Dentatorubrothalamic tract localization with postmortem MR diffusion tractography compared to histological 3D reconstruction.

Diffusion-weighted imaging (DWI) tractography is a technique with great potential to characterize the in vivo anatomical position and integrity of white matter tracts. Tractography, however, remains an estimation of white matter tracts, and false-positive and false-negative rates are not available. The goal of the present study was to compare postmortem tractography of the dentatorubrothalamic tract (DRTT) by its 3D histological reconstruction, to estimate the reliability of the tractography algorithm in this specific tract. Recent studies have shown that the cerebellum is involved in cognitive, language and emotional functions besides its role in motor control. However, the exact working mechanism of the cerebellum is still to be elucidated. As the DRTT is the main output tract it is of special interest for the neuroscience and clinical community. A postmortem human brain specimen was scanned on a 7T MRI scanner using a diffusion-weighted steady-state free precession sequence. Tractography was performed with PROBTRACKX. The specimen was subsequently serially sectioned and stained for myelin using a modified Heidenhain-Woelke staining. Image registration permitted the 3D reconstruction of the histological sections and comparison with MRI. The spatial concordance between the two modalities was evaluated using ROC analysis and a similarity index (SI). ROC curves showed a high sensitivity and specificity in general. Highest measures were observed in the superior cerebellar peduncle with an SI of 0.72. Less overlap was found in the decussation of the DRTT at the level of the mesencephalon. The study demonstrates high spatial accuracy of postmortem probabilistic tractography of the DRTT when compared to a 3D histological reconstruction. This gives hopeful prospect for studying structure-function correlations in patients with cerebellar disorders using tractography of the DRTT.

A probabilistic atlas of the cerebellar white matter.

Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders.

Syringomyelia: a practical, clinical concept for classification.

BACKGROUND: The term syringomyelia describes many pathogenetically different disorders, and a variety of attempts to group these based on different criteria have been proposed in the literature. As a consequence a lack of consensus regarding classification and terminology exists. This inconsistency extends to the ICD-10 classification of diseases in regards to syringomyelia (G95.0) and hydromyelia (Q06.4). We propose a new unifying concept for classification that also incorporates diagnostics and treatment. METHODS: The PubMed online database was used to gain a general overview of the existing pathogenetic theories in relation to syringomyelia. Illustrative cases at our department were included and similar cases of the literature were found using the PubMed database. All material was reviewed with main focus on the classification and terminology used. RESULTS: Despite syringomyelia (G95.0) and hydromyelia (Q06.4) existing as independent ICD-10 entities, we have shown that the use of classifying terminology for fluid-filled cavities in the spinal cord is indiscriminate and inconsistent. Even though a general agreement on the believed pathogenetic mechanism exists, and the general treatment methods are used in accordance with this mechanism, the terminology fails to function as a simple and universal link between theory and treatment. CONCLUSIONS: We propose a new causal concept for an ICD classification with syringomyelia (G95.0) as the only describing terminology, thus abandoning the use of hydromyelia (Q06.4). Syringomyelia is divided into five subgroups according to the associated pathologies. The classification is based on applied diagnostics and serves as a clinical guidance for treatment.

Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas.

CONTEXT: Although the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now. OBJECTIVE: To gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas. DESIGN: Retrospective cohort study. PATIENTS AND METHODS: The medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤ 50 nmol/l either basal or after 1 mg dexamethasone. RESULTS: The remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71 ± 39 months of follow-up (mean ± S.D., range 10-165 months). CONCLUSIONS: Endoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.

Early passage bone marrow stromal cells express genes involved in nervous system development supporting their relevance for neural repair.

PURPOSE: The assessment of the capacity of bone marrow stromal cells (BMSC) to repair the nervous system using gene expression profiling. The evaluation of effects of long-term culturing on the gene expression profile of BMSC. METHODS: Fourty four k whole genome rat microarrays were used to study gene expression of cultured BMSC at passage (P)3 and to compare expression profiles between P3 and P14 BMSC. Quantitative PCR was employed to validate the microarray results. RESULTS: P3 BMSC expressed genes involved in neural developmental events such as glial differentiation, neuron proliferation, and neurite formation. They also express genes encoding for growth factors and for proteins involved in growth factor signaling. A total of 6687 genes were co-expressed in P3 and P14 BMSC. Of these co-expressed genes, 3% (202 genes) was differentially expressed with 159 genes higher in P3 BMSC and 43 genes higher in P14 BMSC. The gene expression patterns were independently validated using quantitative PCR. Functional data mining by Gene Ontology (GO)-analysis revealed that 85/159 and 22/43 genes were annotated in the GO database. In P3 BMSC, 53 GO-classes were overrepresented with several involved in organ development, cell proliferation, and neural repair. In P14 BMSC, three GO-classes were overrepresented with one involved in organ development. CONCLUSIONS: Our gene profiling results suggested a decreased plasticity and repair aptitude of long-term cultured BMSC. Our data indicated the use of early passage BMSC for neural repair approaches.

CME for neurosurgeons in the Netherlands: the "quality" conferences.

In 1993 the Netherlands Society for Neurosurgery started a yearly event, a "Quality Conference", specifically devoted to continuous medical education (CME). These conferences differ from "normal" scientific meetings, in the choice for specific topics, in the preparation with inquiries among all the Dutch neurosurgical centres, and in the way the results of these inquiries are discussed, preceded by lectures concerning the chosen topic by guest faculty and Dutch neurosurgeons. Each year's principal guest delivers the "Beks Lecture", named after the former professor in Neurosurgery in Groningen, Jan Beks. On several occasions, the foreign guests suggested to present this format for a larger neurosurgical forum. Therefore, it was decided to describe the various aspects of this format for CME in the Netherlands in a paper for Acta Neurochirugica. Examples of topics are given, a summary of two recent inquiries are presented and discussed, and the way of organizing such a conference including finance and the obligatory character are described.

The combined supraorbital keyhole-endoscopic endonasal transsphenoidal approach to sellar, perisellar and frontal skull base tumors: surgical technique.

INTRODUCTION: Extended endoscopic endonasal transsphenoidal approaches (extended EETA) are increasingly being explored for lesions around the sella and the frontal skull base. These approaches, however, require significant surgical expertise and training that can only be obtained in high-volume centers and therefore these approaches are not generalizable to the whole neurosurgical community. Also, these approaches require significant skull base destruction and reconstruction, which comes with a high risk of CSF fistulas. The aim of this article is to describe a combined supraorbital keyhole-endoscopic endonasal transsphenoidal approach as an alternative surgical strategy to the extended EETA that is easier to perform and that leaves the skull base anatomy more intact. TECHNIQUE: Two fairly common neurosurgical approaches, the supraorbital keyhole approach and the endoscopic endonasal transsphenoidal approach, are combined into a single-stage or two-stage surgical procedure. The procedure can be performed as a single neurosurgeon-serial approach and as a two neurosurgeon-parallel simultaneous approach. The philosophy and technique of this combined approach will be described. CONCLUSION: The combined supraorbital keyhole-EETA approach can be used without extra surgical training or expertise and with preservation of skull base anatomy for sellar, perisellar and frontal skull base tumors.

Repeated transsphenoidal pituitary surgery (TS) via the endoscopic technique: a good therapeutic option for recurrent or persistent Cushing's disease (CD).

BACKGROUND: No data on results of repeated transsphenoidal surgery via the endoscopic technique for patients with persistent or recurrent Cushing's disease are available. DESIGN AND PATIENTS: We retrospectively evaluated the remission rates and complications of repeated transsphenoidal surgery via the endoscopic technique in 14 patients with persistent (N = 6) or recurrent (N = 8) Cushing's disease treated in our centre between 1999 and 2007. MAIN OUTCOMES: Remission was defined as the disappearance of symptoms of hypercortisolism with basal plasma cortisol level < or = 50 nmol/l 24-48 h after glucocorticoid withdrawal and/or suppression of plasma cortisol level < or = 50 nmol/l after 1 mg dexamethasone overnight within the first 3 months after transsphenoidal surgery. RESULTS: With repeated endoscopic transsphenoidal surgery a remission rate of 10/14 (71%) was achieved. No patient had a relapse during a median follow-up of 24 months. Cerebrospinal fluid leakage was the most frequent complication (6 patients) and 11 patients required hormonal substitution after surgery. The success of repeated transsphenoidal surgery could not be predicted by visualization of an adenoma on MRI before first or second surgery, histopathological confirmation of an ACTH secreting adenoma after first or second surgery, treatment with cortisol lowering agents before first or second surgery, the operation technique used during the first surgery, persistent vs. recurrent disease after the first surgery, age, gender and interval between the two surgeries. CONCLUSION: Repeated transsphenoidal surgery via the endoscopic technique is a good treatment option for selected patients with recurrent or persistent Cushing's disease following primary pituitary surgery.

Criteria for transcranial electrical motor evoked potential monitoring during spinal deformity surgery A review and discussion of the literature.

Transcranial electrical stimulated motor evoked potential monitoring (TES-MEP) has proven to be a successful and reliable neuromonitoring technique during spinal correction surgery. However, three criteria for TES-MEP monitoring have been described in the literature. This study aims at discussing and comparing the following criteria: (1) the "threshold level criterion" introduced by Calancie et al. (J Neurosurg 88 (1998) 457-70): a more than 100V over more than 1h increase of threshold level to get useful TES-MEP responses indicated neurological impairment; (2) the "amplitude criterion": for TES-MEP monitoring in corrective surgery of the spine, a more than 80% decrease of one or more response amplitudes was considered a valuable criterion for impending neurological deficits by Langeloo et al. (Spine 28 (2003) 1043-50); (3) "the morphology criterion": introduced in 2005 by Quinones et al. (Neurosurgery 56 (2005) 982-93), it is based on the morphology of the MEP-compound muscle action potentials (CMAP). The criterion was applied during TES-MEP monitoring during intramedullary spinal cord tumour resection. Neurological events are defined by a sharp decrease of response duration and/or waveform complexity and an increase in voltage threshold of 100V or greater. Although all methods have been reported to be successful during spinal surgery, the threshold criterion and the morphology change criterion carry several drawbacks. We consider the amplitude reduction method to be most useful during corrective spinal surgery. The sequences of observations and decisions during a TES-MEP monitoring that is based on this criterion are schematized in a flowchart.

Giant cavernous hemangiomas: report of three cases.

Giant cavernous hemangiomas occur very rarely, and little has been reported about their behavior. In this case report three cavernous hemangiomas with a diametric measure between 6 cm and 7 cm and distinct features will be described. A 36-year-old female patient presented with headache and nausea. A CT scan disclosed a large circumscribed tumor with strong contrast enhancement in the temporo-parieto-occipital region of the right cerebral hemisphere and extension into the right cerebellar hemisphere. A 35-year-old woman was admitted to our emergency ward with a generalized seizure and a dilated pupil. The CT scan showed an extensive left frontal lesion containing a substantial hyperintense part, suspicious for hemorrhage. A 3-year-old girl was admitted with generalized seizure and progressively declining consciousness. A large left frontotemporal paraventricular multi-cystic lesion was encountered on the CT scan. All three patients were operated on. Two recovered very well. In the case of the 3-year-old girl stable disease was reached. Giant cavernomas do not differ from average-sized cavernomas in clinical, surgical or histopathological presentation but may differ radiologically. However, the possible diagnosis of cavernoma can be overlooked, due to their size and possible differential diagnosis.

Transsphenoidal pituitary surgery via the endoscopic technique: results in 35 consecutive patients with Cushing's disease.

OBJECTIVE AND DESIGN: The endoscopic technique has been recently introduced in the field of transsphenoidal pituitary surgery. This technique allows inspection of sellar, supra- and parasellar structures and removal of the tumor under direct visualization, is minimally traumatic and permits easier reoperations. This is the first report on the results of endoscopic surgery for patients with Cushing's disease. Our aim was to retrospectively analyze the results of pituitary surgery in 35 consecutive patients with Cushing's disease operated in our hospital after the introduction of the endoscopic technique (1998-2004). METHODS: Remission was defined as suppression of plasma cortisol (< or =50 nmol/L) after 1 mg dexamethasone overnight determined in the first 3 months after surgery and disappearance of clinical signs and symptoms of hypercortisolism. The patients were followed for an average of 27 months (range 4 to 81 months, median 20 months). RESULTS: Pituitary MRI showed a macroadenoma in 6 patients, a microadenoma in 17 patients and no adenoma in 12 patients. After the initial surgery 27 patients (77%) were in remission. None of the patients had a relapse during follow-up. In the remaining 8 patients hypercortisolemia persisted after surgery. Three of them had a second endoscopic pituitary surgery resulting in remission in two patients. In one patient a second endoscopic pituitary surgery will soon follow. The remaining four patients were treated with radiotherapy postoperatively. Two of them were at the time of data collection in remission. One patient from the remission group had a serious epistaxis and three patients had cerebrospinal fluid leakage, one requiring an external lumbar drain, shortly after surgery. No complications were recorded in the failure group. Postoperatively 34% of all patients required substitution with levothyroxine, 40% required substitution with glucocorticoids, 17% received estrogens or testosterone and 6% still required desmopressin. CONCLUSIONS: Endoscopic transsphenoidal pituitary surgery resulted in our series of patients with Cushings disease in an excellent postoperative remission rate. A randomized clinical trial, comparing endoscopic and conventional pituitary surgery in patients with Cushings disease, is needed to determine the pros and cons of both techniques.

Cerebrospinal fluid leakage as complication of treatment with cabergoline for macroprolactinomas.

Treatment of patients with prolactinomas consists primarily of dopamine agonists (DA). Cerebrospinal fluid (CSF) leakage has sporadically been reported in patients with macroprolactinomas treated with short-acting DA such as bromocriptine. Little is known on the incidence of this complication in patients treated with the long-acting D2 specific DA cabergoline. We report three patients with CSF leakage shortly after initiation of cabergoline treatment for macroprolactinoma. All three patients responded rapidly to cabergoline (CAB) by shrinkage of the tumor and release of the optic chiasm compression. The CSF leakage occurred within 10 days after initiation of treatment. CAB treatment was not discontinued. In one patient the CSF leakage ceased spontaneously, with no additional therapy. The second patient had a surgical repair of the CSF fistula, permitting cabergoline to be continued without a recurrence of the CSF leakage. The third patient refused surgical repair of the sellar defect. In this patient the cabergoline dosage was temporarily decreased with no effect on the CSF leakage. Four years later, the CSF leakage is unchanged in this patient, whilst no other complications occurred during the follow-up. No infectious complications occurred in these three patients. In conclusion, patients with large, invasive macroprolactinomas are at risk of CSF leakage during medical treatment with CAB. It is advisable to warn these patients for occurrence of this complication and to monitor them closely especially during the first months of treatment.

In utero repair of an experimental neural tube defect in a chronic sheep model using biomatrices.

OBJECTIVE: Persistent exposure of the unprotected spinal cord to amniotic fluid and the uterine wall can lead to progressive damage of neural tissue in case of a myelomeningocele (two-hit hypothesis). The aim of this study was to evaluate whether in utero repair of an experimental neural tube defect in a fetal lamb could protect neural tissue from secondary injury and save neurologic functions after birth. METHODS: In 19 fetal lambs, a neural tube defect was created at 79 days' gestation. In 12 lambs the defect was covered either with a novel, molecular defined collagen-based biocompatible and biodegradable matrix (UMC) or with a small intestinal submucosa (SIS) biomatrix (Cook) or by closing the skin over the defect. RESULTS: All lambs with the defect covered showed no or minor neurologic morbidity in contrast to the lambs with the defect uncovered in which major neurologic morbidity was seen. CONCLUSIONS: These results demonstrate that long-term exposure of the open spinal cord to the intrauterine environment can lead to damage of neural tissue and, consequently loss of neurologic functions and that coverage of the defect can lead to a better neurologic outcome. Furthermore, we could show that a UMC biomatrix and an SIS biomatrix are useful for in utero coverage of a surgically created neural tube defect in our model.

Anterior submuscular transposition of the ulnar nerve. For post-operative focal neuropathy at the elbow.

Outcome studies of revision surgical treatment for recurrent or persistent neuropathy of the ulnar nerve at the elbow are relatively rare and none involves patient self-assessment. In this study of 40 patients (41 elbows), a clear discrepancy is shown between clinical assessment and the patient's own view. From clinical assessment, 20% of patients had an excellent result, whereas only one (2.5%) patient self-reported a complete cure. More reports using patient self-assessment and validated scores are required.

Inverse correlation between genetic aberrations and malignancy grade in ependymal tumors: a paradox?

OBJECTIVE: The goal of our study was to investigate the inverse correlation between number of genetic aberrations and malignancy grade in ependymal tumors at the ploidy level. METHODS: we examined seven myxopapillary ependymomas (mpEs) (WHO grade I), 28 spinal and cerebral ependymomas (Es) (WHO grade II), and 18 cerebral anaplastic ependymomas (aEs) (WHO grade III) using image DNA cytometry. The ploidy status was correlated with clinicopathological characteristics and with the results obtained by comparative genomic hybridization (CGH) analysis that we performed in about half of these tumors. RESULTS: mpEs were exclusively located in the spinal cord and aEs in the cerebrum only, whereas Es were located in both the spinal cord and brain. We found aneuploidy or tetraploidy to be common in the group of mpEs (6 out of 7) and much less frequent in Es (6 out of 28) and aEs (4 out of 18). Three-year postoperative survival was 100% for mpEs, 100% for spinal Es, 92% for cerebral Es, and 33% for aEs. Our CGH results in a selection of these tumors revealed the highest number of genetic aberrations in the mpEs (average 16; n = 2), a lower number in Es (average 12; n = 11) and the lowest number in aEs (average 5; n = 6). Interestingly, in the group of Es and aEs, a high number of genetic aberrations as detected by CGH was not correlated with aneuploidy or tetraploidy. Three patients, all with mpEs had local seeding. CONCLUSION: These results underline that mpEs are distinctly different from Es and aEs at the genetic level and that extensive genomic alterations and aneuploidy in ependymal tumors are not in itself an indicator of malignant behavior.

The use of a head-mounted display for visualization in neuroendoscopy.

OBJECTIVE: To evaluate the clinical use of a head-mounted display (HMD) for visualization in all neuroendoscopic procedures. MATERIALS AND METHODS: We retrospectively evaluated all endoscopic and endoscope-controlled procedures in which the HMD was used in our department between July 1999 and June 2002. RESULTS: A total of 269 endoscopic procedures were performed. In 147 cases intraventricular endoscopic procedures were carried out, mostly third ventriculocisternostomies, for which a fiberscope was used exclusively. Thirty intracranial cysts were fenestrated or removed (colloid cysts) with the help of various endoscopes. A total of 87 endoscopic transsphenoidal surgeries were performed with a lensscope. In only one case was it necessary to abandon use of the HMD due to inferior visualization; in all other cases visualization by the HMD was thought to be sufficient. Fatigue of the surgeon due to wearing the helmet did not occur. All surgeons had the impression that visual strain was decreased in comparison to looking at a monitor from a distance. The working position was considered to be more comfortable when wearing the HMD, and eye-hand coordination was improved. No technical problems occurred with the system. CONCLUSIONS: The HMD is a new visualization tool in neurosurgery that may improve the ergonomics of neuroendoscopic and endoscope-controlled procedures.

The arcade of Struthers: an anatomical study.

BACKGROUND: The arcade of Struthers has been described as possible cause of compression of the ulnar nerve but several authors and our own experience have doubt cast on its existence. We, therefore, performed an anatomical study to determine whether or not the arcade of Struthers exists. METHODS: Ten arms from fresh frozen cadavers were dissected. Special attention was given to the fascial layers of the medial aspect of the upper arm and the medial intermuscular septum and their relation ships to the ulnar nerve. FINDINGS: An arcade of Struthers was not found in any specimen. INTERPRETATION: The arcade of Struthers does not exist and is not an anatomical structure, but a man-made construct.