The present preliminary results from a relatively large sample size suggest that the present technique can be considered a viable treatment option for the immediate rehabilitation of both mandible and maxilla.

Background and purpose: Q336H is a rare MAPT mutation, previously found in a single patient with behavioral variant frontotemporal dementia and tau pathology (Pick bodies).Here, we describe the clinical characteristics of two members of a new family carrying the Q336H MAPT mutation.Methods: Clinical, genetic, and neuroradiological assessment and follow-up of the proband were made.Results: At age 37 years, the proband developed naming and object recognition impairment, due to a lack of knowledge. After 3 years, he developed behavioral disorders.Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography showed the involvement of the left temporal pole. A diagnosis of semantic variant primary progressive aphasia (svPPA) was made. At follow-up after 6 and 12 months, a rapid worsening of cognitive deficits occurred. His parent presented, at age 65 years, slowly progressive memory deficits without behavioral impairment, and, on MRI, evidence of mesial temporal atrophy, consistent with a clinical diagnosis of Alzheimer disease (AD).Conclusions: This is the second family carrying the MAPT Q336H mutation reported so far. We showed that svPPA and AD-like phenotype can be associated with this mutation. A wide clinical variability exists at the intrafamilial level for Q336H MAPT mutation, pointing to genetic and/or environmental influencing factors on disease expression. We also confirmed that svPPA can be associated with MAPT mutations, suggesting that this gene should be analyzed also in patients with svPPA, especially with early onset. In addition, an AD-like phenotype may be associated with this mutation, suggesting its different effects on protein misfolding and aggregation.

Background and Objectives.MRI connectomics is an ideal tool to test a network-based model of pathological propagation from a disease epicenter in neurodegenerative disorders. Here, we used a novel graph-theory-based MRI paradigm to explore functional connectivity reorganization, discerning between direct and indirect connections from disease epicenters, and its relationship with neurodegeneration across clinical presentations of the frontotemporal dementia (FTD) spectrum, including behavioral variant of FTD (bvFTD), non-fluent (nfvPPA) and semantic variants of primary progressive aphasia (svPPA).Methods.In this observational, cross-sectional study, disease epicenters were defined as the peaks of atrophy of a cohort of patients with high confidence of FTLD pathology (Mayo Clinic). These were used as seed regions for stepwise functional connectivity (SFC) analyses in an independent (Milan) set of FTD patients, to assess connectivity in regions directly and indirectly connected to the epicenters. Correlations between SFC architecture in healthy conditions and atrophy patterns in FTD patients were also tested.Results.As defined by comparing the 42 Mayo Clinic patients with 15 controls, disease epicenters were the left anterior insula for bvFTD, left supplementary motor area for nfvPPA, and left inferior temporal gyrus (ITG) for svPPA. Compared with 94 age-matched controls, bvFTD (n=64) and nfvPPA patients (n=34) of the Milan cohort showed widespread decreased SFC in bilateral cortical regions with direct/indirect connections with epicenters, and increased SFC either in directly connected regions, physically close to the respective seed region, or in more distant cortical/cerebellar areas with indirect connections. Across all link-steps, svPPA (n=36) showed SFC decrease mostly within the temporal lobes, with co-occurrent SFC increase in cerebellar regions at indirect link-steps. Average stepwise topological distance from the left ITG in a reference group of 50 young healthy controls correlated with regional grey matter volume in svPPA, consistent with network-based degeneration.Discussion.Our findings demonstrate that each FTD syndrome is associated with a characteristic interplay of decreased and increased functional connectivity with the disease epicenter, affecting both direct and indirect connections. SFC revealed novel insights regarding the topology of functional disconnection across FTD syndromes, holding the promise to be used to model disease progression in future longitudinal studies.

Semantic and right temporal variant of frontotemporal dementia (svFTD and rtvFTD) are rare clinical phenotypes in which, in most cases, the underlying pathology is TDP-43 proteinopathy. They are usually sporadic disorders, but recent evidences suggest a higher frequency of genetic mutations for the right temporal versus the semantic variant. However, the genetic basis of these forms is not clear. In this study we performed a genetic screening of a single-center cohort of svFTD and rtvFTD patients, aiming at identifying the associated genetic variants. A panel of 73 dementia candidate genes has been analyzed by NGS target sequencing including both causal and risk/modifier genes in 23 patients (15 svFTD and 8 rtvFTD) and 73 healthy age-matched controls. We first performed a single variant analysis considering rare variants and then a gene-based aggregation analysis to evaluate the cumulative effects of multiple rare variants in a single gene. We found 12 variants in nearly 40% of patients (9/23), described as pathogenic or classified as VUS/likely pathogenic. The overall rate was higher in svFTD than in rtvFTD. Three mutations were located in MAPT gene and single mutations in the following genes: SQSTM1, VCP, PSEN1, TBK1, OPTN, CHCHD10, PRKN, DCTN1. Our study revealed the presence of variants in genes involved in pathways relevant for the pathology, especially autophagy and inflammation. We suggest that molecular analysis should be performed in all svFTD and rtvFTD patients, to better understand the genotype–phenotype correlation and the pathogenetic mechanisms that could drive the clinical phenotypes in FTD.

We present the case of a man exhibiting a clinical phenotype of behavioral variant of frontotemporal dementia (bvFTD). The man had developed psychiatric disturbances with verbal aggressiveness over a few months, followed by cognitive and frontal behavioral disorders, fulfilling the clinical criteria for bvFTD. Atrophy and hypometabolism in frontotemporal regions were consistent with the diagnosis. However, serum-screening exams for syphilis infection were positive, and CSF analysis, despite a negative Venereal Disease Research Laboratory Test, suggested the diagnosis of neurosyphilis. After specific antibiotic therapy, the man’s behavioral abnormalities and cognitive deficits notably improved, confirming neurosyphilis as the cause of the clinical phenotype. The cognitive deficits completely recovered 1 year post therapy and remained stable for 2 years. After ∼2½ years from the first treatment, the man’s behavioral disorders mildly worsened, at which time we re-evaluated him. His cognition was stable, and a positive Venereal Disease Research Laboratory Test confirmed the diagnosis of neurosyphilis. With this case, we demonstrated that in some instances, neurosyphilis can mimic frontotemporal dementia. As a cause of treatable dementia, it should be considered in the differential diagnosis of bvFTD, particularly when psychiatric symptoms and a rapid cognitive decline are noted, even in the presence of brain atrophy and/or hypometabolism.