Associating IDH and TERT Mutations in Glioma with Diffusion Anisotropy in Normal-Appearing White Matter.

BACKGROUND AND PURPOSE: IDH and TERT mutations might infiltratively manifest within normal-appearing white matter with specific phenotypes such as microstructural changes undetectable by standard MR imaging contrasts but potentially associable with DTI variables. The aim of this retrospective glioma study was to statistically investigate IDH and TERT associations and classifications with DTI reported microstructure in normal-appearing white matter. MATERIALS AND METHODS: Retrospective data from patients imaged between March 2012 and February 2016 were analyzed by grouping them as IDH-TERT subgroups and by IDH and TERT mutation status. DTI variables in the IDH-TERT subgroups were first identified by the Kruskal-Wallis test, followed by Dunn-Sidák multiple comparisons with Bonferroni correction. IDH and TERT mutations were compared with the Mann-Whitney U test. Classification by thresholding was tested using receiver operating characteristic analysis. RESULTS: Of 170 patients, 70 patients (mean age, 43.73 [SD, 15.32] years; 40 men) were included. Whole-brain normal-appearing white matter fractional anisotropy (FA) and relative anisotropy (RA) (P = .002) were significantly higher and the contralateral-ipsilateral hemispheric differences, ΔFA and ΔRA, (P < .001) were significantly lower in IDHonly patients compared with TERTonly, with a higher whole-brain normal-appearing white matter FA and RA (P = .01) and ΔFA and ΔRA (P = .002) compared to double positive patients. Whole-brain normal-appearing white matter ADC (P = .02), RD (P = .001), λ2 (P = .001), and λ3 (P = .001) were higher in IDH wild-type. Whole-brain normal-appearing white matter λ1 (AD) (P = .003), FA (P < .001), and RA (P = .003) were higher, but Δλ1 (P = .002), ΔFA, and ΔRA (P < .001) were lower in IDH mutant versus IDH wild-type. ΔFA (P = .01) and ΔRA (P = .02) were significantly higher in TERT mutant versus TERT wild-type. CONCLUSIONS: Axial and nonaxial diffusivities, anisotropy indices in the normal-appearing white matter and their interhemispheric differences demonstrated microstructural differences between IDH and TERT mutations, with the potential for classification methods.

Anterior clinoidal meningiomas: analysis of 43 consecutive surgically treated cases.

BACKGROUND: Anterior clinoidal meningiomas are considered different from meningiomas of the medial sphenoid wing, but there is still some confusion about identification. The current classification scheme only considers tumour origin and invasion pattern around the clinoid process as indicators of resectability. However, the size of the tumour has important effects on surgical outcome. The purpose of this study was to analyze our clinical experience with anterior clinoidal meningiomas and refine the current classification scheme. METHOD: Forty-three consecutive cases of anterior clinoidal meningioma were retrospectively analyzed. All were surgically treated at the Marmara University Department of Neurosurgery, the Marmara University Institute for Neurological Sciences, and the Department of Neurosurgery at Acibadem Hospital between 1987 and 2006. A pterional approach was used in all cases. FINDINGS: The mean tumour volume was 34.2 +/- 46.6 cc. Sixteen (37.2%) of the tumours were giant (largest diameter >4 cm). Total surgical removal was achieved in 39 cases (90.7%) and subtotal removal in 4 cases (9.3%). Eight patients (18.6%) developed early postoperative complications. The median and range of follow-up time was 39, R = 99 (3, 102) months. Four (9.3%) of the 43 tumours recurred during follow-up and were treated with radiosurgery. CONCLUSION: Anterior clinoidal meningioma is a separate disease entity from other meningiomas of the medial third of the sphenoid wing. Relatively good outcomes can be stated in this specific subgroup if growth criteria competable with true diagnosis are fulfilled. Size should be incorporated into any classification scheme for determining clinical and surgical risk. The standard pterional approach is sufficient for removing anterior clinoidal meningiomas.

Tumor-biology and current treatment of skull-base chordomas.

Chordomas are rare, slow growing tumors of the axial skeleton, which derive from the remnants of the fetal notochord. They can be encountered anywhere along the axial skeleton, most commonly in the sacral area, skull base and less commonly in the spine. Chordomas have a benign histopathology but exhibit malignant clinical behavior with invasive, destructive and metastatic potential. Genetic and molecular pathology studies on oncogenesis of chordomas are very limited and there is little known on mechanisms governing the disease. Chordomas most commonly present with headaches and diplopia and can be readily diagnosed by current neuroradiological methods. There are 3 pathological subtypes of chordomas: classic, chondroid and dedifferentiated chordomas. Differential diagnosis from chondrosarcomas by radiology or pathology may at times be difficult. Skull base chordomas are very challenging to treat. Clinically there are at least two subsets of chordoma patients with distinct behaviors: some with a benign course and another group with an aggressive and rapidly progressive disease. There is no standard treatment for chordomas. Surgical resection and high dose radiation treatment are the mainstays of current treatment. Nevertheless, a significant percentage of skull base chordomas recur despite treatment. The outcome is dictated primarily by the intrinsic biology of the tumor and treatment seems only to have a secondary impact. To date we only have a limited understanding this biology; however better understanding is likely to improve treatment outcome. Hereby we present a review of the current knowledge and experience on the tumor biology, diagnosis and treatment of chordomas.

Outcome determinants of pterional surgery for tuberculum sellae meningiomas.

BACKGROUND: 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 mm(3). 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.

Relief of hemifacial spasm after radiosurgery for intracanalicular vestibular schwannoma.

Secondary hemifacial spasm due to vestibular schwannoma is very rare. This is the first reported case of hemifacial spasm responsive to gamma knife radiosurgery in a patient with an intracanalicular vestibular schwannoma. Both the resolution of the spasm as well as tumor growth control were achieved with a single session of gamma knife radiosurgery. We report a 49-year-old male patient with a 6-month history of right-sided hearing loss and hemifacial spasm. MR examination revealed an intracanalicular vestibular schwannoma. The patient was treated with radiosurgery and received 13 Gy to the 50 % isodose line. Tumor growth control was achieved and no change in the tumor volume was present at the last follow-up at 22 months. The hemifacial spasm completely resolved after one year. Surgical removal of the presumably causative mass lesion has been reported to be the sole treatment in secondary hemifacial spasm. This case report indicates that it may be responsive to gamma knife radiosurgery. Whether or not this might be a treatment option in selected refractory cases of hemifacial spasm remains to be defined.

Effects of valproate, phenytoin, and MK-801 in a novel model of epileptogenesis.

PURPOSE: We have developed and characterized a novel model of epileptogenesis based on the convulsive actions of flurothyl in mice. The hallmark feature of this model is a reliable change in the type of seizure expressed in response to flurothyl from generalized clonic to generalized tonic seizures. The purpose of our study was to evaluate the effects of chronic administration of valproate (VPA), phenytoin (PHT), and MK-801 on the change in seizure phenotype observed in our model system. METHODS: Male C57BL/6J mice received flurothyl seizures on 8 consecutive days. Two hours after the last generalized seizure, chronic drug or vehicle was administered twice daily at 12-h intervals for 28 days. The drugs evaluated were VPA (250 mg/kg), PHT (30 mg/kg), and MK-801 (0.5 mg/kg). After a 7-day drug washout period, mice were retested with flurothyl. RESULTS: Among uninjected or vehicle-injected control mice, there was a significant increase in the proportion of animals expressing tonic seizures after the 28-day stimulation-free interval. Chronic administration of VPA or MK-801, but not PHT, blocked the characteristic change in seizure type from clonic to tonic. CONCLUSIONS: The change in seizure phenotype observed after exposure to our paradigm indicates a fundamental reorganization in the propagation of flurothyl-initiated seizures. As in electrical kindling, VPA and MK-801 are effective at blocking or retarding the reorganization, whereas PHT is not. The concordance in pharmacologic profiles between kindling and our model suggests that the processes underlying changes in seizure susceptibility in these two models share mechanisms in common.