Cranial and ventricular size following shunting or endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: further insights from the International Infant Hydrocephalus Study (IIHS).

PURPOSE: The craniometrics of head circumference (HC) and ventricular size are part of the clinical assessment of infants with hydrocephalus and are often utilized in conjunction with other clinical and radiological parameters to determine the success of treatment. We aimed to assess the effect of endoscopic third ventriculostomy (ETV) and shunting on craniometric measurements during the follow-up of a cohort of infants with symptomatic triventricular hydrocephalus secondary to aqueductal stenosis. METHODS: We performed a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)-a prospective, multicenter study of infants (< 24 months old) with hydrocephalus from aqueductal stenosis who were treated with either an ETV or shunt. During various stages of a 5-year follow-up period, the following craniometrics were measured: HC, HC centile, HC z-score, and frontal-occipital horn ratio (FOR). Data were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and sex. RESULTS: Of 158 enrolled patients, 115 underwent an ETV, while 43 received a shunt. Both procedures led to improvements in the mean HC centile position and z-score, a trend which continued until the 5-year assessment point. A similar trend was noted for FOR which was measured at 12 months and 3 years following initial treatment. Although the values were consistently higher for ETV compared with shunt, the differences in HC value, centile, and z-score were not significant. ETV was associated with a significantly higher FOR compared with shunting at 12 months (0.52 vs 0.44; p = 0.002) and 3 years (0.46 vs 0.38; p = 0.03) of follow-up. CONCLUSION: ETV and shunting led to improvements in HC centile, z-score, and FOR measurements during long-term follow-up of infants with hydrocephalus secondary to aqueductal stenosis. Head size did not significantly differ between the treatment groups during follow-up, however ventricle size was greater in those undergoing ETV when measured at 1 and 3 years following treatment.

Elevated Pro-Inflammatory Cell-Free MicroRNA Levels in Cerebrospinal Fluid of Premature Infants after Intraventricular Hemorrhage.

Intraventricular hemorrhage (IVH) represents a high risk of neonatal mortality and later neurodevelopmental impairment in prematurity. IVH is accompanied with inflammation, hemolysis, and extracellular hemoglobin (Hb) oxidation. However, microRNA (miRNA) expression in cerebrospinal fluid (CSF) of preterm infants with IVH has been unknown. Therefore, in the present study, candidate pro-inflammatory cell-free miRNAs were analyzed in CSF samples from 47 preterm infants with grade III or IV IVH vs. clinical controls (n = 14). miRNAs were quantified by RT-qPCR, normalized to "spike-in" cel-miR-39. Oxidized Hb and total heme levels were determined by spectrophotometry as well as IL-8, VCAM-1, ICAM-1, and E-selectin concentrations by ELISA. To reveal the origin of the investigated miRNAs, controlled hemolysis experiments were performed in vitro; in addition, human choroid plexus epithelial cell (HCPEpiC) cultures were treated with metHb, ferrylHb, heme, or TNF-α to replicate IVH-triggered cellular conditions. Levels of miR-223, miR-155, miR-181b, and miR-126 as well as Hb metabolites along with IL-8 were elevated in CSF after the onset of IVH vs. controls. Significant correlations were observed among the miRNAs, oxidized Hb forms, and the soluble adhesion molecules. During the post-IVH follow-up, attenuated expression of miRNAs and protein biomarkers in CSF was observed upon elimination of Hb metabolites. These miRNAs remained unaffected by a series of artificially induced hemolysis, which excluded red blood cells as their origin, while stimulation of HCPEpiCs with oxidized Hb fractions and heme resulted in increased extracellular miRNA levels in the cell culture supernatant. Overall, the hemorrhage-induced CSF miRNAs reflected inflammatory conditions as potential biomarkers in preterm IVH.

Surgical treatment of tethered cord syndrome-comparing the results of surgeries with and without electrophysiological monitoring.

PURPOSE: To compare the short- and long-term outcomes after surgical treatment of tethered cord syndrome with and without electrophysiological monitoring. METHOD: We collected the preoperative data of 102 tethered cord surgeries of 91 patients. We compared the outcomes regarding the presence of intraoperative electrophysiology, the types of surgeries and the preoperative neurological condition. We also analysed the long-term outcomes in the cases of 69 patients. RESULTS: We found that intraoperative electrophysiology can reduce the perioperative surgical risk significantly (from 9.4 to 2.9%, p < 0.001), and electrophysiology is also beneficial in avoiding long-term progression in 88.7% (p = 0.03341). CONCLUSION: Tethered cord surgeries are safe and effective. With the use of intraoperative electrophysiology, the risk of postoperative worsening is as low as 2.9%, and long-term progression can be avoided in the majority of the patients.

Clinical and genetic characteristics of craniosynostosis in Hungary.

Craniosynostosis, the premature closure of cranial sutures, is a common craniofacial disorder with heterogeneous etiology and appearance. The purpose of this study was to investigate the clinical and molecular characteristics of craniosynostoses in Hungary, including the classification of patients and the genetic analysis of the syndromic forms. Between 2006 and 2012, 200 patients with craniosynostosis were studied. Classification was based on the suture(s) involved and the associated clinical features. In syndromic cases, genetic analyses, including mutational screening of the hotspot regions of the FGFR1, FGFR2, FGFR3, and TWIST1 genes, karyotyping and FISH study of TWIST1, were performed. The majority (88%) of all patients with craniosynostosis were nonsyndromic. The sagittal suture was most commonly involved, followed by the coronal, metopic, and lambdoid sutures. Male, twin gestation, and very low birth weight were risk factors for craniosynostosis. Syndromic craniosynostosis was detected in 24 patients. In 17 of these patients, Apert, Crouzon, Pfeiffer, Muenke, or Saethre-Chotzen syndromes were identified. In one patient, multiple-suture craniosynostosis was associated with achondroplasia. Clinical signs were not typical for any particular syndrome in six patients. Genetic abnormalities were detected in 18 syndromic patients and in 8 relatives. In addition to 10 different, known mutations in FGFR1,FGFR2 or FGFR3, one novel missense mutation, c.528C>G(p.Ser176Arg), was detected in the TWIST1 gene of a patient with Saethre-Chotzen syndrome. Our results indicate that detailed clinical assessment is of paramount importance in the classification of patients and allows indication of targeted molecular testing with the highest possible diagnostic yield.

[Intraoperativ electrophysiological monitoring during neurosurgery on eloquent structures]. / Intraoperatív elektrofiziológia elokvens idegrendszeri struktúrákat erinto idegsebészeti beavatkozások során.

OBJECTIVE: We summarize our experiences on intraoperative electrophysiological monitoring during neurosurgical procedures on eloquent neuronal structures. PATIENTS, METHODS: Sixty patients were enrolled retrospectively in our study with pathologies involving eloquent neuronal structures. They were operated between May 2011. and March 2012. at the University of Debrecen, Department of Neurosurgery and at the National Institute of Neurosciences. Patients underwent standard preoperative examinations due to the primary pathology. In all cases we used intraoperative electrophysiological monitoring. We had 22 cases with cranial nerve monitoring, 10 cases with cauda monitoring, 16 cases with motor system monitoring, six cases with complex spinal cord monitoring, three degenerative spine reconstructions and 3 awake surgeries. RESULTS: We found that with the use of intraoperative electrophysiology we could make these neurosurgical procedures safer, and were able to optimize the extent of resection in the cases of oncological pathologies. CONCLUSIONS: Our experiences as well as the international literature suggests that in certain high risk neurosurgical procedures intraoperative electrophysiology is indispensible for safe and optimally extended operation.

D-wave recording during the surgery of a 10-month-old child.

PURPOSE: The purpose of this study is to evaluate the possibility of d-wave recording in very young patients during spinal cord surgery. METHOD: A 10-month-old patient was operated on cystic intramedullary pathology and myelon tethering at level cervical VI. to thoracal III. During the surgical detethering, we did d-wave recording for experimental purposes. After transcranial electric stimulation, we tried to detect the responses with epidural d-wave electrodes proximally and distally from the pathology. RESULTS: We found that proximally from the pathology, we could detect reproducible d-waves. CONCLUSION: Though earlier papers reported that due to the immature condition of the myelon d-wave recording is not possible under the age of 21 months, we proved that even in very young patients, the possibility of d-wave recording should not be excluded.

Minor micro-rheological alterations in the presence of an artificial saphenous arteriovenous shunt, as an arteriovenous malformation model in the rat.

BACKGROUND: Arteriovenous malformations (AVMs) are vascular anomalies characterized by abnormal shunting between arteries and veins. The progression of the AVMs and their hemodynamic and rheological relations are poorly studied, and there is a lack of a feasible experimental model. OBJECTIVE: To establish a model that cause only minimal micro-rheological alterations, compared to other AV models. METHODS: Sixteen female Sprague Dawley rats were randomly divided into control and AVM groups. End-to-end anastomoses were created between the saphenous veins and arteries to mimic AVM nidus. Hematological and hemorheological parameters were analyzed before surgery and on the 1st, 3rd, 5th, 7th, 9th, and 12th postoperative weeks. RESULTS: Compared to sham-operated Control group the AVM group did not show important alterations in hematological parameters nor in erythrocyte aggregation and deformability. However, slightly increased aggregation and moderately decreased deformability values were found, without significant differences. The changes normalized by the 12th postoperative week. CONCLUSIONS: The presented rat model of a small-caliber AVM created on saphenous vessels does not cause significant micro-rheological changes. The alterations found were most likely related to the acute phase reactions and not to the presence of a small-caliber shunt. The model seems to be suitable for further studies of AVM progression.

Achondroplasia with multiple-suture craniosynostosis: a report of a new case of this rare association.

We report on a female patient with an exceedingly rare combination of achondroplasia and multiple-suture craniosynostosis. Besides the specific features of achondroplasia, synostosis of the metopic, coronal, lambdoid, and squamosal sutures was found. Series of neurosurgical interventions were carried out, principally for acrocephaly and posterior plagiocephaly. The most common achondroplasia mutation, a p.Gly380Arg in the fibroblast growth factor receptor 3 (FGFR3) gene, was detected. Cytogenetic and array CGH analyses, as well as molecular genetic testing of FGFR1, 2, 3 and TWIST1 genes failed to identify any additional genetic alteration. It is suggested that this unusual phenotype is a result of variable expressivity of the common achondroplasia mutation.

Ventriculosubgaleal shunt in the treatment of posthemorrhagic and postinfectious hydrocephalus of premature infants.

PURPOSE: The aim of the study was to compare the characteristics of ventriculosubgaleal shunts during the clinical course of posthemorrhagic and postinfectious hydrocephalus in the neonatal period. PATIENTS AND METHODS: The study comprised 102 premature babies in whom subgaleal shunt was consecutively inserted between 2006 and 2011. Seventy-two patients had posthemorrhagic hydrocephalus (mean gestational age 27.3 ± 2.1 weeks, mean birth weight 1,036.9 ± 327.7 g, mean age at insertion 51.4 ± 56.2 days) and 30 patients were operated postinfectiously (27.5 ± 2.2 weeks, 1,064.7 g ± 310.7 g, 115.9 ± 47.8 days). RESULTS: The mean survival of subgaleal shunts was 87.9 days for the posthemorrhagic group and 75.6 days for the postinfectious group. Only six infants (8.3 %) did not need ventriculoperitoneal shunts later, all posthemorrhagic. There were meaningful differences between two groups with regard to ventriculosubgaleal shunt-related infections (8.3 % in posthemorrhagic versus 20.0 % in postinfectious) and shunt revision rate (6.9 % in posthemorrhagic versus 13.3 % in postinfectious), but these were not statistically significant. The need of ventriculoscopic procedures was notably more frequent in postinfectious group (1.4 versus 23.3 %). CONCLUSION: In premature infants with ventriculomegaly, the subgaleal shunt is an effective temporary diversion tool. The complications were less with posthemorrhagic than with postinfectious hydrocephalus. With previous severe infections of prematures, the risk for complications regarding infection and obstruction will be 2.75 and 2.06 (odds ratios) times higher and more frequent need of ventriculoscopic procedures should be considered (odds ratio 21.6).

Shunt insufficiency due to knot formation in the peritoneal catheter.

The authors report a rare case of the peripheral obstruction of a ventriculoperitoneal shunt. Premature baby was operated on hydrocephalus due to germinal matrix bleeding. After two months of implantation of venticuloperitoneal shunt peripheral insufficiency of the system was emerged. During the shunt revision extensive knot formation became visible. We simply cut the catheter above the knot and the working shunt was replaced into the abdominal cavity. The postoperative course was uneventful and the baby was free of complaints for more than one year. The pathomechanism of knot formation is not clear thus the discovery of the problem during the operation is an unexpected event. In our opinion tight knot cannot be spontaneously formed intraabdominally. Loose knots can be developed and can reduce the capacity of liquor flow. We think that the knot tightens during pulling out. Longer peritoneal catheters can precipitate multiple looping and/or axial torquations and increase the peripheral resistance of the shunt. In such cases when the pulling out is challenged conversion to laparotomy is suggested.

Custom-made 3D printing-based cranioplasty using a silicone mould and PMMA.

All types of cranioplasty techniques restore the morphology of the skull and affect patient aesthetics. Safe and easy techniques are required to enhance patients' recovery and the rehabilitation process. We propose a new method of cranioplasty. The 3-dimensional (3D) reconstruction of a thin-layer computed tomography (CT) scan of the skull was used to reflect the intact side onto the defect and subtract the overlapping points from one another. In this way, a 3D model of the planned implant can be built in the required shape and size. The precise fit of the implant can be checked by printing the defective part of the skull in case it can be modified. A sterilisable silicone mould based on the finalized model was created afterwards. Polymethyl methacrylate implants were prepared directly in an aseptic environment in the operating room during surgery. Between 2005 and 2020, we performed 54 cranioplasties on 52 patients whose craniotomies were performed previously for indications of traumatic brain injury, stroke or tumour surgeries. No technical problems were noted during the operations. In 2 cases, septic complications that occurred were not connected to the technique itself, and the implants were removed and later replaced. Our proposed technique based on 3D-printed individual silicone moulds is a reliable, safe, easily reproducible and low-cost method to repair different skull defects.

European survey on neurosurgical management of primary central nervous system lymphomas and preoperative corticosteroid therapy.

Introduction: Preoperative corticosteroid therapy (CST) is common in primary central nervous system lymphoma (PCNSL) and may complicate histopathological diagnosis. There is an ongoing debate on the best management after preoperative CST. Research question: We aimed to survey how different European neurosurgical units treat PCNSL patients after preoperative CST. Methods: An English-language survey consisting of 21 questions addressing the management of patients with suspected PCNSL and preoperative CST was sent to European hospitals. The survey also included three clinical cases to assess the decision-making process in a clinical setting. Results: The survey was completed by 74 European hospitals. There was no clear consensus on how to treat a patient with PCNSL after CST. Accordingly, 24.3% responded that they would generally defer surgery regardless of a possible radiological response, 47.3% would defer surgery only if there is regression in preoperative MRI and the remaining 28.4% would defer surgery only if the tumor had completely vanished. Furthermore, there were distinct discrepancies in responses of neurosurgical units regarding their general management approach and their case-based decision in the three example cases. The results of our survey also showed regional differences and differences in treatment decisions between high-, intermediate- and low-volume centers. Discussion and conclusion: There was no clear consensus on how to treat patients with suspected PCNSL and preoperative CST. Furthermore, most centers also showed inconsistencies in their responses regarding their general approach as well as individual patient treatment. More high-quality evidence-based recommendations are needed to improve consensus and thus patient care.

Administration of preemptive analgesia by diclofenac to prevent acute postcraniotomy headache.

PURPOSE: Postcraniotomy headache (PCH) is a frequent perioperative complication in neuroanesthesia. The aim of the present work was to assess the incidence of PCH and to test the efficacy and safety of preoperatively administered diclofenac. METHODS: Patients undergoing craniotomies for intracranial tumor resections were enrolled. In the case group 100 mg diclofenac p.o. one hour prior to surgery was used as a preemptive analgesic along with infiltration of the surgical site with a combination of lidocaine and epinephrine. In controls only surgical site infiltration was used. VAS scores were assessed preoperatively, on the day of surgery (DoS), on the 1st and 5th postoperative days. RESULTS: We have found that PCH of any severity is between 50-90% during the first five days after surgery. The number of cases characterized as "no pain" significantly decreased in the early postoperative period, but remained in both groups still higher on the 5th postoperative day than observed preoperatively. In both groups, the number of headaches characterized as mild pain remained relatively stable and substantial increases in case numbers were observed in moderate and severe headaches, showing a declining tendency over time in the postoperative period. A significant effect of diclofenac pretreatment was observed compared to controls on DoS (chi2: 10.429, p<0.015), on the 1st (chi2: 8.75, p<0.032) and 5th postoperative days (chi2: 14.3, p<0.002). CONCLUSIONS: The relatively low incidence of severe PCH on day five in the diclofenac group may indicate that preoperatively administered diclofenac effectively reduces postcraniotomy headache. A randomized study is encouraged to test this hypothesis.

[Role of the intraoperative electrical brain stimulation in conserving the speech and language function in neurosurgical procedures on conscious patients]. / Az intraoperatív elektromos agyi stimuláció szerepe a nyelvi és beszédfunkciók megorzése céljából éber betegeken végzett idegsebészeti beavatkozások során.

AIM OF THE STUDY: To summarize the results gained with awake craniotomies, which were performed in either low grade glioma patients or epilepsy surgical patients whose tumor or epileptogenic zone, was in the vicinity of eloquent, mostly language, cortices. PATIENT SELECTION AND METHODS: In our retrospective study we selected 16 patients who were operated awake between 1999-2011 at the Neurosurgical Department of MAV Kórház Budapest, or at the National Institute of Neurosciences in Budapest, or at the Neurosurgical Department of the University of Debrecen in Debrecen. In the presurgical evaluation if it was possible we performed functional magnetic resonance imaging, tractography and detailed neuropsychological testing. At the National Institute of Neurosciences all patients were operated with the aid of MR guided neuronavigation. RESULTS: Anesthesia was carried out without complications in all of the 16 cases. Monitoring of sleep deepness has significantly contributed to the safety of anesthesia during the superficial anesthezied states of the operation. The intraoperative neuropsychological tasks used for testing language were sensitive enough to judge the little disturbances in speech during stimulation. Stimulation evoked seizures could be adequately managed during surgery and did not influence the outcome of the procedures. The use of neuronavigation helped significantly by planning the optimal place for the craniotomy and by intraoperative orientation. CONCLUSIONS: Awake craniotomies require well practiced surgical teams, which requires the cooperation of neuro-anesthesiologits, neurosurgeons, neuropsychologist and electrophysiologists. It has two goals, first to reduce the time of surgery to minimize surgical complications, secondly the detailed intraoperative mapping of cognitive and motor functions to avoid any neurological deficit. The intraoperative anatomical data provided by the neuronavigation and the functional data provided by awake intraoperative stimulation of the patient together serve the safety of the patient which is essential in the neurologically minimal invasive neurosurgical approach of the 21st century.

Intraoperative electrophysiology in children - Single institute experience of 96 examinations.

AIM: To summarize our experience gathered during the use of different intraoperative electrophysiological modalities in children. MATERIALS AND METHODS: We analyzed the data collected from 96 pediatric neurosurgical interventions. During the operations, we used a combination of intraoperative electrophysiological examinations tailored to the actual pathologies. The modalities included cortical and white matter mapping, cranial nerve and cranial nerve nucleus stimulation, motor evoked potential (MEP), somatosensory evoked potential (SSEP), peripheral nerve stimulation, bulbocavernosus reflex, and a special setup for selective dorsal rhizotomy. RESULTS: The success ratio of the different modalities varied between 25% and 100%. All the applied methods could be used in children. CONCLUSION: Although the application of certain intraoperative techniques could be limited due to the ongoing developmental and maturation processes in childhood, we can not exclude the possibility of successful recording in any modality. Thus, we recommend to apply all the available methods in children bearing in mind that the success ratio might be lower than that in the adult population.

Formation and Detection of Highly Oxidized Hemoglobin Forms in Biological Fluids during Hemolytic Conditions.

Hemolytic diseases are characterized by an accelerated breakdown of red blood cells (RBCs) and the release of hemoglobin (Hb). Following, RBC lysis Hb oxidation occurs with the formation of different redox states of Hb (metHb and ferrylHb) and the release of heme. ferrylHb is unstable and decomposes to metHb with the concomitant formation of globin radicals and eventually covalently crosslinked Hb multimers. The goal of the present study was to determine the concentrations of the different redox states of Hb in biological samples during hemolytic conditions. We used plasma and urine samples of mice with intravascular hemolysis and human cerebrospinal fluid (CSF) samples following intraventricular hemorrhage. Because ferrylHb is highly unstable, we also addressed the fate of this species. metHb and free heme time-dependently accumulate in plasma and CSF samples following intravascular hemolysis and intraventricular hemorrhage, respectively. ferrylHb is hardly detectable in the biological samples during hemolytic conditions. Under in vitro conditions, ferrylHb decomposes quickly to metHb, which process is associated with the formation of covalently crosslinked Hb multimers. We detected these covalently crosslinked Hb multimers in plasma, urine, and CSF samples during hemolytic conditions. Because globin modification is specific for these Hb forms, we propose to call this heterogeneous form of Hb produced during ferrylHb decomposition as globin-modified oxidized Hb (gmoxHb). Understanding the formation and the contribution of gmoxHb species to the pathogenesis of hemolytic conditions could have therapeutic implications in the treatment of hemolytic diseases.

The Role of Hemoglobin Oxidation Products in Triggering Inflammatory Response Upon Intraventricular Hemorrhage in Premature Infants.

Intraventricular hemorrhage (IVH) is a frequent complication of prematurity that is associated with high neonatal mortality and morbidity. IVH is accompanied by red blood cell (RBC) lysis, hemoglobin (Hb) oxidation, and sterile inflammation. Here we investigated whether extracellular Hb, metHb, ferrylHb, and heme contribute to the inflammatory response after IVH. We collected cerebrospinal fluid (CSF) (n = 20) from premature infants with grade III IVH at different time points after the onset of IVH. Levels of Hb, metHb, total heme, and free heme were the highest in CSF samples obtained between days 0 and 20 after the onset of IVH and were mostly non-detectable in CSF collected between days 41 and 60 of post-IVH. Besides Hb monomers, we detected cross-linked Hb dimers and tetramers in post-IVH CSF samples obtained in days 0-20 and 21-40, but only Hb tetramers were present in CSF samples obtained after 41-60 days. Vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8) levels were higher in CSF samples obtained between days 0 and 20 than in CSF collected between days 41 and 60 of post-IVH. Concentrations of VCAM-1, intercellular adhesion molecule-1 (ICAM-1), and IL-8 strongly correlated with total heme levels in CSF. Applying the identified heme sources on human brain microvascular endothelial cells revealed that Hb oxidation products and free heme contribute to the inflammatory response. We concluded that RBC lysis, Hb oxidation, and heme release are important components of the inflammatory response in IVH. Pharmacological interventions targeting cell-free Hb, Hb oxidation products, and free heme could have potential to limit the neuroinflammatory response following IVH.

The relative exposure of the operating room staff to sevoflurane during intracerebral surgery.

BACKGROUND: Our primary aim in this study was to investigate whether escape of the volatile anesthetic sevoflurane from the surgical site during craniotomy for tumor resection increases the exposure of the neurosurgeon to the anesthetic when compared with the anesthesiologist. METHODS: Initially, the release of sevoflurane from the surgical site was measured during 35 tumorectomies starting from opening to closure of the dura. Volatile anesthetic absorbers were placed at three detection sites: 1) the surgeon's breathing zone, 2) the anesthesiologist's breathing zone, and 3) the farthest corner of the operation room. In the second sampling series that included 16 patients, the detector that had been in the corner of the operating room in the first series was now placed in the vicinity of the patient's mouth (within 5 cm). Sevoflurane captured by the absorbers was quantified by an independent chemist using chromatography. RESULTS: Absorbers in the surgeon's breathing zone (0.24 +/- 0.04 ppm) captured a significantly lower amount of sevoflurane compared with absorbers in the anesthesiologist's breathing zone (1.40 +/- 0.37 ppm) and comparable with that in the farthest corner of the operation room (0.25 +/- 0.07 ppm). There was no correlation between the amount of absorbed sevoflurane and the size of craniotomy window, even when adjusting for the variation in duration of surgery. In the second series of sampling, absorbers in the proximity of the patient's mouth captured the highest amount of sevoflurane (1.54 +/- 0.55 ppm), followed by the anesthesiologist's (1.14 +/- 0.43 ppm) and the surgeon's (0.15 +/- 0.05 ppm) breathing zones. CONCLUSIONS: The close proximity of the surgeon's breathing zone to the craniotomy window does not appear to be a source of increased exposure to sevoflurane. The observed higher exposure of the anesthesiologist to sevoflurane in the operating room environment warrants further exploration.