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In the present study, we aim at investigating whether education modulates dynamical properties of time-varying whole-brain network connectivity (the chronnectome) in frontotemporal dementia (FTD) at a given level of symptom severity. Dynamic connectivity parameters were evaluated in 128 patients with FTD using independent component analysis, sliding-time window correlation, and k-means approach to resting state-magnetic resonance imaging data. We evaluated the relationship between education, a proxy measure of cognitive reserve, and 4 indexes of metastate dynamic connectivity: (1) the number of distinct metastates a patient passes through, (2) the number of switches from one metastate to another, (3) the span of the realized metastates, and (4) the total distance traveled in the state space. We found a significant inverse correlation between years of education and the 4 indexes of metastate dynamic fluidity (all p-values ≤ 0.03, false discovery rate-corrected). This study suggests that patients with FTD with higher education but comparable clinical severity show more global functional brain impairment, suggesting that patients with higher cognitive reserve can cope with more global brain fluidity reduction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Neurocognitive and psychological dysfunctions associated with pituitary adenomas (PAs) are clinically relevant, though probably under-reported. The aim of the current review is to provide an update on neuropsychological status, psychopathology, and perceived quality of life (QoL) in patients with PAs. A systematic research was performed in PubMed and Scopus in order to identify reports on neurocognitive, psychiatric, and psychological disorders in PAs. Prevalence of alterations, QoL evaluation, and used tests were also recorded. PRISMA guidelines were followed. Of 62,448 identified articles, 102 studies were included in the systematic review. The prevalence of neurocognitive dysfunctions was 15-83% in Cushing's Disease (CD), 2-33% in acromegaly, mostly affecting memory and attention. Memory was altered in 22% of nonfunctioning (NF) PAs. Worsened QoL was reported in 40% of CD patients. The prevalence of psychiatric disorders in CD reached 77% and in acromegaly 63%, mostly involving depression, followed by psychosis, and anxiety. The prevalence of psychopathology was up to 83% in CD, and 35% in acromegaly. Postoperative improvement in patients with CD was observed for: learning processes, overall memory, visuospatial skills, and language skills. Short-term memory and psychomotor speed improved in NFPAs. Postoperative improvement of QoL, somatic symptoms, obsessive-compulsive disorder, and coping strategies was seen in CD and acromegaly. Reports after radiotherapy are discordant. There is wide variability in used tests. PAs have been recently shown to be associated with altered neurocognitive and neuropsychological functions, as well as QoL. These data suggest the importance of a multidisciplinary evaluation for an optimal management.

Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory distress. Here, we described the case of a 60-year-old patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin-8 and tumor necrosis factor-α concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to COVID-19. ANN NEUROL 2020;88:423-427., (© 2020 American Neurological Association.)

The prognostic value of "snake-eyes" sign in spinal cord magnetic resonance imaging (MRI) is unclear and the correlation with different pathological conditions has not been completely elucidated. In addition, its influence on surgical outcome has not been investigated in depth. A literature review according to PRISMA (Preferred reporting items for systematic review and meta-analysis protocols) guidelines on the prognostic significance of "snake-eyes" sign in operated patients was performed. Clinical, neuroradiological, and surgical data of three institutional patients, were also retrospectively collected. The three patients, with radiological evidence of "snake-eyes" myelopathy, underwent appropriate surgical treatment for their condition, with no new post-operative neurological deficits and good outcome at follow-up. The literature review, however, reported conflicting results: the presence of "snake-eyes" sign seems a poor prognostic factor in degenerative cervical myelopathy, even if some cases can improve after surgery. "Snake-eyes" myelopathy represents a rare form of myelopathy; pathophysiology is still unclear. The frequency of this myelopathy may be greater than previously thought and according to our literature review it is mostly a negative prognostic factor. However, from our experience, prognosis might not be so dire, especially when tailored surgical intervention is performed; therefore, surgery should always be considered and based on the complete clinical, neurophysiological, and radiological data.

Background and Purpose: To evaluate outcome and safety of endovascular treatment beyond 6 hours of onset of ischemic stroke due to large vessel occlusion in the anterior circulation, in routine clinical practice., Methods: From the Italian Registry of Endovascular Thrombectomy, we extracted clinical and outcome data of patients treated for stroke of known onset beyond 6 hours. Additional inclusion criteria were prestroke modified Rankin Scale score ≤2 and ASPECTS score ≥6. Patients were selected on individual basis by a combination of CT perfusion mismatch (difference between total hypoperfusion and infarct core sizes) and CT collateral score. The primary outcome measure was the score on modified Rankin Scale at 90 days. Safety outcomes were 90-day mortality and the occurrence of symptomatic intracranial hemorrhage. Data were compared with those from patients treated within 6 hours., Results: Out of 3057 patients, 327 were treated beyond 6 hours. Their mean age was 66.8±14.9 years, the median baseline National Institutes of Health Stroke Scale 16, and the median onset to groin puncture time 430 minutes. The most frequent site of occlusion was middle cerebral artery (45.1%). Functional independence (90-day modified Rankin Scale score, 0-2) was achieved by 41.3% of cases. Symptomatic intracranial hemorrhage occurred in 6.7% of patients, and 3-month case fatality rate was 17.1%. The probability of surviving with modified Rankin Scale score, 0-2 (odds ratio, 0.58 [95% CI, 0.43-0.77]) was significantly lower in patients treated beyond 6 hours as compared with patients treated earlier No differences were found regarding recanalization rates and safety outcomes between patients treated within and beyond 6 hours. There were no differences in outcome between people treated 6-12 hours from onset (278 patients) and those treated 12 to 24 hours from onset (49 patients)., Conclusions: This real-world study suggests that in patients with large vessel occlusion selected on the basis of CT perfusion and collateral circulation assessment, endovascular treatment beyond 6 hours is feasible and safe with no increase in symptomatic intracranial hemorrhage.

Background and Purpose: As numerous questions remain about the best anesthetic strategy during thrombectomy, we assessed functional and radiological outcomes in stroke patients treated with thrombectomy in presence of general anesthesia (GA) versus conscious sedation (CS) and local anesthesia (LA)., Methods: We conducted a cohort study on prospectively collected data from 4429 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke., Results: GA was used in 2013 patients, CS in 1285 patients, and LA in 1131 patients. The rates of 3-month modified Rankin Scale score of 0-1 were 32.7%, 33.7%, and 38.1% in the GA, CS, and LA groups: GA versus CS: odds ratios after adjustment for unbalanced variables (adjusted odds ratio [aOR]), 0.811 (95% CI, 0.602-1.091); and GA versus LA: aOR, 0.714 (95% CI, 0.515-0.990). The rates of modified Rankin Scale score of 0-2 were 42.5%, 46.6%, and 52.4% in the GA, CS, and LA groups: GA versus CS: aOR, 0.902 (95% CI, 0.689-1.180); and GA versus LA: aOR, 0.769 (95% CI, 0.566-0.998). The rates of 3-month death were 21.5%, 19.7%, and 14.8% in the GA, CS, and LA groups: GA versus CS: aOR, 0.872 (95% CI, 0.644-1.181); and GA versus LA: aOR, 1.235 (95% CI, 0.844-1.807). The rates of parenchymal hematoma were 9%, 12.6%, and 11.3% in the GA, CS, and LA groups: GA versus CS: aOR, 0.380 (95% CI, 0.262-0.551); and GA versus LA: aOR, 0.532 (95% CI, 0.337-0.838). After model of adjustment for predefined variables (age, sex, thrombolysis, National Institutes of Health Stroke Scale, onset-to-groin time, anterior large vessel occlusion, procedure time, prestroke modified Rankin Scale score of <1, antiplatelet, and anticoagulant), differences were found also between GA versus CS as regards modified Rankin Scale score of 0-2 (aOR, 0.659 [95% CI, 0.538-0.807]) and GA versus LA as regards death (aOR, 1.413 [95% CI, 1.095-1.823])., Conclusions: GA during thrombectomy was associated with worse 3-month functional outcomes, especially when compared with LA. The inclusion of an LA arm in future randomized clinical trials of anesthesia strategy is recommended.

The craniocervical junction (CCJ) or upper cervical spine (UCS) has anatomic features and a biomechanics completely different from the other spinal segment of the spine. Several ligaments and muscles control its motion and function and ensure the maximum mobility and the visual and auditory spatial exploration. UCS traumas represent approximately one-third of all cervical spine injuries. Most of UCS traumas results from blows to the head and sudden deceleration of the body. Thanks to the improvement of the Advanced Trauma Life Support protocols dissociative injuries of CCJ have become less lethal onsite. In other less severe but unstable injuries, patients are neurologically intact at presentation, but they may deteriorate during the stay in hospital, with important clinical and medico-legal consequences. Knowing the peculiarities of UCS is fundamental for the early detection of imaging findings that influences the patient management and outcome. The classification of UCS traumas is mechanistic. More than in any other spinal segment, fractures of CCJ bones can occur without generating instability; on the contrary highly unstable injuries may not be associated with bone fractures. An early and correct diagnosis of occipito-cervical instability may prevent secondary neurological injury. The goal of imaging is to identify which patients can benefit of surgical stabilization and prevent secondary neurologic damage. Actual helical multidetector-CT (MDCT) offers high sensitivity and specificity for bone lesions and displacements in cervical spine traumas, but magnetic resonance imaging (MRI) is increasingly being used to evaluate soft tissues and ligaments, and mainly to identify possible spinal cord injury., Competing Interests: Declaration of Competing Interest The Authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The applicability of the current models for predicting functional outcome after thrombectomy in strokes with large vessel occlusion (LVO) is affected by a moderate predictive performance., Aims: We aimed to develop and validate a nomogram with pre- and post-treatment factors for prediction of the probability of unfavorable outcome in patients with anterior and posterior LVO who received bridging therapy or direct thrombectomy <6 h of stroke onset., Methods: We conducted a cohort study on patients data collected prospectively in the Italian Endovascular Registry (IER). Unfavorable outcome was defined as three-month modified Rankin Scale (mRS) score 3-6. Six predictors, including NIH Stroke Scale (NIHSS) score, age, pre-stroke mRS score, bridging therapy or direct thrombectomy, grade of recanalization according to the thrombolysis in cerebral ischemia (TICI) grading system, and onset-to-end procedure time were identified a priori by three stroke experts. To generate the IER-START, the pre-established predictors were entered into a logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve (AUC-ROC)., Results: A total of 1802 patients with complete data for generating the IER-START was randomly dichotomized into training ( n  = 1219) and test ( n  = 583) sets. The AUC-ROC of IER-START was 0.838 (95% confidence interval [CI]): 0.816-0.869) in the training set, and 0.820 (95% CI: 0.786-0.854) in the test set., Conclusions: The IER-START nomogram is the first prognostic model developed and validated in the largest population of stroke patients currently candidates to thrombectomy which reliably calculates the probability of three-month unfavorable outcome.

Background: Alzheimer's Disease (AD) is a multifactorial disorder driven by genetic and modifiable lifestyle risk factors. Lifestyle primary prevention initiatives may reduce the prevalence and incidence of dementia in older adults., Objectives: The E.Mu.N.I study is a randomized controlled trial investigating the effect of multilevel non-pharmacologic interventions on cognitive performances (primary outcome) and structural and vascular brain MRI markers (secondary outcome), as well as markers of brain functional connectivity change (exploratory outcome), in older adults with subjective memory decline (SMD). Here, we present the study design and the baseline features of the sample., Methods: Cognitively intact older adults with SMD, enrolled between February 2016 and June 2017, were randomly assigned to one of the 3 interventions for 1 year: Active Control Intervention (ACI), i.e., educational lessons; Partial Intervention (PI), i.e., homotaurine administration (100 mg/die) and lessons on the Mediterranean diet; Multilevel Intervention (MI), i.e., PI plus computerized cognitive training and physical exercise training., Results: One-hundred and twenty-eight eligible participants were enrolled (66% female; age: 68 ± 5 years). Eighty-two percent of the sample was composed of volunteers with SMD from the community. Participants were randomly allocated to the interventions as follows: ACI (N = 40), PI (N = 44), MI (N = 44). No significant differences among groups emerged on socio-demographic, clinical-neuropsychological variables and MRI markers at baseline., Conclusions: The outcomes obtained from the E.Mu.N.I. study will clarify the efficacy of multilevel non-pharmacologic interventions on cognitive and neuroimaging markers in SMD individuals. This is a crucial step forward for the development of cost-effective non-pharmacologic primary prevention initiatives for AD.

Multidisciplinary approaches have demonstrated that the brain is potentially modulated by the long-term acquisition and practice of specific skills. Chess playing can be considered a paradigm for shaping brain function, with complex interactions among brain networks possibly enhancing cognitive processing. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) can be useful to explore the effect of chess playing on whole-brain fluidity/dynamism (the chronnectome). Dynamic connectivity parameters of 18 professional chess players and 20 beginner chess players were evaluated applying spatial independent component analysis (sICA), sliding-time window correlation, and meta-state approaches to rs-fMRI data. Four indexes of meta-state dynamic fluidity were studied: i) the number of distinct meta-states a subject pass through, ii) the number of switches from one meta-state to another, iii) the span of the realized meta-states (the largest distance between two meta-states that subjects occupied), and iv) the total distance travelled in the state space. Professional chess players exhibited an increased dynamic fluidity, expressed as a higher number of occupied meta-states (meta-state numbers, 75.8 ± 7.9 vs 68.8 ± 12.0, p = 0.043 FDR-corrected) and changes from one meta-state to another (meta-state changes, 77.1 ± 7.3 vs 71.2 ± 11.0, p = 0.043 FDR-corrected) than beginner chess players. Furthermore, professional chess players exhibited an increased dynamic range, with increased traveling between successive meta-states (meta-state total distance, 131.7 ± 17.8 vs 108.7 ± 19.7, p = 0.0004 FDR-corrected). Chess playing may induce changes in brain activity through the modulation of the chronnectome. Future studies are warranted to evaluate if these potential effects lead to enhanced cognitive processing and if "gaming" might be used as a treatment in clinical practice.

Hereditary neuropathies may be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A correct diagnosis is crucial for avoiding unnecessary therapies and access genetic counseling. We report on nine patients (seven men, mean age 49.2 ± 16.1) diagnosed with and treated as CIDP, in whom mutations or variants of unknown significance (VUS) in genes associated with hereditary neuropathies were reported. All underwent neurological and neurophysiological examination, eight also cerebrospinal fluid (CSF) analysis. In 4/9, nerve ultrasound and/or MR-neurography were performed. All the patients complained of progressive upper or lower limbs sensory-motor symptoms, with heterogeneous disease duration (1-34 years, mean 8.6 ± 10.8). Neurophysiology showed demyelinating signs in seven patients, mixed findings with predominant axonal damage in two patients. Neuroimaging disclosed diffuse abnormalities at proximal and distal segments. Molecular screening showed PMP22 duplication in two patients, mutations in the MPZ, EGR2, and GJB1 genes were reported in each of the remaining patients. The two patients with mixed neurophysiological findings had p.Val30Met mutation in the transthyretin gene. Two patients had VUS in the MARS and HSPB1 genes. Four patients had partial response to immunomodulant therapies, and CSF and neurophysiological features suggesting an inflammatory condition concomitant with the hereditary neuropathy. Hereditary neuropathy may be misdiagnosed with CIDP. The most common pitfalls are CSF (high protein levels and oligoclonal bands), incorrect interpretation of neurophysiology, and transient benefit from therapies. Neuroimaging may be helpful in cases with atypical presentations or when severe axonal damage complicate the neurophysiological interpretation., (© 2020 Peripheral Nerve Society.)

Background: Post-traumatic cerebral infarction (PTCI) is common after traumatic brain injury (TBI). It is unclear what the occurrence of a PTCI is, how it impacts the long-term outcome, and whether it adds incremental prognostic value to established outcome predictors., Methods: This was a prospective multicenter cohort study of moderate and severe TBI patients. The primary objective was to evaluate if PTCI was an independent risk factor for the 6-month outcome assessed with the Glasgow Outcome Scale (GOS). We also assessed the PTCI occurrence and if it adds incremental value to the International Mission for Prognosis and Clinical Trial design in TBI (IMPACT) core and extended models., Results: We enrolled 143 patients, of whom 47 (32.9%) developed a PTCI. In the multiple ordered logistic regression, PTCI was retained in both the core and extended IMPACT models as an independent predictor of the GOS. The predictive performances increased significantly when PTCI was added to the IMPACT core model (AUC = 0.73, 95% C.I. 0.66-0.82; increased to AUC = 0.79, 95% CI 0.71-0.83, p = 0.0007) and extended model (AUC = 0.74, 95% C.I. 0.65-0.81 increased to AUC = 0.80, 95% C.I. 0.69-0.85; p = 0.00008). Patients with PTCI showed higher ICU mortality and 6-month mortality, whereas hospital mortality did not differ between the two groups., Conclusions: PTCI is a common complication in patients suffering from a moderate or severe TBI and is an independent risk factor for long-term disability. The addition of PTCI to the IMPACT core and extended predictive models significantly increased their performance in predicting the GOS., Trial Registration: The present study was registered in ClinicalTrial.gov with the ID number NCT02430324.

Background: It is still unknown if serum glial fibrillary acidic protein (GFAP) is a useful marker in frontotemporal lobar degeneration (FTLD)., Objective: To assess the diagnostic and prognostic value of serum GFAP in a large cohort of patients with FTLD., Methods: In this retrospective study, performed on 406 participants, we measured serum GFAP concentration with an ultrasensitive Single molecule array (Simoa) method in patients with FTLD, Alzheimer's disease (AD), and in cognitively unimpaired elderly controls. We assessed the role of GFAP as marker of disease severity by analyzing the correlation with clinical variables, neurophysiological data, and cross-sectional brain imaging. Moreover, we evaluated the role of serum GFAP as a prognostic marker of disease survival., Results: We observed significantly higher levels of serum GFAP in patients with FTLD syndromes, except progressive supranuclear palsy, compared with healthy controls, but not compared with AD patients. In FTLD, serum GFAP levels correlated with measures of cognitive dysfunction and disease severity, and were associated with indirect measures of GABAergic deficit. Serum GFAP concentration was not a significant predictor of survival., Conclusion: Serum GFAP is increased in FTLD, correlates with cognition and GABAergic deficits, and thus shows promise as a biomarker of disease severity in FTLD.

Invasiveness in pituitary adenomas has been defined and investigated from multiple perspectives, with varying results when its predictive value is considered. A systematic literature review, following PRISMA guidelines, was performed, searching PubMed and Scopus databases with terms that included molecular markers, histological, radiological, anatomical and surgical data on invasiveness of pituitary adenomas. The results showed that differing views are still present for anatomical aspects of the sellar region that are relevant to the concept of invasiveness; radiological and histological diagnoses are still limited, but might improve in the future, especially if they are related to surgical findings, which have become more accurate thanks to the introduction of the endoscope. The aim is to achieve a correct distinction between truly invasive pituitary adenomas from those that, in contrast, present with extension in the parasellar area through natural pathways. At present, diagnosis of invasiveness should be based on a comprehensive analysis of radiological, intra-operative and histological findings., Competing Interests: The authors declare no conflict of interest.

Background: Whether mechanical thrombectomy alone may achieve better or at least equal clinical outcome than mechanical thrombectomy combined with intravenous thrombolysis is a matter of debate., Methods: From the Italian Registry of Endovascular Stroke Treatment, we extracted all cases treated with intravenous thrombolysis followed by mechanical thrombectomy or with primary mechanical thrombectomy for anterior circulation stroke due to proximal vessel occlusion. We included only patients who would have qualified for intravenous thrombolysis. We compared outcomes of the two groups by using multivariate regression analysis and propensity score method., Results: We included 1148 patients, treated with combined intravenous thrombolysis and mechanical thrombectomy therapy (n = 635; 55.3%), or with mechanical thrombectomy alone (n = 513; 44.7%). Demographic and baseline clinical characteristics did not differ between the two groups, except for a shorter onset to groin puncture time (p < 0.05) in the mechanical thrombectomy group. A shift in the 90-day modified Rankin Scale distributions toward a better outcome was found in favor of the combined treatment (adjusted common odds ratio  = 1.3; 95% confidence interval: 1.04-1.66). Multivariate analyses on binary outcome show that subjects who underwent combined treatment had higher probability to survive with modified Rankin Scale 0-3 (odds ratio = 1.42; 95% confidence interval: 1.04-1.95) and lower case fatality rate (odds ratio = 0.6; 95% confidence interval: 0.44-0.9). Hemorrhagic transformation did not differ between the two groups., Conclusion: These data seem to indicate that combined intravenous thrombolysis and mechanical thrombectomy could be associated with lower probability of death or severe dependency after three months from stroke due to large vessel occlusion, supporting the current guidelines of treating eligible patients with intravenous thrombolysis before mechanical thrombectomy.

Objective: Cognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, we examine the effect of education on grey matter loss over time., Methods: Two-hundred twenty-nine subjects at-risk of carrying a pathogenic mutation leading to FTD underwent longitudinal cognitive assessment and T1-weighted MRI at baseline and at 1 year follow-up. The first principal component score of the graph-Laplacian Principal Component Analysis on 112 grey matter region-of-interest volumes was used to summarise the grey matter volume (GMV). The effects of education on cognitive performances and GMV at baseline and on the change between 1 year follow-up and baseline (slope) were tested by Structural Equation Modelling., Results: Highly educated at-risk subjects had better cognition and higher grey matter volume at baseline; moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers., Conclusions: This longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Migraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated., Methods: In a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status., Results: A cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm3 [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm3 [IQR, 0.8 to 10.1], P<0.001), and the largest volumes were observed in patients with migraine with aura (median, 9.0 cm3 [IQR, 3.4 to 16.6]). In a linear regression model, migraine was an independent predictor of increased log (acute infarct volumes) (median ratio [MR], 1.64; 95% confidence interval [CI], 1.22 to 2.20), an effect that was more prominent for migraine with aura (MR, 2.92; 95% CI, 1.88 to 4.54)., Conclusion: s These findings reinforce the experimental observation of larger acute cerebral infarcts in migraineurs, extend animal data to human disease, and support the hypothesis of increased vulnerability to ischemic brain injury in people suffering migraine.

Maturational processes in the developing brain are disrupted by exposure to environmental toxicants, setting the stage for deviant developmental trajectories. Manganese (Mn) is an essential nutrient that is neurotoxic at high levels of exposure, particularly affecting the basal ganglia and prefrontal cortex. Both the intensity and timing of exposure matter; deciduous teeth can be used to retrospectively and objectively determine early-life windows of vulnerability. The aim of this pilot study was to examine associations between prenatal, early postnatal and childhood dentine Mn concentrations and intrinsic functional connectivity (iFC) of adolescents' brains. 14 adolescents (12-18 years; 6 girls) from northern Italian regions with either current, historic or no Mn contamination, completed a 10-minute resting state functional Magnetic Resonance Imaging (MRI) scan in an 1.5T MRI scanner. We estimated prenatal, early postnatal and childhood Mn concentrations in deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses, focusing on six subcortical seeds (left and right caudate, putamen, pallidum) and one cortical seed (bilateral middle frontal gyrus) from Harvard-Oxford atlases. We examined linear and quadratic correlations between log-transformed Mn concentrations and seed-based iFC (Bonferroni-corrected p<0.0023), controlling for either socio-economic status, sex or age. Dentine Mn concentrations (Mn:Calcium ratio) were highest during the prenatal period (median = 0.48) and significantly declined during the early postnatal (median = 0.14) and childhood periods (median = 0.006). Postnatal Mn concentrations were associated with: 1) increased iFC between the middle frontal gyrus and medial prefrontal cortex; 2) decreased iFC between the right putamen and pre- and postcentral gyrus. Together, these findings suggest that early postnatal Mn concentrations are associated with increased iFC within cognitive control brain areas, but decreased iFC between motor areas in adolescents. Future studies should replicate these findings in larger samples, and link brain connectivity measures to cognitive and motor outcomes., Competing Interests: The authors have declared that no competing interests exist.

Axillary nerve injuries are uncommon, although the incidence is higher in athletes, both related to direct contusion or quadrilateral space syndrome. While few studies have investigated conservative strategies that could be proposed to avoid surgery, no previous case report documented the possible role of rehabilitation in axillary nerve reinjuries. Our patient is a 27-year-old male professional rugby player who experienced a recurrent episode of deltoid strength loss, after a previous axillary nerve injury. The MRI of the brachial plexus showed increased signal intensity of C5 spinal root, together with denervation edema in infraspinatus muscle, related to a recent traction injury while the EMG confirmed the persistence of traumatic paresis of axillary nerve and the chronic sufferance of C5 myotome. Our conservative treatment consists in a 2-phases rehabilitation protocol builded up on the basis of a shoulder kinematic test, electrostimulation test and a further EMG. The purpose of this report was to bring attention on axillary nerve conservative management. Premature return to sport may predispose the patient to the risk of re-injury. A prompt diagnosis and a timely specific rehabilitation protocol allow to a safe full-return to professional sport activity and may prevent recurrences.

Background: endovascular therapy (ET) is the standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). The role of adjunctive intravenous thrombolysis (IVT) in these patients remains unclear. The present study aims to investigate whether IVT followed by ET (CoT, combined therapy) provides additional benefits over direct ET for anterior circulation AIS with LVO., Methods: we achieved a single center retrospective study of patients with AIS caused by anterior circulation LVO, referred to our center between January 2014 and January 2017 and treated with ET. Functional recovery (modified Rankin at 3-months follow-up), recanalization rate (thrombolysis in cerebral infarction [TICI] score) and time, early follow-up brain CT scan infarct volume (EFIV) (for recanalized patients only), symptomatic intracerebral hemorrhage (sICH) and 3-month mortality were the outcomes of interests. Independent predictors of the outcomes were explored with multivariable logistic regression., Results: 145 subjects were included in the study, of whom 70 underwent direct ET and 75 were treated with CoT. Functional independence at 3-months was more frequent in CoT subjects compared to patients who received direct ET (mRS score 0-1: 48.5% vs 18.6%; P < 0.001. mRS score 0-2: 67.1% vs 37.3%; P < 0.001); CoT patients had also higher first-pass success rate (62.7% vs 38.6%, P < 0.05), higher recanalization rate (84.3% vs 65.3%; P = 0.009) and, in recanalized subjects, smaller EFIV (16.4 ml vs 62.3 ml; P = 0.003). Mortality and intracranial bleeding did not differ between the two groups. In multivariable regression analysis, low baseline NIHSS score (P < 0.05), vessel recanalization (P = 0.05) and CoT (P = 0.03) were independent predictors of favorable outcome at three months., Conclusions: CoT appears more effective than ET alone for anterior circulation AIS with LVO, with similar safety profile.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with anti-neurofascin-155 antibodies is a subgroup of CIDP with tremor and poor response to intravenous immunoglobulins. A 23-year-old male presented with a 6-month history ataxic-stepping gait, stocking tactile hypoesthesia, areflexia, tremor at limbs and tongue. Neurophysiology and cerebrospinal fluid analysis supported the diagnosis of CIDP. Tongue EMG was negative. Serum was positive for neurofascin-155 IgG4. His symptoms improved with intravenous methylprednisolone and then immunoglobulins, but not the tremor. Neurofascin-155 antibodies binding to cerebellar neurons suggests its central origin. This is the first neurofascin-155 antibody-seropositive patient with also tongue tremor, who is candidate to rituximab., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a "chronnectome" approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background and Purpose- As a reliable scoring system to detect the risk of symptomatic intracerebral hemorrhage after thrombectomy for ischemic stroke is not yet available, we developed a nomogram for predicting symptomatic intracerebral hemorrhage in patients with large vessel occlusion in the anterior circulation who received bridging of thrombectomy with intravenous thrombolysis (training set), and to validate the model by using a cohort of patients treated with direct thrombectomy (test set). Methods- We conducted a cohort study on prospectively collected data from 3714 patients enrolled in the IER (Italian Registry of Endovascular Stroke Treatment in Acute Stroke). Symptomatic intracerebral hemorrhage was defined as any type of intracerebral hemorrhage with increase of ≥4 National Institutes of Health Stroke Scale score points from baseline ≤24 hours or death. Based on multivariate logistic models, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver operating characteristic curve. Results- National Institutes of Health Stroke Scale score, onset-to-end procedure time, age, unsuccessful recanalization, and Careggi collateral score composed the IER-SICH nomogram. After removing Careggi collateral score from the first model, a second model including Alberta Stroke Program Early CT Score was developed. The area under the receiver operating characteristic curve of the IER-SICH nomogram was 0.778 in the training set (n=492) and 0.709 in the test set (n=399). The area under the receiver operating characteristic curve of the second model was 0.733 in the training set (n=988) and 0.685 in the test set (n=779). Conclusions- The IER-SICH nomogram is the first model developed and validated for predicting symptomatic intracerebral hemorrhage after thrombectomy. It may provide indications on early identification of patients for more or less postprocedural intensive management.

Brain functional disruption and cognitive shortfalls as consequences of neurodegeneration are among the most investigated aspects in current clinical research. Traditionally, specific anatomical and behavioral traits have been associated with neurodegeneration, thus directly translatable in clinical terms. However, these qualitative traits, do not account for the extensive information flow breakdown within the functional brain network that deeply affect cognitive skills. Behavioural variant Frontotemporal Dementia (bvFTD) is a neurodegenerative disorder characterized by behavioral and executive functions disturbances. Deviations from the physiological cognitive functioning can be accurately inferred and modeled from functional connectivity alterations. Although the need for unbiased metrics is still an open issue in imaging studies, the graph-theory approach applied to neuroimaging techniques is becoming popular in the study of brain dysfunction. In this work, we assessed the global connectivity and topological alterations among brain regions in bvFTD patients using a minimum spanning tree (MST) based analysis of resting state functional MRI (rs-fMRI) data. Whilst several graph theoretical methods require arbitrary criteria (including the choice of network construction thresholds and weight normalization methods), MST is an unambiguous modeling solution, ensuring accuracy, robustness, and reproducibility. MST networks of 116 regions of interest (ROIs) were built on wavelet correlation matrices, extracted from 41 bvFTD patients and 39 healthy controls (HC). We observed a global fragmentation of the functional network backbone with severe disruption of information-flow highways. Frontotemporal areas were less compact, more isolated, and concentrated in less integrated structures, respect to healthy subjects. Our results reflected such complex breakdown of the frontal and temporal areas at both intra-regional and long-range connections. Our findings highlighted that MST, in conjunction with rs-fMRI data, was an effective method for quantifying and detecting functional brain network impairments, leading to characteristic bvFTD cognitive, social, and executive functions disorders.

The peripheral nervous system may be involved at any stage in the course of lymphoproliferative diseases. The different underlying mechanisms include neurotoxicity secondary to chemotherapy, direct nerve infiltration (neurolymphomatosis), infections, immune-mediated, paraneoplastic or metabolic processes and nutritional deficiencies. Accordingly, the clinical features are heterogeneous and depend on the localization of the damage (ganglia, roots, plexi, and peripheral nerves) and on the involved structures (myelin, axon, and cell body). Some clinical findings, such a focal or diffuse involvement, symmetric or asymmetric pattern, presence of pain may point to the correct diagnosis. Besides a thorough medical history and neurological examination, neurophysiological studies, cerebrospinal fluid analysis, nerve biopsy (in selected patients with suspected lymphomatous infiltration) and neuroimaging techniques (magnetic resonance neurography and nerve ultrasound) may be crucial for a proper diagnostic workup., (© 2018 Peripheral Nerve Society.)

Children with cerebral palsy often present with cognitive-visual dysfunctions characterized by visuo-perceptual and/or visuo-spatial deficits associated with a malfunctioning of visual-associative areas. The neurofunctional model of this condition remains poorly understood due to the lack of a clear correlation between cognitive-visual deficit and morphological brain anomalies. The aim of our study was to quantify the pattern of white matter abnormalities within the whole brain in children with cerebral palsy, and to identify white matter tracts sub-serving cognitive-visual functions, in order to better understand the basis of cognitive-visual processing. Nine subjects (three males, mean age 8 years 9 months) with cerebral palsy underwent a visual and cognitive-visual evaluation. Conventional brain MRI and diffusion tensor imaging were performed. The fractional anisotropy maps were calculated for every child and compared with data from 13 (four males, mean age 10 years 7 months) healthy children. Children with cerebral palsy showed decreased fractional anisotropy (a marker of white matter integrity) in corticospinal tract bilaterally, left superior longitudinal fasciculus and bilateral hippocampus. Focusing on the superior longitudinal fasciculus, the mean fractional anisotropy values were significantly lower in children affected by cerebral palsy with cognitive-visual deficits than in those without cognitive-visual deficits. Our findings reveal an association between cognitive-visual profile and the superior longitudinal fasciculus integrity in children with cerebral palsy, supporting the hypothesis that visuo-associative deficits are related to changes in fibers connecting the occipital cortex with the parietal-frontal cortices. Decreased fractional anisotropy within the superior longitudinal fasciculus could be considered a biomarker for cognitive-visual dysfunctions., (© 2018 Wiley Periodicals, Inc.)

Background: Acute basilar artery occlusion (BAO) is considered among the most severe medical emergencies, with very high morbidity and mortality. The aims of this study are to present 5 years experience of 12 centers in Lombardy region on BAO endovascular treatment and to evaluate prognostic factors that may improve clinical outcomes and recanalization rates., Materials and Methods: Registro Endovascolare Lombardo Occlusione Basilar Artery (RELOBA) registry is a retrospective multicentric collection of patients with acute BAO who underwent endovascular treatment between 2010 and 2015. A total of 102 patients (mean age 65 years) were included. Clinical, procedural, and neuroradiological data were collected. Angiographic results (Treatment in Cerebral Ischemia scale [TICI] score 2b-3) were assessed by each center's interventional neuroradiologist. Good clinical outcome was considered as a modified Rankin Scale score ranging between 0 and 2 in a 3-month follow-up., Results: Thirty-nine percent of patients showed good clinical outcome at 3 months. Mortality rate was 30%. TICI 2b-3 was achieved in 62% of patients. Univariate analysis showed that age, National Institutes of Health Stroke Scale (NIHSS) at onset, time to recanalization, and TICI score were all statistically significant clinical outcome predictors (P < .05). Multivariate logistic regression showed that time to recanalization, age, and NIHSS at onset were significant independent predictors of good outcome., Conclusions: BAO treatment needs more efforts to assure patients better clinical outcomes. Mechanical thrombectomy is feasible and effective in patients with acute BAO. These results must be confirmed by further prospective studies within randomized controlled settings., (Copyright © 2018. Published by Elsevier Inc.)

The aim of the present study was to assess the role of action observation treatment (AOT) in the rehabilitation of upper limb motor functions in children with cerebral palsy. We carried out a two-group, parallel randomized controlled trial. Eighteen children (aged 5-11 yr) entered the study: 11 were treated children, and 7 served as controls. Outcome measures were scores on two functional scales: Melbourne Assessment of Unilateral Upper Limb Function Scale (MUUL) and the Assisting Hand Assessment (AHA). We collected functional scores before treatment (T1), at the end of treatment (T2), and at two months of follow-up (T3). As compared to controls, treated children improved significantly in both scales at T2 and this improvement persisted at T3. AOT has therefore the potential to become a routine rehabilitation practice in children with CP. Twelve out of 18 enrolled children also underwent a functional magnetic resonance study at T1 and T2. As compared to controls, at T2, treated children showed stronger activation in a parieto-premotor circuit for hand-object interactions. These findings support the notion that AOT contributes to reorganize brain circuits subserving the impaired function rather than activating supplementary or vicariating ones.

Context: The persisting embryonal infundibular recess (PEIR) is a rare anomaly of the floor of the third ventricle with a debated pathogenesis. It can be a cause of misdiagnosis in the case of cystic lesions of the sellar and suprasellar area., Objective: To describe two recently evaluated cases and provide a systematic literature review., Evidence Acquisition and Case Descriptions: PEIR has been previously reported in six adult patients. Because in some cases it was associated with hydrocephalus and/or empty sella, a possible role of altered intracranial pressure in PEIR formation has been postulated. We evaluated two female patients, aged 34 and 50 years, referred to the Pituitary Surgery Clinic of the University of Brescia with the diagnosis of a sellar cyst and craniopharyngioma, respectively. Endocrine screening and visual field testing were normal. No signs of hydrocephalus or empty sella, as well as other indirect signs of intracranial hypertension, were visible on MRI scans. After a multidisciplinary reevaluation, diagnosis of PEIR was made in both cases. Both patients are followed but have not developed any disturbance related to the PEIR in the following 18 months., Conclusions: PEIR is a rare condition, probably unrecognized and the result of dysembriogenesis, which should be included in the differential diagnosis of cystic sellar lesions. Imaging features (funnel pituitary stalk and cyst in the sella) appear pathognomonic. A normal endocrine evaluation might help in the diagnosis and warrants conservative treatment.

Frontotemporal dementia (FTD) is characterized by behavioural and language impairment, accompanied by atrophic changes in fronto-temporo-insular cortices. In the presymptomatic phases of genetic FTD, subtle or no volumetric changes have been reported. Transcranial magnetic stimulation (TMS) represents an approach to explore cortical connectivity, and some TMS measures have been demonstrated to be impaired in Granulin (GRN) mutation carriers. We aimed at exploring cross-sectional changes in cortical thickness (CT) and surface area (SA) in the presymptomatic phases of GRN-related FTD, and their relationship with TMS parameters. Nineteen presymptomatic GRN mutation carriers and seventeen age and sex-matched non-carriers underwent 3T MRI scanning and a paired-pulse TMS protocol. The surface-based pipeline of FreeSurfer was applied in order to obtain cortical volumes (CVs), CT and SA measures. Then, between groups differences and correlation with TMS parameters were assessed. GRN carriers showed increased CT and decreased SA of the right parietal lobe, without significant volume changes. TMS parameters of intracortical inhibition and facilitation, which were significantly impaired in presymptomatic GRN mutation carriers, correlated with reduced SA and CV of the right insula. Our results suggest that splitting CV into its two main components could improve the sensitivity when exploring structural brain changes in presymptomatic or early phases of neurodegenerative conditions. TMS parameters might reflect damage within cortical regions reported to be affected early in the conversion to the symptomatic phase of the disease.

Background and Purpose: Cerebral hyperexcitability in migraine experiencers might sensitize brain tissue to ischemia. We investigated whether a personal history of migraine is associated with vulnerability to brain ischemia in humans., Methods: Multicenter cohort study of patients with acute ischemic stroke who underwent a brain computed tomography perfusion and were scheduled to undergo reperfusion therapy. In a case-control design, we compared the proportion of subjects with no-mismatch, the volume of penumbra salvaged, as well as the final infarct size in a group of patients with migraine and a group of patients with no history of migraine., Results: We included 61 patients with migraine (34 [55.7%] men; mean age, 52.2±15.1 years; migraine without aura/migraine with aura, 44/17) and 61 patients with no history of migraine. The proportion of no-mismatch among migraineurs was significantly higher than among nonmigraineurs (17 [27.9%] versus 7 [11.5%]; P =0.039) and was more prominent among patients with migraine with aura (6 [35.3%]; P =0.030) while it was nonsignificantly increased in patients with migraine without aura (11 [25.0%]; P =0.114). Migraine, especially migraine with aura, was independently associated with a no-mismatch pattern (odds ratio, 2.65; 95% CI, 0.95-7.41 for migraine; odds ratio, 5.54; 95% CI, 1.28-23.99 for migraine with aura), and there was a linear decrease of the proportion of patients with migraine with aura with increasing quartiles of mismatch volumes. Patients with migraine with aura had also smaller volumes of salvaged penumbra (9.8±41.2 mL) compared with patients with migraine without aura (36.4±54.1 mL) and patients with no migraine (45.1±55.0 mL; P =0.056). Conversely, there was no difference in final infarct size among the 3 migraine subgroups ( P =0.312)., Conclusions: Migraine is likely to increase individual vulnerability to ischemic stroke during the process of acute brain ischemia and might represent, therefore, a potential new therapeutic target against occurrence and progression of the ischemic damage., (© 2018 American Heart Association, Inc.)

Frontotemporal dementia is a heterogeneous neurodegenerative disorder with around a third of cases having autosomal dominant inheritance. There is wide variability in phenotype even within affected families, raising questions about the determinants of the progression of disease and age at onset. It has been recently demonstrated that cognitive reserve, as measured by years of formal schooling, can counteract the ongoing pathological process. The TMEM106B genotype has also been found to be a modifier of the age at disease onset in frontotemporal dementia patients with TDP-43 pathology. This study therefore aimed to elucidate the modulating effect of environment (i.e. cognitive reserve as measured by educational attainment) and genetic background (i.e. TMEM106B polymorphism, rs1990622 T/C) on grey matter volume in a large cohort of presymptomatic subjects bearing frontotemporal dementia-related pathogenic mutations. Two hundred and thirty-one participants from the GENFI study were included: 108 presymptomatic MAPT, GRN, and C9orf72 mutation carriers and 123 non-carriers. For each subject, cortical and subcortical grey matter volumes were generated using a parcellation of the volumetric T1-weighted magnetic resonance imaging brain scan. TMEM106B genotyping was carried out, and years of education recorded. First, we obtained a composite measure of grey matter volume by graph-Laplacian principal component analysis, and then fitted a linear mixed-effect interaction model, considering the role of (i) genetic status; (ii) educational attainment; and (iii) TMEM106B genotype on grey matter volume. The presence of a mutation was associated with a lower grey matter volume (P = 0.002), even in presymptomatic subjects. Education directly affected grey matter volume in all the samples (P = 0.02) with lower education attainment being associated with lower volumes. TMEM106B genotype did not influence grey matter volume directly on its own but in mutation carriers it modulated the slope of the correlation between education and grey matter volume (P = 0.007). Together, these results indicate that brain atrophy in presymptomatic carriers of common frontotemporal dementia mutations is affected by both genetic and environmental factors such that TMEM106B enhances the benefit of cognitive reserve on brain structure. These findings should be considered in evaluating outcomes in future disease-modifying trials, and support the search for protective mechanisms in people at risk of dementia that might facilitate new therapeutic strategies., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Purpose: The aim of this study was to test the hypothesis that patients with spontaneous cervical artery dissection (CeAD) have increased arterial tortuosity, and the objective quantification of such a tortuosity may aid in the identification of subjects at increased risk of disease., Methods: In the setting of a hospital-based, case-control study, we used the vertebral tortuosity index (VTI) measured on magnetic resonance angiography, a validated method for the assessment and quantification of arterial tortuosity, to compare the degree of tortuosity in a series of consecutive patients with spontaneous CeAD and of age- and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) and stroke-free subjects., Results: The study group was composed of 102 patients with CeAD (mean age, 44.5 ± 7.8 years; 66.7% men), 102 with non-CEAD IS, and 102 stroke-free subjects. The VTI was higher in the group of patients with CeAD (median, 7.3; 25th-75th percentile, 10.2) compared with that of non-CeAD IS (median, 3.4; 25th-75th percentile, 4.4) and of stroke-free subjects (median, 4.0; 25th-75th percentile, 2.9; p ≤ 0.001), and was independently associated to the risk of CeAD (OR, 1.18; 95% CI, 1.09-1.29) in multivariable regression analysis. The degree of tortuosity also tended to be higher in CeAD patients who experienced short-term recurrence (5.8%; median, 20.2; 25th-75th percentile, 31.2) than in those without recurrent events (median, 7.2; 25th-75th percentile, 9.4; p = 0.074)., Conclusion: CeAD patients exhibit increased arterial tortuosity. This might have potential implications for better understanding of the pathophysiology of the disease as well as clinical utility in evaluation, prognostication, and decision-making of affected individuals.

Technical advances are rapidly changing the clinical and instrumental approach to peripheral nerve diseases. Magnetic resonance neurography, diffusion tensor imaging and nerve ultrasonography are increasingly entering the diagnostic workup of peripheral neuropathies as tools that complement neurophysiology and enable investigation of proximal structures, such as plexuses and roots. Progress in the design of magnetic resonance scanners and sequences, and the development of high-frequency ultrasound probes mean that high-resolution peripheral nerve imaging is possible, enabling detailed examination of nerve size, morphology and internal fascicular structure that can integrate nerve conduction studies into clinical practice. In the growing field of small-fibre neuropathy, in which traditional nerve conduction studies are of little or no use, skin biopsy has become a reliable tool for diagnosis. Corneal confocal microscopy, nociceptive evoked potentials and microneurography are emerging techniques that are mainly used in clinical research settings, but have increasing relevance to clinical practice. We review these new and emerging techniques and their effects on diagnosis, treatment strategies and prognosis in a variety of peripheral neuropathies, including entrapments, brachial plexopathies, immune and inherited neuropathies, and small-fibre neuropathies. We discuss the most promising research findings and their potential for future application in clinical practice.

Futile recanalization occurs when successful recanalization fails to improve clinical outcome in acute ischemic stroke patients. Predictors of futile recanalization are still debated and may help in selecting patients for reperfusion strategies. We aim to determine whether leukoaraiosis may be useful in predicting futile recanalization in acute ischemic stroke patients treated by endovascular mechanical thrombectomy. We included in the analysis patients with acute ischemic stroke due to anterior circulation large vessel occlusion undergoing endovascular mechanical thrombectomy obtaining complete vessel recanalization. Demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale score, time from symptoms onset to recanalization, Alberta Stroke Program Early CT Score, and leukoaraiosis graded on a 4-point van Swieten scale were collected. We dichotomized patients into those with moderate-severe leukoaraiosis (2-4) versus those with absent-slight leukoaraiosis (0, 1). Outcome measures were symptomatic intracranial hemorrhage, and modified Rankin scale score at 90 days. The relationships among radiological parameters and clinical data with outcome measures were studied with univariate and multivariable analyses. Sixty-eight patients were identified. Recanalization was futile in 32.4% of cases. On multivariable logistic regression analysis, the presence of moderate-severe LA was independent predictors of FR (P = 0.01). Furthermore, higher NIHSS score at baseline (P < 0.01) end endovascular mechanical thrombectomy alone treatment (P < 0.01) resulted associated with futile recanalization. Our results showed that the presence of moderate-severe leukoaraiosis is associated with poor outcome in recanalized patients.

Background: DYT1 mutation is characterized by focal to generalized dystonia and incomplete penetrance. To explore the complex perturbations in the different neural networks and the mutual interactions among them, we studied symptomatic and asymptomatic DTY1 mutation carriers by resting-state functional MRI., Methods: A total of 7 symptomatic DYT1, 10 asymptomatic DYT1, and 26 healthy controls were considered. Resting-state functional MRI (Oxford Centre for Functional MRI of the Brain) [FMRIB] Software Library) (FSL) MELODIC, dual regression, (as a toolbox of FSL, with Nets is referred to "networks") (FSLNets) (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FSLNets) was performed on 9 resting-state neural networks., Results: DYT1 mutation signature (symptomatic DYT1 and asymptomatic DYT1) was characterized by increased connectivity in the dorsal attention network and in the left fronto-parietal network. Functional correlates of symptomatic DYT1 patients (symptomatic DYT1 vs healthy controls) showed increased connectivity in the sensorimotor network., Discussion: This study argues that DYT1 dystonia is a network disorder, with crucial nodes in sensory-motor integration of posterior parietal structures. A better characterization of cortical networks involved in dystonia is crucial for possible neurophysiological therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society., (© 2016 International Parkinson and Movement Disorder Society.)

Agrammatic variant primary progressive aphasia is a neurodegenerative disorder specifically characterized by language deficits. A recent study has demonstrated a beneficial effect of transcranial direct current stimulation (tDCS) in combination with language training on naming accuracy in these patients. The aim of the study was to evaluate whether the improvement of naming accuracy after tDCS during language training was related to regional grey matter (GM) density. Eighteen avPPA patients underwent a brain magnetic resonance imaging before receiving a treatment that consisted of tDCS over the left dorsolateral prefrontal cortex during individualized language training (10 daily therapy sessions, 5 days per week from Monday to Friday). Performances on neuropsychological tests and naming of objects (treated and untreated) and actions were assessed at baseline, post-treatment  and 3 months after treatment. Correlations between individual changes after treatment on neuropsychological tests and on picture naming task and voxel-based GM volume at baseline were performed. We found that the improvement in the naming of treated objects was positively correlated with GM volume in the left fusiform, left middle temporal, and right inferior temporal gyri whereas action naming change was related to GM density in the left middle temporal gyrus. In conclusion baseline density of GM in these brain regions was associated with greater treatment response on naming performances, suggesting that intervention in early disease stages might be most successful. These findings have implication for designing future rehabilitation protocols in language variants of frontotemporal dementia.

Variations within genes associated with dyslexia result in a language network vulnerability, and in patients with Frontotemporal Dementia (FTD), language disturbances represent a disease core feature. Here we explored whether variations within three related-dyslexia genes, namely KIAA0319, DCDC2, and CNTNAP, might affect cortical thickness measures in FTD patients. 112 FTD patients underwent clinical and neuropsychological examination, genetic analyses and brain Magnetic Resonance Imaging (MRI). KIAA0319 rs17243157 G/A, DCDC2 rs793842 A/G and CNTNAP2 rs17236239 A/G genetic variations were assessed. Cortical thickness was analysed by Freesurfer. Patients carrying KIAA0319 A*(AG or AA) carriers showed greater cortical thickness atrophy in the left fusiform and inferior temporal gyri, compared to KIAA0319 GG (p ≤ 0.001). Patients carrying CNTNAP2 G*(GA or GG) showed reduced cortical thickness in the left insula thenCNTNAP2 AA carriers (p≤0.001). When patients with both at-risk polymorphisms were considered (KIAA0319 A* and CNTNAP2 G*), greater and addictive cortical thickness atrophy of the left insula and the inferior temporal gyrus was demonstrated (p ≤ 0.001). No significant effect of DCDC2 was found. In FTD, variations of KIAA0319 and CNTNAP2 genes were related to cortical thickness abnormalities in those brain areas involved in language abilities. These findings shed light on genetic predisposition in defining phenotypic variability in FTD.

Background: Infective endocarditis (IE) can be complicated by intracranial bleeding (ICB) caused by different pathologic mechanisms. The occurrence of ICB in patients with IE significantly influences therapeutic decisions and has a negative impact on outcome., Case Report: We describe the clinical courses of 3 patients with aortic prosthetic valve IE presenting with ICB. Patients 1 and 2 experienced subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), respectively, caused by rupture of an intracranial infectious aneurysm (IIA). Both underwent endovascular treatment of IIA with good outcome. In patient 3, ICB was the hemorrhagic conversion of an acute ischemic lesion from septic brain embolization. In the subacute phase of the disease, aortic valve replacement was performed, with excellent outcome. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ICB is a relevant complication and sometimes the first clinical feature of IE. Imaging of brain vessels should be performed to investigate the pathologic mechanism underlying ICB. The prevalence of IIA is probably underestimated and may influence the therapeutic strategy. Cerebrovascular imaging may therefore also be considered in asymptomatic subjects with left-sided IE. Withdrawal of anticoagulant treatment and delay of cardiac surgery are recommended in all cases of IE complicated by ICB. Because of the impact of ICB on IE management and outcome, a high level of clinical suspicion and prompt recognition and treatment of this complication are necessary., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Frontotemporal dementia (FTD) is characterized by executive dysfunctions, behavioral disturbances, language deficits and extrapyramidal symptoms. Frontotemporal lobar degeneration-modified Clinical Dementia Rating Scale (FTLD modified-CDR) has been proposed to measure disease severity in behavioral variant FTD (bvFTD). No tools of global disease severity are available in the other FTLD phenotypes [primary progressive aphasias (PPAs), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS)]. This would be strategic as outcome measures in clinical trials. To this aim, we evaluated the association between brain volume (voxel based morphometry) and available clinical scales in FTD. In 176 FTD patients (64 bvFTD, 40 PPAs, 32 PSP, 40 CBS), instrumental activities of daily living (ADLs), FTLD-modified CDR, Mini-Mental State Examination (MMSE), Frontal Behavioral Inventory (FBI), and Neuropsychiatry Inventory (NPI) were administered and MRI performed. Whole-brain linear correlation between each clinical rating scale and brain volume was performed. In bvFTD and PPAs, FTLD-modified CDR was associated with regional brain volume, thereby providing evidence for validity of the FTLD-modified CDR. In PSP, none of the clinical indicators were associated with regional brain volume. In CBS, ADLs and MMSE correlated with frontotemporal lower volume. Considering monogenic disease, FTLD-modified CDR was the best measure. In FTD continuum, different measures able to correlate with brain damage should be considered for the different clinical phenotypes or genetic traits.

Ischemic stroke due to basilar artery occlusion (BAO) is frequently associated with a poor prognosis. To date the most effective therapeutic approach has not been established and little is known about the predictors of clinical outcome. The aim of this study was to describe safety and efficacy of intra-arterial mechanical thrombectomy (IAMT) through latest generation devices in patients with BAO, focusing on those variables that may affect recanalization and clinical outcome. We analyzed retrospectively a series of 32 patients with BAO who underwent IAMT. We assessed the association of some clinical and neuroradiological features with recanalization rate and clinical outcome. Successful recanalization was achieved in 28 out of 32 patients (87.5 %). Symptomatic intracerebral hemorrhage (SICH) was observed in 2/32 patients (6.3 %) and mortality in the first 3 months was 25.0 %. At 3-month follow up evaluation, 13/32 patients (40.6 %) showed a good functional outcome (mRS score ≤2). There were no statistical differences in term of age, gender, risk factors, cause of stroke, recanalization rate, pre-treatment pc-ASPECTS score and SICH frequencies between patients with favorable and unfavorable outcome. Increased length of thrombi was associated with unfavorable clinical outcome at 3 months. Recanalization rate was not affected by any of the variables considered. In BAO, IAMT through newest generation devices has high recanalization rates and low complication frequencies. Length of BAO is an important predictor of clinical outcome.

No study but one has suggested the presence of white matter hyperintensities (WMHs) in frontotemporal dementia (FTD), limited to 4 cases carrying pathogenic Granulin (GRN) gene mutations. We investigated the presence of WMHs in a cohort of 14 FTD patients with pathogenic GRN mutations (GRN+), 28 patients without GRN mutations (GRN-) and 18 healthy controls (HC). We further considered 11 asymptomatic GRN+ subjects and 11 young age-matched healthy controls (yHC). The WMH burden was automatically computed and a voxelwise-based analysis was carried out to explore the differences in WMH brain spatial distribution. FTD-GRN+ patients had increased total WMH burden than both HC (p < 0.001) and FTD-GRN-(p = 0.01) groups. WMHs were mainly localized in the right middle frontal and superior temporal gyri, in the left superior frontal in the left parietal gyri. No significant differences of WMH burden between asymptomatic GRN+ and yHC were observed. The presence of WMHs in cases of FTD may suggest a novel mechanism of GRN disease-related neurodegeneration, may be of help in the differential diagnosis, and in guiding genetic screening., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Long-term exposure to environmental manganese (Mn) affects not only attention and neuromotor functions but also olfactory functions of a pre-adolescent local population who have spent their whole life span in contaminated areas. In order to investigate the effect of such exposure at the level of the central nervous system we set up a pilot fMRI experiment pointing at differences of brain activities between a non-exposed population (nine subjects) and an exposed one (three subjects). We also measured the volume of the olfactory bulb as well as the identification of standard olfactory stimuli. Our results suggest that young subjects exposed to Mn exhibit a reduction of BOLD signal, subjective odor sensitivity and olfactory bulb volume. Moreover a region of interest SPM analysis showed a specifically reduced response of the limbic system in relation to Mn exposure, suggesting an alteration of the brain network dealing with emotional responses.

In light of future pharmacological interventions, neuroimaging markers able to assess the response to treatment would be crucial. In Granulin (GRN) disease, preclinical data will prompt pharmacological trials in the future. Two main points need to be assessed: (1) to identify target regions in different disease stages and (2) to determine the most accurate functional and structural neuroimaging index to be used. To this aim, we have taken advantage of the multivariate approach of multi-voxel pattern analysis (MVPA) to explore the information of brain activity patterns in a cohort of GRN Thr272fs carriers at different disease stages (14 frontotemporal dementia (FTD) patients and 17 asymptomatic carriers) and a group of 33 healthy controls. We studied structural changes by voxel-based morphometry (VBM), functional connectivity by assessing salience, default mode, fronto-parietal, dorsal attentional, executive networks, and local connectivity by regional homogeneity, amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), degree centrality, and voxel-mirrored homotopic connectivity. In FTD patients with GRN mutation, the most predictive measure was VBM structural analysis, while in asymptomatic carriers the best predictor marker was the local connectivity measure (fALFF). Altogether, all indexes demonstrated fronto-temporo-parietal damage in GRN pathology, with widespread structural damage of fronto-parietal and temporal regions when disease is overt. MVPA could be of aid in identifying the most accurate neuroimaging marker for clinical trials. This approach was able to identify both the target region and the best neuroimaging approach, which would be specific in the different disease stages. Further studies are needed to simultaneously integrate multimodal indexes in a classifier able to trace the disease progression moving from preclinical to clinical stage of the disease.