromatosis type 2–associated tumors. Although epigenetic inactivation through aberrant CpG island methylation of the NF2 5′ flanking region has been documented in schwannoma (another NF2‐associated neoplasm), data on participation of this epigenetic modification in meningiomas are not yet widely available. Using methylation‐specific PCR (MSP) plus sequencing, we assessed the presence of aberrant promoter NF2 methylation in a series of 88 meningiomas (61 grade I, 24 grade II, and 3 grade III), in which the allelic constitution at 22q and the NF2 mutational status also were determined by RFLP/microsatellite and PCR‐SSCP analyses. Chromosome 22 allelic loss, NF2 gene mutation, and aberrant NF2 promoter methylation were detected in 49%, 24%, and 26% of cases, respectively. Aberrant NF2 methylation with loss of heterozygosity (LOH) at 22q was found in five cases, and aberrant methylation with NF2 mutation in another; LOH 22q and the mutation were found in 16 samples. The aberrant methylation of the NF2 gene also was the sole alteration in 15 samples, most of which were from grade I tumors. These results indicate that aberrant NF2 hypermethylation may participate in the development of a significant proportion of sporadic meningiomas, primarily those of grade I. ©2005 Wiley‐Liss, Inc.

Estrogen- and progesterone-receptor proteins in intracranial tumors

Estrogen and progesterone receptors have been measured in 13 intracranial tumors (eight meningiomas, two acoustic neurinomas, one primary tumor of neuroectodermal origin, one giant-celled glioblastoma, and one metastasis of carcinoma). Evidence is provided of the presence of progesterone receptors in meningiomas (87.5%). We could not find clear evidence of estrogen receptors in any tumor of this series. Presence of progesterone receptors in meningiomas suggests an explanation for the greater incidence of these tumors in women and their rapid growth during pregnancy.