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Supplemental Material for The angio-architectural features of brain arteriovenous malformations: is it possible to predict the probability of rupture? by Arianna Rustici, Francesca Vari, Carmelo Sturiale, Alfredo Conti, Antonino Scibilia, Carlo Bortolotti, Raffaele Agati, Caterina Tonon, Raffaele Lodi, Diego Mazzatenta, Matteo Zoli, Ciro Princiotta, Massimo Dall’Olio and Luigi Cirillo in The Neuroradiology Journal

IVIM perfusion in the assessment of brain tumors

We describe the case of a man whose initial clinical presentation included sensorineural hearing loss and orthostatic hypotension. The patient was diagnosed with superficial siderosis associated with peripheral autonomic failure and tetraventricular hydrocephalus.

Fin dalle sue origini, negli anni Novanta, la tecnica dell'attivazione funzionale cerebrale (functional Magnetic Resonance lmaging, fMRI) è stata molto usata non solo per la definizione incruenta di molte funzioni fisiologiche cerebrali, ma anche per le ampie possibilità d'impiego nella pratica clinica. In questo capitolo saranno presi in considerazione i meccanismi neurofisiologici alla base dell'attivazione corticale, partendo dalla genesi del contrasto BOLD e dall'accoppiamento neurovascolare, fino ad arrivare alla risposta emodinamica. Saranno, quindi, descritte le motivazioni relative all'uso dei paradigmi, saranno illustrati alcuni paradigmi usati nella pratica clinica e verrà spiegato come viene acquisito ed elaborato un esame di attivazione funzionale corticale. Si esamineranno, poi, vantaggi e limiti della tecnica e le principali applicazioni cliniche. Infine, sarà brevemente esaminato un nuovo approccio funzionale della fMRI: lo studio del cosiddetto Default Mode Network (DMN).

INTRODUCTION In our experience, tools as fMRI and H1-MRI spectroscopy may add valuable information to the standard clinical assessment and prognosis in patients characterized vegetative state (VS), minimally conscious state (MCS) and severe disability (SD). Such information could have an impact on clinical decision making, may guide therapeutic options and could be used to stream rehabilitation programs. AIM We used fMRI to study both the presence and the degree of functional activation in VS and MCS and SD patients and tried to discover any possible changes in the markers of neuronal turn-over by H1-MRI spectroscopy. MATERIALS & METHODS We enrolled 24 patients (age comprised between 17 and 58) with outcome of comas: 20 of them had polytrauma outcomes, 3 of them had cerebral anoxia, 1 of them had encephalitis outcome. Each patient underwent morphological, fMRI and H1-MRS spectroscopy analysis. A 3T Signa Excite system and an 8 channel phased array coil were used to acquire morphological sequences fMRI and H1-MRS spectroscopy. fMRI. Functional (Axial Single Shot, SS, EchoPlanar Image, EPI, Gradient Echo, GE), and morphological (isovolumetric SPoiled GRass - Inversion Recovery, SPGR-IR) sequences were acquired. We used a block paradigm of the kind: 30 s stimulus vs 30 s rest, for a total length of 5 min. Three different paradigms were applied: 1) in the stimulus phase, the patient heard the voice of a relative telling an emotionally significant episode, vs silence; 2) in the stimulus phase, the patient heard the same voice telling the same episode as in point 1), but the voice was played in the reverse order, vs silence; 3) in the stimulus phase, the patient heard the same voice as in 1), whereas in the rest phase the patient heard the same reverse voice as in point 2). fMRI analysis was performed off-line by using BrainWave GE proprietary software. Briefly, the processing of this software is semi-automatic and consists in segmentation and coregistration of the morphologic sequence to the fMRI sequence, after the appropriate corrections (motion correction, smoothing, etc.). The final parametric maps were calculated at a p

Objective: The purpose of this study was to investigate if vessel-wall magnetic resonance imaging (VW-MRI) could differentiate among primary headaches disorders, such as migraine and cluster headache (CH), and detect the presence of neurogenic inflammation. Background: The pathophysiology of primary headaches disorders is complex and not completely clarified. The activation of nociceptive trigeminal afferents through the release of vasoactive neuropeptides, termed "neurogenic inflammation," has been hypothesized. VW-MRI can identify vessel wall changes, reflecting the inflammatory remodeling of the vessel walls despite different etiologies. Methods: In this case series, we enrolled seven patients with migraine and eight patients with CH. They underwent a VW-MRI study before and after the intravenous administration of contrast medium, during and outside a migraine attack or cluster period. Two expert neuroradiologists analyzed the magnetic resonance imaging (MRI) studies to identify the presence of vessel wall enhancement or other vascular abnormalities. Results: Fourteen out of 15 patients had no enhancement. One out of 15, with migraine, showed a focal parietal enhancement in the intracranial portion of a vertebral artery, unmodified during and outside the attack, thus attributable to atherosclerosis. No contrast enhancement attributable to neurogenic inflammation was observed in VW-MRI, both during and outside the attack/cluster in all patients. Moreover, MRI angiography registered slight diffuse vasoconstriction in one of seven patients with migraine during the attack and in one of eight patients with cluster headache during the cluster period; both patients had taken triptans as symptomatic therapy for pain. Conclusions: These preliminary results suggest that VW-MRI studies are negative in patients with primary headache disorders even during migraine attacks or cluster periods. The VW-MRI studies did not detect signs of neurogenic inflammation in the intracranial intradural vessels of patients with migraine or CH.

Introduction. Recent advancements in endoscopic endonasal approach (EEA) have favored its adoption for craniopharyngiomas extended to 3rd ventricle (3VCPs). However, for lack of extensive series, its outcome, limits, and indications remain debated. Research question. To assess the EEA results of for 3VCPs and identify those factors determining the choice of this approach. Material and Methods. Records of patients with 3VCPs, consecutively operated through an EEA at our Institution were retrospectively analyzed. Demographic and clinico-radiological data, rate of tumor resection, complications and outcome at follow-up were collected. Results. Thirty-six patients (19 females, mean age: 51.1 ± 15.9 yrs) were included. Extended transplanum-transtuberculum approach was performed in all cases Radical resection was achieved in 33 patients (91.7%). At follow-up, visual deficits improved/normalized in 21 cases (58.3%), and 35 (97.2%) presented with panhypopituitarism and DI. Anatomical (displacement of the chiasm and hypothalamus), clinical (age and pre-operative visual and endocrinological function) and tumoral (consistency, presence of hydrocephalus) parameters resulted relevant in determining the choice of this approach. Discussion and Conclusion. EEA offers a valid and direct route for 3VCPs, which permits to safely manage these tumors. In our series, EEA was chosen for tubero-infundibular forms with chiasm displaces antero-superiorly, and preferred in younger patients, with visual disturbances, comprimesed endocrinological function and no hydrocephalus. It requires a specific training and should be reserved in dedicated centers. Because no single approach is ideal for every 3VCP, all surgical options should be considered as complementary and selected basing on clinical, anatomical and tumoral features of each case.

Antiangiogenic agents can induce a distinct MRI pattern in glioblastoma, characterized by a decrease in the contrast enhancement on T1‐weighted images and a simultaneous hyperintensity on T2‐weighted or fluid‐attenuated inversion recovery images.

Introduction. Role of surgery for loco-regional recurrences of clivus chordomas (CCs) is still debated. It has been proposed in selected cases with a curative or with palliative intent, eventually followed by radiation or chemo/radiation treatments. Only limited data on the endoscopic endonasal approach (EEA) are available. Research question. To assess the role of EEA for loco-regional recurrent CCs. Materials and Methods. All consecutive loco-regional recurrent CCs operated by EEA at our Institution from 1998 to 2021 were identified. The extension of tumor resection, symptoms control, overall survival (OS), and progression free survival (PFS) were assessed. Results. Series includes 54 patients (53.7% females, mean age 55± 14 years). Surgery was planned with a resective aim in 35 (64.8%) patients, while it was palliative in 19 (35.2%). Gross tumor removal was achieved in 24 cases (44.4%). Main complications consisted of 2 (3.7%) CSF leaks. Further local relapses were observed in 30 (55.5%) patients after 25± 24 months; 29 (53.7%) patients deceased after 34 ± 31 months. OS and PFS were lower in these cases than primary surgeries (p

// Alba A. Brandes 1 , Gaetano Finocchiaro 2 , Vittorina Zagonel 3 , Michele Reni 4 , Alessandra Fabi 5 , Claudia Caserta 6 , Alicia Tosoni 1 , Marica Eoli 2 , Giuseppe Lombardi 3 , Matteo Clavarezza 7 , Alexandro Paccapelo 1 , Stefania Bartolini 1 , Luigi Cirillo 8 , Raffaele Agati 8 and Enrico Franceschi 1 1 Department of Medical Oncology, Bellaria-Maggiore Hospitals, Azienda USL, IRCCS Institute of Neurological Sciences, Bologna, Italy 2 Molecular Neuro-Oncology Unit, IRCCS Foundation Carlo Besta, Milan, Italy 3 Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology, IRCCS, Padua, Italy 4 Department of Medical Oncology, IRCCS San Raffaele, Milan, Italy 5 Medical Oncology 1, Regina Elena National Cancer Institute, Rome, Italy 6 Oncology Department, Santa Maria Hospital, Terni, Italy 7 Medical Oncology Unit, Ente Ospedaliero Ospedali Galliera, Genova, Italy 8 Department of Neuroradiology, Bellaria Hospital, IRCCS Institute of Neurological Sciences, Bologna, Italy Correspondence to: Alba A. Brandes, email: // Keywords : glioblastoma, RANO, bevacizumab, fotemustine, ETS Received : January 21, 2017 Accepted : February 08, 2017 Published : February 25, 2017 Abstract BACKGROUND: Disease assessment for recurrent glioblastoma (GBM) represents a challenge, especially with the use of antiangiogenic agents. Moreover, validated neuroradiological predictors of outcome are lacking. Recently, the concept of early tumor shrinkage (ETS) has been developed to better assess the ability of treatments in determining a rapid and remarkable tumor response. The aim of the study was to evaluate the role of ETS in predicting survival of GBM patients treated with BEV METHODS: We examined the radiological data of patients with recurrent GBM treated with bevacizumab (BEV) or fotemustine (FTM) in the randomized phase II AVAREG trial (EudraCT: 2011-001363-46). Radiologic assessments at first disease assessment (day 46) were used to calculate the relative change in the sum of the products of perpendicular diameters of all measurable lesions determined by either T1 contrast and T2/FLAIR. RESULTS: In patients treated with BEV, the best ETS cut-off was reduction of 15% with T1 contrast and of 40% with T2/FLAIR. Adopting this cut-off for T1 contrast radiological changes, ETS was a significant predictor of OS for patients treated with BEV (HR = 0.511, 95%CI:0.269-0.971, p = 0.040). The cut-off obtained for T2/FLAIR was not significantly correlated with OS ( p = 0.102), but we found a trend for correlation with survival when considering the variable as continuous ( p = 0.058). CONCLUSIONS: ETS evaluating T1 contrast reduction is a helpful predictor of survival in patients with recurrent GBM treated with BEV, and if validated in a larger prospective trial could be a helpful surrogate endpoint.

Background: To determine the prevalence of Idiopathic intracranial hypertension without papilledema (IIHWOP) testing revised diagnostic criteria by Friedman in refractory chronic headache (CH) patients. Methods: This is a prospective observational study. Each patient underwent ophthalmologic evaluation and Optical Coherence Tomography; brain magnetic resonance venography (MRV) and a lumbar puncture (LP) with opening pressure (OP) measurement. CSF withdrawal was performed in patients with CSF OP > 200 mmH20. IIHWOP was defined according Friedman's diagnostic criteria. Effect of CSF withdrawal was evaluated clinically in a 6-month follow-up and with a MRV study at 1 month. Results: Forty-five consecutive patients were enrolled. Five were excluded due to protocol violations. Analyses were conducted in 40 patients (32 F, 8 M; mean age 49.4 ± 10.8). None had papilledema. Nine patients (22.5%) had OP greater than 200 mmH2O, two of them above 250 mmH2O. Two (5%) had neuroimaging findings suggestive of elevated intracranial pressure. One of them (2.5%) met the newly proposed diagnostic criteria by Friedman for IIHWOP. After CSF withdrawal seven (77.8%) of the nine patients improved. No changes in neuroimaging findings were found. Conclusions: We found a low prevalence (2.5%) of IIHWOP in refractory CH patients according to current diagnostic criteria. In agreement with Friedman's criteria, our results confirm that a diagnosis of IIHWOP should be based on CSF OP and the combination of neuroradiological findings. However, where to set the CSF OP upper limit in IIHWOP needs further field testing. Although IIHWOP is a rare clinical condition, it should be considered and treated in refractory CH patients.

Since 1936, Pauling and Coryell [1] had discovered that the magnetic susceptibility of hemoglobin changed as a function of whether it was bound to oxygen or not: oxyhemoglobin had magnetic moment zero, whereas deoxyhemoglobin was paramagnetic.

Medulloblastoma is the most common central nervous system tumor in children, while it is extremely rare in adults. Multimodal treatment involving surgery, radiotherapy and chemotherapy can improve the prognosis of this disease, and recent advances in molecular biology have allowed the identification of molecular subgroups (WNT, SHH, Groups 3 and 4), each of which have different cytogenetic, mutational and gene expression signatures, demographics, histology and prognosis. The present review focuses on the state of the art for adult medulloblastoma treatment and on novel molecular advances and their future implications in the treatment of this disease.

The optimal end point for phase II studies for recurrent glioblastoma (GBM) is unclear and a matter of debate. Moreover, data about post-progression survival (PPS) after the first disease progression in GBM patients treated according to EORTC 26981/22981/NCIC CE.3 trial are limited. The aim of this study was to evaluate the PPS in GBM patients. The analysis was made with a database on 1,006 GBM patients followed prospectively between 06/2005 and 06/2010. Eligibility criteria for the study were: age ≥ 18 years; PS: 0-2; chemotherapy given at disease progression after RT/TMZ. 232 patients (mean age 52 years, range 18-77 years) were enrolled. The median PFS following second line chemotherapy (PFS2) was 2.5 months (95 % CI 2.1-2.9) and the rate of patients free of progression at 6 months (PFS2-6 mo), was 21.6 % (95 % CI 16.3-26.9 %). The median PPS was 8.6 months (95 % CI 7.4-9.8), PPS rates were: PPS-6: 66 % (95 % CI 60.3-72.9 %), PPS-9: 48.2 % (95 % CI 41.5-54.9 %) and PPS-12: 31.7 % (95 % CI 25.2-38.2 %). PPS in unselected patients treated with alkylating agents is about 8 months. PPS rates could be of interest as an end point in future studies in recurrent GBM.

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.

BACKGROUND: 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. METHODS: Newly diagnosed GBM patients ≥65 years were considered eligible. Treatment comprised radiotherapy (60 Gy in 30 fractions over 6 weeks) plus continuous daily temozolomide (75 mg/m2/day), followed by 12 maintenance temozolomide cycles (150 mg/m2 once a day for 5 consecutive days every 28 days) if MRI showed no enhancement suggesting a tumor; otherwise, chemotherapy was delivered until complete response or unequivocal progression. RESULTS: A total of 58 patients (34 males; median age, 68 years; range, 65-82 years) were enrolled. Sixteen patients (43%) presented MGMT promoter methylated and 21 unmethylated (57%) status. The median progression-free survival and median survival time (MST) were 9.5 months (95% confidence interval [CI], 8.6-10.5) and 13.7 months (95% CI, 10-17.3 months), respectively. Mental status deterioration grade 3-4 was detected in 25% of patients. Leukoencephalopathy was diagnosed in 10% of patients. CONCLUSIONS: The overall and progression-free survival of patients given concomitant and adjuvant temozolomide are greater than in those given radiotherapy alone; however, this regimen incurs a greater deterioration in mental status. Further randomized trials should, therefore, be conducted to investigate the efficacy and against the toxicity of this regimen as first-line therapy in patients with GBM. Cancer 2009. © 2009 American Cancer Society.

fMRI has proved to be a reliable, safe, reproducible method with which to presurgically define eloquent areas. This technique gives us the opportunity to know in advance the actual situation of a lesion so that the surgeonsmay plan their approach strategy. This technique also allows the establishment of a presurgical evaluation of risk and enables the patient to be fully aware at the moment of informed consent. Despite the increase in its clinical applications, fMRI is still underused in the clinical field and should be performed almost routinely before surgery.