Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience.

PURPOSE: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. METHODS: Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. RESULTS: At the time of diagnosis, the median age was 48 (17-77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1-68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). CONCLUSION: Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.

Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4 gene.

We report an association between a new causative gene and spastic paraplegia, which is a genetically heterogeneous disorder. Clinical phenotyping of one consanguineous family followed by combined homozygosity mapping and whole-exome sequencing analysis. Three patients from the same family shared common features of progressive complicated spastic paraplegia. They shared a single homozygous stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous mutation (c.853_871del19) in the gene coding the kinesin light chain 4 protein (KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a stop codon and thus a truncated messenger RNA and protein. The association of a KLC4 mutation with spastic paraplegia identifies a new locus for the disease.

Neural tube defect family with recessive trait linked to chromosome 9q21.12-21.31.

PURPOSE: Meningomyelocele is one of the most common and socioeconomically, psychologically, and physically debilitating neurodevelopmental diseases. A few chromosomal locus and genes have been identified as responsible for the disease; however, clear evidence still needs to be produced. This study aimed to show evidence of a strong genetic linkage in a novel chromosomal locus in a family with this neural tube defect. METHODS: We identified a neural tube defect family in eastern Turkey, where two of six offspring had operations due to thoracolumbar meningomyelocele. The parents were of a consanguineous marriage. We collected venous blood from six offspring of the family. Whole genome linkage analysis was performed in all offspring. RESULTS: A theoretical maximum logarithm of an odds score of 3.16 was identified on chromosome 9q21.12-21.31. This result shows a strong genetic linkage to this locus. CONCLUSIONS: Our results identified a novel chromosomal locus related to meningomyelocele and provide a base for further investigations toward the discovery of a new causative gene.

Anatomy of the spinal dorsal root entry zone: its clinical significance.

BACKGROUND: The posterolateral sulcus (PLS) is an important surgical landmark, especially for DREZ (dorsal root entry zone) operations. METHODS: The present study aimed to show the variations of the PLS using human spinal cord histological sections and report the variability in the number of dorsal rootlets of the spinal nerves in each the spinal cord segment. Further, measure the height and width of the dorsal horn on histological sections for cervical, thoracic, and lumbar levels. RESULTS: The results of the present study showed various patterns of PLS 1.clearly present PLS, 2. short PLS, 3. absent PLS or 4. irregular PLS. Height and width measurements of the dorsal horn showed that the average width was greatest at lower cervical (0.48 ± 0.04 mm) and least at lower thoracic levels (0.41 ± 0.04 mm), whereas the average height was greatest at upper cervical (3.0 ± 0.06 mm) and smallest at lower lumbar levels (1.8 ± 0.08 mm). The average number of rootlets varied considerably, at cervical level it was 7.6 ± 1.4 mm, at thoracic 6.6 ± 0.8 mm and at lumbar 6.1 ± 0.4 mm. CONCLUSIONS: The detailed anatomy of the variations of the PLS and the average number of rootlets at each spinal level can increase the success of regional surgery. Further, fine measurements on histological sections can give detailed knowledge on the size necessary for lesioning in DREZ operations.

Posterolateral Paramass Approach to Lesions Located at the Anterior C1-2 Level: A Cadaver Study.

OBJECTIVE: A novel posteriolateral surgical approach is described that will provide safe access to intradural and extradural lesions located in the anterior part of the spinal cord (SC) at the C1-2 level and to the odontoid in single session. METHODS: A total of five cadavers and two dry C1 vertebrae were used in this study. The study involved obtaining computed tomography magnetic resonance imaging scans and magnetic resonance imaging of all cadaver groups before and after the procedures. Group 1: Control; Group 2: Unilateral C1 posterior arch was removed, the inferomedial part of C1 lateral mass was removed, and access the anterior and lateral aspects of the SC. Group 3: In addition, odontoid was removed, Group 4: In addition, unilateral C1- C2 screw was placed. Group 5: In addition, bilateral C1-C2 screw was placed. RESULTS: The median distance from the midpoint of C1 posterior tubercle to vertebral groove which was removed in groups is 21.4 ± 2.88 mm. The average width of C1 lateral mass was 13.4±2.4 mm. After the lateral mass was drilled, its width decreased to 10,2 mm.This area was sufficient to open a surgical corridor and reach the anterior of SC and odontoid. After the procedure, no instability was found in group 2 without instrumentation on computed tomography and magnetic resonance imaging scans. CONCLUSIONS: It is possible to access the anterior C1-C2 via a posterolateral paramass approach by drilling 20%-30% of the lateral mass, providing an open pathway for easy intervention in C1-C2 intradural lesions. It is also possible to perform odontoid resection using this approach.

Effects of intramuscular parecoxib administration on vasospasm in an experimental subarachnoid hemorrhage model.

AIM: We examined whether intramuscular parecoxib administration has a preventive or therapeutic effect on vasospasm following experimental subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Twenty New Zealand White Rabbits were assigned randomly to one of four groups. Animals in Group I were not subjected to SAH (control group). Animals in all other groups were subjected to SAH. Animals in Group II received no treatment after SAH induction (SAH group). Animals in Group III received intramuscular parecoxib (diluted with saline) injection at 6 and at 30 hours after SAH (treatment group). Animals in Group IV received only intramuscular saline injection at 6 and at 30 hours after SAH (vehicle group). Animals were euthanized by perfusion and fixation 48 hours after SAH induction. Basilar artery cross-sectional areas and wall thicknesses were measured. Statistical comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests. RESULTS: Basilar artery cross-sectional areas in the treatment group were significantly higher than in the SAH or vehicle group (p<.05). Basilar artery wall thickness in the treatment group was significantly smaller than in the SAH or vehicle group (p<.05). CONCLUSION: Our study revealed that intramuscular administration of parecoxib significantly attenuates vasospasm following experimental SAH.

Spontaneous nonpulsatile aneurysm of the superficial temporal artery mimicking a subcutaneous mass lesion.

True superficial temporal artery (STA) aneurysms are extremely rare and usually atherosclerotic in origin. Here the authors report a 62-year-old man with a nonpulsatile mass lesion at the trace of the right STA that was surgically excised with a preoperative diagnosis of subcutaneous mass lesion, preoperatively and histopathologically found out to be a thrombosed true STA aneurysm. Preoperative evaluation, differential diagnosis, and management of such lesions are discussed.

Effects of Ozone on Injury after Gamma Knife Radiosurgery.

BACKGROUND: At present, gamma knife radiosurgery plays an important role in neurosurgical procedures. Gamma knife radiosurgery has been used to treat many types of brain tumors and as a functional intervention. However, gamma knife treatment has a devastating effect on the normal brain parenchyma surrounding the target point. It causes increased vascular permeability, vasodilation, and swelling in endothelial cells. Ozone has antioxidant, antiapoptotic, and anti-inflammatory effects in the body. Thus, we evaluated the radioprotective effects of ozone in rats undergoing gamma knife radiation. METHODS: In the present study, 24 Sprague-Dawley male rats weighing 250-300 g in 3 groups of 8 rats each were used. The rats were selected randomly. The control group did not receive any gamma knife radiation. The other 2 groups received 50 Gy of radiation, with 1 group given ozone treatment and the other group not given ozone treatment after gamma knife radiosurgery. At 12 weeks after gamma knife radiation, the rats were sacrificed with high-dose anesthetic agents and the tissues prepared for evaluation. The slides were evaluated for necrosis, vacuolization, glial proliferation, and vascular proliferation using hematoxylin-eosin staining. Vascular endothelial growth factor (VEGF) and extracellular matrix metalloproteinase inducer (also known as CD147) were evaluated using immunohistochemical staining. RESULTS: VEGF expression in glial tissue was significantly less in the group receiving ozone (χ2 = 15.00; df = 4; P = 0.005) compared with the group that had not received ozone and was similar to the expression in the control group. CONCLUSIONS: The lower expression of VEGF in the group receiving ozone might cause less edema in the surrounding tissue owing to less degradation of vascular permeability in the rat brain tissue.

Bilateral Temporal Bone Xanthomas in Type II Hypercholesterolemia.

We present a very rare case of intracranial xanthoma with bilateral temporal bone involvement. The lesion caused destruction and remodelling in mastoid air cells. On the right side, cerebellar compression was obvious. The patient was operated on the symptomatic side and the lesion was totally removed.

The effects of intravenous cilostazol and nimodipine on cerebral vasospasm after subarachnoid hemorrhage in an experimental rabbit model.

AIM: Our aim in this study was to investigate the efficacy of intravenous administration of cilostazol and compare these effects with intravenous usage of nimodipine in subarachnoid hemorrhage model. MATERIAL AND METHODS: Twenty-five male New Zealand White rabbits were assigned randomly to 1 of 5 groups. Animals in group 1 (n=5) served as controls, group 2 (n=5) was the SAH-only group, group 3 (n=5) was treated with intravenous 10 mg/kg cilostazol, group 4 (n=5) was treated with 0.05 mg/kg intravenous nimodipine, and group 5 (n=5) served as the vehicle group and treated with a mixture of dimethyl sulfoxide and phosphate buffer solution. Basilar arteries were removed from the brain stems and analyzed. The vessels were measured using computer-assisted morphometry (SPOT for Windows Version 4.1). Statistical comparisons were performed using the Kruskall-Wallis and Mann-Whitney U tests. RESULTS: Basilar artery wall thicknesses in group 3 and 4 were smaller than the group 2 and this was statistically significant at p < 0.05. The mean arterial cross-sectional areas in group 3 and 4 were higher than group 2 and this was also statistically significant at p < 0.05. CONCLUSION: Our results demonstrate that intravenous administration of both cilostazol and nimodipine significantly attenuates cerebral vasospasm after SAH.

In Vitro Effects of Mesenchymal Stem Cells and Various Agents on Apoptosis of Glioblastoma Cells.

AIM: To investigate a new anti-tumor treatment method using stem cells transfected with specific genes and proteins that induce apoptosis in tumor cells. MATERIAL AND METHODS: We used glioblastoma (GBM) cells and human adipose tissue-derived mesenchymal stem cells (ADMSCs) in this study. The AD-MSCs were transfected with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To overcome apoptosis resistance in tumor cells, we used suberoylanilide hydroxamic acid (SAHA) as the histone deacetylase inhibitor and embelin as the X-linked inhibitor of apoptosis protein (XIAP). In addition, we silenced the XIAP gene on GBM cells with the shXIAP plasmid. Following the determination of half-maximal effective concentration (EC50%) doses of SAHA and embelin, GBM cells were incubated with them for 24 hours. XIAP-silenced and XIAP-non-silenced GBM cells were cultured with TRAIL-nontransfected and TRAIL-transfected stem cells for 24 hours. Viability and cell cycle analysis of all groups were determined using annexin V/propidium iodide and cell cycle method via flow cytometry. RESULTS: TRAIL-transfected AD-MSCs, XIAP silencing, embelin, and SAHA induced apoptosis in GBM cells and decreased their proliferation, whereas TRAIL-non-tranfected AD-MSCs did not. CONCLUSION: Engineered stem cell therapies and molecular studies show promise in developing combination therapies for effective treatment of GBM.

Existence of cotton granuloma after removal of a parasagittal meningioma: clinical and radiological evaluation -a case report-.

Hemostatic agents, routinely used in neurosurgery to achieve intraoperative hemostasis may cause foreign body reaction. These may produce clinically symptomatic and radiologically apparent mass lesions. It should be kept in mind that retained cotton or rayon materials may mimic the appearance of a tumor or an abscess on MRI scan, especially at sides of previous craniotomies. Here we report a case of intracranial foreign body granuloma which occurred due to remained cottonoid after removal of a parasagittal meningioma. This entity was also documented by MR imaging technics included diffusion weighted, flair and ADC mapping.

Enlargement of postoperative aqueductal air due to elevated body temperature. Case report.

Pneumocephalus has been reported after posterior fossa surgery especially with procedures performed in the sitting position. The gravitational effect is the decisive factor in the development of pneumocephalus. The entrapped air in the aqueduct may enlarge due to several factors such as elevated body temperature and may cause to deterioration in neurological status. We report a rare case of tension pneumocephalus associated with the enlargement of massive air in aqueduct due to elevated body temperature, following removal of a cervicomedullary tumor. We believe her neurological deterioration was due to the compression of the reticular formation by dilatation of postoperative air in the aqueduct due to the elevation of her body temperature.

A perspective for the selection of surgical approaches in patients with upper thoracic and cervicothoracic junction instabilities.

OBJECTIVE: To reach the upper thoracic vertebrae, a number of extensive approaches have been proposed. The purpose of this study is to provide a clear perspective for the selection of surgical approaches in patients who undergo vertebral body resection, reconstruction, and stabilization for upper thoracic and cervicothoracic junction instabilities. METHODS: Seventeen patients with upper thoracic or cervicothoracic junction (C7-T6) instability underwent surgery between January 1999 and May 2004. All patients presented with pain and/or neurological deficits. The causes of instabilities were 10 traumas and 7 pathological fractures. The approach chosen was primarily dictated by 3 factors including (1) type of injury, (2) level of lesion, and (3) time of admission. Ventral surgical approach was performed to all pathological and traumatic fractures causing anterior spinal cord compression. Level of lesion determined the selection of the type of ventral surgical approach, namely, supramanubrial, transmanubrial, or lateral transthoracic. On the other hand, combined (anterior and posterior) approach was performed to all late admitted trauma patients. RESULTS: Twelve anterior, 2 combined (anterior and posterior), and 3 posterior approaches were performed in this study. Anterior approaches included 3 transmanubrial, 5 upper lateral transthoracic, and 4 supramanubrial cervical dissection procedures for decompression, fusion, and plate-screw fixation depending on the levels of the lesion. The mean follow-up period was 18 months, ranging from 10 to 58 months. Nonunion or instrument-related complications were not observed. The postoperative neurological conditions were statistically significantly better than the preoperative ones (P = .003). CONCLUSION: Consideration of the type of injury, level of lesion, and time of admission can provide a perspective for the selection of side of surgical approach for this transitional part of the spinal column. This study also suggests that supramanubrial cervical approach achieves sufficient exposure up to T2, transmanubrial approach for T3, and lateral transthoracic approach below T3.

Spontaneous resolution of syringomyelia without Chiari malformation.

A 30-year-old woman presented with a cervical syrinx manifesting as hemihypesthesia. Neuroimaging found no evidence of Chiari malformation or tight cisterna magna. Serial magnetic resonance imaging studies over a 6-year period demonstrated spontaneous and complete resolution of the syrinx accompanied by an asymptomatic clinical course. The natural history of syringomyelia is highly unpredictable. The outcome of surgical treatment for patients with syringomyelia is not always satisfactory, so the indications for surgery are controversial. Spontaneous resolution of syringomyelia unrelated with foramen magnum lesion has various causes. Close follow up of the patient is necessary to monitor for recurrence.

Abducens nerve palsy in a patient with a parasagittal meningioma--case report.

A 67-year-old female presented with isolated unilateral abducens nerve palsy progressing in 10 days. There were no signs of elevated intracranial pressure. Magnetic resonance imaging revealed a right parasagittal meningioma. The tumor was grossly totally removed and the patient's nerve palsy gradually improved within 3 weeks. The mechanism of the isolated abducens nerve palsy in this case is attributed to compression of the abducens nerve by entrapment of the cerebrospinal fluid just before entering Dorello's canal under the petrolingual ligament. Linear forces in the midsagittal plane due to the mass effect of the tumor may have temporarily increased the local cerebrospinal fluid pressure and caused 'pseudoentrapment' of the abducens nerve.

Long-term Results of ABI in Children With Severe Inner Ear Malformations.

OBJECTIVE: To report the long-term outcomes of children who received auditory brainstem implant (ABI) because of severe inner ear malformations. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral otolaryngology clinic. SUBJECTS AND METHODS: Between July 2006 and October 2014, 60 children received ABI at Hacettepe University. Preoperative work up included otolaryngologic examination, audiological assessment, radiological evaluation together with assessment of language development and psychological status. The surgeries were performed via retrosigmoid approach with a pediatric neurosurgeon. Intraoperatively, electrical auditory brainstem response was utilized. Initial stimulation was done 4 to 5 weeks postoperatively. Outcomes were evaluated with Categories of Auditory Performance (CAP), speech intelligibility rate (SIR), functional auditory performance of cochlear implant (FAPCI) and Manchester Spoken Language Development Scale scores; receptive and expressive language ages were determined. RESULTS: Sixty children who received ABI were between ages of 12 and 64 months. Thirty-five patients with follow up period of at least 1 year, were reported in means of long-term audiological and language results. The most prevelant inner ear malformation was cochlear hypoplasia (n = 19). No major complication was encountered. Majority of the patients were in CAP 5 category, which implies that they can understand common phrases without lip reading. SIR was found out to be better with improving hearing thresholds. Children with ABI were performing worse than average cochlear implantation (CI) users when FAPCI scores were compared. Patients with the best hearing thresholds have expressive vocabulary of 50 to 200 words when evaluated with Manchester Spoken Language Development Scale. There was no relationship between the number of active electrodes and hearing thresholds. The type of inner ear anomaly with the best and the worst hearing thresholds were common cavity and cochlear aperture aplasia, respectively. Patients with additional handicaps had worse outcomes. Among 35 children, 29 had closed set discrimination and 12 developed open set discrimination above 50%. It was determined that, progress of the patients is faster in the initial 2 years when compared with further use of ABI. CONCLUSION: ABI is an acceptable and effective treatment modality for pediatric population with severe inner ear malformations. Bilateral stimulation together with CI and contralateral ABI should be utilized in suitable cases.

Minimally invasive anterior contralateral approach for the treatment of cervical disc herniation.

BACKGROUND: During the practice of ipsilateral approach to the offending lesion in anterior simple discectomy, the authors realized that it achieves better surgical exposure of the opposite foraminal area. In addition, it was also realized that routine procedures for better visualization of the foraminal area, such as stripping longus colli muscles, further excising of the anterior longitudinal ligament, or using a spreader, which cause more invasive surgery during the standard anterior approach, are not necessary because the contralateral approach already achieves sufficient exposure of the target foraminal area. OBJECTIVE: Evaluation of the results and effectiveness of this minimal invasive technique in patients with either soft or hard disc herniations. METHODS: Between January 1994 and April 2002, 216 patients underwent anterior contralateral microdiscectomy without fusion for cervical disc herniation at 1 or 2 adjacent levels. Anterior contralateral microdiscectomy is a less invasive technique than standard anterior simple discectomy in which longus colli muscles are not stripped, and the lateral part of annulus fibrosis at the side of intervention and ventrolateral part of it at the opposite side are not removed. In addition, a mini Zenker handheld retractor is used for retraction of paravertebral soft tissues and a spreader is not used during the discectomy procedure. There were 182 patients diagnosed with radiculopathy and 34 patients with myelopathy. Assessments of the neurological status of patients with radiculopathy were done by physical examinations, and of those with myelopathy according to the modified Japanese Orthopaedic Association cervical spine functional assessment scale. These neurological assessments were repeated in the 18th month after surgery. In the follow-up period, the outcomes of surgery were also assessed for all patients in 4 categories, from failure to excellent. RESULTS: Surgery outcomes generally have been good to excellent and none of the patients were made worse by the procedure. The outcomes were significantly better in the radiculopathy and soft disc herniation groups. Other positive outcome factors were short duration and sudden onset of symptoms, normal cervical curvature, and single-level disease. Follow-up radiological studies revealed fibrous healing with normal or slight loss of disc height in 199 (92.1%) patients and total obliteration of the involved disc space representing radiological fusion signs in 13 (6%) patients. The overall complications observed in this study were 2 spontaneous and 2 postinfection collapses of disc level, 1 excessive fibrosis of disc level, and 2 adjacent-level diseases. CONCLUSION: Anterior contralateral microdiscectomy without fusion achieves better exposure for resection of the offending foraminal or far lateral lesions, ventral osteophytes, or a disc fragment under direct microscopic visualization. Collapse and instability of the involved disc level can also be avoided via this less invasive technique.

Proposed classification of segments of the internal carotid artery: anatomical study with angiographical interpretation.

The nomenclature and borders of the segments of the internal carotid artery (ICA) remain confusing. A classification of segments of the ICA is proposed based on constant anatomical structures, such as the carotid foramen and canal, the petrous bone, the petrolingual ligament (PLL), and the proximal and distal dural rings. The bilateral ICAs were dissected in 15 cadaveric head specimens using different neurosurgical approaches. The bilateral lacerum foramina were studied in five dry skulls. The bilateral segments of the ICA were also examined on carotid angiograms of 10 normal patients and another with the ophthalmic artery originating from the intracavernous portion of the ICA. The present classification divides the ICA into five segments in the direction of the blood flow. The cervical segment is extradural and extracranial, the petrous segment is extradural and intraosseous, the cavernous segment is interdural and intracavernous, the clinoidal segment is interdural and paracavernous, and the cisternal segment is intradural and intracisternal. The ICA did not pass through the lacerum foramen in any specimen. In all specimens, 1/8 to 5/8 of the lacerum foramen was under the deep dural layer of the cavernous sinus. The term 'lacerum segment' as used previously and called the 'trigeminal segment' by us cannot be justified. The PLL is the posterolateral border of the cavernous sinus and the lacerum and trigeminal segments should be included in the cavernous and petrous segments. The ophthalmic artery may originate from the clinoidal ICA, from the cavernous ICA, or from the middle meningeal artery. Instead of using the term 'ophthalmic segment,' the term 'cisternal segment' should be used for the anatomically distinct ICA in the subarachnoid space. This classification should be minimally affected by anatomical variations.