Endovascular embolization of prominent intercavernous sinuses for successful transsphenoidal resection of Cushing microadenoma: case report.

BACKGROUND AND IMPORTANCE: Prominent intercavernous sinuses may result in vigorous bleeding during transsphenoidal resection of pituitary microadenomas and lead to incomplete or aborted tumor resection. We report the use of coil embolization of the intercavernous sinuses to prevent uncontrollable bleeding before transsphenoidal surgery is reattempted. CLINICAL PRESENTATION: A 40-year-old man with Cushing disease underwent an attempt for transsphenoidal resection of an adrenocorticotrophic hormone--producing pituitary microadenoma. This approach was aborted secondary to profuse intercavernous sinus bleeding. The patient underwent endovascular coil embolization of the anterior intercavernous sinuses with complete obliteration. Six weeks later, he underwent successful transsphenoidal resection of the microadenoma. CONCLUSION: To the best of our knowledge, this is the first report of successful coil embolization of the intercavernous sinuses to prevent uncontrolled bleeding before transsphenoidal resection of pituitary microadenomas.

Contemporary postnatal plastic surgical management of meningomyelocele.

BACKGROUND: The goals of this study were to review the outcome of the surgical procedure and hospitalization associated with meningomyelocele repair, and to examine the results of different closure strategies. METHODS: Eighty-three consecutive patients having surgery for meningomyelocele over a ten year period form the basis of this study. Thirty-two closures with a mean defect size preoperatively of 11.5 cm(2) were performed by the neurosurgeon (ADP), and fifty-one closures with a mean defect size of 28.4 cm(2) by the plastic surgeon (MFA). RESULTS: Defects up to 12 cm(2) were closed with local advancement fasciocutaneous flaps. As defect size increased, latissimus muscle flaps were added in 30 (36%) and gluteus muscle in 16 (19%). In recent years, 18 patients (21.6%) with a mean defect of 29 cm(2) were treated with overlapping of deepithelialized fasciocutaneous flaps to add an additional layer of coverage to the dural closure. There were 9 major complications, 6 requiring reoperation. There were 10 minor wound failures managed conservatively. Mean hospital stay was 24.2 days. Re-operation increased length of stay to 45 days (p < 0.0001). Minor wound problems added 6 days to mean hospital stay. Wound failure did not correlate with either defect size or closure technique. Thoracic location was associated with increased wound failure (p < 0.05). Use of a shunt did not increase morbidity. All closures remained durable after discharge. CONCLUSIONS: Location in the thoracic area predicts major wound failure and need for reoperation. Wound complications significantly increase hospital stay. The use of a variety of techniques to achieve multi-layered closures leads to durable coverage for defects of all sizes.

What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?

INTRODUCTION: Malignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. Similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death. CASE REPORT: A 25-year-old white man developed severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MRI) showed a 4 x 3 x 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (ACTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725-891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. Repeat MRI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. Sixty percent (60%) of tumor cells were positive for p53. Cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient then underwent proton beam radiation to the area of concern involving the sella. Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MRI showing tumor in the right cavernous sinus. A 15 mm dural-based right temporal mass believed to be a metastasis was also noted. Following this scan, he was considered too high risk for debulking surgery and instead underwent gamma knife irradiation to the sella area. This shrank the right cavernous sinus tumor mass, while the right temporal mass increased in size. The patient developed blindness and left-sided weakness and required enteral feeding and tracheostomy after prolonged intubation. A trial of chemotherapy with temozolomide (350 mg daily for 5 days) near the end of his life was unsuccessful. He died on home hospice 31 months after his first surgery. CONCLUSION: Headaches, vision changes, and symptoms of androgen deficiency syndrome can be manifestations of an aggressive prolactinoma that might require surgery and additional medical therapy including cabergoline and temozolomide with an unpredictable time of survival.

Treatment and outcomes for pediatric head injuries in Mississippi.

OBJECT: This report summarizes the treatments and outcomes of a large series of patients with pediatric head injuries (PHIs), who were admitted to a tertiary pediatric trauma center at the University of Mississippi Medical Center from January 1, 2003 through December 31, 2006. METHODS: Data were retrieved from the Department of Neurosurgery's Brain Trauma Registry (BTR) on patients who are ≤16 years old. Data include Glasgow Coma Scale (GCS) and injury severity scores (ISS) on admission and Glasgow Outcome Scale (GOS) scores at 6 months follow-up. RESULTS: The BTR registered 554 patients with accidental and nonaccidental PHIs. Follow-up was complete in 98.2%. Aggressive first-tier management with ventricular drainage was used to lower intracranial pressure. Vasopressors were used only to correct hypotension. Second-tier therapies were used infrequently. Craniectomies (14 patients) were associated with good outcomes (GOS 4-5) in nine patients; hypothermia (six patients) and barbiturate (four patients) therapies were ineffective. All 439 patients with ISS <25 showed good outcomes. Fifteen of 16 patients with GCS >8 and ISS ≥25 had good outcomes. In 134 patients with severe PHIs (GCS ≤8), all 45 with ISS <25 and 46 with ISS ≥25 showed good outcomes. Forty-three patients with GCS ≤8 and ISS ≥25 had poor outcomes. Of these patients, 38 died; 22 died within 3 days of admission. CONCLUSIONS: This study indicated that poor outcomes occurred only in PHIs with severe generalized trauma. While 28.4% of patients with GSC ≤8 died, more than half of these sustained nonsurvivable injuries. Aggressive medical management with ventricular drainage was the mainstay of therapy.

Epidemiology of intracranial aneurysms of Mississippi: a 10-year (1997-2007) retrospective study.

BACKGROUND: Despite massive efforts, progress so far has been modest in isolating the genetic determinants for intracranial aneurysm (IA). More detailed epidemiology data might be essential for successful genome-wide association study. Here, we aimed to investigate epidemiology and identify the key risk factors associated with the pathogenesis of IA in a large specific population. METHODS: We investigated the epidemiology and analyzed the risk factors of IA pathogenesis by using an International Classification of Diseases, Ninth Revision database search of the patients treated at the University of Mississippi Medical Center, Jackson, MS, within the past 10-year period (1998-2007). All recruited patients were interviewed to assess multiple risk factors and comorbidities (hypertension, tobacco abuse, females sex, diabetes mellitus, coronary artery disease, coronary obstructive pulmonary disease, alcohol abuse, stroke, hyperlipidemia, illicit drug use, and family history). RESULT: In this retrospective study, we identified several significant risk factors among well-defined human subjects. The 3 major risk factors identified for our IA population are hypertension, tobacco abuse, and female sex. However, African American race was not a significant risk factor in our study. Furthermore, top two risk factors (hypertension, tobacco abuse) were found to be highly associated with familial cases. CONCLUSIONS: In this study, using a specific and well-defined large population, we reported that some key risk factors were further confirmed to be strongly associated with the pathogenesis of IA whereas further investigation into racial factors is apparently needed. Our finding of the confounding effects of top risks with familial cases further complicated the genetic analysis of IA.

Phenotypical manifestations of partial trisomy 9 and monosomy 4 in two siblings.

In this case report, we describe two siblings with a previously unreported partial monosomy 4q and partial trisomy 9q. The sibling karyotypes were determined to be 46,XX,der(4)t(4;9)(q33;q33)pat and 46,XY,der(4)t(4;9)-(q33;q33)pat. The siblings share several common pathological features, including VSD, PDA, low-set ears and digit anomalies as well as features consistent with Pierre-Robin syndrome and hydrocephalus. We review previously reported phenotypes associated with monosomy 4q and partial trisomy 9q and discuss potential mechanisms for these morphological insults with particular emphasis on neuropathology.

Insulin-like growth factor-I decreased etoposide-induced apoptosis in glioma cells by increasing bcl-2 expression and decreasing CPP32 activity.

AIMS: In a variety of tumors, the susceptibility of the tumor cells to apoptotic cell death following chemotherapy is a major determinant of therapeutic outcome. Gliomas are resistant to most chemotherapeutic agents, and its mechanism is not known in detail. In an attempt to understand the mechanism of chemo-resistance, we investigated the roles of insulin-like growth factor-I (IGF-I), IGF-I receptors (IGF-IR), and their relationship with the apoptotic response of two glioma cell lines to etoposide, a chemotherapeutic agent for malignant gliomas. METHODS: Two human glioma cell lines, U-87MG and KNS-42, were used. Etoposide-induced cell growth inhibition was quantified using a modified MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide), colorimetric assay. Hoechst 33258 staining, DNA fragmentation assay, and western blot were used for the evaluation of apoptosis. ApoAlert caspase assay was used for measuring the activity of caspase-3 (CPP32) and interleukin-1 beta -converting enzyme (ICE) protease. In addition, the effect of IGF-IR antisense was tested in U-87MG and KNS-42 glioma cell lines. RESULTS: Etoposide inhibited the growth of U-87MG and KNS-42 cells in a concentration-dependent manner. Etoposide increased the expression of wild-type p53, activated CPP32 (but not ICE) activity, and induced apoptosis in these cells. IGF-I prevented etoposide-induced apoptosis by increasing the expression of bcl-2 and decreasing the activity of CPP32. IGF-IR antisense enhanced the apoptotic effect of etoposide. CONCLUSIONS: IGF-I decreased etoposide-induced apoptosis in glioma cells by increasing the expression of bcl-2 and decreasing the activity of CPP32. The antisense of IGF-IR increased etoposide-induced apoptosis. The anti-apoptotic effect of IGF-I and IGF-IR might be related to the chemo-resistance of glioma to chemotherapeutic agents.

alpha,beta-MeATP augments the UTP contraction of rabbit basilar artery.

The mechanism underlying the interaction between alpha,beta-methyleneadenosine 5'-triphosphate (alpha,beta-MeATP) and uridine 5'-triphosphate (UTP) was investigated using the basilar artery of a rabbit. UTP induced a concentration-dependent contraction, whereas P2X receptor agonists, such as alpha,beta-MeATP and 2-methylthioadenosine 5'-triphosphate (2-MeSATP), did not induce any contraction up to 100 microM. alpha,beta-MeATP augmented the UTP contraction two-fold, immediately and reversibly. This effect was observed with ectonucleotidase inhibition with 1 mM Ni(2+), the removal of extracellular Ca(2+) or Evans blue. The contractile response to adenosine 5'-O-(3-triphosphate) (ATPgammaS), a selective agonist for P2Y(4), was augmented by pretreatment with alpha,beta-MeATP also. ATPgammaS had no additional effect on the UTP contraction fully activated with alpha,beta-MeATP. UTP (100 microM) did not induce an increase in cytosolic Ca(2+) in a rabbit basilar arterial strip; however, in the presence of 1 mM alpha,beta-MeATP, UTP induced a significant increase in cytosolic Ca(2+). These results suggest that alpha,beta-MeATP facilitates the activation by UTP of the P2Y receptor (P2Y(4)) of the rabbit basilar artery through mechanisms other than nucleotidase inhibition, and that it does not do so via a P2X receptor.

Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model.

The hypothesis was tested that hyperbaric oxygen therapy (HBO) reduced brain infarction by preventing apoptotic death in ischemic cortex in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and subsequently were exposed to HBO (2.5 atmospheres absolute) for 2 h, at 6 h after reperfusion. Rats were killed and brain samples were collected at 24, 48, 72 h, and 7 days after reperfusion. Neurologic deficits, infarction area, and apoptotic changes were evaluated by clinical scores, 2,3,7-triphenyltetrazolium chloride staining, caspase-3 expression, DNA fragmentation assay, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL)-hematoxylin and eosin (H&E) costaining. In MCAO/R without HBO treatment animals, DNA fragmentation was observed in injured cortex at 24, 48, and 72 h but not in samples at 7 days after reperfusion. Double labeling of brain slides with NeuN and caspase-3 demonstrated neurons in the injured cortex labeled with caspase-3. TUNEL+H&E costaining revealed morphologic apoptotic changes at 24, 48, and 72 h after reperfusion. Hyperbaric oxygen therapy abolished DNA fragmentation and reduced the number of TUNEL-positive cells. Hyperbaric oxygen therapy reduced infarct area and improved neurologic scores at 7 days after reperfusion. One of the molecular mechanisms of HBO-induced brain protection is to prevent apoptosis, and this effect of HBO might preserve more brain tissues and promote neurologic functional recovery.

Inhibition of H-ras as a treatment for experimental brain C6 glioma.

The oncogene H-ras plays an important role in tumor growth and maintenance and could serve as a target treatment for brain tumors. In this study, diallyl disulfide (DADS), an inhibitor of H-ras was used to treat experimental brain glioma in a rat model. One hundred and twenty-five Sprague-Dawley rats (175-200 g) were implanted with 2 x 10(5) C6 glioma cells into the intra striatal region of the brain. Animals were treated with DADS (33 micromol) either before or after implantation of tumor cells. Control animals received soybean oil. Treatment outcome was evaluated based on H-ras expression in tumor tissue, animal's neurological status, tumor size, and life span. Application of DADS 7 days before implantation of tumor cells reduced the tumor size (P<0.05), improved neurological status (P<0.05), and increased the animal life span (P<0.05) when compared to the control group (no treatment). The expression of H-ras was significantly (P<0.05) reduced in brain tumor tissue of animals treated with DADS before implantation. Application of DADS after tumor implantation failed to improve clinical status or life span. This study demonstrates that pretreatment with DADS is capable of inhibiting the expression of H-ras in experimental brain C6 glioma which leads to an improved neurological status and an extended life span in the rat. Higher doses of DADS or other more potent inhibitors need to be used after tumor has been implanted.

Evaluation of the microvasculature and cerebral ischemia after experimental subarachnoid hemorrhage in dogs.

OBJECT: Whether cerebral vasospasm occurs only in surface vessels or also in parenchymal arterioles is debatable. The present study was undertaken to evaluate comprehensively the microvasculature of the brainstem after experimental subarachnoid hemorrhage (SAH). METHODS: Nine mongrel dogs of either sex, each weighing between 18 and 24 kg, underwent double blood injections spaced 48 hours apart; the injections were infused into the cisterna magna immediately after angiography of the basilar arteries (BAs). Three additional dogs assigned to a control group received no blood injections. The dogs were killed on Day 7. Axial sections obtained from the midpontine region of both control dogs and animals subjected to SAH were evaluated with respect to the morphological characteristics of vessels and neurons, and for ultrastructural changes. Severe vasospasm occurred in the BAs of all dogs subjected to SAH. Nevertheless, in these animals, the luminal areas and vessel perimeter in parenchymal arterioles, but not in parenchymal venules, were observed to have increased when compared with those of control dogs (p < 0.01, t-test). No corrugation of the internal elastic lamina was observed and smooth-muscle and endothelial cells remained normal at the ultrastructural level in the dogs with SAH. CONCLUSIONS: In this model, vasospasm of the BAs did not extend into the region of the pons to affect the intraparenchymal arterioles. Dilation of the parenchymal arterioles might serve as compensation for reduced blood flow. Thus, no neuronal ischemia or infarction resulted in the pontine region of the brain.

Hyperbaric oxygenation prevented brain injury induced by hypoxia-ischemia in a neonatal rat model.

The occurrence of hypoxia-ischemia (HI) during early fetal or neonatal stages of an individual leads to the damaging of immature neurons resulting in behavioral and psychological dysfunctions, such as motor or learning disabilities, cerebral palsy, epilepsy or even death. No effective treatment is currently available and this study is the first to use hyperbaric oxygen (HBO) as a treatment for neonatal HI. Herein, we sought out to determine if HBO is able to offer neuroprotectivity against an HI insult. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O(2) at 37 degrees C). HBO treatment was administered by placing pups in a chamber (3 ATA for 1 h) 1 h after hypoxia exposure. Brain injury was assessed based on ipsilateral hemispheric weight divided by contralateral hemispheric weight, light microscopy, and EM. Sensorimotor functional tests were administered at 5 weeks after hypoxia exposure. After HI, the ipsilateral hemisphere was 52.65 and 57.64% (P<0.001) of the contralateral hemisphere at 2 and 6 weeks, respectively. In HBO treated groups, the ipsilateral hemisphere was 77.77 and 84.19% (P<0.001) at 2 and 6 weeks. There was much less atrophy and apoptosis in HBO treated animals under light or electron microscopy. Sensorimotor function was also improved by HBO at 5 weeks after hypoxia exposure (Chi-square, P<0.050). The results suggest that HBO is able to attenuate the effects of HI on the neonatal brain by reducing the progression of neuronal injury and increasing sensorimotor function.

Preliminary study of the effects of caspase inhibitors on vasospasm in dog penetrating arteries.

This preliminary study was undertaken to explore the possible protective effect of caspase inhibitors Z-VDVAD-FMK and Z-DEVD-FMK in apoptosis and vasospasm in penetrating arteries during cerebral vasospasm. Experimental subarachnoid hemorrhage (SAH) was induced in 16 dogs by an intracisternal injection of autologous arterial blood (0.4 ml/kg) on Day 0 and Day 2. The dogs were then randomly divided into four groups: control-SAH, vehicle-control, and two treatment groups. In the treatment groups, caspase inhibitors (10 microM) were intracisternally injected each day beginning on Day 2 until Day 6. Effects of the inhibitors were analyzed utilizing angiography, the clinical status of the dogs (activity, appetite, and neurological deficits), and transmission electron microscopy of the penetrating arteries. All the dogs were sacrificed on Day 7. In control-SAH and vehicle-control groups, severe angiographic vasospasm, poor clinical status, and penetrating vasospasm were registered in all the dogs. In the treatment groups, all the dogs developed angiographic vasospasm and vasospasm in penetrating arteries, however, with benign clinical statues. The occurrence of apoptosis in endothelial cells was reduced by caspase-2 but not by caspase-3 inhibitor. Caspase inhibitors failed to prevent vasospasm either in major or in penetrating arteries. The improvement of clinical scores by the caspase inhibitors may be related to their protection of the endothelial cells. Further investigations using more rigorous clinical scoring system and quantitative information on the degree of apoptosis in the vessels, as well as in the brain parenchyma are recommended.

Encephalocele as a late complication of cranial vault reconstruction in a patient with Crouzon's syndrome.

Encephalocele is a rare late complication of craniosynostosis repair. An undiagnosed nick to the dura is the etiology of this complication. It usually presents within a few months to years after repair. This case report describes a patient with Crouzon's Disease who had a craniosynostosis repair as an infant and presents 22 years later with an encephalocele. The patient had a thorough physical exam, 2D, and 3D CT Scans as a preoperative workup. Surgical intervention included repair of the encephalocele, cranialization of the frontal sinus with bone grafting, and Lefort III osteomies for mid face advancement. The patient benefited from a two-team simultaneous approach between Neurosurgery and Plastic Surgery. The patient also benefited from an aggressive one-stage repair of all her defects and deformities.

Chronic headache as a sequela of rigid fixation for craniosynostosis.

Rigid fixation has been used over the past 20 years for the long-lasting correction of traumatic and congenital craniofacial defects. It has been noted that the use of plates and screws can result in the migration of the hardware through the skull to the inner cerebral cortex where it embeds in the dura. In addition, there is controversy concerning the safety of using titanium plates in the pediatric population. We report here on an 8-year-old boy who presented to our clinic with a chronic headache after rigid craniofacial fixation using titanium plates 7 years before.

Inhibitory effect with antisense mitogen-activated protein kinase oligodeoxynucleotide against cerebral vasospasm in rats.

BACKGROUND AND PURPOSE: Mitogen-activated protein kinase (MAPK) may be associated with the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). This study aimed to clarify the role of MAPK expression and activation during cerebral vasospasm and to evaluate the therapeutic effect on cerebral vasospasm using an antisense MAPK oligodeoxynucleotide (ODN). METHODS: Antisense MAPK, sense MAPK, or scrambled ODN was injected into the rats intracisternally. We used a single-hemorrhage experimental SAH model to assess vasospasm in the basilar arteries at 30 minutes, 1 day, and 2 days after SAH by cross-sectional area measurement and other histological parameters. Immunohistochemistry and Western blot analysis were used to quantify MAPK expression and activation. In addition, a double-hemorrhage rat SAH model was used to test the effect of post-SAH treatment with antisense MAPK ODN. RESULTS: Antisense MAPK therapy significantly inhibited cerebral vasospasm when compared with sense MAPK or scrambled ODN treatment on day 2. The immunohistochemistry and Western blotting performed in the basilar artery of rats that received antisense MAPK ODN demonstrated inhibition of MAPK and phosphorylated MAPK on day 2. In post-SAH treatment study, antisense ODN reduced MAPK and phosphorylated MAPK in the basilar artery and attenuated cerebral vasospasm. CONCLUSIONS: MAPK activation, but not expression, might be implicated with sustained smooth muscle contraction during cerebral vasospasm after SAH. This study suggests that antisense MAPK ODN strategy is an effective treatment against cerebral vasospasm.