The problem of long-term ICP drift assessment: improvement by use of the ICP drift index.

BACKGROUND: Intracranial pressure (ICP) monitoring is dependent on the precise measurement of absolute pressures and low drifts of the different transducers in use. Our investigations have shown that probes sometimes appear to reveal positive and negative drifts consecutively. There is no regard for any of these important pressure changes by the mere result of the traditional drift. Therefore, we have developed a more precise way of assessing the behavior of the ICP drift. METHOD: A special laboratory set up for the simulation of constant pressures, at definite temperatures, was designed. We examined the Camino-110-4B, Gaeltec ICT/B, HanniSet and Spiegelberg transducers. Drift index is a new term that has been developed by our group to provide a better description of the actual pressure changes over long-term measurement. The drift index consists of three parameters: the percentage of measurements which show a pressure change during the 10 days of measurement; the maximum absolute pressure deviation that occurred during a ten day measurement; and the mean absolute pressure deviation during a 10 day measurement. FINDINGS: The median proportion of pressure changes during ten days were: Camino: 1.59%; Gaeltec: 0.71%; HanniSet: 0.08%; Spiegelberg: 4.00%; The median maximum absolute pressure changes were 6; 9.5; 1; and 11 mmHg for the four types and the median mean absolute pressure changes were 2.9; 5.1; 0; and 2.4 mmHg, respectively. The median 10 day classical drift in each type of transducer was 4; 9; 0; and 2 mmHg, respectively. INTERPRETATION: We recommend the use of the drift index to be used by manufacturers. This is an additional vital parameter in order to improve ICP measurement accuracy and the proficiency of ICP monitoring.

Methods of experimental and clinical assessment of the relative measurement accuracy of an intracranial pressure transducer. Technical note.

The assessment of the actual measurement accuracy of an intracranial pressure (ICP) transducer is imperative but still very difficult in practice. The authors tested the Codman MicroSensor ICP transducer experimentally. Additionally, a bedside test for assessment of measurement accuracy was used before and after clinical monitoring. For laboratory testing, seven new transducers were examined for measurement accuracy at increasing pressures ranging from 0 to 75 mm Hg. Drift was evaluated for 10 days at six different pressure levels ranging from 0 to 50 mm Hg. Temperature drift was assessed over a temperature range from 20 to 45 degrees C. The percentage absolute difference was used in the assessment of measurement accuracy. For clinical testing, measurement accuracy was assessed intraoperatively just before the insertion of the transducer and in an open water bath after its explantation, at 10 cm H2O both times. The maximum percentage absolute difference was 9% at a pressure of 10 mm Hg, and declined toward 2.3% at a pressure of 75 mm Hg. The maximum drift over 10 days was -4 mm Hg. Within the range of 30 to 40 degrees C, temperature drift was negligible. Over a period of 2 years, between June 1997 and June 1999, 40 ICP transducers were implanted in 35 patients by one surgeon. Of these devices, a malfunction was detected in two of them by testing them in a water bath before insertion. Experimental and clinical results indicate that this miniature strain-gauge transducer measures accurately; however, control readings for the probe by means of measurement in an open water bath just before insertion are strongly recommended.

Quality planning for minimally invasive procedures in neurosurgery.

Parallel to the introduction of a minimally invasive method in a department, a documentation system should be introduced for quality management. The first step of quality management of an innovation is quality planning. During the course of patients being treated neuroendoscopically, the pre- and postoperative imaging, the intraoperative video recording, the patient-relevant files and the data of the planning have to be documented. These amounts of data require a multimedial documentation concept. We found the CD-ROM as an optimal documentation media because the discs are both cheap and easily accessible and once stored extremely robust against external influences. Therefore, every neuroendoscopically treated patient is documented with all relevant pictures, files and video sequences on a single CD-ROM.

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(+) macrophage/microglial and glioma cells clustered in the immediate vicinity of focal necrosis of the human gliomas as well as of the rat C6 glioblastoma. The labeling score of IGFBP-1 accumulation in endothelial cells correlated negatively (P: = 0.0229), and that of IGFBP-2 accumulation in glioma cells correlated positively (P: < 0.0006) with the tumor grade of the gliomas. In addition, RT-PCR analysis confirmed mRNA expression of IGFBP-1, -2, and -3 by the gliomas and glial cells. Small amounts of IGFBP-1 and -3 mRNA, but high amounts of IGFBP-2 mRNA, were detectable in macrophage-like and glioma cell lines. The results suggest cell type-specific accumulation of IGFBP-1, -2, and -3 in human glial tumors of the brain. The increase in IGFBP-2 expression with this malignancy suggests a role of IGFBP-2 in the biology of human gliomas.

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.

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.

Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme.

The aim of the study was to characterize the interendothelial junctions in tumor microvessels of five cases of human glioblastoma multiforme. In addition to morphological analysis, tumors were screened for the expression of junctional proteins, such as occludin, claudin-1, ZO-1 and catenins. The expression of the tight junction protein claudin-1 was lost in the majority of tumor microvessels, whereas claudin-5 and occludin were significantly down-regulated only in hyperplastic vessels. As shown by freeze-fracture analysis, under the conditions of tumor growth tight junction particles of endothelial cells were almost exclusively associated with the exocytoplasmic fracture face, providing evidence for a switch of the particles from the protoplasmic to the external leaflet of the endothelial membrane. These results suggest a relationship between claudin-1 suppression and the alteration of tight junction morphology, which is likely to correlate with the increase of endothelial permeability. Underlining the undifferentiated state of tumor microvessels, plakoglobin, a crucial protein for mature endothelial junctions, was not detectable in most microvessels, whereas beta-catenin was abundantly labeled. In this context, it is of particular interest that the majority of microvascular pericytes were negative for alpha-smooth muscle actin, which is a marker of differentiated pericytes, although pericytes were frequently found in electron micrographs. In conclusion, the data suggest that the increase in microvascular permeability in human gliomas, contributing to the clinically severe symptoms of brain edema, is a result of a dysregulation of junctional proteins.

A role for preirradiation PCV chemotherapy for oligodendroglial brain tumors.

Oligodendroglial tumors have been identified as a subgroup of glial neoplasms with a distinctly better response to chemotherapy and overall survival than purely astrocytic gliomas. Here we report our experience with adjuvant postirradiation and preirradiation chemotherapy using procarbazine, lomustine, and vincristine (PCV) in 27 patients with WHO grade II or III oligodendroglioma or oligoastrocytoma. The efficacy of chemotherapy was assessed according to the Macdonald response criteria (complete response, CR; partial response, PR; stable disease, SD; progressive disease, PD) and progression-free survival intervals by computed tomography or magnetic resonance imaging. First, we confirm that PCV salvage therapy for patients progressing after radiotherapy is highly effective (n = 11, 1 CR, 5 PR, 5 SD; median progression-free survival has not yet been reached, but is longer than 18 months). Second, 3 patients who received radiotherapy plus PCV as first-line therapy achieved CR and 2 achieved SD, and all 5 are progression-free with a median follow-up of 12 months. Third, given these encouraging results, 11 patients received postoperative preirradiation PCV chemotherapy and were given radiotherapy only upon progression. Preirradiation PCV chemotherapy was also effective (2 CR, 3 PR, 6 SD; median progression-free survival has not been yet reached, but is longer than 14 months). Patients with anaplastic oligoastrocytomas were as likely to respond to PCV chemotherapy, as were patients with anaplastic oligodendroglioma. Three patients who had previously responded to PCV were successfully treated with a second course of PCV upon recurrence. PCV chemotherapy was also effective in patients with leptomeningeal spread of oligodendrogliomas. A randomized prospective trial is required to compare the effectiveness and neurotoxicity of first-line PCV chemotherapy followed by radiotherapy to the traditional reverse sequence.

Combined treatment effects after embolization and radiosurgery in high-grade arteriovenous malformations. Case report and review of the literature.

In recent years the multimodal therapy concept has been established for high-grade intracerebral arteriovenous malformations (AVM). One strategy of a multimodal treatment approach for patients with AVM (Spetzler grade V) is reported. After endovascular embolization, the patient underwent radiosurgical treatment of the remaining nidus with a linear accelerator, after which he developed a left-sided hemiparesis in conjunction with severe edema. Angiographic control 44 months after radiation showed an occlusion of the radiosurgically treated nidus. The remaining nidus could be removed by microsurgery. The combination of embolization and radiosurgery may provoke prolonged edema and permanent neurological deficits due to inflammatory perivascular changes.

ICP measurement control: laboratory test of 7 types of intracranial pressure transducers.

Intracranial pressure (ICP) monitoring has become an important parameter in the assessment of comatose patients, with raised intracranial pressure. The transducers in use have to fulfill the criteria of measurement accuracy, practicability and cost-effectiveness. However, these requirements are not always met in clinical practice. The need for ongoing quality control through independent laboratories remains. We have developed a laboratory set-up for the evaluation of intracranial pressure probes. Seven different types of currently used transducers have been tested for measurement accuracy. Under in vitro conditions 3 parameters were assessed: measurement accuracy, a 24 h drift and 10 day drifts. Tests for measurement accuracy were performed at increasing pressure levels of up to 80 mmHg. They were repeated 10 times per probe. This test allowed the simultaneous assessment of 5 different ICP probes. Drift was evaluated for 24 h and 10 days, at 6 pressure levels between 0 and 50 mmHg. Seven different types of ICP probes were tested (HanniSet, Camino, Codman, Spiegelberg, Medex, Epidyn and Gaeltec). Measurement accuracy was best with HanniSet probes. The maximum errors with this transducer were 3 mmHg. Camino and Codman showed similar results. Spiegelberg had slightly larger deviations. With Epidyn and Gaeltec the highest error were noted, up to 10 mmHg in the high pressure range. The 24 h drift was lowest with HanniSet (0.2 mmHg) and Camino (0.8 mmHg). The largest drifts were seen with Medex, Spiegelberg and Gaeltec (1.8 mmHg). Ten day drift was lowest with HanniSet (0.1 mmHg/day) and Codman (0.2 mmHg/day). The highest long-term drifts were found with Epidyn and Gaeltec (1.5 mmHg/day). Drift did not exhibit a linear pattern. After an initial rise in drift during the first 24-72 h, it decreased slowly during the next 7 days. Most ICP probes revealed measurement inaccuracy and drift. These results emphasize the necessity for ongoing evaluations of ICP probes. Therefore, tests for quality assurance are essential to establish a consistent standard of proficiency of ICP transducers.

[Measurement technique. Systems and methods for intracranial pressure monitoring]. / Messtechnik. Systematik und Methoden der intrakraniellen Druckmessung.

GOAL: Intracranial pressure (ICP) monitoring has a key role within the neuromonitoring, although ICP does not monitor processes of the central neuron directly and only with delay. One of the important factors in ICP monitoring is measurement accuracy. For a better understanding of ICP probes and their differences, the function and principles of intracranial pressure transducers should be evaluated from a technical point of view. METHOD: The principles of ICP measurement were analyzed and compared. Practical applications of these principles were examined and examples of different ICP probes were discussed regarding their mode of pressure transformation. The technical advances of ICP monitoring were analyzed. RESULTS: Since LUNDBERG, a variety of different types of transducers has been developed. Ventricular ICP monitoring has been supplemented by extradural and intraparenchymatous probes. An increasing miniaturization of the transducers has emerged. Additionally, fiberoptic systems have been developed. Latest developments include multifunctional ICP probes. So far, the main problem of most types of transducers consists in the inability to assess measurement accuracy of a probe during the period of patient monitoring. CONCLUSION: ICP probes should be tested better for correct function by the manufacturer prior to sale. External controls of the measurement accuracy should be performed more frequently to ensure constant quality. Future ICP transducers have still to be more cost-effective.

Radiosurgery for the treatment of brain metastases in renal cell carcinoma.

BACKGROUND: In the treatment of brain metastases using a stereotactically modified linear accelerator it could be shown that a single dose between 15 and 25 Gy leads to partial or complete remission of so-called radioresistant metastases from melanoma and hypernephroma. Radiosurgery of brain metastases then started in centers all over the world, however, experiences with brain metastases of renal cell carcinoma are yet limited. The aim of this analysis is therefore to present the treatment results of radiosurgery of brain metastases. Furthermore, in this paper prognostic subgroups shall be defined, in order to establish guidelines for an optimal therapy strategy. MATERIALS AND METHODS: Radiosurgery means stereotactically guided high-precision irradiation methods by extremely focussing ionizing radiation within the target volume as a single dose application. The characteristic steep dose decrease allows the selective destruction of small intracranial lesions, while the surrounding brain tissue is optimally protected. Two methods, Gamma Knife and stereotactic modified linear accelerator are clinically available. RESULTS: In larger studies from different groups all over the world, local tumor control rates from 85% to 95%, recurrence rates from 6% to 15% and side effects between 3% and 15% have been attained, independent of the system used. Prognostic factors, like volume of metastases < 10 ml, applied dose > 18 Gy, one or two metastases, absence of extracranial metastases, good patient performance with a Karnofsky score > 70%, primary treatment and more than one year between primary diagnosis and brain metastases showed a trend toward improved survival. Depending on the prognostic factors the median survival after radiosurgery ranged from 6 to 12 months. Retrospective comparison of radiosurgery and surgical series suggest that both modalities attain similar results. The dose can be applied with an accuracy of 0.3 mm. DISCUSSION: Based on these experiences, brain metastases can be treated by radiosurgery, primarily in patients with one or two metastases or in combination with whole brain irradiation as a boost in patients with more than two metastases. Furthermore with radiosurgery a new treatment modality exists to re-irradiate patients who have been failed after surgery or whole brain irradiation.

Clinical syndromes, natural history, and pathophysiology of vascular lesions of the spinal cord.

With superselective angiography and careful clinical evaluation, dural fistulas were found to be the most important and most frequent origin of spinal arteriovenous malformations. Diagnosis may not be made for months or years, however, because dural fistulas never bleed and clinical deterioration is slow. Therapy with interventional techniques or microsurgery is relatively safe. Perimedullary fistulas and intramedullary angiomas mostly deteriorate quickly because of hemodynamic or hemorrhagic problems. Close teamwork of interventionalists and neurosurgeons is mandatory.

[75 years after Dandy, Fay and Mixter--looking back on the history of neuroendoscopy]. / 75 Jahre nach Dandy, Fay und Mixter--Ein Rückblick auf die Geschichte der Neuroendoskopie.

The first neuroendoscopic operation was done in the year 1910 by the urologically practicing doctor Victor Darwin Lespinasse (1878-1946). Lespinasse never published this procedure. He only reported the case in front of a local surgical society. Several years later (1922/23) the first endoscopic operations in the brain were published by three neurological surgeons within one year (Dandy, Fay and Mixter). This 75 year anniversary is the background for the following historical overview.

Postoperative limited volume irradiation in a child with a solitary brain metastasis from Wilms tumor: a case report.

An 11-year-old boy presented with a solitary cerebral metastasis 2.5 years after initial diagnosis and 4 months after successful combined modality treatment of a stage II recurrent Wilms tumor in the chest. Resection of the brain metastasis was followed by limited volume irradiation with 30.0 Gy total dose. After a follow-up of 2.5 years the boy is in complete remission and shows no neurological or neuropsychological deficits indicating the possibility of curative postoperative radiotherapy of low toxicity and restricted to the tumor site in the presence of solitary brain metastases.

Primary Candida albicans empyema associated with epidural hematomas in craniocervical junction.

The case of a 27-year-old patient with chronic candida empyema in the craniocervical junction is presented. Occlusive hydrocephalus at admittance, primary subdural candida empyema, and recurrent epidural bleedings are the outstanding features in the clinical course. Despite intact immunity this patient acquired primary candidosis of CNS. Pathological changes in dura, ventricular system, and CSF required multiple shunt revisions. Antimycotic therapy was performed with a combination of 3 antimycotics. The clinical improvement was prolonged by several complications.

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

Intracranial 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 occurred 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.

Five years of stereotactic radiosurgery at the University of Tübingen--a critical review of the method.

At the University of Tübingen a Linac based stereotactic system for radiosurgery has been used since 1991. The floorstand system (SRS 200, Phillips) developed at Gainsville is used in combination with a Cosman Roberts Weels system by Radionics. The floorstand enables the gantry to be rotated vertically and the table to be rotated in the horizontal plane. Additionally, patient's movements are reduced by the fixation of the stereotactic ring to the stereotactic floorstand. We report our experience with the first 50 patients treated between December 1991 and June 1995. The patients were treated with an interdisciplinary approach. This cooperation eases the transition from radiosurgery to other methods such as embolization, operation, and other radiooncologic treatment options.