Antonella Bacci

Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status.

A recent randomized study conducted on newly diagnosed glioblastoma (GBM) patients demonstrated that concomitant and adjuvant temozolomide added to standard radiotherapy had a survival advantage compared with radiotherapy alone. The overall survival benefit of this aggressive treatment, however, was attenuated in older or poor performance status patients. The aim of the present study was to verify the activity and the toxicity of temozolomide administration concurrent and adjuvant to radiotherapy as first‐line treatment for elderly GBM patients, and to explore correlations between clinical outcome and O6 methylguanine‐DNA methyltransferase (MGMT) promoter methylation status.

O6-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications

O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age > or = 18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval > or = 3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27-67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.

Granulomatous Hypophysitis Caused by a Ruptured Intrasellar Rathke's Cleft Cyst: Report of a Case and Review of the Literature

OBJECTIVE AND IMPORTANCE Ruptured Rathkes cleft cyst is a rare cause of giant cell granulomatous hypophysitis. Chronic inflammatory reaction is caused by extravased cyst content into the adjacent gland. We provide a demonstration that mucins produced by cells lining the cyst wall caused the granulomatous giant cell reaction. CLINICAL PRESENTATION A 37-year-old nonpregnant woman presented with a 3-year-history of headache and amenorrhea. She had experienced normal sexual maturation, and her medical history was unremarkable. Radiologically, the lesion appeared as an intrasellar mass with a cystic component indistinguishable from a pituitary adenoma with cystic degeneration. TECHNIQUE The patient underwent a transsphenoidal approach. Because no demarcation between normal and affected tissue was evident at surgery, the lesion and residual pituitary were radically removed. Tissue was studied using routine hematoxylin and eosin and histochemical stainings for mucins and immunocytochemical techniques. CONCLUSION This study demonstrates that mucins that had spilled out from the cyst caused the granulomatous reaction. Using computed tomography, magnetic resonance imaging, and gross inspection, distinction between granulomatous hypophysitis and pituitary adenoma was virtually impossible. Nevertheless, a granulomatous reaction of the pituitary gland should be suspected in a case of a sellar mass having a cystic area. In such cases, intraoperatory diagnosis on frozen sections is mandatory because adoption of a conservative treatment allows preservation of the gland.

Sturge-Weber syndrome without port-wine facial nevus: report of 2 cases studied by CT

2 cases of Sturge-Weber syndrome without facial nevus are reported. The patients presented different forms of epilepsy. The diagnosis was made by computed tomography (CT) which showed typical intracranial calcifications in both occipital regions. The problems concerning the atypical and incomplete forms of the syndrome are briefly discussed. The importance of CT as a diagnostic procedure for this disease is emphasized.

Metabolic Abnormalities in Pain-Processing Regions of Patients with Fibromyalgia: A 3T MR Spectroscopy Study

As neuroradiologists we see many spine studies for fibromyalgia and wonder about the significance of this condition (is it a real disease?). Here, the authors used MR spectroscopy to assess metabolic alterations in brain regions associated with pain reception (thalami and ventrolateral prefrontal cortex). Using 3T single-voxel MRS, they studied 12 patients and 12 healthy controls and analyzed their data using an LCModel. Glx/Cr and Glu/Cr ratios in the cortex were significantly higher in patients than in controls but no differences were found in the thalami. The authors conclude that these MRS abnormalities support an imbalance in the pain processing areas that underlie fibromyalgia. BACKGROUND AND PURPOSE: A growing body of evidence suggests the involvement of the brain in FM. The purpose of this proton MRS study was to test the hypothesis that there are metabolic alterations in some brain regions processing pain (VLPFC and thalamus) in patients with FM compared with HC. MATERIALS AND METHODS: Twelve patients with FM (30–54 years of age; mean age, 43.2 years), and 12 HC, matched for age and sex, underwent 1 session of single-voxel MRS performed on a 3T MR imaging scanner. MRS spectra were acquired with a PRESS for localization. The raw data from each spectrum was evaluated with an LCModel. T tests were used to evaluate differences of brain metabolites between groups. The Pearson correlation tested the relationship of metabolite ratios and clinical symptoms. RESULTS: Glx/Cr and Glu/Cr ratios within the VLPFC of both sides were significantly higher in patients than in HC (P < .01). No significant differences of metabolites between groups were found in the thalami. Positive correlations were found between Glu/Cr in the left thalamus and the VAS for pain (r = 0.730, P = .007) and between mIns/Cr in the right VLPFC and the VAS for pain (r = 0.607, P = .037) and the FIQ (r = 0.719, P = .008). CONCLUSIONS: The presence of elevated Glu/Cr levels in VLPFC strengthens the opinion that a complex neurophysiologic imbalance of different brain areas involved in pain processing underlies FM. These data may be useful in the diagnosis and development of more effective pharmacologic treatments.

Ophthalmoplegic migraine: From questions to answers

Introduction The International Classification of Headache Disorders classifies ophthalmoplegic migraine (OM) under “cranial neuralgias and central causes of facial pain.” OM is diagnosed when all the following criteria are satisfied: At least two attacks fulfilling criterion B. Migraine-like headache accompanied or followed within four days of its onset by paresis of one or more of the III, IV and/or VI cranial nerves. Parasellar orbital fissure and posterior fossa lesions ruled out by appropriate investigations. In children the syndrome is rare and magnetic resonance (MR) shows strongly enhancing thickened nerve at the root entry zone (REZ). Method The authors review the literature focusing on pathogenesis theories. Results The authors suggest that ischemic reversible breakdown of the blood-nerve barrier is the most probable cause of OM and to include MR findings in the hallmarks of the disease. Conclusion OM is the same disease in adulthood and childhood, even if in adults the MR imaging findings are negative. In the authors’ opinion, OM should be classified as migraine.

The changing faces of corticotroph cell adenomas: the role of prohormone convertase 1/3

The spectrum of corticotroph cell adenomas is very wide. Though rarely, silent corticotroph cell adenomas (SCA) may transform into corticotroph cell adenomas associated with Cushing’s disease (CD). The aim of the study was to investigate the role of prohormone convertase 1/3 (PC1/3) in the transformation of SCA into CD. We reviewed the records of 1259 consecutive endoscopic endonasal procedures for pituitary adenomas from 1998 to 2013. Of these, 132 were CD and 44 were SCA. During the follow-up, three patients with SCA showed a clear transformation from SCA into CD and underwent surgery once again to remove the recurrent tumour. The PC1/3 expression was analysed by both immunohistochemistry and quantitative real time-polymerase chain reaction (qRT-PCR) in primary and recurrent tumours. The immunohistochemical PC1/3 expression was negative or weak in the three patients in the initial phase of SCA, while a strong expression was observed in the majority of neoplastic cells in tissue specimens obtained from the same three patients at the time of recurrence as CD. The immunohistochemical PC1/3 expression showed a strict correlation with the PC1/3 levels obtained by qRT-PCR. In 14 cases of SCA with no change of phenotype during the follow-up, the immunohistochemical PC1/3 expression was low and strictly associated with the level of PC1/3 obtained by qRT-PCR both in primary (14/14 cases) and in recurrent tumours (4/4 cases). Our study provides insight into the crucial role of the PC1/3 protein in the transformation of phenotype from SCA to CD.

Intradural Extramedullary Ewing's Sarcoma Recurrence with Acute Clinical Presentation and Literature Review

The intradural extramedullary space is an extremely unusual site for the onset of Ewings sarcoma. We describe a case of recurrence of intradural extramedullary Ewings sarcoma and review the literature available on this topic.

Patient outcomes following second surgery for recurrent glioblastoma

BACKGROUND The most appropriate management of recurrent glioblastoma is still controversial. In particular, the role of surgery at recurrence remains uncertain. PATIENTS & METHODS From our Institutional data warehouse we analyzed 270 consecutive patients who received second surgery for recurrent glioblastoma, to assess survival after second surgery, and to evaluate prognostic factors. RESULTS Complete resection was found in 128 (47.4%) and partial resection in 142 patients (52.6%). Median survival from second surgery was 11.4 months (95% CI: 10.0-12.7). Multivariate analysis showed that age (p = 0.001), MGMT methylation (p = 0.021) and extent of surgery (p < 0.001) are associated with better survival. CONCLUSION A complete resection should be the goal for second resection and younger age and MGMT methylation status might be considered in the selection of patients.

Coexisting clinical and CT findings of progressive supranuclear palsy and normal pressure hydrocephalus. Case report

We report the case of a patient presenting clinical symptoms and signs of progressive supranuclear palsy (PSP) and normal pressure hydrocephalus (NPH). CT revealed the findings typical of both PSP and NPH. The possible pathogenetic mechanisms of the coexistence of these two diseases are briefly discussed.SommarioViene riferito il caso di un paziente con sintomi e segni di paralisi sopranucleare progressiva e di idrocefalo normotensivo. La TAC ha rivelato le tipiche espressioni delle due malattie. Vengono brevemente discussi i meccanismi patogenetici di coesistenza di queste due forme morbose.