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Intracranial physiology and biomechanics

Clinical data on pressure-volume relationships and their interpretation

Eugeny I. Paltsev and Edward B. Sirovsky

✓ The intracranial pressure-volume (PV) relationship was examined postoperatively after removal of brain tumors in two groups of patients (13 in all). Changes of ventricular fluid pressure were analyzed by a method involving fluid injection into the lateral ventricle. A technique has been developed which provides quantitative data on the PV relationship with minimal error. The results confirm the exponential nature of the PV relationships. Various parameters characterizing the intracranial volume compliance, the cerebrospinal fluid pressure, and their interrelationship were investigated. It was found that 1) intracranial PV dependence is accurately defined by three parameters; 2) in patients who are not critically ill, ΔP/ΔV at P = Pmean does not vary statistically, and may be used as one of the important parameters to determine the regulation of the intracranial PV relationships. Examples are presented of the use of the data from the PV test for the control of the intracranial PV relationship. Examples are also given of the computation of volume redistribution in the cranium, both spontaneous and evoked by clinical tests. Analysis of the results allows the conclusion that the intracranial volume compliance concerned is an active compliance, which is controlled by the systems maintaining brain function.

Open access


Julia Shawarba, Cand Med, Matthias Tomschik, and Karl Roessler

Facial and cochlear nerve preservation in large vestibular schwannomas is a major challenge. Bimanual pincers or plate-knife dissection techniques have been described as crucial for nerve preservation. The authors demonstrate a recently applied diamond knife dissection technique to peel the nerves from the tumor capsule. This technique minimizes the nerve trauma significantly, and complete resection of a large vestibular schwannoma without any facial nerve palsy and hearing preservation is possible. The authors illustrate this technique during surgery of a 2.6-cm vestibular schwannoma in a 27-year-old male patient resulting in normal facial function and preserved hearing postoperatively.

The video can be found here:

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John F. Stover, Nils-Kristian Dohse, and Andreas W. Unterberg

Object. Identification of new therapeutic agents aimed at attenuating posttraumatic brain edema formation remains an unresolved challenge. Among others, activation of bradykinin B2 receptors is known to mediate the formation of brain edema. The purpose of this study was to investigate the protective effect of the novel nonpeptide B2 receptor antagonist, LF 16-0687Ms, in brain-injured rats.

Methods. Focal contusion was produced by controlled cortical impact injury. Five minutes after trauma, the rats received a single dose of no, low- (3 mg/kg body weight), or high- (30 mg/kg) dose LF 16-0687Ms. After 24 hours, the amount of brain swelling and hemispheric water content were determined. Low and high doses of LF 16-0687Ms significantly reduced brain swelling by 25% and 27%, respectively (p < 0.03). Hemispheric water content tended to be increased in the nontraumatized hemisphere.

In a subsequent series of 10 rats, cisternal cerebrospinal fluid (CSF) samples were collected to determine whether changes in substances associated with edema formation could clarify why LF 16-0687Ms increases water content. For this, the volume regulator amino acid taurine, the excitatory transmitter glutamate, and the adenosine triphosphate degradation products hypoxanthine and xanthine were measured. In CSF, the levels of taurine, hypoxanthine, and xanthine were significantly decreased following a single administration of LF 16-0687Ms (p < 0.005); the level of glutamate, however, was double that found in control animals (p < 0.05).

Conclusions. Using the present study design, a single administration of LF 16-0687Ms successfully reduced posttraumatic brain swelling. The decreased levels of taurine, hypoxanthine, and xanthine may reflect reduced posttraumatic brain edema, whereas the increased level of glutamate could account for the elevated water content observed in the nontraumatized hemisphere.

Free access


Philine Behrens, Anna Tietze, Elisabeth Walch, Petra Bittigau, Christoph Bührer, Matthias Schulz, Annette Aigner, and Ulrich-Wilhelm Thomale


A standardized guideline for treatment of posthemorrhagic hydrocephalus in premature infants is still missing. Because an early ventriculoperitoneal shunt surgery is avoided due to low body weight and fragility of the patients, the neurosurgical treatment focuses on temporary solutions for CSF diversion as a minimally invasive approach. Neuroendoscopic lavage (NEL) was additionally introduced for early elimination of intraventricular blood components to reduce possible subsequent complications such as shunt dependency, infection, and multiloculated hydrocephalus. The authors report their first experience regarding neurodevelopmental outcome after NEL in this patient cohort.


In a single-center retrospective cohort study with 45 patients undergoing NEL, the authors measured neurocognitive development at 2 years with the Bayley Scales of Infant Development, 2nd Edition, Mental Developmental Index (BSID II MDI) and graded the ability to walk with the Gross Motor Function Classification System (GMFCS). They further recorded medication with antiepileptic drugs (AEDs) and quantified ventricular and brain volumes by using 3D MRI data sets.


Forty-four patients were alive at 2 years of age. Eight of 27 patients (30%) assessed revealed a fairly normal neurocognitive development (BSID II MDI ≥ 70), 28 of 36 patients (78%) were able to walk independently or with minimal aid (GMFCS 0–2), and 73% did not require AED treatment. Based on MR volume measurements, greater brain volume was positively correlated with BSID II MDI (rs = 0.52, 95% CI 0.08–0.79) and negatively with GMFCS (rs = −0.69, 95% CI −0.85 to −0.42). Based on Bayesian logistic regression, AED treatment, the presence of comorbidities, and also cerebellar pathology could be identified as relevant risk factors for both neurodevelopmental outcomes, increasing the odds more than 2-fold—but with limited precision in estimation.


Neuromotor outcome assessment after NEL is comparable to previously published drainage, irrigation, and fibrinolytic therapy (DRIFT) study results. A majority of NEL-treated patients showed independent mobility. Further validation of outcome measurements is warranted in an extended setup, as intended by the prospective international multicenter registry for treatment of posthemorrhagic hydrocephalus (TROPHY).

Free access


Johannes Sarnthein, Nader Hejrati, Marian C. Neidert, Alexander M. Huber, and Niklaus Krayenbühl


During surgeries that put the facial nerve at risk for injury, its function can be continuously monitored by transcranial facial nerve motor evoked potentials (FNMEPs) in facial nerve target muscles. Despite their advantages, FNMEPs are not yet widely used. While most authors use a 50% reduction in FNMEP response amplitudes as a warning criterion, in this paper the authors' approach was to keep the response amplitude constant by increasing the stimulation intensity and to establish a warning criterion based on the “threshold-level” method.


The authors included 34 consecutive procedures involving 33 adult patients (median age 47 years) in whom FNMEPs were monitored. A threshold increase greater than 20 mA for eliciting FNMEPs in the most reliable facial nerve target muscle was considered a prediction of reduced postoperative facial nerve function, and subsequently a warning was issued to the surgeon. Preoperative and early postoperative function was documented using the House-Brackmann grading system.


Monitoring of FNMEPs was feasible in all 34 surgeries in at least one facial nerve target muscle. The mentalis muscle yielded the best results. The House-Brackmann grade deteriorated in 17 (50%) of 34 cases. The warning criterion was reached in 18 (53%) of 34 cases, which predicted an 83% risk of House-Brackmann grade deterioration. Sensitivity amounted to 88% (CI 64%–99%) and specificity to 82% (CI 57%–96%). Deterioration of FNMEPs and a worse House-Brackmann grade showed a high degree of association (p < 0.001). The impact of FNMEP monitoring on surgical strategy is exemplified in an illustrative case.


In surgeries that put the facial nerve at risk, the intraoperative increase in FNMEP stimulation threshold was closely correlated to postoperative facial nerve dysfunction. Monitoring of FNMEPs is a valid indicator of facial nerve function in skull base surgery. It should be used as an adjunct to direct electrical facial nerve stimulation and continuous electromyographic monitoring of facial nerve target muscles.

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Walter Stummer, Alexander Novotny, Herbert Stepp, Claudia Goetz, Karl Bise, and Hans Jürgen Reulen

Object. It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department.

Methods. Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. Fluorescing tissue was removed whenever it was considered safely possible. Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection. Survival was analyzed using the Kaplan—Meier method and multivariate analysis was performed in which the Karnofsky Performance Scale (KPS) score, residual fluorescence, patient age, and residual enhancement on MR images were considered.

Intraoperatively, two fluorescence qualities were perceived: solid fluorescence generally reflected coalescent tumor, whereas vague fluorescence mostly corresponded to infiltrative tumor. Complete resection of contrast-enhancing tumor was accomplished in 33 patients (63%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 18 of the 19 remaining patients. Age, residual solid fluorescence, and absence of contrast enhancement in MR imaging were independent explanatory factors for survival, whereas the KPS score was significant only in univariate analysis. No perioperative deaths and one case of permanent morbidity were encountered.

Conclusions. The observations in this study indicate the usefulness of 5-ALA—induced tumor fluorescence for guiding tumor resection. The completeness of resection, as determined intraoperatively from residual tissue fluorescence, was related to postoperative MR imaging findings and to survival in patients suffering from GBM.

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Matthias Simon, Tjoung-Won Park, Sven Leuenroth, Volkmar H. J. Hans, Thomas Löning, and Johannes Schramm

Object. In recent reports, 6 to 19% of meningiomas have been classified as atypical or anaplastic/malignant. Some atypical and anaplastic meningiomas appear to arise from benign tumors by progression. Telomerase activation has recently been associated with malignant progression of human tumors. The authors have investigated a series of benign, atypical, and anaplastic/malignant meningiomas for telomerase activity and expression of the telomerase catalytic subunit human telomerase reverse transcriptase (hTERT).

Methods. A quantitative telomeric repeat amplification protocol was used to detect telomerase enzyme activity in seven (21%) of 34 benign, but in nine (75%) of 12 atypical and in seven (100%) of seven anaplastic/malignant meningiomas. Very high levels of telomerase activity were observed only in highly aggressive tumors. Messenger (m)RNA expression of the catalytic subunit hTERT was found in 11 (33%) of 33 benign, 12 (92%) of 13 atypical, and all seven anaplastic/malignant tumors. All telomerase-positive lesions were also positive for hTERT mRNA, whereas no telomerase activity was detected in six (21%) of 29 hTERT-positive tumors. This indicates that upregulation of hTERT is the rate-limiting step for telomerase activation in the majority of meningiomas. Expression of telomerase and hTERT was seen in all four tumors with gross brain invasion. All recurrent tumors or meningiomas recurring during follow up expressed hTERT.

Conclusions. The results are consistent with a role for telomerase activation during the development of malignancy in meningiomas. Hence, expression of telomerase activity and hTERT might prove to be potentially useful markers for the evaluation of these tumors.

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Bernhard Olzowy, Cornelia S. Hundt, Susanne Stocker, Karl Bise, Hans Jürgen Reulen, and Walter Stummer

Object. Accumulation of protoporphyrin IX (PPIX) in malignant gliomas is induced by 5-aminolevulinic acid (5-ALA). Because PPIX is a potent photosensitizer, the authors sought to discover whether its accumulation might be exploited for use in photoirradiation therapy of experimental brain tumors, without injuring normal or edematous brain.

Methods. Thirty rats underwent craniotomy and were randomized to the following groups: 1) photoirradiation of cortex (200 J/cm2, 635-nm argon-dye laser); 2) photoirradiation of cortex (200 J/cm2) 6 hours after intravenous administration of 5-ALA (100 mg/kg body weight); 3) cortical cold injury for edema induction; 4) cortical cold injury with simultaneous administration of 5-ALA (100 mg/kg body weight) and photoirradiation of cortex (200 J/cm2) 6 hours later; or 5) irradiation of cortex (200 J/cm2) 6 hours after intravenous administration of Photofrin II (5 mg/kg body weight). Tumors were induced by cortical inoculation of C6 cells and 9 days later, magnetic resonance (MR) images were obtained. On Day 10, animals were given 5-ALA (100 mg/kg body weight) and their brains were irradiated (100 J/cm2) 3 or 6 hours later. Seventy-two hours after irradiation, the brains were removed for histological examination.

Irradiation of brains after administration of 5-ALA resulted in superficial cortical damage, the effects of which were not different from those of the irradiation alone. Induction of cold injury in combination with 5-ALA and irradiation slightly increased the depth of damage. In the group that received irradiation after intravenous administration of Photofrin II the depth of damage inflicted was significantly greater. The extent of damage in response to 5-ALA and irradiation in brains harboring C6 tumors corresponded to the extent of tumor determined from pretreatment MR images.

Conclusions. Photoirradiation therapy in combination with 5-ALA appears to damage experimental brain tumors selectively, with negligible damage to normal or perifocal edematous tissue.

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Christian Strauss, Barbara Bischoff, Mandana Neu, Michael Berg, Rudolf Fahlbusch, and Johann Romstöck

Object. Delayed hearing loss following surgery for acoustic neuroma indicates anatomical and functional preservation of the cochlear nerve and implies that a pathophysiological mechanism is initiated during surgery and continues thereafter. Intraoperative brainstem auditory evoked potentials (BAEPs) typically demonstrate gradual reversible loss of components in these patients.

Methods. Based on this BAEP pattern, a consecutive series of 41 patients with unilateral acoustic neuromas was recruited into a prospective randomized study to investigate hearing outcomes following the natural postoperative course and recuperation after vasoactive medication. Both groups were comparable in patient age, tumor size, and preoperative hearing level. Twenty patients did not receive postoperative medical treatment. In 70% of these patients anacusis was documented and in 30% hearing was preserved. Twenty-one patients were treated with hydroxyethyl starch and nimodipine for an average of 9 days. In 66.6% of these patients hearing was preserved and in 33.3% anacusis occurred.

Conclusions. These results are statistically significant (p < 0.05, χ2 = 5.51) and provide evidence that these surgically treated patients suffer from a disturbed microcirculation that causes delayed hearing loss following removal of acoustic neuromas.

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Makoto Nakamura, Florian Roser, Mehdi Dormiani, Madjid Samii, and Cordula Matthies

Object. Meningiomas of the cerebellopontine angle (CPA) can either arise from or secondarily grow into the inner auditory canal (IAC). This location may have a great impact on hearing function following surgery to remove these lesions. The aim of this retrospective study was to investigate the reliability and predictive importance of auditory brainstem responses (ABRs) for the determination of postoperative auditory function in patients with CPA meningiomas in comparison with results obtained in patients who undergo surgery for vestibular schwannomas.

Methods. In a consecutive series of 1800 meningiomas surgically treated between 1978 and 2002, 421 lesions were located in the CPA. In 38 patients with CPA meningiomas involving the IAC, the findings of intraoperative ABR monitoring and the hearing status of each patient before and after surgery were retrospectively analyzed.

On analysis, ABR monitoring demonstrated stable findings in 24 patients throughout tumor resection and fluctuating signals in 10 patients. Among the 24 patients with stable ABRs, postoperative hearing function improved in three patients, remained the same in 15, and worsened in six patients, including one patient who displayed postoperative deafness. There was even one patient recovering from preoperative deafness. Among the 10 patients with unstable ABRs, intermittent decreases in amplitude and deformations of variable duration in the ABR wave were noted. The risk of deafness was considerably higher in patients with prolonged phases of intermittent ABR deterioration.

Conclusions. The presence and absence of ABRs during surgery for CPA meningiomas reliably predicted the presence and absence of postoperative auditory function. Intermittent deterioration of ABRs may result in postoperative deafness, depending on the duration of these events during surgery. Improvements in hearing are only seen when the ABRs are stable for amplitudes and latencies throughout surgery.