M. Memet Özek

Expression of structural proteins and angiogenic factors in cerebrovascular anomalies.

OBJECTIVE The goal of this study was to describe the expression of matrix proteins and angiogenic factors in cerebrovascular malformations. METHODS Forty-six cerebrovascular malformations were immunohistochemically investigated with a battery of staining for five structural proteins (collagen IV, collagen III, smooth muscle actin, fibronectin, and laminin), and three angiogenic factors (vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], and transforming growth factor alpha [TGFalpha]). The lesions consisted of 34 arteriovenous malformations (AVMs), 10 cavernous malformations (CMs), and 2 venous angiomas. Expression intensity for each histological layer in the abnormal vessel wall was graded and compared. RESULTS AVM endothelia and subendothelia expressed more laminin and collagen IV than the same layers of CMs. Conversely, CMs expressed more fibronectin than AVMs. CM endothelia exhibited more prominent staining for smooth muscle actin than AVM endothelia. AVMs and CMs expressed VEGF in the endothelium and subendothelium, and TGFalpha in endothelial and perivascular layers. However, unlike AVMs, CMs expressed bFGF in the endothelium as well. The brain tissue intermingled within AVMs also expressed growth factors. Modified glial cells in the brain tissue adjacent to CMs expressed bFGF and TGFalpha, but not VEGF. Venous angiomas did not express the studied growth factors and mainly consisted of structural proteins of angiogenically mature tissue. CONCLUSION Expression characteristics of structural proteins reveal that AVMs and CMs have different immunohistological properties. This study provides strong confirmation of previous findings of VEGF and bFGF immunoexpression in AVMs and CMs. It adds new information on TGFalpha expression in these malformations and on expression of the angiogenic factors in venous angiomas.

Cervical spondylotic myelopathy: surgical results and factors affecting prognosis.

OBJECTIVE A variety of factors may affect surgical outcome in patients with cervical spondylotic myelopathy. The aim of this study is to determine these factors on the basis of preoperative radiological and clinical data. METHODS To assess the factors affecting postoperative outcome after surgery for cervical spondylotic myelopathy, the clinical and radiological data of 27 patients with cervical spondylotic myelopathy were reviewed. Functional and neurological statuses were assessed using the Japanese Orthopaedic Association (JOA) scale modified by Benzel. In all patients, the effect of age, symptom duration, cervical curvature, presence or absence of preoperative high signal intensity within the spinal cord as revealed by T2-weighted magnetic resonance imaging, and diameters of the spinal canal and vertebral body on pre- and postoperative neurological statuses were investigated. Plain radiographs were obtained for all patients, magnetic resonance images for 21 patients (77.8%), computed tomographic scans for 13 patients (48.1%), myelograms for 6 patients (22.2%), and computed tomographic myelograms for 4 patients (14.8%). There were five patients with a JOA score of 10, six patients with a JOA score of 11, six patients with a JOA score of 12, four patients with a JOA score of 13, four patients with a JOA score of 14, one patient with a JOA score of 15, and one patient with a JOA score of 16. All patients underwent cervical laminectomies. The mean follow-up period was 54.1 months. The final neurological examinations revealed improvement in the JOA scores of 85.1 % of the patients. RESULTS Statistical analysis of all patients revealed mean JOA scores of 12.185 +/- 1.618 and 14.370 +/- 2.15 before surgery and at final examination, respectively. The difference between the preoperative JOA score and the final JOA score was determined to be statistically significant (P < 0.0001). Statistical analyses also showed better neurological improvement in patients younger than 60 years and in patients with normal preoperative cervical lordosis. Although patients without preoperative high signal intensity of the spinal cord showed a better improvement rate than did patients with preoperative high signal intensity, the determined difference was statistically insignificant. CONCLUSION It can be concluded that age and abnormal cervical curvature predict less postoperative neurological improvement. The presence of preoperative high signal intensity within the spinal cord may also reflect less neurological improvement.

First intraoperative, shared-resource, ultrahigh-field 3-Tesla magnetic resonance imaging system and its application in low-grade glioma resection

OBJECT The authors describe the first shared-resource, 3-T intraoperative MR (ioMR) imaging system and analyze its impact on low-grade glioma (LGG) resection with an emphasis on the use of intraoperative proton MR spectroscopy. METHODS The Acibadem University ioMR imaging facility houses a 3-T Siemens Trio system and consists of interconnected but independent MR imaging and surgical suites. Neurosurgery is performed using regular ferromagnetic equipment, and a patient can be transferred to the ioMR imaging system within 1.5 minutes by using a floating table. The ioMR imaging protocol takes < 10 minutes including the transfer, and the authors obtain very high-resolution T2-weighted MR images without the use of intravenous contrast. Functional sequences are performed when needed. A new 5-pin headrest-head coil combination and floating transfer table were specifically designed for this system. RESULTS Since the facility became operational in June 2004, 56 LGG resections have been performed using ioMR imaging, and > 19,000 outpatient MR imaging procedures have been conducted. First-look MR imaging studies led to further resection attempts in 37.5% of cases as well as a 32.3% increase in the number of gross-total resections. Intraoperative ultrasonography detected 16% of the tumor remnants. Intraoperative proton MR spectroscopy and diffusion weighted MR imaging were used to differentiate residual tumor tissue from peritumoral parenchymal changes. Functional and diffusion tensor MR imaging sequences were used both pre- and postoperatively but not intraoperatively. No infections or other procedure-related complications were encountered. CONCLUSIONS This novel, shared-resource, ultrahigh-field, 3-T ioMR imaging system is a cost-effective means of affording a highly capable ioMR imaging system and increases the efficiency of LGG resections.

Outcome determinants of pterional surgery for tuberculum sellae meningiomas

SummaryBackground. Current literature on tuberculum sellae meningiomas is very heterogenous due to wide variation in nomenclature, diagnostic and operative techniques. The aim of this study is specifically to analyze the results of pterional craniotomy for tuberculum sellae meningiomas. A homogenous cohort of 42 consecutively operated tuberculum sellae meningioma cases are reviewed with special emphasis on the effects of pterional microsurgery on visual outcome. Methods. This is a retrospective clinical analysis. 42 consecutive patients operated upon during the period of 15 years in a single institution using standard imaging protocols and pterional microsurgery are presented and effect of various variables on visual outcome analysed. Findings. 81% of the patients presented with visual symptoms. The mean duration of symptoms was 12 months. Tumour volumes ranged from 7.5 to 210 mm3. A right sided pterional microsurgery was used in all patients. Complete resection rate was 81%. Vision improved in 58%, worsened in 14%. Non-visual morbidity was 7.1% and mortality was 2.4%. The follow up period of patients ranged from 3 to 192 months (median: 30 months). The mean was 37.5 months (SD = ±36.7 months) and a recurrence rate of 2.4% was observed. Conclusions. A standard pterional craniotomy using microsurgical technique provides the necessary exposure enabling total removal while keeping the complications to a minimum. Upon analysis of our findings we found that patient age of more than 60, duration of visual symptoms longer than 1 year, severe visual symptomatology, predominantly vertical growth, presence of significant peri-tumoural oedema, absence of an intact arachnoid plane and subtotal removal were correlated with a dismal visual outcome.

Findings and outcome of revision lumbar disc surgery.

One hundred fourteen patients (64 men, 50 women) with prior lumbar disc surgery underwent a reexploration for intractable back and/or leg pain. The finding in revision surgery included disc herniation in 89 cases (78%), epidural fibrosis in 14 cases (12.2%), adhesive arachnoiditis in 4 cases (3.5%), isolated lateral spinal stenosis in 3 cases (2.6%), and iatrogenic instability in 4 cases (3.5%). Review of operative reports of patients who underwent a first operation in our institute revealed that seven cases (12.5%) had a second laminotomy without a discectomy in addition to the previous laminotomy and discectomy performed in the same session. Fifty-six of the patients with disc hemiation in revision surgery had a true recurrence. Disc hemiation was protruded in 38 cases (42.8%), extruded in 44 cases (49.4%), and sequestrated in 7 cases (7.8%). The outcome was assessed using Prolos functional and economic scale. According to Prolos scale, a good outcome was detected in 79 cases (69.2%), moderate in 22 (19.2%), and a poor outcome was detected in 13 cases (11.4%). The best outcome was achieved in patients with disc hemiation. It is concluded that recurrent disc disease is the most important cause of reexploration. This fact dictates a careful preoperative workup and discectomy in the first intervention. The likelihood of occurrence of disc herniation in the negative laminotomy level (i.e., laminotomy without discectomy procedure) also requires a careful preoperative radiologic workup before lumbar disc surgery.

Complications of central nervous system hydatid disease.

Central nervous system hydatid cyst disease presents with different clinical pictures depending on the involvement of cerebral and spinal structures. The majority of cerebral echinococcosis cases are

Multimodality management of 26 skull-base chordomas with 4-year mean follow-up: experience at a single institution

SummaryObjective. To analyze a series of patients with pathologically confirmed skull-base chordoma, and to develop an algorithm for the management of this challenging disease based on the data, our experience, and the current literature. Material and methods. Between the years 1986 and 2001, 26 chordoma patients received multimodality treatment with various combinations of conventional surgery, skull-base surgical techniques, and gamma-knife surgery at the Marmara University Faculty of Medicine. A total of 57 procedures (43 tumor excision surgeries, 7 gamma-knife procedures, and 7 other operations to treat complications) were performed. The mean follow-up period was 4 years (48.5 months). Karnofsky scoring was used to follow the patients’ clinical conditions, and magnetic resonance image analysis was used to measure tumor volume over time. Results. Seven patients died during follow-up. Two of the deaths were due to surgical complications, four resulted from clinical deterioration related to tumor recurrence, and one was unrelated to neoplasia. The rate of tumor recurrence after the first surgical treatment was 58%. Residual tumor volume was lower in the cases in whom skull-base approaches were used as first-line management. The 19 survivors showed little change in clinical status from initial diagnosis to the most recent follow-up check. The mean follow-up time after gamma-knife treatment was 23.3 months. During this period, mean tumor volume increased 28% above the mean volume at the time of gamma-knife surgery. The mean Karnofsky score decreased by 6% during the same time frame. Conclusions. The most effective first-line treatment for chordoma patients is surgery. The findings for residual tumor volume indicated that skull-base approaches are the best surgical option, and the complication rates for these techniques are acceptable. However, it is rare that surgery ever biologically eradicates this disease, and the data showed that these chordomas almost always progress if the tumor volume at the time of diagnosis exceeds 20 cm3. Based on our experience and the biological character of the disease, we now advocate radiosurgical treatment (gamma-knife in our case) immediately after the first-line skull-base surgery when the tumor residual volume is <30 cm3.

Detection of KIAA1549-BRAF fusion transcripts in formalin-fixed paraffin-embedded pediatric low-grade gliomas.

Alterations of BRAF are the most common known genetic aberrations in pediatric gliomas. They frequently are found in pilocytic astrocytomas, where genomic duplications involving BRAF and the poorly characterized gene KIAA1549 create fusion proteins with constitutive B-Raf kinase activity. BRAF V600E point mutations are less common and generally occur in nonpilocytic tumors. The development of BRAF inhibitors as drugs has created an urgent need for robust clinical assays to identify activating lesions in BRAF. KIAA1549-BRAF fusion transcripts have been detected in frozen tissue, however, methods for FFPE tissue have not been reported. We developed a panel of FFPE-compatible quantitative RT-PCR assays for the most common KIAA1549-BRAF fusion transcripts. Application of these assays to a collection of 51 low-grade pediatric gliomas showed 97% sensitivity and 91% specificity compared with fluorescence in situ hybridization or array comparative genomic hybridization. In parallel, we assayed samples for the presence of the BRAF V600E mutation by PCR pyrosequencing. The data further support previous observations that these two alterations of the BRAF, KIAA1549 fusions and V600E point mutations, are associated primarily with pilocytic astrocytomas and nonpilocytic gliomas, respectively. These results show that fusion transcripts and mutations can be detected reliably in standard FFPE specimens and may be useful for incorporation into future studies of pediatric gliomas in basic science or clinical trials.

Anatomic Landmarks of the Glossopharyngeal Nerve: A Microsurgical Anatomic Study

OBJECTIVECompared with other lower cranial nerves, the glossopharyngeal nerve (GPhN) is well hidden within the jugular foramen, at the infratemporal fossa, and in the deep layers of the neck. This study aims to disclose the course of the GPhN and point out landmarks to aid in its exposure. METHODSThe GPhN was studied in 10 cadaveric heads (20 sides) injected with colored latex for microsurgical dissection. The specimens were dissected under the surgical microscope. RESULTSThe GPhN can be divided into three portions: cisternal, jugular foramen, and extracranial. The rootlets of the GPhN emerge from the postolivary sulcus and course ventral to the flocculus and choroid plexus of the lateral recess of the fourth ventricle. The nerve then enters the jugular foramen through the uppermost porus (pars nervosa) and is separated from the vagus and accessory nerves by a fibrous crest. The cochlear aqueduct opens to the roof of this porus. On four sides in the cadaver specimens (20%), the GPhN traversed a separate bony canal within the jugular foramen; no separate canal was found in the other cadavers. In all specimens, the Jacobson’s (tympanic) nerve emerged from the inferior ganglion of the GPhN, and the Arnold’s (auricular branch of the vagus) nerve also consisted of branches from the GPhN. The GPhN exits from the jugular foramen posteromedial to the styloid process and the styloid muscles. The last four cranial nerves and the internal jugular vein pass through a narrow space between the transverse process of the atlas (C1) and the styloid process. The styloid muscles are a pyramid shape, the tip of which is formed by the attachment of the styloid muscles to the styloid process. The GPhN crosses to the anterior side of the stylopharyngeus muscle at the junction of the stylopharyngeus, middle constrictor, and hyoglossal muscles, which are at the base of the pyramid. The middle constrictor muscle forms a wall between the GPhN and the hypoglossal nerve in this region. Then, the GPhN gives off a lingual branch and deepens to innervate the pharyngeal mucosa. CONCLUSIONTwo landmarks help to identify the GPhN in the subarachnoid space: the choroid plexus of the lateral recess of the fourth ventricle and the dural entrance porus of the jugular foramen. The opening of the cochlear aqueduct, the mastoid canaliculus, and the inferior tympanic canaliculus are three landmarks of the GPhN within the jugular foramen. Finally, the base of the styloid process, the base of the styloid pyramid, and the transverse process of the atlas serve as three landmarks of the GPhN at the extracranial region in the infratemporal fossa.

Intraoperative MR imaging: preliminary results with 3 tesla MR system

UNLABELLED Aim of this study is to present the initial clinical experience with 3 tesla intraoperative MR (ioMR). MATERIAL AND METHODS The 3T MRI suite is built adjacent to the neurosurgical operation theatre. The magnet room and the operation theatre are interconnected by a door and both RF-shielded. Before the operation, the magnet (3T Trio, Siemens) and the console rooms are disinfected. Whenever imaging is needed during the operation, the door is opened and the patient is transferred from the operation table to the magnet cradle. Axial, sagittal and/or coronal TSE T2, SE T1 and 3D Flash T1 weighted images (4-6 mm section thickness, 1 mm interslice gap) are obtained according to the lesion. Total examination time is approximately 10 minutes. RESULTS Twenty-six patients were examined with ioMR. There were ten female and seven male patients. Lesions were pituitary adenoma in 10, low grade glial tumor in 9, meningioma and high grade glial tumor in 2 each and metastasis, haemangioblastoma and chordoma in one each. Follow-up time was 1 to 9 months. In 16 patients the first intraoperative examination revealed gross total tumor excision. However, in 10 patients due to tumor remnants surgical intervention was continued and a second examination revealed gross total tumor excision in all. Postoperative routine MR examinations confirmed total tumor excision in all patients. No complication occurred in this series. CONCLUSION This small group of patients examined with ioMR demonstrated that the procedure is simple, helpful in achieving gross total tumor excision without complications.