Notes: Abstract : 5-Aminolevulinic acid (5-ALA) is a precursor of porphyrins and heme that has been implicated in the neuropsychiatric symptoms associated with porphyrias. It is also being used clinically to delineate malignant gliomas. The blood-CSF barrier may be an important interface for 5-ALA transport between blood and brain as in vivo studies have indicated 5-ALA is taken up by the choroid plexuses whereas the normal blood-brain barrier appears to be relatively impermeable. This study examines the mechanisms of 5-[3H]ALA uptake into isolated rat lateral ventricle choroid plexuses. Results suggest that there are two uptake mechanisms. The first was a Na+-independent uptake system that was pH dependent (being stimulated at low pH). Uptake was inhibited by the dipeptide Gly-Gly and by cefadroxil, an α-amino-containing cephalosporin. These properties are the same as the proton-dependent peptide transporters PEPT1 and PEPT2, which have recently been shown to transport 5-ALA in frog oocyte expression experiments. Choroid plexus uptake was not inhibited by captopril, a PEPT1 inhibitor, suggesting PEPT2-mediated uptake. The presence of PEPT2 and absence of PEPT1 in the choroid plexus were confirmed by western blotting. The second potential mechanism was both Na+ and HCO3- dependent and appears to be an organic anion transporter, although it is possible that removal of Na+ and HCO3- may indirectly affect PEPT2 by affecting intracellular pH. The presence of PEPT2 and a putative Na+/HCO3--dependent organic anion transporter is important not only for an understanding of 5-ALA movement between blood and brain but also because these transporters may affect the distribution of a number of drugs between blood and CSF.

Notes: Summary  Deep-seated astrocytomas within the basal ganglia and the thalamus are considered unfavourable for microsurgical removal since the circumferential neighbourhood of critical structures limits radical resection. On closer assessment, the thalamus has a unique configuration within the basal ganglia. Its tetrahedric shape has 3 free surfaces and only the ventrolateral border is in contact with vital and critical functional structures, e.g. the subthalamic nuclei and the internal capsule. The purpose of the present study was to investigate the feasibility of maximum microsurgical removal in a series of intrinsic thalamic astrocytomas.  14 patients with intrathalamic astrocytomas grades 1 to 4 as diagnosed by previous stereotactic biopsy or intra-operative frozen section were selected for maximum microsurgical removal. The infratentorial supracerebellar approach from the contralateral side was used for 4 limited neoplasms of the pulvinar. For the other 10 larger and more extensive processes a parieto-occipital transventricular approach was chosen.  Final histology gave the result of astrocytoma grade 1 or 2 in 4 patients, and of astrocytoma grade 3 or 4 in 10 patients. Postoperative MRI confirmed reduction of the tumor mass by 80 to 100% in 11 of 14 cases. Regional ancillary radiotherapy with 60 Gy was administered postoperatively for astrocytomas grades 3 and 4. Two patients operated on via the posterior transventricular approach had new postoperative partial hemianopia. Five of the 14 patients finally needed a ventriculo-peritoneal shunt. During the follow-up time of 6 to 52 months, tumor progression/recurrence was observed in 6 of the 10 high grade and none of the low grade neoplasms.  The present pilot series demonstrates the feasibility of the microsurgical concept. Comparison with other treatment modalities, such as brachytherapy, requires future consideration.

Notes: Summary  Malignant gliomas accumulate fluorescing protoporphyrin IX intracellularly after exposure to 5-aminolevulinic acid, a metabolic precursor of haem. This phenomenon has been exploited for intra-operative identification of residual tumour to enable greater completeness of tumour removal. The present report describes the necessary modifications to the operating microscope to enable microsurgical, fluorescence-guided tumour removal.  The system consists of a xenon light source coupled to the microscope, which can be switched from normal white light to violet-blue excitation light (375–440 nm). A longpass filter is introduced into the observer light path to enable observation of tumour fluorescence. Transmission characteristics of excitation and observation filters are chosen to transmit part of the remitted excitation light. Thereby the observer retains an impression of tissue detail, next to tumour porphyrin fluorescence. An integrating three chip CCD camera optimized for red light detection enables documentation of fluorescence findings.  The present modifications allow uncomplicated and rapid recognition of red tumour fluorescence and its borders to normal tissue, without interrupting the course of the operation. Tissue detail is great enough to enable tumour resection under violet-blue excitation light during parts of the operation. The system appears to constitute a useful tool for optimizing removal of malignant gliomas on a routine basis.

Notes: Summary Severe head injury is frequently associated with focal or global disturbances of cerebral blood flow and metabolism. Routine monitoring of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in these patients does not provide information about critically reduced local or global cerebral blood flow. Measurements of cerebral lactate difference, Lactate-Oxygen-Index (LOI) and cerebral oxygen extraction were evaluated for advanced monitoring by comparing these parameters with ICP, cranial computed tomography (CCT) findings, and outcome in a group of severely head-injured patients. In 21 patients with severe brain trauma (GCS ⩽8), arterial as well as jugular venous lactate levels and oxygen saturation were measured in vitro every 6 h after admission of patients to the intensive care unit (ICU) throughout the acute course of treatment. Arterial blood pressure, blood gases, and ICP were assessed by standard monitoring measurements. CCT was performed initially after admission of the patients to the hospital, during the acute period in the ICU, if indicated, and 10 to 14 days after trauma. Outcome was classified according to the Glasgow outcome scale (GOS) at six months after injury. Data were averaged in each patient for every day after trauma and over the entire monitoring period. Resulting values were tested for correlation by regression analysis. Additionally, the data of the group of patients with normal to minimally elevated mean ICP (ICP〈20 mmHg, n=12) were compared to those of the patients with increased mean ICP (ICP〉20 mmHg, n=9). The cerebral lactate difference in all patients on the day of trauma was significantly increased as compared to the later period (0.20 vs. 0.11-0.07 mmol/L, p〈0.05), but was not different with high or normal to minimally elevated ICP. In patients with intracranial hypertension, the cerebral lactate difference remained significantly increased from the first to the fifth day after injury, whereas it normalized in this period in the group with normal to minimally elevated ICP. Averaged over the acute course, patients with increased ICP had significantly higher mean lactate differences (0.18±0.16 vs. 0.067±0.025 mmol/L, p=0.001) and higher mean LOIs (0.072±0.071 vs. 0.028±0.013, p=0.011). There was a significant correlation of increased mean cerebral lactate difference to poor outcome (r=0.46, p=0.035). Cerebral oxygen extraction in all patients tended to increase on the day of trauma (36.7% vs. 29.2% to 31.5% during the subsequent course), but this difference was not significant. The initial degree of brain swelling, classified by CCT according to Marshallet al. (1991), showed no correlation with cerebral lactate differences, ICP, O2-extraction, or outcome. Neither was there a correlation of cerebral oxygen extraction to ICP nor to outcome. In conclusion, the severity of brain trauma and outcome of patients was reflected by increased cerebral lactate production. Unchanged values of global cerebral oxygen extraction suggest that the regulatory mechanisms of brain oxygen supply were not impaired by trauma. Measurements of cerebral lactate differences and brain oxygen extraction may contribute to advanced monitoring in severe head injury.