Controlled Hypercapnia Enhances Cerebral Blood Flow and Brain Tissue Oxygenation After Aneurysmal Subarachnoid Hemorrhage: Results of a Phase 1 Study

Background

This study investigated if cerebral blood flow (CBF) regulation by changes of the arterial partial pressure of carbon dioxide (PaCO₂) can be used therapeutically to increase CBF and improve neurological outcome after subarachnoid hemorrhage (SAH).

Methods

In 12 mechanically ventilated poor-grade SAH-patients, a daily trial intervention was performed between day 4 and 14. During this intervention, PaCO₂ was decreased to 30 mmHg and then gradually increased to 40, 50, and 60 mmHg in 15-min intervals by modifications of the respiratory minute volume. CBF and brain tissue oxygen saturation (StiO₂) were the primary and secondary endpoints. Intracranial pressure was controlled by an external ventricular drainage.

Results

CBF reproducibly decreased during hyperventilation and increased to a maximum of 141 ± 53 % of baseline during hypercapnia (PaCO₂ 60 mmHg) on all days between day 4 and 14 after SAH. Similarly, StiO₂ increased during hypercapnia. CBF remained elevated within the first hour after resetting ventilation to baseline parameters and no rebound effect was observed within this time-span. PaCO₂-reactivities of CBF and StiO₂ were highest between 30 and 50 mmHg and slightly decreased at higher levels.

Conclusion

CBF and StiO₂ reproducibly increased by controlled hypercapnia of up to 60 mmHg even during the period of the maximum expected vasospasm. The absence of a rebound effect within the first hour after hypercapnia indicates that an improvement of the protocol is possible. The intervention may yield a therapeutic potential to prevent ischemic deficits after aneurysmal SAH.

     

Prognostic relevance of localization and grading in intracranial ependymomas of childhood

Intracranial ependymomas represent one of the most frequent brain tumors in childhood. Their preferred midline localization and their often controversially discussed classification prompted the present study of 67 intracranial ependymomas in children less than 15 years of age who were operated on from 1951 to 1990. Clinical data and follow-up of all children were retrospectively analyzed by calculation and statistical comparison of progression-free survival (PFS). According to the WHO classification as revised in 1993, 1 grade I subependymoma, 38 grade II ependymomas, and 28 grade III anaplastic (malignant) ependymomas were differentiated. Grade II ependymomas were predominantly located in the IV ventricle and in the supratentorial midline, which often made complete tumor resection impossible. In contrast, the majority of grade III tumors, most often situated in the cerebral hemispheres, could be totally removed. Operative mortality was higher in grade II than in grade III tumors. After recovery from operation, PFS was mainly determined by the histological grading. Median postoperative PFS was 120 months in grade II, but only 18 months in grade III ependymomas (P = 0.1417). Thus, despite varying therapeutic concepts, analysis of this 40-year collective study confirms the prognostic relevance of localization and WHO grading in the case of intracranial ependymoma in children.Part of this paper was presented at the 10th European Congress of Neurosurgery, Berlin, Germany, 7–12 May 1995     

Spontaneous intracerebral hemorrhage from an unsuspected ependymoin early infancy

A case of spontaneous intracerebral hemorrhage from an occipital ependymoma grade 2 in a 3-month-old boy is reported. The infant died 3 days after surgery. The clinical and pathomorphological characteristics are described. Despite the usually rich vascularization of these tumors, hemorrhages from inracranial ependymomas are relatively uncommon. The different forms and probable cause of bleedings are discussed.     

Lacking immunocytological GD2 expression in neuroblastoma: report of 3 cases

Immunocytological bone marrow assessment for contamination with neuroblastoma cells is based on their characteristic GD2 surface staining. Neuroblastoma without GD2 expression have been rarely and only after antibody therapy reported. Conventional cytology was performed using Pappenheim staining. For immunocytology, the APAAP method was utilized with the 14G2a anti-GD2 mouse monoclonal antibody. 7 x 10(5) cells on cytospin preparations were investigated. In 2003, 288 bone marrow samples from 191 neuroblastoma patients were investigated by cytology and immunocytology. Three cases demonstrated GD2 negativity on cytologically unambiguous neuroblastoma cells. Two female cases (94 and 37 months of age) with stage 4 neuroblastoma had GD2 expressing neuroblastoma cells in bone marrow at diagnosis. At 2nd relapse 25 and 23 months after diagnosis and 8 months and 12 months after anti-GD2 antibody treatment (ch14.18), the bone marrow infiltrating neuroblastoma cells lacked GD2 staining. The third patient, a 63-month-old girl with bone marrow replacement by neuroblastoma cells showed at diagnosis a mixture of GD2-unstained tumor clumps and very weakly stained neuroblastoma cells. Neuroblastoma cells may lack GD2 expression at diagnosis and at recurrence. This observation has diagnostic and therapeutic implications.     

Spinal metastases of intracranial ependymomas. Four case reports and review of the literature

Intracranial ependymomas tend to spread along on the liquor pathways and thus to seed subarachnoid metastatic implants. According to autopsy data, spinal seeding can be expected in 25% of cases subsequent to surgery of the primary tumor.Analysis of four of our own cases (out of 125 primary intracranial ependymomas) together with those described in the literature suggests clinical evidence of seeding in 75% of patients. 47 of 75 metastases originated from malignant infratentorial ependymomas.Malignant ependymomas metastasize earlier than benign ones. They are characterized by disseminated seeding of tumor implants along the entire spinal subarachnoid space.The median survival time after diagnosis of seeding was 6 months. 80% of all patients died within the first 12 months following diagnosis.The necessity of prophylactic spinal radiation therapy in the course of the initial treatment of intracranial ependymomas has not yet been proven.     

Localized proton NMR spectroscopy of experimental gliomas in rat brain in vivo.

Experimental brain tumors produced in rats (n = 10) by stereotactic implantation of cells from the F98 anaplastic glioma clone into the right caudate nucleus were studied in vivo using localized proton NMR and in vitro using high-resolution proton NMR, bioluminescent imaging of lactate, ATP and glucose distributions, and fluorescent imaging of regional pH. In vivo spectra from normal brain contralateral to the tumor regions showed resonances assignable to N-acetyl aspartate (NAA), creatines, choline-containing compounds, myo-inositol, glutamate and glucose in a pattern similar to those obtained from normal anaesthetized rats. In vivo tumor spectra were characterized by the almost complete absence of NAA, a substantial reduction of total creatine and glucose, and an increase of cholines. Based on the in vitro spectra the increase of the myo-inositol signal observed in vivo was mainly attributed to glycine. Histological examination as well as bioluminescent and fluorescent imaging indicated two stages of tumor development, i.e., solid vital tumors and tumors with necrosis. However, there was no consistent relationship between proton NMR observations and tumor development.     

Histological Study of Lumbar Intervertebral Disc Herniation in Adolescents

Herniated intervertebral discs are rare in children and adolescents constituting approximately 1-5% of all patients undergoing surgery for lumbar and lumbosacral intervertebral disc herniation. Preceding traumata and congenital anomalities have been reported as important factors for the pathogenesis of intervertebral disc prolapses in young patients. The present histological study is based upon 15 patients with lumbar disc herniation within an age range from 14 to 19 years. Only in one case, was adequate trauma reported. All patients exhibited degenerative changes of the disc, similiar to those observed in adults. These changes were marked in 11 patients (73%). Thus, as known from adults, also in isolated traumatic disc herniation of adolescence, pre-existing degeneration of the disc has to be considered. If such changes are present, trauma has the significance of only transitory deterioration of the previous disc degeneration.     

Lymphocytic adenohypophysitis mimicking a pituitary macroadenoma

A 24-year-old woman developed headache and rapidly progressive visual disturbances during the last trimester of her first pregnancy. Magnetic resonance tomography (MRI) of the brain documented an intra- and suprasellar mass lesion. For preservation of vision, transsphenoidal microsurgical decompression was performed. Immediately postoperatively, visual acuity improved and hemianopia resolved. Histological examination yielded the diagnosis of primary lymphocytic adenohypophysitis. This is a rare inflammatory pituitary disease. There are no typical clinical, laboratory, or radiological findings that allow precise preoperative diagnosis. Even though this autoimmune disorder is principally steroid-responsive, an improvement of visual disturbances under steroid therapy cannot be predicted. Therefore, surgery is justified not only to establish the diagnosis, but also to restore vision by decompression of the optic nerves and the chiasm.