Implementation of a mobile 0.15-T intraoperative MR system in pediatric neuro-oncological surgery: feasibility and correlation with early postoperative high-field strength MRI.

INTRODUCTION: We analyze our preliminary experience using the PoleStar N20 mobile intraoperative MR (iMR) system as an adjunct for pediatric brain tumor resection. METHODS: We analyzed 11 resections in nine children between 1 month and 17 years old. After resection, we acquired iMR scans to detect residual tumor and update neuronavigation. We compared final iMR interpretation by the neurosurgeon with early postoperative MR interpretation by a neuroradiologist. RESULTS: Patient positioning was straightforward, and image quality (T1 7-min 4-mm sequences) sufficient in all cases. In five cases, contrast enhancement suspect for residual tumor was noted on initial postresection iMR images. In one case, a slight discrepancy with postoperative imaging after 3 months was no longer visible after 1 year. No serious perioperative adverse events related to the PoleStar N20 were encountered, except for transient shoulder pain in two. CONCLUSIONS: Using the PoleStar N20 iMR system is technically feasible and safe for both supra- and infratentorial tumor resections in children of all ages. Their small head and shoulders favor positioning in the magnet bore and allow the field of view to cover more than the area of primary interest, e.g., the ventricles in an infratentorial case. Standard surgical equipment may be used without significant limitations. In this series, the use of iMR leads to an increased extent of tumor resection in 45 % of cases. Correlation between iMR and early postoperative MR is excellent, provided image quality is optimal and interpretation is carefully done by someone sufficiently familiar with the system.

In vivo assessment of the human cerebral microcirculation and its glycocalyx: A technical report.

INTRODUCTION: The cerebral microcirculation and its glycocalyx, a matrix coating the luminal endothelium, are key regulators of capillary permeability and cerebral blood flow. Microvascular abnormalities are described in several neurological disorders. However, assessment of the cerebral microcirculation and glycocalyx has mainly been performed ex vivo. NEW METHOD: Here, the technical feasibility of in vivo assessment of the human cerebral microcirculation and its glycocalyx using sidestream dark field (SDF) imaging is discussed. Intraoperative assessment requires the application of a sterile drape covering the camera (slipcover). First, sublingual measurements with and without slipcover were performed in a healthy control to assess the impact of this slipcover. Subsequently, using SDF imaging, the sublingual (reference), cortical, and hippocampal microcirculation and glycocalyx were evaluated in patients who underwent resective brain surgery as treatment for drug-resistant temporal lobe epilepsy. Finally, vessel density, and the perfused boundary region (PBR), a validated gauge of glycocalyx health, were calculated using GlycoCheck© software. RESULTS: The addition of a slipcover affects vessel density and PBR values in a control subject. The cerebral measurements in five patients were more difficult to obtain than the sublingual ones. This was probably at least partly due to the introduction of a sterile slipcover. Results on vessel density and PBR showed similar patterns at all three measurement sites. COMPARISON WITH EXISTING METHODS: This is the first report on in vivo assessment of the human cerebrovascular glycocalyx. Assessment of the glycocalyx is an additional application of in vivo imaging of the cerebral microcirculation using SDF technique. This method enables functional analysis of the microcirculation and glycocalyx, however the addition of a sterile slipcover affects the measurements. CONCLUSIONS: SDF imaging is a safe, quick, and straightforward technique to evaluate the functional cerebral microcirculation and glycocalyx. Because of their eminent role in cerebral homeostasis, this method may significantly add to research on the role of vascular pathophysiology underling various neurological disorders.

Validation of reference genes in human chordoma.

BACKGROUND: Chordoma are rare slow-growing tumors of the axial skeleton, which are thought to arise from remnants of the notochord. Little is known about the underlying mechanisms that drive this tumor. However, the assessment of gene expression levels by quantitative real-time polymerase chain reaction (qRT-PCR) is hampered due to a lack of validated reference genes. Using an unstable reference gene in qRT-PCR may lead to irreproducible results. METHODS: The expression of 12 candidate reference genes (ACTB, B2M, T, EF1a, GAPDH, HPRT, KRT8, KRT19, PGK1, RS27a, TBP, and YWHAZ) was analyzed by qRT-PCR in flash frozen chordoma samples from 18 patients. GeNorm and NormFinder algorithms were used to rank the stability of the genes. RESULTS: From most to least stably expressed, the top six genes found by geNorm were PGK1, YWHAZ, ACTB, HPRT, EF1A, and TBP. When analyzed by NormFinder, the top six genes were ACTB, YWHAZ, PGK1, B2M, TBP, and HPRT. GAPDH alone, which is often used as a reference gene in chordoma gene expression studies, is not stable enough for reliable results. CONCLUSION: In gene expression studies of human chordomas, PGK1, ACTB, and YWHAZ are more stably expressed, and therefore, are preferred reference genes over the most often used reference gene so far, GAPDH.

Notochord isolation using laser capture microdissection.

BACKGROUND: Chordoma are malignant tumors of the axial skeleton, which arise from remnants of the notochord. The Notochord (chorda dorsalis) is an essential embryonic structure involved in the development of the nervous system and axial skeleton. Therefore, the notochord seems to be the most biologically relevant control tissue to study chordoma in molecular biology research. Nevertheless, up to now mainly different tissues but not the notochord have been used as control for chordoma, due to difficulty of isolating notochordal tissue. Here, we describe a fast and precise method of isolating notochordal cells. METHODS: Examination of human fetuses, with a gestation of 9, 11 and 13 weeks, using (immuno)histochemical methods was performed. To isolate pure notochord cells for further molecular biology investigation five flash frozen fetuses between 9 and 10 weeks of gestation were dissected by microtome slicing. Thereafter pure notochord cells for further molecular biology investigation where harvested by using laser capture microdissection (LCM). RNA was extracted from these samples and used in quantitative PCR. RESULTS: This study illustrates notochord of embryonic spines in three different stages of gestation (9-11-13 weeks). Immunohistochemical staining with brachyury showed strong staining of the notochord, but also weak staining of the intervertebral disc and vertebral body. LCM of notochord slices and subsequent total RNA extraction resulted in a good yield of total RNA. qPCR analysis of two housekeeping genes confirmed the quality of the RNA. CONCLUSION: LCM is a fast and precise method to isolate notochord and the quality and yield RNA extracted from this tissue is sufficient for qPCR analysis. Therefore early embryo notochord isolated by LCM is suggested to be the gold standard for future research in chordoma development, classification and diagnosis.

Protocol for intraoperative assessment of the human cerebrovascular glycocalyx.

INTRODUCTION: Adequate functioning of the blood-brain barrier (BBB) is important for brain homoeostasis and normal neuronal function. Disruption of the BBB has been described in several neurological diseases. Recent reports suggest that an increased permeability of the BBB also contributes to increased seizure susceptibility in patients with epilepsy. The endothelial glycocalyx is coating the luminal side of the endothelium and can be considered as the first barrier of the BBB. We hypothesise that an altered glycocalyx thickness plays a role in the aetiology of temporal lobe epilepsy (TLE), the most common type of epilepsy. Here, we propose a protocol that allows intraoperative assessment of the cerebrovascular glycocalyx thickness in patients with TLE and assess whether its thickness is decreased in patients with TLE when compared with controls. METHODS AND ANALYSIS: This protocol is designed as a prospective observational case-control study in patients who undergo resective brain surgery as treatment for TLE. Control subjects are patients without a history of epileptic seizures, who undergo a craniotomy or burr hole surgery for other indications. Intraoperative glycocalyx thickness measurements of sublingual, cortical and hippocampal microcirculation are performed by video microscopy using sidestream dark-field imaging. Demographic details, seizure characteristics, epilepsy risk factors, intraoperative haemodynamic parameters and histopathological evaluation are additionally recorded. ETHICS AND DISSEMINATION: This protocol has been ethically approved by the local medical ethical committee (ID: NL51594.068.14) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Informed consent is obtained before study enrolment and only coded data will be stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NTR5568.

A vertebral extra dural chordoma at C5, possibly deriving from a clival chordoma.

BACKGROUND: Clival chordomas are a rare type of cancer with low metastatic potential and primary metastasize to the lung or bones. CASE DESCRIPTION: This case report describes a possible metastatic, paravertebral chordoma at level C4-C5 in a patient with a past medical history of a clival chordoma. CONCLUSION: Chordomas are unpredictable and may metastasise.

Deep brain stimulation in tinnitus: current and future perspectives.

Chronic tinnitus, also known as ringing in the ears, affects up to 15% of the adults and causes a serious socio-economic burden. At present, there is no treatment available which substantially reduces the perception of this phantom sound. In the past few years, preclinical and clinical studies have unraveled central mechanisms involved in the pathophysiology of tinnitus, replacing the classical periphery-based hypothesis. In subcortical auditory and non-auditory regions, increased spontaneous activity, neuronal bursting and synchrony were found. When reaching the auditory cortex, these neuronal alterations become perceptually relevant and consequently are perceived as phantom sound. A therapy with a potential to counteract deeply located pathological activity is deep brain stimulation, which has already been demonstrated to be effective in neurological diseases such as Parkinson's disease. In this review, several brain targets are discussed as possible targets for deep brain stimulation in tinnitus. The potential applicability of this treatment in tinnitus is discussed with examples from the preclinical field and clinical case studies.

Identification of subgroups of high-grade oligodendroglial tumors by comparative genomic hybridization.

In contrast to astrocytic tumors, approximately two thirds of anaplastic oligodendrogliomas are reported to be chemosensitive. Relatively little is known about the genetic aberrations in oligodendroglial tumors (OTs). In order to elucidate oligodendroglial oncogenesis and to find specific genetic aberrations that may have prognostic and therapeutic implications, we performed comparative genomic hybridization (CGH) to detect chromosomal copy number changes in 17 low-grade OTs (LG-OTs) and 12 high-grade OTs (HG-OTs) lacking a prominent astrocytic component. Loss of chromosome 1p (79%) and 19q (76%) were most frequently detected by CGH, all LG-OTs and 50% of the HG-OTs contained -1p (including 1p36-32), -19q (including 19q13.3), or both, and the rest of the HG-OTs showed +7, -10, or both. Since losses of 1p36-32 and 19q13.3 were mutually exclusive with +7 or -10, the HG-OTs could be divided in -1p/-19q and +7/-10 tumors. While the -1p/-19q tumors can be considered as pure anaplastic oligodendrogliomas, the +7/-10 tumors may rather be glioblastomas with prominent oligodendroglial differentiation. We conclude that CGH is a powerful tool to assist in the identification of 2 major subgroups of HG-OTs with prognostic and possibly therapeutic relevance.

PTEN mutation analysis in two genetic subtypes of high-grade oligodendroglial tumors. PTEN is only occasionally mutated in one of the two genetic subtypes.

We recently identified two genetic subtypes of high-grade oligodendroglial tumors (HG-OT): 1p-/19q- HG-OT are characterized by a loss of chromosome 1p32-36 (del(1)(p32-p36) and/or a del(19)(q13. 3); whereas +7/-10 HG-OT harbor a gain of chromosome 7 (+7) and/or a -10 without a loss of 1p32-36 and 19q13.3. Because a -10 and a +7 are most frequently detected in glioblastomas (GBM), the genotype of +7/-10 HG-OT suggests that these tumors are GBM with a prominent oligodendroglial phenotype rather than anaplastic oligodendrogliomas. PTEN is a tumor suppressor gene, located at 10q23.3, which is involved in tumor progression of GBM and other neoplasms. In this study, we screened for PTEN mutations in six low-grade oligodendroglial tumors (LG-OT), five 1p-/19q- HG-OT, seven +7/-10 HG-OT, and nine xenografted GBM. PTEN mutations were detected in none of the LG-OT and 1p-/19q- HG-OT, once in +7/-10 HG-OT, and frequently in GBM. As one of the +7/-10 HG-OT harbored a PTEN mutation, this demonstrates that PTEN can be involved in the oncogenesis of this genetic subtype of HG-OT. The lower frequency of PTEN mutations in +7/-10 HG-OT compared to GBM suggests that these tumors are of a distinct tumor type rather than GBM. Published by Elsevier Science Inc.

Lumbar cerebrospinal fluid drainage for symptomatic sacral nerve root cysts: an adjuvant diagnostic procedure and/or alternative treatment? Technical case report.

OBJECTIVE AND IMPORTANCE: The treatment of symptomatic sacral nerve root cysts is difficult and challenging. A major role has been ascribed to the hydrostatic and pulsatile forces of cerebrospinal fluid (CSF) for the symptomatology of sacral nerve root cysts. Theoretically, lowering those pressures should have a beneficial effect on the symptoms. Lowering the hydrostatic and pulsatile pressures may be achieved by lumbar CSF drainage. The effect of lumbar CSF drainage on the symptomatology of sacral nerve root cysts is described. CLINICAL PRESENTATION: Three patients suffered from leg and/or low back pain as a result of sacral nerve root cysts. INTERVENTION: First, CSF was drained through an external lumbar drain that was connected to a CSF bag. Mobilization was not restricted. All patients became free of symptoms. Eventually, a lumboperitoneal shunt was inserted in two patients. Those two patients remained free of complaints for 11 and 9 months, respectively. CONCLUSION: To our knowledge, this is the first report that clearly establishes the role of CSF forces in the symptomatology of sacral nerve root cysts. Lumbar external CSF drainage is a diagnostic tool to investigate the clinical significance of sacral nerve root cyst(s). Lumboperitoneal CSF shunting is a promising alternative in the treatment of symptomatic sacral nerve root cysts.

Occipitotranstentorial approach for lesions of the superior cerebellar hemisphere: technical report.

OBJECTIVE: The occipitotranstentorial approach is well accepted for lesions of the pineal region, superior cerebellar vermis, or mesencephalon. Although evidently suitable, this approach has not, to our knowledge, been reported for lesions of the superior cerebellar hemisphere in adults. Experience with this approach is reported. METHODS: Four patients underwent surgery between August 1995 and March 1997. The findings obtained are evaluated. RESULTS: All lesions were situated in the quadrangular lobules (one extending into the vermis), and all were completely removed. Postoperative deficits, especially visual field deficits, did not occur. CONCLUSION: Lesions of the superior cerebellar hemispheres are easily approached by an occipitotranstentorial route. The major advantages over a supracerebellar approach are that the surgical route is nearly perpendicular to the lesion and to the tentorium instead of parallel, and wide exposure is thereby possible.

Protective coating of cranial nerves with fibrin glue (Tissucol) during cranial base surgery: technical note.

OBJECTIVE: Cranial nerve deficit, either transient or permanent, is a common postoperative complication after cranial base surgery. Frequently, this occurs because intracranial nerves are directly involved in the cranial base lesion. However, any cranial nerve adjacent to the lesion can be damaged because of direct or indirect manipulation during surgery, leading to severe morbidity. We describe a new technique in which the adjacent intracranial nerves are protected from surgical trauma by coating the nerves with a biological two-component fibrin glue (Tissucol; Immuno A.G., Vienna, Austria). SURGICAL TECHNIQUE: The technique was performed in patients who underwent cranial base surgery for different types of lesions. After exposure of the operating field, the cranial nerves that were at risk of operative trauma were coated with a thin layer of fibrin glue using a double lumen catheter within a traditional suction device. RESULTS: With the application of fibrin glue, a protective layer of a rubbery consistency is formed around the nerve. No intraoperative complications or adverse effects of the application were noted. Moreover, no surgical injury of the nerves occurred and no or minimal postoperative cranial nerve deficit was noted in the coated nerves. CONCLUSION: Although it is difficult to compare the postoperative cranial nerve deficit in the coated nerves with a control group, we think that this technique is a valuable method to minimize or avoid intraoperative cranial nerve injury during cranial base surgery.

Charles Labbé (1851-1889).

The vein of Labbé is a very important structure and every neurosurgeon is acquainted with its anatomy. Because of the recent increasing interest and experience in skull base surgery, the vein of Labbé has received a great deal of attention. Intraoperative damage to this vein should be avoided and several methods to prevent this have been described. Despite these developments, nothing is written in the neurosurgical literature about the man who described this vein for the first time: Charles Labbé. The authors therefore conducted an extensive search of the literature and uncovered several public records in France to learn more about Charles Labbé.

Falcine sinus and occipital encephalocele: a magnetic resonance venography study.

OBJECT: Occipital encephaloceles are relatively frequently encountered. Many investigators have addressed the embryogenesis of these formations, but the dural system has never before been studied. In this retrospective analysis the authors sought to gain a better understanding of the origins of these defects. METHODS: The charts and radiological examinations, especially the magnetic resonance venography studies, were reviewed in seven patients. In six patients the straight sinus was absent. Drainage of the galenic system took place through a sinus within the falx, also known as a falcine sinus. The tentorium was not seen in five patients. CONCLUSIONS: The combination of an absent straight sinus and dysplastic tentorium is no coincidence: both develop within the same mesenchyme in the mesencephalic flexure. Distortion of the mesenchyme by a neural tube defect, causing an occipital encephalocele, will lead not only to disorders of the tentorium but also of the straight sinus.

Intracranial repair of a divided trochlear nerve. Case report.

The authors report the case of a 37-year-old woman in whom the trochlear nerve was transected during removal of a meningioma in the cavernous sinus and subsequently repaired by using microsurgical techniques. This patient presented with a tumor in the posterior part of the right cavernous sinus with expansion over the tentorium. Preoperatively, she suffered from partial deficit of the right trochlear nerve. Intraoperatively, the trochlear nerve was noted to be completely encased by the tumor and was totally divided during removal of the lesion. After tumor resection, the trochlear nerve was repaired by using a sural nerve fascicle secured with sutures and fibrin glue. Six months after the operation, trochlear nerve regeneration became evident as the patient's binocular vision gradually improved. The patient regained normal functioning of the superior oblique muscle 3.5 years after surgery. It is concluded that repair of a divided trochlear nerve is worthwhile and can be followed by successful regeneration and an excellent functional recovery of the superior oblique muscle.

Surgical management of ulnar nerve compression at the elbow: an analysis of the literature.

OBJECT: Surgical treatment for cubital ulnar nerve compression includes medial epicondylectomy, simple decompression, or anterior transposition (subcutaneous, intramuscular, or submuscular). There is a dearth of prospective randomized studies on which to base guidelines for choosing one operative treatment over another. The authors review the literature on this subject and present their findings. METHODS: The authors reviewed the literature from January 1970 to July 1997. Two authors decided independently whether an article should be included for review based on previously formulated inclusion and exclusion criteria. In addition to demographic information, data concerning preoperative status and outcome were extracted. For statistical analyses chi-square and Kruskal-Wallis tests were performed. Irrespective of their preoperative status, patients with simple decompression had the best outcome, whereas those with anterior subcutaneous and submuscular transposition had the worst. If outcome was related to the patient's preoperative status, a significant difference was not found among the various groups for those patients with a preoperative McGowan Grade 2. However, for those with McGowan Grade 3 (severe) symptoms, patients with anterior intramuscular transposition had the best outcome followed by those with simple decompression and anterior submuscular transposition. Statistical analysis was not possible for patients with McGowan Grade 1 because of the small numbers of patients in several treatment modality groups. CONCLUSIONS: Formulating a uniform guideline for operative treatment is not possible based on the results of this study. However, the authors believe that support is given to their policy, which is primarily to perform a simple decompression. Its surgical simplicity with preservation of the anatomy, especially the vascularization, and the possibility of rapid postoperative rehabilitation are also taken into consideration. If subluxation is found intraoperatively, anterior transposition is proposed.

Genetic reflection of glioblastoma biopsy material in xenografts: characterization of 11 glioblastoma xenograft lines by comparative genomic hybridization.

OBJECT: Human tumors implanted as subcutaneous xenografts in nude mice are widely used for the study of tumor biology and therapy. Validation of these models requires knowledge of the genetic makeup of the xenografts. The aim of this study was to establish whether chromosomal imbalances in 11 xenograft lines derived from human glioblastomas multiforme (x-GBMs) are similar to those found in GBM biopsy samples. The authors also studied genetic stability during serial passaging of three xenograft lines. METHODS: Chromosomal imbalances in x-GBMs were detected using comparative genomic hybridization (CGH). The authors compared the CGH results in x-GBMs with those in the original GBMs (o-GBMs) that were used to establish three of the xenograft lines and with the GBM biopsy results reported in the literature (1-GBMs). In three xenograft lines two different passages were analyzed. CONCLUSIONS: The results show that the chromosomal imbalances in x-GBMs are similar to those in o-GBMs and 1-GBMs, indicating that the GBM xenograft lines used were valid models from a genetic point of view. The CGH analysis of two different passages of three xenograft lines indicates that x-GBMs (like 1-GBMs) show intratumoral genetic heterogeneity and do not acquire chromosomal imbalances as a result of serial passaging.

Anatomy of the sympathetic pathways in the cavernous sinus.

We studied sympathetic fibres in the cavernous sinus in 40 unfixed specimens obtained from human cadavers. Sympathetic fibres in the cavernous sinus are understood to be grouped in a plexiform configuration surrounding the internal carotid artery and have a diffuse distribution among the sympathetic nerves. Our study, however, suggests that a more systematic arrangement of sympathetic pathways exists in the cavernous sinus. A detailed anatomical description of intracavernous sympathetic fibres contributes to academic anatomical knowledge and may have practical applications for 1. diagnostic interpretation of pathologic conditions involving the cavernous sinus, 2. recognition and orientation of anatomical structures during intracavernous surgical procedures, and 3. a deeper understanding of the sympathetic nerve supply to cerebral vasculature.

The cavernous sinus syndrome. An anatomical and clinical study.

The cavernous sinus is often involved pathologically, which can cause ocular motor nerve palsies with or without facial sensory disturbances. Consequently several clinical features of ocular motor nerve palsies have been described. In this article we present a study of the cavernous sinus syndrome, and compare this syndrome with other nerve palsy syndromes caused by lesions in or adjacent to the cavernous sinus. The clinical features are explained by means of an anatomical study of the cavernous sinus.

On the mechanism of transient postoperative deficit of cranial nerves.

BACKGROUND: Transient cranial nerve deficit is a common postoperative complication after surgery at the cranial base. In this type of surgery, the cranial nerves are often not macroscopically damaged or transected, but more or less manipulated during surgery. In this article, the cellular mechanisms of postoperative cranial nerve deficit are reviewed. METHODS: Experimental and clinical papers concerning cranial and peripheral nerve damage during surgery were critically reviewed. RESULTS: There are definite differences in the anatomical and histological structure between peripheral and intracranial nerves, which make the latter much more prone to intraoperative damage. Several pathological mechanisms are responsible for postoperative deficit, such as segmental demyelination of the nerve, comprised microcirculation within the nerve, postoperative edema, and "synaptic stripping" around the cell bodies of the affected neurons, which can be regarded as a regenerative response of the nervous system. CONCLUSIONS: Several cellular mechanisms are responsible for postoperative cranial nerve deficit after skull base surgery. Understanding these mechanisms is important for all surgeons involved in the treatment of skull base lesions.