Risk factors for postoperative seizures in patients with chronic subdural haematomas.

Postoperative seizures are a frequently occurring yet not well-understood complication in patients undergoing surgical treatment of chronic subdural haematomas (cSDHs). Therefore, we investigated surgical and non-surgical risk factors that are commonly considered causal in provoking epileptic seizures, paying special attention to the intracranial course of the subdural drain (SDD) and the configuration of the haematoma. Data of patients with a cSDH, that were treated at our neurosurgical department between 2008 and 2014 were analysed. Patients suffering from severe pre-existing conditions and those who have been treated conservatively were excluded. Epidemiologic data as well as relevant clinical data were collected. Pre- and postoperative CT scans were analysed regarding morpho- and volumetric parameters. In order to objectify the influence of the SDD, its intracranial course and localisation (entering angle as well as the angle between drain and brain surface) were measured. For statistical analysis, univariate and multiple logistic regression models as well as Fisher's exact test were used. Two hundred eleven consecutive patients have been included. Mean age was 75.6 years, and 69% were male. Nineteen (9%) patients suffered from postsurgical seizures. Membranes within the haematoma were present in 81.5%. Pre- to postoperative haematoma reduction was significant (mean of difference - 12.76 mm/ - 9.47 mm in coronal/axial CT planes, p = 0.001/ < 0.001). In 77.9%, SDD showed cortical contact with eloquent regions and had an unfavourable course in 30 cases (14.2%). Surgical complications consisted of cortical bleeding in 2.5%, fresh subdural haematoma in 33.5% and wound infections in 1.4% of patients. Neither in univariate nor in multiple regression analyses any of the following independent variates was significantly correlated with postsurgical seizures: pre-existing epilepsy, alcohol abuse, right-sided haematomas, localization and thickness of haematoma, presence of septations, SDD-localization and to-brain angle, subdural air, and electrolyte levels. Instead, in multiple regression analyses, we found the risk of postsurgical seizures to be significantly correlated and increased with left-sided cSDH treated via craniotomy (p = 0.03) and an unfavourable course of the SDD in left-sided cSDH (p = 0.033). Burr hole trepanation should be preferred over craniotomy and care must be taken when placing a SDD to avoid irritating cortical tissue. The configuration of the haematoma does not appear to affect the postoperative seizure rate.

Oculo-Auriculo-Vertebral Dysplasia With Craniocervical Instability and Occult Tethered Cord Syndrome. An Addition to the Spectrum? First Case Report and Review of the Literature.

Oculo-auriculo-vertebral spectrum (OAVS) is an uncommon congenital disorder of abnormal development of the first and second pharyngeal arches. This spectrum is characterized by craniofacial microsomia, epibulbar dermoids, ear abnormalities, renal and cardiac defects, and a wide range of vertebral segmentation and formation disorders. Frequently, the cervicothoracic spine is involved. Only recently, the morbidity attributed to the spinal abnormalities has gained attention. Strategy and timing of spine surgery has become increasingly important in patients with OAVS. Here, we report a case of OAVS with characteristic vertebral cervical and thoracic involvement and its sequelae requiring multiple spinal procedures, further complexed by an unprecedented occult tethered cord syndrome, which was successfully treated by surgical detethering. In this context, the recent literature on spinal anomalies is reviewed.

Information needs of patients in spine surgery: development of a question prompt list to guide informed consent consultations.

BACKGROUND CONTEXT: Informed consent is mandatory before surgery and fundamental in the physician-patient interaction. However, communication is sometimes suboptimal. PURPOSE: The objective was to develop a question prompt list (QPL) for patients undergoing spine surgery (spinal neurosurgery-QPL, "SN-QPL") to encourage them to acquire information during the informed consent consultation (ICC) and assess patients' information needs. STUDY DESIGN/SETTING: We conducted a prospective uncontrolled single center study in order to develop a QPL for patients undergoing spine surgery. PATIENT SAMPLE: Patients inclusion criteria were as follows: (1) planned spinal surgery, (2) age 18 to 80 years, (3) legal capacity, (4) ability to understand and respond to questionnaires, and (5) informed consent. OUTCOME MEASURES: We applied the following self-report measures: the developed preliminary QPL with regard to surgery topics and assessment of patients' information needs. METHODS: First, we performed a literature review, patient interviews, and two expert rounds. Subsequently, we validated a preliminary SN-QPL including 37 items before and after ICC with regard to importance of items and fulfillment of information needs in 118 patients. A principal component analysis followed by varimax rotation revealed the final SN-QPL. RESULTS: For the final version of the SN-QPL, 27 items with following four reliable subscales were derived with satisfactory internal consistency: (1) scale SN-QPL-C, "complications and possible postoperative deficits" (n  =  8 items, Cronbach α = 0.88); (2) scale SN-QPL-P, "prognosis and follow-up" (n = 8 items, Cronbach α = 0.86); (3) scale SN-QPL-I, "preoperative inpatient stay and organizational issues" (n = 5 items, Cronbach α = 0.75); and (4) scale SN-QPL-S: "safety of the surgical procedure" (with n = 6 items, Cronbach α = 0.84). The most unmet information needs were found in SN-QPL-P. The item with the greatest unmet information needs was "How much professional experience does my surgeon have?" CONCLUSIONS: Our SN-QPL was well-accepted and perceived as helpful by patients awaiting spinal surgeries. It seems to address meaningful items and questions. It could therefore be useful in optimizing pre- and postoperative satisfaction. Further, our study identified many unaddressed questions warranting communication interventions.

Navigation and Image Injection for Control of Bone Removal and Osteotomy Planes in Spine Surgery.

BACKGROUND AND IMPORTANCE: In contrast to cranial interventions, neuronavigation in spinal surgery is used in few applications, not tapping into its full technological potential. We have developed a method to preoperatively create virtual resection planes and volumes for spinal osteotomies and export 3-D operation plans to a navigation system controlling intraoperative visualization using a surgical microscope's head-up display. The method was developed using a Sawbone ® model of the lumbar spine, demonstrating feasibility with high precision. Computer tomographic and magnetic resonance image data were imported into Amira ® , a 3-D visualization software. Resection planes were positioned, and resection volumes representing intraoperative bone removal were defined. Fused to the original Digital Imaging and Communications in Medicine data, the osteotomy planes were exported to the cranial version of a Brainlab ® navigation system. A navigated surgical microscope with video connection to the navigation system allowed intraoperative image injection to visualize the preplanned resection planes. CLINICAL PRESENTATION: The workflow was applied to a patient presenting with a congenital hemivertebra of the thoracolumbar spine. Dorsal instrumentation with pedicle screws and rods was followed by resection of the deformed vertebra guided by the in-view image injection of the preplanned resection planes into the optical path of a surgical microscope. Postoperatively, the patient showed no neurological deficits, and the spine was found to be restored in near physiological posture. CONCLUSION: The intraoperative visualization of resection planes in a microscope's head-up display was found to assist the surgeon during the resection of a complex-shaped bone wedge and may help to further increase accuracy and patient safety.

Three-dimensional Cross-Platform Planning for Complex Spinal Procedures: A New Method Adaptive to Different Navigation Systems.

STUDY DESIGN: A feasibility study. OBJECTIVE: To develop a method based on the DICOM standard which transfers complex 3-dimensional (3D) trajectories and objects from external planning software to any navigation system for planning and intraoperative guidance of complex spinal procedures. SUMMARY OF BACKGROUND DATA: There have been many reports about navigation systems with embedded planning solutions but only few on how to transfer planning data generated in external software. MATERIALS AND METHODS: Patients computerized tomography and/or magnetic resonance volume data sets of the affected spinal segments were imported to Amira software, reconstructed to 3D images and fused with magnetic resonance data for soft-tissue visualization, resulting in a virtual patient model. Objects needed for surgical plans or surgical procedures such as trajectories, implants or surgical instruments were either digitally constructed or computerized tomography scanned and virtually positioned within the 3D model as required. As crucial step of this method these objects were fused with the patient's original diagnostic image data, resulting in a single DICOM sequence, containing all preplanned information necessary for the operation. By this step it was possible to import complex surgical plans into any navigation system. RESULTS: We applied this method not only to intraoperatively adjustable implants and objects under experimental settings, but also planned and successfully performed surgical procedures, such as the percutaneous lateral approach to the lumbar spine following preplanned trajectories and a thoracic tumor resection including intervertebral body replacement using an optical navigation system. To demonstrate the versatility and compatibility of the method with an entirely different navigation system, virtually preplanned lumbar transpedicular screw placement was performed with a robotic guidance system. CONCLUSIONS: The presented method not only allows virtual planning of complex surgical procedures, but to export objects and surgical plans to any navigation or guidance system able to read DICOM data sets, expanding the possibilities of embedded planning software.

In Situ Activation of Pituitary-Infiltrating T Lymphocytes in Autoimmune Hypophysitis.

Autoimmune hypophysitis (AH) is a chronic inflammatory disease characterized by infiltration of T and B lymphocytes in the pituitary gland. The mechanisms through which infiltrating lymphocytes cause disease remain unknown. Using a mouse model of AH we assessed whether T lymphocytes undergo activation in the pituitary gland. Infiltrating T cells co-localized with dendritic cells in the pituitary and produced increased levels of interferon-γ and interleukin-17 upon stimulation in vitro. Assessing proliferation of CD3- and B220-postive lymphocytes by double immunohistochemistry (PCNA-staining) and flow cytometry (BrdU incorporation) revealed that a discrete proportion of infiltrating T cells and B cells underwent proliferation within the pituitary parenchyma. This proliferation persisted into the late disease stage (day 56 post-immunization), indicating the presence of a continuous generation of autoreactive T and B cells within the pituitary gland. T cell proliferation in the pituitary was confirmed in patients affected by autoimmune hypophysitis. In conclusion, we show that pituitary-infiltrating lymphocytes proliferate in situ during AH, providing a previously unknown pathogenic mechanism and new avenues for treatment.

Alternative radiation-free registration technique for image-guided pedicle screw placement in deformed cervico-thoracic segments.

BACKGROUND: Image-guided pedicle screw placement in the cervico-thoracic region is a commonly applied technique. In some patients with deformed cervico-thoracic segments, conventional or 3D fluoroscopy based registration of image-guidance might be difficult or impossible because of the anatomic/pathological conditions. Landmark based registration has been used as an alternative, mostly using separate registration of each vertebra. We here investigated a routine for landmark based registration of rigid spinal segments as single objects, using cranial image-guidance software. METHODS: Landmark based registration of image-guidance was performed using cranial navigation software. After surgical exposure of the spinous processes, lamina and facet joints and fixation of a reference marker array, up to 26 predefined landmarks were acquired using a pointer. All pedicle screws were implanted using image guidance alone. Following image-guided screw placement all patients underwent postoperative CT scanning. Screw positions as well as intraoperative and clinical parameters were retrospectively analyzed. RESULTS: Thirteen patients received 73 pedicle screws at levels C6 to Th8. Registration of spinal segments, using the cranial image-guidance succeeded in all cases. Pedicle perforations were observed in 11.0%, severe perforations of >2 mm occurred in 5.4%. One patient developed a transient C8 syndrome and had to be revised for deviation of the C7 pedicle screw. No other pedicle screw-related complications were observed. CONCLUSIONS: In selected patients suffering from pathologies of the cervico-thoracic region, which impair intraoperative fluoroscopy or 3D C-arm imaging, landmark based registration of image-guidance using cranial software is a feasible, radiation-saving and a safe alternative.

A novel minimally invasive, dorsolateral, tubular partial odontoidectomy and autologous bone augmentation to treat dens pseudarthrosis: cadaveric, 3D virtual simulation study and technical report.

OBJECTIVE The goal of this study was to demonstrate the clinical and technical nuances of a minimally invasive, dorsolateral, tubular approach for partial odontoidectomy, autologous bone augmentation, and temporary C1-2 fixation to treat dens pseudarthrosis. METHODS A cadaveric feasibility study, a 3D virtual reality reconstruction study, and the subsequent application of this approach in 2 clinical cases are reported. Eight procedures were completed in 4 human cadavers. A minimally invasive, dorsolateral, tubular approach for odontoidectomy was performed with the aid of a tubular retraction system, using a posterolateral incision and an oblique approach angle. Fluoroscopy and postprocedural CT, using 3D volumetric averaging software, were used to evaluate the degree of bone removal of C1-2 lateral masses and the C-2 pars interarticularis. Two clinical cases were treated using the approach: a 23-year-old patient with an odontoid fracture and pseudarthrosis, and a 35-year-old patient with a history of failed conservative treatment for odontoid fracture. RESULTS At 8 cadaveric levels, the mean volumetric bone removal of the C1-2 lateral masses on 1 side was 3% ± 1%, and the mean resection of the pars interarticularis on 1 side was 2% ± 1%. The median angulation of the trajectory was 50°, and the median distance from the midline of the incision entry point on the skin surface was 67 mm. The authors measured the diameter of the working channel in relation to head positioning and assessed a greater working corridor of 12 ± 4 mm in 20° inclination, 15° contralateral rotation, and 5° lateral flexion to the contralateral side. There were no violations of the dura. The reliability of C-2 pedicle screws and C-1 lateral mass screws was 94% (15 of 16 screws) with a single lateral breach. The patients treated experienced excellent clinical outcomes. CONCLUSIONS A minimally invasive, dorsolateral, tubular odontoidectomy and autologous bone augmentation combined with C1-2 instrumentation has the ability to provide excellent 1-stage management of an odontoid pseudarthrosis. The procedure can be completed safely and successfully with minimal blood loss and little associated morbidity. This approach has the potential to provide not only a less invasive approach but also a function-preserving option to treat complex C1-2 anterior disease.

A Modified Microsurgical Endoscopic-Assisted Transpedicular Corpectomy of the Thoracic Spine Based on Virtual 3-Dimensional Planning.

BACKGROUND AND OBJECTIVE: The main difficulties of transpedicular corpectomies are lack of space for vertebral body replacement in the neighborhood of critical structures, the necessity for sacrifice of nerve roots in the thoracic spine. and the extent of hemorrhage due to venous epidural bleeding. We present a modified technique of transpedicular corpectomy by using an endoscopic-assisted microsurgical technique performed through a single posterior approach. A 3-dimensional (3D) preoperative reconstruction could be helpful in the planning for this complex anatomic region. METHODS: Surface and volume 3D reconstruction were performed by Amira or the Dextroscope. The clinical experience of this study includes 7 cases, 2 with an unstable burst fracture and 5 with metastatic destructive vertebral body disease, all with significant retropulsion and obstruction of the spinal canal. We performed a comparison with a conventional cohort of transpedicular thoracic corpectomies. RESULTS: Qualitative parameters of the 3D virtual reality planning included degree of bone removal and distance from critical structures such as myelon and implant diameter. Parameters were met in each case, with demonstration of optimal positioning of the implant without neurological complications. In all patients, the endoscope was a significant help in identifying the origins of active bleeding, residual tumor, extent of bone removal, facilitating cage insertion in a minimally invasive way, and helping to avoid root sacrifice on both sides. CONCLUSIONS: Microsurgical endoscopic-assisted transpedicular corpectomy may prove valuable in enhancing the safety of corpectomy in destructive vertebral body disease. The 3D virtual anatomic model greatly facilitated the preoperative planning.

Common molecularcytogenetic alterations in tumors originating from the pineal region.

Tumors of the pineal region (PR) are rare and can be subdivided into four main histomorphological groups: Pineal-parenchymal tumors (PPT), germ cell tumors (GCT), glial tumors and miscellaneous tumors. The appropriate pathological classification and grading of these malignancies is essential for determining the clinical management and prognosis. However, an early diagnosis is often delayed due to unspecific clinical symptoms, and histological support is not always decisive to identify the diversity of tumors of the PR. The present study aimed to characterize 18 tumors of the PR using comparative genomic hybridization. All the tumors were primarily surgically resected without any previous irradiation or chemotherapy. In addition to chromosomal aberrations in PPT and different GCTs of the PR, the present study described, for the first time, the chromosomal changes in a few rare entities (solitary-fibrous and neuroendocrine tumors) of the PR. The tumors in the study, regardless of histology and World Health Organization grade, were characterized by frequent gains at 7, 9q, 12q, 16p, 17 and 22q, and losses at 13q. While the detection of chromosomal aberrations in these tumors appears not to be indicative enough of histological entities and their grade of malignancy, the present data may be of use to select genes of interest for higher resolution genomic analyses.

Stereoscopic neuroanatomy lectures using a three-dimensional virtual reality environment.

INTRODUCTION: Three-dimensional (3D) computer graphics are increasingly used to supplement the teaching of anatomy. While most systems consist of a program which produces 3D renderings on a workstation with a standard screen, the Dextrobeam virtual reality VR environment allows the presentation of spatial neuroanatomical models to larger groups of students through a stereoscopic projection system. MATERIALS AND METHODS: Second-year medical students (n=169) were randomly allocated to receive a standardised pre-recorded audio lecture detailing the anatomy of the third ventricle accompanied by either a two-dimensional (2D) PowerPoint presentation (n=80) or a 3D animated tour of the third ventricle with the DextroBeam. Students completed a 10-question multiple-choice exam based on the content learned and a subjective evaluation of the teaching method immediately after the lecture. RESULTS: Students in the 2D group achieved a mean score of 5.19 (±2.12) compared to 5.45 (±2.16) in the 3D group, with the results in the 3D group statistically non-inferior to those of the 2D group (p<0.0001). The students rated the 3D method superior to 2D teaching in four domains (spatial understanding, application in future anatomy classes, effectiveness, enjoyableness) (p<0.01). CONCLUSION: Stereoscopically enhanced 3D lectures are valid methods of imparting neuroanatomical knowledge and are well received by students. More research is required to define and develop the role of large-group VR systems in modern neuroanatomy curricula.

Blurring the boundaries between frame-based and frameless stereotaxy: feasibility study for brain biopsies performed with the use of a head-mounted robot.

OBJECT: Frame-based stereotactic interventions are considered the gold standard for brain biopsies, but they have limitations with regard to flexibility and patient comfort because of the bulky head ring attached to the patient. Frameless image guidance systems that use scalp fiducial markers offer more flexibility and patient comfort but provide less stability and accuracy during drilling and biopsy needle positioning. Head-mounted robot-guided biopsies could provide the advantages of these 2 techniques without the downsides. The goal of this study was to evaluate the feasibility and safety of a robotic guidance device, affixed to the patient's skull through a small mounting platform, for use in brain biopsy procedures. METHODS: This was a retrospective study of 37 consecutive patients who presented with supratentorial lesions and underwent brain biopsy procedures in which a surgical guidance robot was used to determine clinical outcomes and technical procedural operability. RESULTS: The portable head-mounted device was well tolerated by the patients and enabled stable drilling and needle positioning during surgery. Flexible adjustments of predefined paths and selection of new trajectories were successfully performed intraoperatively without the need for manual settings and fixations. The patients experienced no permanent deficits or infections after surgery. CONCLUSIONS: The head-mounted robot-guided approach presented here combines the stability of a bone-mounted set-up with the flexibility and tolerability of frameless systems. By reducing human interference (i.e., manual parameter settings, calibrations, and adjustments), this technology might be particularly useful in neurosurgical interventions that necessitate multiple trajectories.

Microglia inflict delayed brain injury after subarachnoid hemorrhage.

Inflammatory changes have been postulated to contribute to secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH). In human specimens after SAH as well as in experimental SAH using mice, we show an intracerebral accumulation of inflammatory cells between days 4 and 28 after the bleeding. Using bone marrow chimeric mice allowing tracing of all peripherally derived immune cells, we confirm a truly CNS-intrinsic, microglial origin of these immune cells, exhibiting an inflammatory state, and rule out invasion of myeloid cells from the periphery into the brain. Furthermore, we detect secondary neuro-axonal injury throughout the time course of SAH. Since neuronal cell death and microglia accumulation follow a similar time course, we addressed whether the occurrence of activated microglia and neuro-axonal injury upon SAH are causally linked by depleting microglia in vivo. Given that the amount of neuronal cell death was significantly reduced after microglia depletion, we conclude that microglia accumulation inflicts secondary brain injury after SAH.

Video-Assisted Navigation for Adjustment of Image-Guidance Accuracy to Slight Brain Shift.

BACKGROUND: Information supplied by an image-guidance system can be superimposed on the operating microscope oculars or on a screen, generating augmented reality. Recently, the outline of a patient's head and skull, injected in the oculars of a standard operating microscope, has been used to check the registration accuracy of image guidance. OBJECTIVE: To propose the use of the brain surface relief and superficial vessels for real-time intraoperative visualization and image-guidance accuracy and for intraoperative adjustment for brain shift. METHODS: A commercially available image-guidance system and a standard operating microscope were used. Segmentation of the brain surface and cortical blood vessel relief was performed manually on preoperative computed tomography and magnetic resonance images. The overlay of segmented digital and real operating-microscope images was used to monitor image-guidance accuracy. Adjustment for brain shift was performed by manually matching digital images on real structures. RESULTS: Experimental manipulation on a phantom proved that the brain surface relief could be used to restore accuracy if the primary registration shifted. Afterward, the technique was used to assist during surgery of 5 consecutive patients with 7 deep-seated brain tumors. The brain surface relief could be successfully used to monitor registration accuracy after craniotomy and during the whole procedure. If a certain degree of brain shift occurred after craniotomy, the accuracy could be restored in all cases, and corticotomies were correctly centered in all cases. CONCLUSION: The proposed method was easy to perform and augmented image-guidance accuracy when operating on small deep-seated lesions.

Predictive chromosomal clusters of synchronous and metachronous brain metastases in clear cell renal cell carcinoma.

Synchronous (early) and metachronous (late) brain metastasis (BM) events of sporadic clear cell renal cell carcinoma (ccRCC) (n = 148) were retrospectively analyzed using comparative genomic hybridization (CGH). Using oncogenetic tree models and cluster analyses, chromosomal imbalances related to recurrence-free survival until BM (RFS-BM) were analyzed. Losses at 9p and 9q appeared to be hallmarks of metachronous BM events, whereas an absence of detectable chromosomal changes at 3p was often associated with synchronous BM events. Correspondingly, k-means clustering showed that cluster 1 cases generally exhibited low copy number chromosomal changes that did not involve 3p. Cluster 2 cases had a high occurrence of -9p/-9q (94-98%) deletions, whereas cluster 3 cases had a higher frequency of copy number changes, including loss at chromosome 14 (80%). The higher number of synchronous cases in cluster 1 was also associated with a significantly shorter RFS-BM compared with clusters 2 and 3 (P = 0.02). Conversely, a significantly longer RFS-BM was observed for cluster 2 versus clusters 1 and 3 (P = 0.02). Taken together, these data suggest that metachronous BM events of ccRCC are characterized by loss of chromosome 9, whereas synchronous BM events may form independently of detectable genetic changes at chromosomes 9 and 3p.

Organotypic slice cultures of human glioblastoma reveal different susceptibilities to treatments.

BACKGROUND: Glioblastoma multiforme is the most common lethal brain tumor in human adults, with no major therapeutic breakthroughs in recent decades. Research is based mostly on human tumor cell lines deprived of their organotypic environment or inserted into immune-deficient animals required for graft survival. Here, we describe how glioblastoma specimens obtained from surgical biopsy material can be sectioned and transferred into cultures within minutes. METHODS: Slices were kept in 6-well plates, allowing direct observation, application of temozolomide, and irradiation. At the end of experiments, slice cultures were processed for histological analysis including hematoxylin-eosin staining, detection of proliferation (Ki67), apoptosis/cell death (cleaved caspase 3, propidium iodide), DNA double-strand breaks (γH2AX), and neural subpopulations. First clinical trials employed irradiation with the heavy ion carbon for the treatment of glioblastoma patients, but the biological effects and most effective dose regimens remain to be established. Therefore, we developed an approach to expose glioblastoma slice cultures to (12)C and X-rays. RESULTS: We found preservation of the individual histopathology over at least 16 days. Treatments resulted in activation of caspase 3, inhibition of proliferation, and cell loss. Irradiation induced γH2AX. In line with clinical observations, individual tumors differed significantly in their susceptibility to temozolomide (0.4%-2.5% apoptosis and 1%-15% cell loss). CONCLUSION: Glioblastoma multiforme slice cultures provide a unique tool to explore susceptibility of individual tumors for specific therapies including heavy ions, thus potentially allowing more personalized treatments plus exploration of mechanisms of (and strategies to overcome) tumor resistance.

Use of a clinicoradiological score to determine the presurgical diagnosis of autoimmune hypophysitis in a teenage girl.

The distinction between autoimmune hypophysitis and other non-hormone secreting pituitary masses is often difficult to determine with certainty without pituitary biopsy and pathological examination. To aid in this distinction, the authors recently published a clinicoradiological scoring system, which they used in the case of a 15-year-old girl presented here. The patient presented with headache, visual field defects, polydipsia, and polyuria, and she was found to have secondary hypogonadism and hypoadrenalism. Magnetic resonance imaging showed a pituitary mass of approximately 2 cm in diameter. Application of the clinicoradiological parameters gave a score of -6, which favored a diagnosis of hypophysitis over that of adenoma. The presence of pituitary autoantibodies substantiated the diagnosis of hypophysitis. The patient was treated conservatively with high-dose prednisolone, and her symptoms improved markedly. This case illustrates the utility of using a clinicoradiological score when autoimmune hypophysitis is suspected since it can identify patients who can be treated without the need for pituitary surgery.

Necrotizing infundibulo-hypophysitis: an entity too rare to be true?

We report a young woman with sudden and severe retroorbital headache, neck pain, and a large sellar mass extending to the suprasellar cistern. A presumptive diagnosis of non-secreting pituitary macroadenoma undergoing apoplexy was made and transphenoidal surgery performed. Histopathology revealed mononuclear infiltration and marked non-hemorrhagic necrosis of the anterior pituitary consistent with a diagnosis of necrotizing infundibulo-hypophysitis. The possible pathogenesis of this rare variant of hypophysitis is discussed.

From pituitary expansion to empty sella: disease progression in a mouse model of autoimmune hypophysitis.

Lymphocytic hypophysitis has a variable clinical course, where a swelling of the pituitary gland at presentation is thought to be followed by pituitary atrophy and empty sella. Data in patients, however, are scanty and contradictory. To better define the course of hypophysitis, we used an experimental model based on the injection of pituitary proteins into SJL mice. A cohort of 33 mice was divided into three groups: 18 cases were immunized with pituitary proteins emulsified in complete Freund's adjuvant; six controls were injected with adjuvant only; and nine controls were left untreated. Mice were followed by cranial magnetic resonance imaging (MRI) for up to 300 d, for a total of 106 MRI scans, and killed at different time points to correlate radiological and pathological findings. Empty sella was defined as a reduction in pituitary volume greater than 2 sd below the mean volume. All immunized mice showed by MRI a significant expansion of pituitary volume during the early phases of the disease. The volume then decreased gradually in the majority of cases (14 of 18, 78%), reaching empty sella values by d 300 after immunization. In a minority of cases (four of 18, 22%), the decrease was so rapid and marked to induce a central area of necrosis accompanied by hemorrhages, mimicking the condition known in patients as pituitary apoplexy. No radiological or pathological changes were observed in controls. Overall, these findings indicate that the evolution of hypophysitis is complex but can lead, through different routes, to the development of empty sella.

Evaluation of efficacy and biocompatibility of a novel semisynthetic collagen matrix as a dural onlay graft in a large animal model.

BACKGROUND: Semisynthetic collagen matrices are promising duraplasty grafts with low risk of cerebrospinal fluid (CSF) fistulas, good tissue integration and minor foreign body reaction. The present study investigates the efficacy and biocompatibility of a novel semisynthetic bilayered collagen matrix (BCM, B. Braun Aesculap) as dural onlay graft for duraplasty. METHODS: Thirty-four pigs underwent osteoclastic trepanation, excision of the dura, and placement of a cortical defect, followed by duraplasty using BCM, Suturable DuraGen™ (Integra Neuroscience), or periosteum. CSF tightness and intraoperative handling of the grafts were evaluated. Pigs were sacrificed after 1 and 6 months for histological analysis. FINDINGS: BCM and DuraGen™ showed superior handling than periosteum with a trend for better adhesion to dura and CSF tightness for BCM. Periosteum, which was sutured unlike the synthetic grafts, had the highest intraoperative CSF tightness. Duraplasty time with periosteum was significantly higher (14.4 ± 2.7 min) compared with BCM (2.8 ± 0.8 min) or DuraGen™ (3.0 ± 0.5 min). Tissue integration by fibroblast infiltration was observed after 1 month for all devices. More adhesions between graft and cortex were observed with DuraGen™ compared with BCM and periosteum. No relevant adhesions between leptomeninges and BCM were observed and all devices showed comparable lymphocytic reaction of the brain. All devices were completely integrated after 6 months. BCM and DuraGen™ showed a trend for an enhanced lymphocytic reaction of the brain parenchyma compared with periosteum. Implant rejection was not observed. CONCLUSION: Semisythetic collagen matrices are an attractive alternative in duraplasty due to their easy handling, lower surgical time, and high biocompatibility.