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Background: Impulse Control Disorder symptoms (ICD) in Parkinson's disease (PD) has been recently associated by magnetic Resonance imaging with impaired cortico-striatal connectivity, especially between left putamen and frontal associative areas.Methods: 84 patients entered the study (21 PD-ICD+ and 64 PD-ICD-) and underwent DATSCAN imaging. The striatal tracer uptake was evaluated using BRASS software (Hermes, Sweden). The whole-brain analysis was performed with Statistical Parametric Mapping (SPM).Results: PD-ICD+ showed a significant reduction of left putaminal and left inferior frontal gyrus tracer uptake compared to PD-ICD-. Functional covariance analysis using left putamen as the seed point showed that, in contrast to ICD-patients, ICD+ patients had no functional covariance with contralateral basal ganglia and ipsilateral cingulate cortex, as index of an impaired inter- and intra-hemispheric dopamine binding in PD-ICD+.Discussion: the results support and expand the concept of a functional disconnection syndrome linked to ICD symptoms in PD patients through an asymmetric molecular frontostriatal network breakdown with left basal ganglia as central hub. [ABSTRACT FROM AUTHOR]

α-Synucleinopathies, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), are characterized by α-synuclein accumulation from brainstem structures to the neocortex. PD and DLB are clinically distinguishable, while discrimination between Parkinson Disease Dementia (PDD) and DLB can be subtle and based on the temporal relationship between motor and cognitive symptoms. To explore patterns of subcortical atrophy in PD, PDD and DLB, and assess specific differences between PD and PDD, and between DLB and PDD. 16 PD, 11 PDD and 16 DLB patients were recruited and underwent 1.5 Tesla structural MRI scanning. Segmentation of subcortical structures was performed with a well-validated, fully-automated tool, and volume and shape for each structure were compared between groups. PDD and DLB patients showed global subcortical atrophy compared to PD patients. Greater hippocampal atrophy was the specific trait that distinguished PDD from PD, while greater atrophy of the pallidi discriminated DLB from PDD. Vertex analysis revealed specific shape differences in both structures. Our results suggest that automated, time-sparing, subcortical volumetry may provide diagnostically useful information in α-synucleinopathies. Future studies on larger samples and with iron-sensitive MRI contrasts are needed. [ABSTRACT FROM AUTHOR]

Keywords: COVID-19; novel coronavirus; neurology; stroke; cerebrovascular disease; mortality EN COVID-19 novel coronavirus neurology stroke cerebrovascular disease mortality e4 e5 2 12/28/20 20210101 NES 210101 Italy was the first European country to be affected by the COVID-19 epidemic, with the outbreak estimated to have started in late February 2020. For ischaemic stroke, in March 2020, 82 cases were observed, of which 35 (39%) with COVID-19, compared to an average of 49.7 (95% confidence interval 45.5-53.9) in March 2010-2019, whilst in April 2020 78 cases were observed, of which 17 (21.8%) with COVID-19, compared to an average of 48.2 (95% confidence interval 43.6-52.8) in April 2010-2019 (Fig. COVID-19, novel coronavirus, neurology, stroke, cerebrovascular disease, mortality. [Extracted from the article]

Background: Frontotemporal lobar degeneration (FTLD is a progressive neurodegenerative disorder with a stron genetic background. It has been reported that modifiabl factors, i.e. education (E), might act as proxies for reserve capacity. Objective:To evaluate the impact of genetic background (positive family history, FH) on reserve mechanisms by measuring regional cerebral blood flow (rCBF) correlate in FTLD patients. Methods: 145 FTLD patients were recruited and underwent clinical, neuropsychological, behaviora assessment, and SPECT study. The main effect of E and FH on rCBF was evaluated. To test the potential interaction between the E and rCBF in FTLD patients with or withou positive FH, a difference of slope analysis in the two groups was calculated. All the analyses were controlled for disease severity (Clinical Dementia Rating Scale, FTD-CDR). Result A main effect of education (E+

Primary progressive aphasia (PPA) is a heterogeneous disorder characterized by progressive language impairment. Polymorphisms within forkhead box P2 gene (FOXP2) gene have been associated with speech and language impairment. Apolipoprotein E (APOE) genotype and PRNP 129 codon status have been demonstrated to increase the risk of PPA, but with contrasting results. In the present study, we have evaluated the impact of FOXP2, APOE and PRNP genetic variations as risk factors and/or disease-modulators in PPA. 94 PPA patients and 200 age-matched healthy controls were considered and FOXP2 polymorphisms (rs1456031, rs17137124), APOE genotype, and PRNP codon 129 polymorphism analyzed. In 34 PPA patients, SPECT imaging data were analyzed by Statistical Parametric Mapping (SPM8). Genetic distributions and allele frequencies of FOXP2 and PRNP polymorphisms did not differ between groups while APOE ε4 was more represented in PPA as compared to controls. PPA patients carrying at-risk FOXP2 polymorphisms (rs1456031 and/or rs17137124) showed greater hypoperfusion in the frontal areas, namely the left inferior frontal gyrus and the right cingulated gyrus compared to non-carriers (p < 0.005). PPA patients carrying at least one ε4 allele had greater hypoperfusion in orbitofrontal regions (superior frontal gyrus and orbital gyrus) as compared to non-carriers ε4 (p < 0.005). PRNP codon 129 homozigosity correlated with left frontotemporal hypoperfusion (p < 0.005). Genetic variations within FOXP2, APOE, and PRNP modulate PPA disease, leading to a specific regional hypoperfusion according to different molecular pathways. APOE ε4 is overrepresented in PPA, thus likely acting as genetic risk factor on disease development. [ABSTRACT FROM AUTHOR]

Background: Literature data on Alzheimer’s disease suggest that years of schooling and occupational level are associated with a reserve mechanism. No data on patients with behavioral variant frontotemporal dementia (bvFTD) are available yet. Objective: To evaluate the impact of education, occupation, and midlife leisure activities on brain reserve in bvFTD. Methods: Fifty-four bvFTD patients entered the study and underwent neuropsychological and behavioral assessment, including the FTD-modified Clinical Dementia Rating for FTD (FTD-modified CDR), and SPECT imaging. We tested for the linear correlation of educational and occupational level, and midlife leisure activities with regional cerebral blood flow (rCBF), controlling for demographic variables (age and gender) and for cognitive performance (FTD-modified CDR) (statistical parametric mapping). Results: A significant relationship between higher educational and occupational attainments and lower rCBF in medial frontal cortex and dorsolateral frontal cortex, bilaterally, was found (p < 0.005). When midlife leisure activities were considered, no correlation was found. The correlation between a reserve index, accounting for both educational and occupational level, and rCBF showed the same pattern of hypoperfusion. Conclusions: This study suggests that education and occupation act as proxies for reserve capacity in bvFTD. These lifestyle attainments may counteract the onset of this genetic-based disease in at-risk individuals. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and purpose: Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome, defined by a distinctive clinical‐radiological profile, with Alzheimer's disease (AD) pathology accounting for the majority of cases. The aim of this report was to present the case of a patient with impairment of visual and constructional abilities as initial manifestations. Method: The patient underwent a multidimensional assessment, including neuropsychological evaluation, structural and functional imaging and genetic screening. Results: Neurological and neuropsychological assessment showed an impairment of constructive and visuo‐spatial skills, associated with dyscalculia, simultanagnosia, optic ataxia and oculomotor apraxia. In accordance with the latest consensus criteria, a diagnosis of PCA was made. Consistent with the clinical findings, structural and functional imaging showed a peculiar pattern of atrophy with primary involvement of right parieto‐occipital cortices, whereas cerebrospinal fluid biochemical analysis did not reveal a profile compatible with AD pathology. Genetic screening identified a known pathogenic GRN mutation. Conclusion: We present a case of PCA in a GRN mutation carrier in whom a concomitant AD pathological process was excluded. Consequently, although lacking histological data, our case suggests GRN‐related pathology causative of PCA. Through this report we provide further evidence for a new neurodegenerative pathway leading to PCA, extending the clinical spectrum of GRN‐associated phenotypes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Behavioural variant of frontotemporal dementia (bvFTD) frequently presents complex behavioural changes, that rarely occur in isolation. Targeting behavioural phenotypes instead of single behavioural symptoms may potentially provide a disease model in which to investigate brain substrates of behavioural abnormalities. Objective: To identify behavioural phenotypes and to assess the associated brain correlates in a cohort of patients with bvFTD. Methods: Two hundred and seven consecutive individuals fulfilling clinical criteria for bvFTD were enrolled. Each participant''s caregiver completed frontal behavioural inventory on 24 key behavioural disturbances. Confirmatory factor analysis (CFA) models were applied, and behavioural phenotypes identified. For each phenotype, a score was derived based on the “best” CFA model (Bifactor CFA). One hundred two participants underwent SPECT scan. A regression analysis between scores for each factor and regional cerebral blood flow was carried out (P <0.001). Results: One “general” behavioural phenotype and four factors were identified, that were termed “disinhibited”, “apathetic”, “aggressive”, and “language” phenotypes. The most robust brain correlate was identified for “disinhibited” phenotype, in the region of the anterior cingulated and anterior temporal cortex, bilaterally, and for apathetic phenotype in the left dorsolateral frontal cortex. As expected, language phenotype correlated with greater hypoperfusion in the left frontotemporal lobes. No significant correlation between aggressive phenotype and regional cerebral blood flow was found. Moreover, the “general” behavioural severity was associated with greater damage in the right frontal lobe. Conclusions: Behavioural phenotypes are associated with specific brain damage in bvFTD, involving distinct cerebral networks. [Copyright &y& Elsevier]

Prediction of survival in frontotemporal lobar degeneration (FTLD) is guesswork. The aim of the present study was to evaluate whether SPECT scan may be useful to predict prognosis of long term survival in FTLD patients. A cohort of 125 patients with FTLD who underwent brain SPECT scan at the time of enrollment and who were further followed up for at least one year were considered. In each subject, volume of interests (VOIs) covering frontotemporal and parietal regions, bilaterally, were drawn. Principal component analysis (PCA) was applied on VOIs, and a Cox regression model was carried out to find out best predictors of survival. A two-pattern PCA solution was chosen, explaining more than 70% of variance, and "frontal" PC1 and "temporal" PC2 components were identified. The frontal PC1 was associated with higher rate of faster progression (HR = 2.06, 95% CI = 1.23-3.44, p = 0.006 for univariate model, and HR = 1.85, 95% CI = 1.04-3.28, p = 0.03 for multivariate model). In particular, right orbitofrontal cortex showed the higher loadings in PC1; the worse the scores of this region the shorter the survival was reported. We suggest that SPECT imaging, beyond a helpful tool in diagnostic assessment, may be an easily and accessible marker of disease outcome in FTLD. Further studies considering structural neuroimaging are warranted. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal Lobar Degeneration (FTLD) is a heterogeneous disorder characterized by impairment in executive functions, behavioural disturbance and language deficit. Reliable scales of global impairment are under evaluation. A consortium of Mayo Clinic and University of California FTLD Centers has recently developed the FTLD-modified Clinical Dementia Rating (CDR) scale to assess FTLD severity. Objective: To evaluate whether FTLD-modified CDR scores correlate with the pattern and degree of brain SPECT hypoperfusion in patients with FTLD. Methods: Ninety-nine patients with FTLD entered the study. Patients underwent a clinical evaluation and a wide standardized neuropsychological assessment, including mini-mental state examination (MMSE) and FTLD-modified CDR. A brain SPECT perfusion imaging study was carried out in each patient. A linear correlation analysis between frontotemporal dementia-modified CDR or neuropsychological tests scores and perfusion data was performed. Results: There was a significant relationship between higher FTLD-modified CDR score and lower global regional cerebral blood flow in the frontal and temporal lobes, bilaterally. No significant correlation between MMSE and brain frontotemporal hypoperfusion was found. The correlation between brain hypoperfusion pattern and neuropsychological test scores tapping different cognitive domains fitted with previously published data. Conclusions: The recently introduced FTLD-modified CDR scale correlates with the degree of frontotemporal hypoperfusion in patients with FTLD. This study confirms and further supports the usefulness of FTLD-modified CDR in future clinical trials to monitor disease progression. [ABSTRACT FROM AUTHOR]

Background: Establishing survival rate in frontotemporal lobar degeneration (FTLD) is a clinical challenge for defining disease outcomes and monitoring therapeutic interventions. Using the latent profile analysis (LPA) approach, we have previously suggested that FTLD patients can be grouped into specific phenotypes- "pseudomanic behavior" (LC1), "cognitive" (LC2), and "pseudodepressed behavior" (LC3)-on the basis of neuropsychological, functional, and behavioral data.Objective: The aim of this study was to evaluate the rate of survival in FTLD, to identify predictors of survival, and to determine the likely usefulness of LPA in defining prognosis.Methods: A total of 252 FTLD patients entered the study. A clinical evaluation and standardized assessment were carried out, as well as a brain imaging study. LPA on neuropsychological, functional, and behavioral data was performed. Each patient was followed up over a 5-year period, and institutionalization or death was considered.Results: The survival rate was associated neither with demographic characteristics, co-morbidities, family history for dementia, nor clinical diagnosis. The presence of the three LC phenotypes was confirmed by LPA. A different survival rate was predicted by LCs, the worse prognosis being found in LC1 (hazard ratio [HR] = 15.7, 95% confidence interval [CI] = 7.2-34.9, p < 0.001, reference LC3). LC2 had a worse prognosis compared to LC3 (HR = 2.07, 95% CI = 0.98-4.37, p = 0.06). Greater hypoperfusion in the orbitomesial frontal cortex was specifically associated with LC1 compared with the other LCs.Conclusions: A data-driven approach regarding neuropsychological and behavioral assessment might be useful in clinical practice for defining a FTLD prognosis and hopefully will lead to the possibility of identifying patient groups for the evaluation of treatment response in future trials. [ABSTRACT FROM AUTHOR]

Frontotemporal dementia (FTD) is one of the most important neurodegenerative conditions and Granulin ( GRN) is one of the major genes associated to the disease. FTD-GRN patients are still orphan for any evidence-based target-therapy approach. Interestingly, it has been recently found that alkalizing agents rescued haploinsufficiency in cellular models expressing FTD- GRN mutations. We set up a pilot phase II clinical trial in five FTD patients with GRN Thr272s(g.1977_1980delCACT) mutation, to determine if amiodarone (200 mg/day) may (1) reverse progranulin deficiency and (2) delay disease progression. Each patient was scheduled for 7 study visits over 12 months period. We assessed GRN levels at baseline and after amiodarone administration during the treatment course. Somatic and neurologic examinations, along with cognitive and behavioral assessment were recorded as well. No significant effect on peripheral GRN levels was observed. In treated FTD, disease course did not differ when compared with a group of untreated FTD-GRN patients. This is the first trial targeting progranulin rescue in FTD-GRN patients using amiodarone. Despite the negative findings, it may be interesting to extend this attempt to a larger sample of subjects and to other alkalizing agents to restore granulin haploinsufficiency. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Transient Global Amnesia as a Presenting Aura or Epilepsy?" in a previous issue is presented.

The article presents a case study of a 70 year-old woman who was admitted to hospital for evaluation for repeated episodes of memory loss. The patient underwent several examinations and she was presented a clinically well-defined migraine attack after the conclusion of the amnesic episodes. She was diagnosed with transient epileptic amnesia.