Ernst H. Grote

In vivo expression of insulin-like growth factor-binding protein-2 in human gliomas increases with the tumor grade

Human central nervous system tumors and glioma cell lines highly express the insulin-like growth factor-binding protein (IGFBP)-2. As IGFBP-2 can affect tumor growth, we studied the relationship between IGFBP-2 expression and the malignancy of brain tumors in vivo. To do so, we investigated by immunohistochemistry the accumulation of IGFBP-1, -2, and -3 in 50 human gliomas classified by the WHO Malignancy Scale. Double labeling using anti-CD68 (monocytes/macrophages), antiglial fibrillary acidic protein, and anti-CD3 (T cells) antibodies was performed to further characterize the IGFBP-1, -2, and -3+ cells. The expression of IGFBP messenger RNAs (mRNAs) was tested by RT-PCR in tumor samples from nine gliomas of different grades and in eight cell lines representing the cellular composition of human glioma. As controls, the accumulation of IGFBP-2 was investigated in normal brain and in the rat C6 glioblastoma model. IGFBP-1 and -3 accumulated in endothelial and macrophage/microglial cells. IGFBP-2+ macropha...

Peritumoural brain oedema in intracranial meningiomas: Influence of tumour size, location and histology

SummaryPeritumoural brain oedema was examined retrospectively in 175 patients with 179 intracranial meningiomas. The influence of tumour size, location and histology were investigated.Tumour volume and localization, and the presence of peritumoural brain oedema (PTBOe) were determined by computed tomography (CT). The oedema-tumour volume ratio was defined as Oedema Index (Oel). All patients underwent microsurgical removal of the tumour. Surgically resected meningiomas were classified histopathologically based on criteria of the new World Health Organization (WHO) classification. A close relationship was found between the tumour size and the incidence of peritumoural oedema: with increasing size of the tumour the incidence of oedema also rises, the oedema index, however decreases. Frontobasal and temporobasal meningiomas showed a significant increase in the oedema incidence and the mean oedema index. If major parts of the surface of meningiomas were adjacent to subarachnoid cisterns only a slight tendency for the development of oedema was observed. WHO-III-meningiomas showed a significantly higher oedema incidence (61.1% vs. 94.4%; p<0.004) and mean oedema index (Oel=2.7 vs. 3.7; p<0.0009) than WHO-I-meningiomas. Brain tissue was affected in 59 cases. 19 meningiomas with infiltration into adjacent brain parenchyma revealed a statistically significant increase in oedema incidence (94.7% vs. 51.7%; p<0.0003) and mean oedema index (Oel=3.9 vs. Oel=2.2; p<0.0001) when compared to tumours without any brain tissue involvement in the histopathological specimens. Tumours with large volume, fronto-temporo-basal location and anaplastic histology were not only associated with the highest incidence of oedema formation but also presented with an overproportionate infiltrative growth. Thus, a disruption of the arachnoid or a true brain infiltration may be an essential factor for the development of a PTBOe.

Heme oxygenase (HO)-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression.

Heme oxygenase (HO-1, HSP32) catalyzes the oxidation of heme to biliverdin and carbon monoxide, a putative neurotransmitter. In the brain, HO-1 expression has been associated with neuroprotection during oxidative stress and hypoxia. However, consecutive downstream mediation is involved in neoangiogenesis and consequent neoplastic outgrowth. We have analyzed HO-1 expression in 69 oligodendroglioma tissue samples, in rat intracranially transplanted C6 gliomas, and neuropathologically unaltered control brains by immunohistochemistry. Double labeling experiments confirmed the nature of HO-1 expressing cells. Reverse transcription-polymerase chain reaction was used to demonstrate HO-1 gene expression. HO-1 immunoreactivity was predominantly observed in macrophages/microglial cells. The number of HO-1 expressing macrophages/microglial cells was significantly lower in primary oligodendrogliomas than in their matched relapses (P<0.0001) and lower in primary anaplastic oligodendrogliomas than in their relapses (P=0.0006). Prominent accumulation of HO-1 expressing macrophages/microglial cells was observed in perinecrotic areas of both experimental rat and human glioblastoma relapses. HO-1 expressing neurons, macrophages/microglial cells and astrocytes were scattered in areas of infiltrative tumor growth. Surprisingly, HO-1 mRNA was detected in only one glioblastoma multiforme relapse. We conclude from these data that HO-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression in areas of focal necrosis. However, overall biological function of this phenomenon remains to be determined.

Repeated decompressive craniectomy after head injury in children: Two successful cases as result of improved neuromonitoring

BACKGROUND Decompressive craniectomy in the treatment of posttraumatic brain swelling is not generally accepted. Until now the efficacy of operative decompressive craniectomy in posttraumatic brain swelling of children appeared more promising. However, the criteria for such procedures remain unclearly defined. METHODS We present two children who had repeated decompressive craniectomy following head injury, in order to control intracranial pressure (ICP) sufficiently. Our indications for performing a decompressive craniectomy in the presence of conservatively uncontrollable raised ICP are: (1) Patient is between the ages of 3 and 35 years. (2) An initial Glasgow Coma Scale (GCS) ranging between 4 and 8. (3) Three criteria have to be fulfilled at the same time: The cerebral perfusion pressure (CPP) has to drop to values of less than 60 mm Hg. It is impossible to control the ICP values (up to 45 mm Hg) conservatively. The diastolic velocity of the transcranial doppler sonography (TCD) has to decrease until only a systolic flow pattern is obtained. (4) No other mass lesion should be detected on cranial computed tomography (CCT) that could account for the rise in pressure. In both cases we performed bifrontal decompressive craniectomies. RESULTS Both patients survived. Seven months after the accident, patient No. 1 was oriented and could walk on her own with a mild right-side hemiparesis. Patient No. 2 could attend school 12 months postinjury. Both patients developed hygromas after the craniectomy. A shunt operation, however, was not necessary. CONCLUSIONS ICP monitoring, together with CCT examination, simultaneous recording of TCD, and systemic parameters, will reveal a patient at risk at a time when impending damage due to uncontrollable ICP may still be prevented. The simultaneous assessment of cerebral blood flow by transcranial doppler (TCD), in this situation, proves most valuable. It improves the guidelines of patient selection for decompressive craniectomy, in the presence of conservatively uncontrollable ICP.

Cyclooxygenase (COX)-1 expressing macrophages/microglial cells and COX-2 expressing astrocytes accumulate during oligodendroglioma progression.

Cyclooxygenases (COX, prostaglandin endoperoxide synthases, PGG/H synthases) are potent mediators of edema, impeding blood flow and immunomodulation in the pathologically altered brain. Two COX iso-enzymes have been associated with brain disease, the constitutively expressed COX-1 and the cytokine-inducible COX-2. We have used single and double labeling immunohistochemistry to analyse COX-1 and COX-2 expression in twenty-six primary WHO grade II oligodendrogliomas, sixteen primary WHO grade III anaplastic oligodendrogliomas, twenty-seven matched recurrences and ten neuropathologically unaltered brains. COX-1 immunoreactivity was predominantly observed in macrophages/microglial cells. The number of COX-1 expressing macrophages/microglial cells was significantly lower in primary oligodendrogliomas than in primary anaplastic oligodendrogliomas (P<0.0001) and in anaplastic oligodendroglioma relapses (P=0.011). Patients with low COX-1 labeling scores in the primary tumors had significantly longer time to progression and overall survival (P=0.0285) than those with high COX-1 labeling scores. COX-2 immunoreactivity was predominantly observed in disseminated neurons and astrocytes. In glioblastoma multiforme relapses, accumulation of COX-2 expressing astrocytes was observed surrounding areas of focal necrosis. The number of COX-2 expressing astrocytes was significantly (P=0.0471) lower in primary oligodendrogliomas than in high grade oligodendroglioma relapses. These data provide convincing evidence for the differential accumulation of cyclooxygenase isoforms during oligodendroglioma progression in vivo.

Periventricular neurocytoma: A pathological entity

Three cases of periventricular neurocytomas are presented. All patients had a large but well-circumscribed, hyperdense tumor with insignificant contrast enhancement in the lateral and third ventricle, causing hydrocephalus. Calcification was present in one patient. Angiography revealed a blush tumor enhancement in two cases. Surgical removal was complete in two patients and incomplete in one. Light microscopy showed a cell pattern that resembled either ependymoma or oligodendroglioma. However, in all cases the tumor was confirmed to be a neurocytoma by immunocytochemical analysis that showed reactivity for synaptophysin and/or neuron-specific enolase in a high percentage of neoplastic cells. With respect to the literature it is concluded that neurocytomas represent an individual pathological entity of supratentorial midline tumors. Complete surgical removal without irradiation is the recommended treatment.

Recurrence of a Cerebral Arteriovenous Malformation after Surgical Excision

Complete resection of a cerebral arteriovenous malformation (AVM) should eliminate the future risk of an associated intracranial bleeding. Because total removal of an AVM may be difficult to assess at the time of surgery, postoperative angiography has become the accepted standard for documenting that complete removal has been achieved. However, even angiographically confirmed excision of an AVM does not completely exclude the possibility of rebleeding. Regrowth of an AVM with subsequent haemorrhage has been documented in children and is attributed to forces acting on the immature vasculature. The authors report the case of a 21-year-old man whose AVM recurred 5 years after angiographically proven complete excision. According to the presented case, the authors emphasise that, even in adults, angiographic documentation of total removal does not always eliminate the risk of reformation of an AVM.

ICP monitoring with a re-usable transducer: Experimental and clinical evaluation of the Gaeltec ICT/b pressure probe

SummaryIntracranial pressure monitoring requires reliable transducers at a justifiable price. At present, transducers for single or repeated use are available. We examined the Gaeltec model ITC/b solid state miniature transducer experimentally and clinically. Measurement accuracy was assessed in vitro at increasing steps of 5 mmHg from 0 to 80 mmHg. While new and recently serviced probes revealed minimal deviations from the preset values, frequently used transducers differed up to 7 mmHg. This occured especially in the high pressure range above 50 mmHg. Additionally the drift was investigated at different pressure levels. After 24 hours we already found drifts of 2 mmHg with new and serviced probes and up to 4 mmHg with used ones. In clinical practice we implanted 150 transducers in 121 patients from 1983 until 1995. The probes were re-used up to twelve times, the average time being 7 times, 32.7% of all measurements were regarded as not reliable. Dislocation (16.7%), inability to calibrate (3.3%) and defect pressure probes (3.3%) were the most common complications. Repeated use of the Gaeltec ICT/b probe also seemed to result in an additional decay of measurement quality.The strain of frequent cleaning and sterilizing may have caused changes of the physical properties of the probes with time. Whether these results also apply to other types of ICP probes for repeated use needs further evaluation.

Early activation of the primary somatosensory cortex without conscious awareness of somatosensory stimuli in tumor patients.

The primary sensory cortex has usually been regarded as a necessary step in the information processing stream leading to conscious awareness. Recently, it has been proposed that that higher order associative areas rather than the primary sensory areas are the neural basis of conscious perception. In two patients with tumors near the central region we recorded magnetic somatosensory evoked fields. Magnetic source imaging revealed early (40 ms) neural activation in primary somatosensory cortex and absence of later (>60 ms) neural activation in the primary and associative areas in these patients. None of the patients showed conscious awareness of somatosensory stimuli applied to the corresponding body site although the first component of the evoked field was within normal limits. The time course of the magnetic responses and additional evidence on intensity ratings of somatosensory stimuli suggest that early activity in the primary somatosensory cortex is not sufficient for conscious experience to emerge.

Traumatic brain swelling studied by computerized tomography and densitometry

Two-hundred and fifty-two computerized tomography (CT) scans of 107 patients with head injuries were analyzed. The most frequent consequence of trauma was a diffuse swelling of the brain in 91% of the cases. The severity of brain swelling and its course can be estimated by the compression of (or absence of) the intracranial cerebrospinal fluid space. These observations may be of prognostic value as well.By measurement of theHounsfield units (HU) in 52 cases the blood or water content in the brain tissues was assessed. An increase in blood content of the tissues (hyperaemia) can account for an increase in Hounsfield values. A decrease in HU suggests brain edema.The density measurements showed that in the first hours and days following head injury, the diffuse brain swelling was caused by severe cerebrovascular congestion in the majority (53%) of the cases. Immediate brain edema without a preceeding hyperaemic phase occurs less frequently (32%).Between the 1st and 4th day after injury, edema started to prevail, and between the 5th and 8th day the edematous type of brain swelling was present almost exclusively.