John A. Lancon

Oxyhemoglobin induces caspase‐mediated cell death in cerebral endothelial cells

Damaged endothelium is one of the pathological changes of the cerebral vasospastic vessels following subarachnoid hemorrhage. Our recent study shows that oxyhemoglobin (OxyHb) induces apoptosis in vascular endothelial cells. Apoptosis generally requires the action of various classes of proteases, including a family of cysteine proteases, known collectively as the caspases. This study was undertaken to investigate the activation of caspases and the efficacy of caspase inhibitors, z‐IETD‐fmk and z‐LEHD‐fmk, for oxyhemoglobin‐induced apoptosis in vascular endothelial cells. Cultured bovine brain microvascular endothelial cells (passages 5–9) were used for this study. OxyHb (10 µmol/L) was added during the 24–72 h incubation with and without caspase‐8 or − 9 inhibitors (z‐IETD‐fmk and z‐LEHD‐fmk). Counting surviving cells, DNA laddering, western blotting of poly(ADP‐ribose) polymerase, and measurement of caspase activities were employed to confirm the cytotoxic effects of OxyHb and the protective effects of the caspase inhibitors. OxyHb produced cell detachment in a time‐dependent manner and increased caspase‐8 and ‐9 activities in the cells. z‐IETD‐fmk and z‐LEHD‐fmk (100 µmol/L) attenuated OxyHb‐induced cell loss, DNA laddering, and proteolytic cleavage of PARP, although a lower concentration (10 µmol/L) of caspase inhibitors showed partial effects. OxyHb activates caspase‐8 and ‐9 in cultured vascular endothelial cells, and blocking the action of the caspases with the inhibitors efficiently prevents loss of vascular endothelial cells from OxyHb‐induced apoptosis in vitro. These results suggest that the caspase cascade participates in OxyHb‐induced apoptosis.

ANATOMY OF THE SHAKEN BABY SYNDROME

Shaken baby syndrome refers to the constellation of nonaccidental injuries occurring in infants and young children as a consequence of violent shaking. The typical victim of shaken baby syndrome is a male infant younger than six months of age who is alone with the perpetrator at the time of injury. Occurrence of the syndrome is unrelated to race, gender, socioeconomic status, or education. The characteristic injuries observed in shaken baby syndrome include subdural hemorrhages, retinal hemorrhages, and fractures of the ribs or long bones. Although each of these injuries may result from violent shaking of the victim, the most severe brain injuries result from the addition of a forceful impact of the infants or childs head against a firm surface. The unique anatomic features of the infants head and skeletal system, which account for the type and pattern of injuries observed in shaken baby syndrome, are emphasized in this article. Anat. Rec. (New Anat.) 253:13–18, 1998.

Endoscopic Treatment of Symptomatic Septum Pellucidum Cysts: With Some Preliminary Observations on the Ultrastructure of the Cyst Wall: Two Technical Case Reports

OBJECTIVE AND IMPORTANCE We describe two patients with symptomatic septum pellucidum cysts managed by endoscopic fenestration. In each case, tissue from the cyst wall was studied to define the origin of the cyst wall and fluid. CLINICAL PRESENTATION The patients, a 6-year-old boy and a 42-year-old man, each presented with headaches and a syncopal episode. Imaging studies demonstrated large septum pellucidum cysts with obstruction of the foramina of Monro. INTERVENTION The patients underwent endoscopic transventricular cyst fenestration with a 4-mm steerable fiberscope. The fenestrations were created to allow communication with the right and left lateral ventricles. In one patient, adhesions between the cyst wall and the foramen of Monro were lysed with endoscopic monopolar cautery. Tissue from the cyst walls was removed for examination by electron microscopy. Postoperatively, the headaches and syncopal episodes resolved in both patients. CONCLUSION Endoscopic fenestration of symptomatic septum pellucidum cysts produces immediate relief of the mass effect of the cyst and resolution of associated symptoms. Cannulation of the lateral ventricle before cyst fenestration prevents inadvertent injury to the fornices, thalamus, internal capsule, caudate nucleus, and septal and thalamostriate veins. The endoscopic approach allows the surgeon to ensure communication within the ventricular system, thus avoiding placement of a shunt. Preliminary ultrastructural analysis indicates that the cyst walls derive from the septum pellucidum rather than the choroid plexus or arachnoid. The cellular machinery necessary for fluid secretion was identified in some specimens.

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, animals 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.

Interventional magnetic resonance imaging guided aspiration and biopsy of a cystic midbrain tumor

Interventional magnetic resonance imaging defines the intraoperative application of magnetic resonance imaging technology, permitting the surgeon to work in an open magnetic field. The application of this technology to pediatric neurosurgery allows precise intraoperative localization of pathology, real-time assessment of the anatomical consequences of surgical and anesthetic interventions, accountability of brain shifts, confirmation of the exact site of biopsy or completeness of lesion removal, and immediate identification of some intraoperative and early postoperative complications. We present the case of a young boy with a cystic left midbrain tumor who underwent interventional magnetic resonance imaging guided aspiration and biopsy to illustrate the surgical advantages of this technology.

Retrograde regeneration following neurotmesis of the ulnar nerve

A 41‐year‐old woman experienced a gunshot wound to the forearm with neurotmesis of the ulnar nerve. Surgery 9 months later revealed a neuroma‐in‐continuity in the midforearm. Intraoperative nerve stimulation failed to elicit direct nerve responses or motor responses from the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. However, neurotonic discharges in response to mechanical irritation of the neuroma were recorded in the FDI, but not the ADM. Surprisingly, after resecting the ulnar nerve distal to the neuroma, neurotonic discharges were still elicited in the FDI following perturbation of the neuroma. Moreover, neurotonic discharges were elicited during ulnar nerve resection 2 cm proximal to the neuroma. No anastomoses or anomalous branches were noted. The findings suggest that regenerating fibers did not reach the FDI through the distal nerve segment. Rather, we speculate that nerve fibers regenerating at random, or impeded by scar tissue, contacted the proximal nerve portion, at which point growth became polarized in a retrograde direction. Retrograde regeneration may have proceeded to a branch point in the forearm (possibly an undetected anomalous branch or fibrous adhesion), where growth of regenerating fibers extended outward into surrounding damaged tissue planes before redirecting distally to reach the FDI. Muscle Nerve 28: 512–514, 2003

Giant Posterior Fossa Arachnoid Cyst

Accessible online at: www.karger.com/pne Posterior fossa arachnoid cysts comprise 20–30% of intracranial arachnoid cysts. The characteristic appearance with magnetic resonance imaging (MRI) is a nonenhancing cystic lesion situated in the cerebellopontine angle or region of the foramen magnum that is hypointense on T1-weighted images and hyperintense on T2weighted images. The fourth ventricle and cisterna magna are formed normally but may be displaced by the mass effect of the cyst. Less commonly, the cyst may be located in the quadrigeminal cistern or dorsal to the cerebellum. Rarely, these cysts may attain considerable size before producing symptoms. The differential diagnosis of a posterior fossa arachnoid cyst includes the Dandy-Walker malformation, mega cisterna magna, pilocytic astrocyto-

Colloid cyst of the third ventricle.

Accessible online at: www.karger.com/journals/pne This previously healthy 11-year-old boy presented with a 3-month history of generalized headaches that were severest in the morning. In recent weeks, the headaches had become more intense and were associated with nausea and emesis. According to the parents, there had been no deterioration in school performance or noticeable changes in the boy’s personality or behavior. There were no cutaneous stigmata of disease. The funduscopic examination and general neurologic examinations were unremarkable. An MRI scan (fig. 1) done at a peripheral hospital showed a 1.8 ! 1 cm round lesion in the roof of the third ventricle immediately posterior to the foramina of Monro. The lesion was homogeneously isointense to brain on T1-weighted images and hyperintense on T2-weighted and flair images. There was moderate ventricular dilatation and early transependymal edema. A small cavum septum pellucidum was present. Using a transcallosal interforniceal approach, we found a cystic mass that contained mucinous material and was adherent to the left internal cerebral vein. The cyst was aspirated and excised completely. Microscopically, the cyst was lined by columnar ciliated epithelium with focal vacuolization consistent with mucin. Most anterior third ventricular masses in children are low-grade astrocytic neoplasms although colloid cysts are occasionally encountered in older children and adolescents. The MRI appearance is highly variable. Most commonly, a colloid cyst is hyperintense to brain on T1weighted images and hypointense on T2-weighted images. However, they can display almost any signal intensity on any imaging sequence.