Predictors of futile recanalization in nonagenarians treated with mechanical thrombectomy: a multi-center observational study.

BACKGROUND: There is a lack of data regarding patients aged 90 years or older undergoing mechanical thrombectomy and their predictors of futile recanalization. AIMS: We sought to evaluate the predictors of futile recanalization in patients ≥ 90 years with large vessel occlusion undergoing mechanical thrombectomy. METHODS: This multi-center observational retrospective study included patients ≥ 90 years consecutively treated with mechanical thrombectomy in four thrombectomy capable centers between January 1st, 2016 and 30th March 2023. Futile recanalization was defined as large vessel occlusion patients experiencing a 90-day poor outcome (mRS 3-6) despite successful recanalization (mTICI ≥ 2b) after mechanical thrombectomy. RESULTS: Our cohort included 139 patients ≥ 90 years with acute ischemic stroke due to anterior circulation large vessel occlusion treated with mechanical thrombectomy. One hundred seventeen of one hundred thirty-nine patients ≥ 90 years who achieved successful recanalization were included in the analysis (seventy-six female (64.9%)), of whom thirty-one (26.49%) experienced effective recanalization and eighty-six (73.51%) experienced futile recanalization. Patients with futile recanalization had higher NIHSS on admission (p < 0.001); they were less frequently treated with intravenous thrombolysis (p = 0.048), had more often general anesthesia (p = 0.011), and longer door to groin puncture delay (p = 0.002). Univariable regression analysis showed that use of intravenous thrombolysis (0.29, 95% CI 0.02-0.79, p = 0.034) and site of occlusion distal vs proximal (0.34, 95% CI 0.11-0.97, p = 0.044) were associated with reduced probability of futile recanalization while NIHSS on admission (1.29, 95% CI 1.16-1.45, p < 0.001), NIHSS at 24 h (1.15, 95% CI 1.07-1.25, p = 0.002), type of anesthesia used (4.18, 95% CI 1.57-11.08, p = 0.004), and door to groin puncture time (1.02, 95% CI 1.00-1.05, p = 0.005) were associated with increased probability of futile recanalization. Multivariable regression analysis showed that use of intravenous thrombolysis (0.44, 95% CI 0.09-0.88, p = 0.039) was associated with reduced probability of futile recanalization. CONCLUSION: Our study seems to suggest that mechanical thrombectomy with intravenous thrombolysis is associated with reduced probability of futile recanalization in a multi-center cohort of patients aged 90 years or older.

Isolated insular stroke: topography is the answer with respect to outcome and cardiac involvement.

Background and purpose: Isolated insular strokes (IIS) are a rare occurrence due to the frequent concomitant involvement of adjacent territories, supplied by the M2 segment of the middle cerebral artery (MCA), and clinical aspects are sometimes contradictory. We aimed to describe clinical and radiological characteristics of a pure IIS case series, focusing on its functional outcome and cardiac involvement. Methods: We identified 15 isolated insular ischemic strokes from a pool of 563 ischemic strokes occurred between January 2020 and December 2021. Data collection consisted of demographic and baseline clinical characteristics, comorbidities, electrocardiograms, echocardiograms, stroke topography and etiology, reperfusive treatments, and outcome measures. Descriptive statistical analysis was carried out. Results: Newly detected cardiovascular alterations were the prevalent atypical presentation. Cardioembolism was the most frequent etiology. Most of patients had major neurological improvement at discharge and good outcome at 3-months follow-up. Discussion and conclusion: IIS are extremely rare, representing according to our study about 2.6% ischemic strokes cases per year, and patients have peculiar clinical manifestations, such as dysautonomia and awareness deficits. Our data suggest the possibility for these patients to completely recover after acute ischemic stroke notwithstanding the pivotal role of the insula in cerebral connections and the frequent association with MCA occlusion. Moreover, given the central role of the insula in regulating autonomic functions, newly detected cardiac arrhythmias must be taken into consideration, as well as a full diagnostic work-up for the research of cardioembolic sources. To our knowledge, this is the largest monocentric case series of IIS and it might be useful for future systematic reviews.

Central nervous system immune-related disorders after SARS-CoV-2 vaccination: a multicenter study.

Background: COVID-19 vaccines have been approved due to their excellent safety and efficacy data and their use has also permitted to reduce neurological complications of SARS-CoV-2. However, clinical trials were underpowered to detect rare adverse events. Herein, the aim was to characterize the clinical spectrum and immunological features of central nervous system (CNS) immune-related events following SARS-CoV-2 vaccination. Methods: Multicenter, retrospective, cohort study (December 1, 2020-April 30, 2022). Inclusion criteria were (1) de novo CNS disorders developing after SARS-CoV-2 vaccination (probable causal relationship as per 2021 Butler criteria) (2); evidence for an immune-mediated etiology, as per (i) 2016 Graus criteria for autoimmune encephalitis (AE); (ii) 2015 Wingerchuk criteria for neuromyelitis optica spectrum disorders; (iii) criteria for myelitis. Results: Nineteen patients were included from 7 tertiary referral hospitals across Italy and France (one of them being a national referral center for AE), over almost 1 year and half of vaccination campaign. Vaccines administered were mRNA-based (63%) and adenovirus-vectored (37%). The median time between vaccination and symptoms onset was 14 days (range: 2-41 days). CSF was inflammatory in 74%; autoantibodies were detected in 5%. CSF cytokine analysis (n=3) revealed increased CXCL-10 (IP-10), suggesting robust T-cell activation. The patients had AE (58%), myelitis (21%), acute disseminated encephalomyelitis (ADEM) (16%), and brainstem encephalitis (5%). All patients but 2 received immunomodulatory treatment. At last follow-up (median 130 days; range: 32-540), only one patient (5%) had a mRS>2. Conclusion: CNS adverse events of COVID-19 vaccination appear to be very rare even at reference centers and consist mostly of antibody-negative AE, myelitis, and ADEM developing approximately 2 weeks after vaccination. Most patients improve following immunomodulatory treatment.

Intravoxel incoherent motion magnetic resonance imaging in the assessment of brain microstructure and perfusion in idiopathic normal-pressure hydrocephalus.

PURPOSE: To determine the relationship between intravoxel incoherent motion (IVIM) MRI parameters and clinical changes post-tap test (TT) in idiopathic normal-pressure hydrocephalus (iNPH) patients. METHODS: Forty-four probable iNPH patients underwent 3 T MRI before and after TT. IVIM parameters were calculated from eight different bilateral regions of interest in basal ganglia, centrum semiovale, and corona radiata. Patients were categorized based on TT response into positive (group 1) and negative (group 2) groups. A Welch two-sample t-test was used to compare differences in D, D*, f, and ADC between the two groups, while a paired t-test was employed to assess the changes within each group before and after TT. These parameters were then correlated with clinical results. RESULTS: In the lenticular and thalamic nuclei, D value was significantly lower in the group 1 compared to group 2 both pre- and post-TT (p = 0.002 and p = 0.007 respectively). Post-TT, the positive response group exhibited a notably reduced D* value (p = 0.012) and significantly higher f values (p = 0.028). In the corona radiata and centrum semiovale, a significant post-TT reduction in D* was observed in the positive response group (p = 0.017). Within groups, the positive response cohort showed a significant post-TT increase in ADC (p < 0.001) and a decrease in D* (p = 0.007). CONCLUSION: IVIM permits the acquisition of important non-invasive information about tissue and vascularization in iNPH patients. Enhanced perfusion in the lenticular and thalamic nuclei may suggest the role of re-established microvascular and glymphatic pathways, potentially elucidating the functional improvement in motor function after TT in iNPH patients.

Ischemic strokes in COVID-19: risk factors, obesity paradox, and distinction between trigger and causal association.

Background and purpose: Stroke has been described as a COVID-19 complication. However, its occurrence rate, risk factors, and causal relationships are still not well established. Methods: We describe the characteristics of confirmed COVID-19-related strokes among all cases of COVID-19 hospitalized in our health network, from November 1, 2020 to April 30, 2021. Risk factor analysis has been conducted for ischemic stroke (IS), which represents 92% of all confirmed cases of Covid-19-related strokes, and a "causal attribution to infection" classification is provided. Results: In all, 62/4105 hospitalized COVID-19 patients had an acute stroke (1.51%). Severe COVID-19 (OR 2.27-CI 1.06-4.77; p = 0.032), atrial fibrillation (OR 3.65-CI 1.63-7.98; p = 0.001), and ischemic heart disease (OR 4.590-CI 1.714-12.137; p = 0.002) proved to be independent risk factors for IS, while obesity was a protective factor (OR 0.90-CI 0.82-0.97; p = 0.012). COVID-19 had a causal role in 32.1% of IS cases, was a relevant cofactor in 28.6% of cases of IS, and was a possible trigger in 39.3% of events. Conclusion: Our stroke occurrence rate is consistent with other population-based reports (range 0.34-2.7%). Prespecified peculiar clinical and radiological features allow the distinction between "IS caused by COVID-19" and "IS triggered by COVID-19." Clinical history of vascular diseases and risk factors is crucial in determining the risk of IS in patients with COVID-19. However, the protective effect of a BMI > 30 kg/m2 seems to suggest an obesity paradox.

The Role of Advanced MRI Sequences in the Diagnosis and Follow-Up of Adult Brainstem Gliomas: A Neuroradiological Review.

The 2021 WHO (World Health Organization) classification of brain tumors incorporated the rapid advances in the molecular, genetic, and pathogenesis understanding of brain tumor pathogenesis, behavior, and treatment response. It revolutionized brain tumor classification by placing great emphasis on molecular types and completely splitting adult-type and pediatric-type diffuse gliomas. Brainstem gliomas (BSGs) are the leading primary tumors of the brainstem, although they are quite uncommon in adults compared with the pediatric population, representing less than 2% of adult gliomas. Surgery is not always the treatment of choice since resection is rarely feasible and does not improve overall survival, and biopsies are not generally performed since the location is treacherous. Therefore, MRI (Magnetic Resonance Imaging) without and with gadolinium administration represents the optimal noninvasive radiological technique to suggest brainstem gliomas diagnosis, plan a multidisciplinary treatment and for follow-up evaluations. The MRI protocol encompasses morphological sequences as well as functional and advanced sequences, such as DWI/ADC (Diffusion-Weighted Imaging/Apparent Diffusion Coefficient), DTI (Diffusion Tensor Imaging), PWI (Perfusion-Weighted Imaging), and MRS (Magnetic Resonance Spectroscopy), which improve the accuracy of the diagnosis of BSGs by adding substantial information regarding the cellularity, the infiltrative behavior toward the v fiber tracts, the vascularity, and the molecular changes. Brainstem gliomas have been divided into four categories on the basis of their MRI radiological appearance, including diffuse intrinsic low-grade gliomas, enhancing malignant gliomas, localized tectal gliomas, and other forms. The aim of our review is to provide insight into the role of advanced MRI sequences in the diagnosis and follow-up of adult brainstem gliomas.

Meningioma-Related Epilepsy: A Happy Ending?

(1) Background: More than one-third of patients with meningiomas experience at least one seizure during the course of their disease, and in the 20-50% of cases, seizure represents the onset symptom. After surgery, up to 30% of patients continue to have seizures, while others may experience them later; (2) Methods: The study analyzed retrospectively the risk factors for pre-operative seizures in a large cohort of 358 patients who underwent surgery for newly diagnosed brain meningioma; (3) Results: We identified age, peritumor edema, and location as risk factors for seizure at the onset. Patients with seizures differed from patients without seizures for the following characteristics: younger average age, lower pre-operative Karnofsky Performance Status (KPS), location on the convexity, lower Simpson Grade, lower incidence of pre-operative neurological deficits, and higher incidence of pre-operative peritumor edema. After 24 months, 88.2% of patients were classified as Engel class Ia, and no correlation with disease progression was observed; (4) Conclusions: Meningioma-related epilepsy has generally a positive outcome following surgery and it seems not to be linked to disease progression, even if further studies are needed.

Clinical applicability of arterial spin labeling magnetic resonance imaging in patients with possible idiopathic normal pressure hydrocephalus: A prospective preliminary study.

PURPOSE: idiopathic Normal Pressure Hydrocephalus (iNPH) patients have a global reduction of cerebral blood flow (CBF) and Arterial Spin Label (ASL) MRI allows a global evaluation of CBF without the injection of contrast agents. This work aims to assess the qualitative evaluation agreement of ASL CBF colored maps between different neuroradiologists and by correlating these data to the Tap Test. METHODS: Thirty - seven patients with the diagnosis of possible iNPH were consecutively submitted to a diagnostic MRI on a 1.5 Tesla Magnet before and after the lumbar infusion test and the Tap Test. Twenty - seven patients improved after the Tap Test and were addressed to surgery while 10 patients did not improve. All the MRI examinations included a 3D-Pulsed ASL sequence. Two different neuroradiologists independently reviewed all ASL images. They were asked to give a score (0 not improved; 1 improved) to global perfusion image quality by comparing ASL images obtained after the Tap Test to those obtained before. Comparison between inter- and intra-reader qualitative scores were performed with Cohen's kappa. RESULTS: Inter-reader agreement between the two neuroradiologists showed that qualitative scores were attributed similarly by two readers (k = 0.83). This technique has a good PPV (90.5 %; CI 95 %, 72.7-97.1 %), NPV (50 %; CI 95 %, 34.1-65.6 %), SN (70.37 %; CI 95 %, 49.8-86.2 %) SP (80 %; CI 95 %, 44.4-97.5 %) and accuracy (73 %; CI 95 %, 55.9-86.2 %) when considered in the setting of possible iNPH patients. CONCLUSION: ASL-MRI seems to be a promising non-invasive technique in the preoperative selection of patients affected by possible iNPH.

Double osseous flaps for simultaneous midfacial and mandible reconstruction: Automation in surgical complexity within an entirely computerized workflow.

Introduction: Broad maxillofacial surgical resections involving both the midface and the mandible represent a challenge in terms of reconstruction. Although several papers have explored the possibility of simultaneously using two microsurgical flaps, reports on the implementation of a dual osseous flap strategy are limited, and mainly addressed to static anatomical reconstruction, regardless of functional implications. In particular, there is a lack in the literature of a unifying protocol which illustrates how technology including virtual planning, statistical shape modeling, virtual occlusion, 3D-printing and patient-specific implants can address the functional and accuracy needs required for an optimal reconstruction. Materials and methods: In this paper, the Authors present their preliminary experience in a two-center study, showing how broad maxillofacial defects, requiring a simultaneous reconstruction in both the mandible and the midface, can be successfully reconstructed using the combination of two osseous flaps in an automated sequence in which all steps are anticipately defined in a virtual plan, accounting for the optimal alignment of temporomandibular joint, predicting the final occlusion and defining a mandibular shape according to a statistical shape model. Results: Average RMSE for the iliac bone crest flap was of 3.2 ± 0.36 mm; for the fibula flap, RMSE value was of 2.3 ± 0.65 mm, for patient-specific implants, for mandibular prostheses the average RMSE was 2.46 mm with 0.76 mm standard deviation. Temporomandibular joint function increased when a TMJ prosthesis was placed. Conclusions: Double bone free flap is a valuable resource to reconstruct wide defects that simultaneously involve two thirds of the cranio-maxillo-facial skeleton, but a careful virtual planning study should be always performed before approaching this surgical option.

MDS-UDPRS-III in the diagnosis of idiopathic Normal Pressure Hydrocephalus and identification of candidates for Ventriculo-Peritoneal Shunting surgery. Results from a retrospective large cohort of patients.

OBJECTIVES: To evaluate the entity of extrapyramidal signs, characterize them and evaluate the dynamics of change by the mean of MDS-UPDRS-III in iNPH patients after the TT to determine if this tool may help the diagnosis of iNPH and the identification of candidates for Ventriculo-Peritoneal Shunting. MATERIALS AND METHODS: We retrospectively collected data from 120 patients with the initial diagnosis of possible iNPH; they underwent neurological examination by the means of MDS-UPDRS-III and other scales before and after Tap Test (TT). They were then classified as defined iNPH (57), probable iNPH (35), and NOT-iNPH (28) based on the clinical response after the Tap Test and VPS. RESULTS: After the Tap Test, defined and probable iNPH groups improved by 3.35 (2.57-4.12, p < 0.001) and 3.43 (2.43-4.4, p < 0.001) points on MDS-UPDRS-III respectively; NOT-iNPH did not improve significantly on MDS-UPDRS-III and on any other variable studies. Defined iNPH also shifted significantly from asymmetric prevalence of symptoms to a more symmetric form (from 70% before to 57% after). CONCLUSION: extrapyramidal signs improved significantly after the Tap Test in definite and probable iNPH patients. MDS-UPDRS-III may be a useful complementary tool in the diagnosis of iNPH and identification of candidates for Ventriculo-Peritoneal Shunting.

Resting-state functional-MRI in iNPH: can default mode and motor networks changes improve patient selection and outcome? Preliminary report.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and partially reversible form of dementia, characterized by impaired interactions between multiple brain regions. Because of the presence of comorbidities and a lack of accurate diagnostic and prognostic biomarkers, only a minority of patients receives disease-specific treatment. Recently, resting-state functional-magnetic resonance imaging (rs-fMRI) has demonstrated functional connectivity alterations in inter-hemispheric, frontal, occipital, default-mode (DMN) and motor network (MN) circuits. Herein, we report our experience in a cohort of iNPH patients that underwent cerebrospinal fluid (CSF) dynamics evaluation and rs-fMRI. The study aimed to identify functional circuits related to iNPH and explore the relationship between DMN and MN recordings and clinical modifications before and after infusion and tap test, trying to understand iNPH pathophysiology and to predict the best responders to ventriculoperitoneal shunt (VPS) implant. METHODS: We prospectively collected data regarding clinical assessment, neuroradiological findings, lumbar infusion and tap test of thirty-two iNPH patients who underwent VPS implant. Rs-fMRI was performed using MELODIC-ICA both before and after the tap test. Rs-fMRI data of thirty healthy subjects were also recorded. RESULTS: At the baseline, reduced z-DMN and z-MN scores were recorded in the iNPH cohort compared with controls. Higher z-scores were recorded in more impaired patients. Both z-scores significantly improved after the tap test except in subjects with a low resistance to outflow value and without a significant clinical improvement after the test. A statistically significant difference in mean MN connectivity scores for tap test responders and non-responders was demonstrated both before (p = 0.0236) and after the test (p = 0.00137). A statistically significant main effect of the tap test on DMN connectivity after CSF subtraction was recorded (p = 0.038). CONCLUSIONS: Our results suggest the presence of a partially reversible plasticity functional mechanism in DMN and MN. Low values compensate for the initial stages of the disease, while higher values of z-DMN were recorded in older patients with a longer duration of symptoms, suggesting an exhausted plasticity compensation. The standardization of this technique could play a role as a non-invasive biomarker in iNPH disease, suggesting the right time for surgery. Trial Registration Prot. IRB 090/2021.

Hyperdense middle cerebral artery sign predicts favorable outcome in patients undergoing mechanical thrombectomy.

Non-contrast computer tomography detects the presence of hyperdense middle cerebral artery sign (HMCAS). Studies on the prognostic value of HMCAS among patients undergoing mechanical thrombectomy (MT) are conflicting. A retrospective analysis of consecutive patients with acute ischemic stroke due to middle cerebral artery occlusion, presenting with or without HMCAS, who underwent MT, was performed. We enrolled 191 patients (HMCAS +, n = 140; HMCAS -, n = 51). Prevalence of successful recanalization was significantly higher in patients with HMCAS than in those without HMCAS (92.1% versus 74.5%, p = 0.001). Patients with HMCAS had a better clinical outcome than those HMCAS - (54.3% versus 37.3%, p = 0.037, for three-month favorable outcome; 62.9% versus 39.3%, p = 0.004, for major neurological improvement at discharge; 8.6% versus 19.6%, p = 0.035, for in-hospital mortality; 14.3% versus 27.5%, p = 0.035, for intracranial hemorrhage; 2.9% versus 17.6%, p = 0.001, for symptomatic intracranial hemorrhage). Multivariate analyses confirmed that HMCAS represents an independent predictor of three-month favorable outcome (OR 2.48, 95% CI 1.10-5.58, p = 0.028), major neurological improvement at discharge (OR 2.40, 95% CI 1.09-5.20, p = 0.030), in-hospital mortality (OR 0.29, 95% CI 0.010-0.81, p = 0.018), presence of ICH (OR 0.49, 95% CI 0.25-0.97, p = 0.042) and presence of SICH (OR 0.16, 95% CI 0.04-0.63, p = 0.009). HMCAS presence predicts favorable outcome in patients undergoing MT. This result may indicate that hyperdense clots are more likely to respond to MT than isodense ones. This effect is mediated by reduction in hemorrhagic transformation.

Anatomical Computerized Exploration to Excise Malignancies in Deep Facial Compartments: An Advanced Virtual Reality Protocol for a Tailored Surgical Approach.

Objective/Hypothesis: This study describes the design and application of a novel advanced protocol for virtual three-dimensional anatomical reconstruction of the deep facial compartments, aiming to improve the preoperative understanding and the intraoperative assistance in complex resective surgeries performed for malignant diseases which extend in complex spaces, including the pterygomaxillopalatine fossa, the masticator space, and the infratemporal fossa. Methods: This study is a non-profit, retrospective, and single-institution case series. The authors clearly describe in detail imaging acquisition protocols which are suitable to segment each target, and a multilayer reconstruction technique is presented to simulate anatomical structures, with particular focus on vascular networks. Virtual surgical planning techniques are individually designed for each case to provide the most effective access to the deep facial compartments. Intraoperative guidance systems, including navigation and virtual endoscopy, are presented, and their role is analyzed. Results: The study included seven patients with malignant disease located in the deep facial compartments requiring radical resection, and all patients underwent successful application of the protocol. All lesions, except one, were subject to macroscopically radical resection. Vascular structures were identified with overall reconstruction rates superior to 90% for major caliber vessels. Prominent landmarks for virtual endoscopy were identified for each case. Conclusions: Virtual surgical planning and multilayer anatomical reconstruction are valuable methods to implement for surgeries in deep facial compartments, providing the surgeon with improved understanding of the preoperative condition and intraoperative guidance in critical phases for both open and endoscopic phases. Such techniques allow to tailor each surgical access, limiting morbidity to strictly necessary approaches to reach the disease target.

Posterior Reversible Encephalopathy Syndrome in Guillain-Barré Syndrome: Just a Problem of Immunoglobulins? Controversy From Two Atypical Case Reports.

Background: Posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), or the coexistence of these two entities shares similar risk factors and clinical features. For these conditions, a common origin has been supposed. Even if the majority of patients show a favorable course and a good prognosis, a small percentage of cases develop neurological complications. Up to date, only about 30 cases of PRES associated with Guillain-Barré syndrome (GBS) have been reported in the literature. Cases: Here, we present two cases of a particularly aggressive PRES/RCVS overlap syndrome, associated with acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) variants of GBS, respectively, presenting with similar initial clinical aspects and developing both an atypical and unfavorable outcome. On MRI examination, the first patient showed typical aspects of PRES, while, in the second case, radiological features were atypical and characterized by diffusion restriction on the apparent diffusion coefficient (ADC) map. The first patient demonstrated rapid worsening of clinical conditions until death; the second one manifested and maintained neurological deficits with a permanent disability. Conclusions: We suggest that PRES may conceal RCVS aspects, especially in most severe cases or when associated with a dysimmune syndrome in which autoimmune system and endothelial dysfunction probably play a prominent role in the pathogenesis. Although the role of IVIg treatment in the pathogenesis of PRES has been proposed, we suggest that GBS itself should be considered an independent risk factor in developing PRES.

Severe stroke in patients admitted to intensive care unit after COVID-19 infection: Pictorial essay of a case series.

Patients infected by COVID-19 could require intensive care unit admission especially due to acute respiratory failure. However, neurological manifestations are very common. Among these, ischemic stroke or cerebral hemorrhage may have unfavorable outcome. The mechanisms leading to cerebral damage by SARS-CoV2 are still under debate. One of the most accepted theories implies an endothelial activation which in turns increase the risk of thrombus formation with the development of stroke, either ischemic or hemorrhagic. The more severe the COVID-19 disease, the higher the risk of stroke. Stroke in ICU patients are not frequent, but cerebral hemorrhage has devastating effects with high mortality. In these pictorial essay of case reports, main clinical aspects are discussed, along with a summary of the evidence about pathophysiology and treatment of these patients.

Glioblastoma: from volumetric analysis to molecular predictors.

BACKGROUND: Decades of therapeutic and molecular refinements, the prognosis of patients with glioblastoma (GBM) still remains unfavorable. Integrative clinical studies allow a better understanding of the natural evolution of GBM. To assess independent predictors of overall survival (OS) and progression free survival (PFS) clinical, surgical, molecular and radiological variables were evaluated. A novel preoperative volumetric magnetic resonance imaging (MRI) Index for tumor prognosis in GBM patients was investigated. METHODS: A cohort of 195 cases of patients operated for newly GBM were analyzed. Extent of tumoral resection (EOR), tumor growth pattern, expressed by preoperative volumetric ΔT1-T2 MRI Index, molecular markers such as O6-methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase 1/2 (IDH1/2) mutation, were analyzed. Analysis of survival was done using Cox-proportional hazard models. RESULTS: The 1-, 2- years estimated OS and PFS rate for the whole population were 61% and 27%, 38% and 17%, respectively. A better survival rate, both in terms of survival and tumor progression, was observed in patient with higher EOR (P=0.000), younger age (P=0.000), MGMT methylation status (P=0.001) and lower preoperative ΔT1-T2 MRI Index (P=0.004). Regarding the tumor growth pattern a cut-off value of 0.75 was found to discriminate patient with different prognosis. Patients with a preoperative ΔT1-T2 MRI Index <0.75 had a 1-year estimated OS of 67%, otherwise patients with a preoperative ΔT1-T2 MRI Index >0.75 had a 1-year estimated OS of 34%. CONCLUSIONS: In this investigation longer survival is associated with younger age, EOR, promoter methylation of MGMT and preoperative tumor volumetric features expressed by ΔT1-T2 MRI Index The preoperative ΔT1-T2 MRI Index could be a promising prognostic factor potentially useful in GBM management. Future investigations based on multiparametric MRI data and next generation sequences analysis, may better clarify this result.

Opportunities and Obstacles Associated With Sequential Immune Reconstitution Therapy for Multiple Sclerosis: A Case Report.

Cladribine is an effective disease-modifying treatment for relapsing-remitting multiple sclerosis that acts as an immune reconstitution therapy and is administered in a pulsed manner. Despite its efficacy, severe disease reactivation early after treatment represents a serious clinical problem, and clear evidence to guide the management of such a situation is lacking. Here, we describe the case of a patient experiencing considerable disease activity during the 1st year after the initiation of cladribine treatment. The patient was switched to alemtuzumab and, therefore, received double immune reconstitution therapy. Data regarding this approach are lacking, and real-world observations may be of interest. Despite achieving good control of disease activity, we observed several serious infectious complications. Our results suggest that sequential immune reconstitution therapies may be effective; however, at the price of higher susceptibility to infections.

Clinical and magnetic resonance study of a case of subacute sclerosing panencephalitis treated with ketogenic diet.

BACKGROUND: Subacute sclerosing panencephalitis is a progressive neurodegenerative disorder caused by a latent and mutant measles virus which is extremely rare in developed countries. The lack of effective treatments leads to the research of other anti-inflammatory and neuroprotective treatments. CASE: Here we present a case of a 17-year-old patient affected by subacute sclerosing panencephalitis who manifest a dramatic improvement in neurological and general clinical conditions, as well as an arrest in the progression of demyelinating process in the central nervous system, after the beginning of a high ratio ketogenic diet. CONCLUSIONS: Given its anti-inflammatory, antioxidant and metabolic effects, we believe that ketogenic diet utilisation could be a rational approach, can be considered a safe add-on therapy, carrying on with only a minimal risk of adverse effects or interactions.