Role of MAPK in chronic cerebral vasospasm.

This study was undertaken to investigate the role of p44/42 MAPK in a dog double hemorrhage model of subarachnoid hemorrhage (SAH), and whether MEK inhibitors can alter the degree of SAH-induced vasoconstriction. The diameter of the basilar artery, which was compared with day 0 angiogram, decreased gradually in a time-dependent manner from day 3 (80%), day 5 (68%) through day 7 (53.5%). The level of MAPK (p44/42) immunoprecipitation peaked on day 3 and remained enhanced through day 7 (P < 0.05). MEK inhibitor PD98059 significantly reduced p44/42 MAPK immunoprecipitation and significantly reversed vasospasm and increased residual diameter to 79.0% on day 7. These results demonstrated that p44/42 MAPK kinase is involved in the pathogenesis of cerebral vasospasm. The MEK inhibitor PD98059 might be useful in the treatment of vasospasm.

Prevention of vasospasm in penetrating arteries with MAPK inhibitors in dog double-hemorrhage model.

BACKGROUND: Vasospasm in the penetrating arteries contributes to ischemic neurological deficit. It may be as important as angiographic vasospasm because it would explain the discrepancies between angiographic vasospasm and clinical symptoms in some patients. It may also underlie the different effects of vasodilators. The present study examined this hypothesis by looking at the effect of the inhibitors of mitogen-activated protein kinase (MAPK) on vasospasm of the penetrating arteries. METHODS: Twenty-two adult mongrel dogs of either sex were used for the dog double-hemorrhage model. The dogs were randomly divided into four groups: control-hemorrhage, vehicle-treated, PD98059-treated, and U0126-treated groups. The drug injections were started on Day 3 after the first subarachnoid hemorrhage (SAH). The clinical status of the dogs was studied, based on their activity, appetite, and focal neurological symptoms. On Day 7, all the dogs were sacrificed, and the penetrating arteries from the brain stem were prepared for transmission electron microscopy. RESULTS: (1) Severe vasospasm developed in the basilar arteries in the SAH-without-treatment group (control), in the DMSO-treated group (DMSO), and in the U0126 treatment group with mean reduction of the basilar artery diameter of 46.57%, 49.3%, and 39.6%, respectively. In the PD98059-treatment group only a mild vasospasm was observed and the mean reduction of the basilar artery diameter was 18.9%. (2) All the dogs in the control SAH and vehicle-treated groups developed severe angiographic and clinical vasospasm. The penetrating arteries were contracted, and the endothelial and smooth muscle cells were dystrophic. (3) The dogs in the U0126-treated group developed severe angiographic, but not clinical, vasospasm. The penetrating arteries were not contracted, and the endothelial and smooth muscle cells were not dystrophic. (4) The dogs in the PD98059 group developed mild angiographic vasospasm. No dog developed clinical symptoms that could be attributed to vasospasm. In morphological studies, the penetrating arteries were slightly contracted, but the cells were not dystrophic. CONCLUSIONS: Vasospasm of the penetrating arteries, but not angiographic vasospasm, is consistent with the clinical symptoms and signs of vasospasm. MAPK may be important in maintaining vasospasm of both major and penetrating cerebral arteries. The correlation of the improvement in the clinical score with the reduction of vasospasm in the penetrating arteries demonstrated an important role of penetrating arteries in the morbidity and mortality caused by SAH.

Morphological changes of cerebral penetrating arteries in a canine double hemorrhage model.

BACKGROUND: Morphological presentations of cerebral vasospasm, such as dystrophy and desquamation of endothelial cells, corrugation of the internal elastic layer, and necrotic changes in smooth muscle cells, are well defined in large cerebral arteries. This study was undertaken to examine pathological changes in cerebral penetrating arteries in a canine double hemorrhage model. METHODS: Eighteen mongrel dogs were subjected to an autologous arterial blood (0.4 mL/kg) injection into the cisterna magna on day 0 and day 2 after withdrawal of an equivalent amount of cerebrospinal fluid. Angiogram was performed on day 0 before the blood injection and on the day the dogs were sacrificed. The dogs were divided into four groups: control (day 0) (n = 4), hemorrhage and sacrificed on day 3 (n = 4), day 5 (n = 5), and day 7 (n = 5). The penetrating arteries were removed and found to be spastic on days 3, 5, and 7, but not in the control group. RESULTS: Endothelial dystrophy and partial desquamation were recorded in all dogs sacrificed on days 5 and 7. Condensation of chromatin, blebbing of the membrane, and condensation of cytoplasm were identified in many endothelial cells, features that are consistent with apoptosis. The morphological changes in the penetrating arteries were more pronounced on days 5 and 7. CONCLUSIONS: Vasospasm occurred in cerebral penetrating arteries in a canine double hemorrhage model. The morphological change in penetrating arteries, especially apoptosis in endothelial cells, is consistent with an early phase of vasospasm. Vasospasm in a penetrating artery may contribute to the cerebral ischemia that occurs during vasospasm.

Spontaneous dural sinus thrombosis in children.

The clinical course of spontaneous dural sinus thrombosis in children varies from indolent to fulminant. Although many different etiologies for the development of dural sinus thrombosis have been described, a full recovery can be anticipated in most children following rehydration and the administration of systemic antibiotics. Steroids, systemic anticoagulation and intrasinus thrombolysis may be beneficial in selected patients, although the efficacy of these therapies has not been established prospectively in children. We reviewed 12 pediatric patients with spontaneous dural sinus thrombosis (1978-1998) to determine the etiology, clinical course and best treatment options. In the absence of a hypercoagulable state, pediatric patients generally recover well with rehydration and antibiotics and do not require anticoagulation.

Hemangioblastoma of the filum terminale: case report.

OBJECTIVE AND IMPORTANCE: Tumors of the cauda equina and specifically the filum terminale are uncommon. We report the fourth case of a hemangioblastoma occurring in the filum terminale. CLINICAL PRESENTATION: This 35-year-old man presented with a 4-year history of low back pain that had been previously diagnosed as a bulging disc and exhibited severe pain in response to percussion of his lower back but was neurologically intact. He was found to have a large, enhancing mass filling the thecal sac at L2-L3. INTERVENTION: The tumor was found to be attached to the filum terminale and was cleanly dissected off en toto. Microscopically, the mass consisted of endothelial cells in addition to abundant fat-laden stromal cells and reticulum. CONCLUSION: We present a case report and a review of the literature. Our patient was the first to exhibit no radicular complaints. The diagnosis was delayed in all four cases and was not determined until the time of surgery. Complete excision offers the best chance for cure, and spinal angiography can aid in diagnosis. However, a high index of suspicion is needed for preoperative detection.

The child as a projectile.

Unintentional injury is the leading cause of death in children under the age of fourteen. The majority of these injuries/deaths occur when the child becomes airborne during an accident. The most common mechanisms by which children become airborne are motor vehicle collisions, bicycling accidents, and falls. A head injury is seen in a significant number of children in this setting. This includes injury to the scalp, skull, coverings of the brain, or the brain itself. These injuries are the most common cause of death in children resulting from unintentional injury. Other typical injuries include external bruises and abrasions, extremity fractures, and bruising or bleeding of internal organs. We propose to name this constellation of injuries the projectile child syndrome. This refers to those injuries occurring in infants and children as a result of becoming airborne during the events of an accident. The pattern of injuries seen as related to the anatomy of the child is stressed. A review of the impact to society and guidelines for prevention are presented.

Should endolymphatic sac tumors be considered part of the von Hippel-Lindau complex? Pathology case report.

OBJECTIVE: Von Hippel-Lindau (vHL) disease is an inherited disorder characterized by numerous cystic and solid neoplasms. Because of the recent identification of the vHL gene, other investigators have demonstrated genetic mutations in this gene in several of the neoplasms associated with the disease. We describe a patient with an endolymphatic sac (ELS) tumor and vHL disease. The purpose of this study was to identify a similar genetic mutation within the vHL gene of the ELS tumor. METHODS: Using the patient's archival pathological slides, neoplastic cells were microdissected to yield a purely neoplastic cell population. The deoxyribonucleic acid of these cells was then extracted and amplified via polymerase chain reaction. After sufficient amplification, the specimen was analyzed on a single-strand conformation polymorphism gel system to detect putative changes in the base sequence. RESULTS: Single-strand conformation polymorphism gel system analysis yielded two bands representing the two single strands of deoxyribonucleic acid that were amplified. The upper band of the specimen was shifted down (compared with controls), representing a conformational change as a result of genetic mutation. CONCLUSION: ELS tumors are uncommon, and, to our knowledge, only seven cases associated with vHL disease have been reported in the literature. Although this association has been previously mentioned, no definitive studies have linked the two together. We report the eighth case of ELS tumor and vHL disease. We have demonstrated through molecular biological techniques, that, in our patient's tumor, a genetic mutation occurred, and that this mutation is similar to mutations previously reported in other neoplasms associated with vHL. We therefore suggest that ELS tumors be considered among the neoplasms associated with vHL.

Maffucci's Syndrome and Intracranial Chondrosarcoma.

Maffucci's syndrome is a rare, congenital mesenchymal dysplasia characterized by multiple enchondromata and hemangimata, both of which may undergo malignant degeneration. Intracranial involvement is uncommon. A literature review yielded only six cases of Maffucci's syndrome with intracranial chondrosarcoma and two cases of Ollier's disease (enchondromata alone) with intracranial chondrosarcoma. We report the seventh case of Maffucci's syndrome in a patient with a very large and extensive skull base chondrosarcoma requiring staged operations for removal.

Complete development of Caryospora bigenetica (Apicomplexa: Eimeriidae) in vitro.

The development of Caryospora bigenetica in vitro is described by light microscopy. Sporozoites from snake-derived oocysts were purified and inoculated onto cultures of primary testicle cells of the cotton rat, cotton rat kidney cells, and human fetal lung cells. Intracellular sporozoites were observed one and two days postinoculation (DPI). Motile, extracellular first-generation merozoites were present 3 DPI, and second-generation merozoites were present 5 DPI. Mature gamonts were observed 9 DPI and developed into unsporulated oocysts by 10 DPI. Oocystes sporulated in vitro, and excystation was observed. Cells that were penetrated by in vitro-produced sporozoites formed caryocysts by 16 DPI. To test infectivity of in vitro-derived stages, merozoites were removed from cultured cells 5 DPI and inoculated intraperitoneally into a mouse; infection resulted. Sporulated oocysts removed from cell cultures 12 DPI produced facial swelling in an orally inoculated cotton rat.