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Background: Semantic behavioral variant frontotemporal dementia (sbvFTD) is a neurodegenerative condition presenting with specific behavioral and semantic derangements and predominant atrophy of the right anterior temporal lobe (ATL). The objective was to evaluate clinical, neuropsychological, neuroimaging, and genetic features of an Italian sbvFTD cohort, defined according to recently proposed guidelines, compared to semantic variant primary progressive aphasia (svPPA) and behavioral variant FTD (bvFTD) patients., Methods: Fifteen sbvFTD, sixty-three bvFTD, and twenty-five svPPA patients and forty controls were enrolled. Patients underwent clinical, cognitive evaluations, and brain MRI. Symptoms of bvFTD patients between onset and first visit were retrospectively recorded and classified as early and late. Grey matter atrophy was investigated using voxel-based morphometry., Results: sbvFTD experienced early criteria-specific symptoms: world, object and person-specific semantic loss (67%), complex compulsions and rigid thought (60%). Sequentially, more behavioral symptoms emerged (apathy/inertia, loss of empathy) along with non-criteria-specific symptoms (anxiety, suspiciousness). sbvFTD showed sparing of attentive/executive functions, especially compared to bvFTD and better language functions compared to svPPA. All sbvFTD patients failed at the famous face recognition test and more than 80% failed in understanding written metaphors and humor. At MRI, sbvFTD had predominant right ATL atrophy, almost specular to svPPA. Three sbvFTD patients presented pathogenic genetic variants., Conclusion: We replicated the application of sbvFTD diagnostic guidelines in an independent Italian cohort, demonstrating that the presence of person-specific semantic knowledge loss and mental rigidity, along with preserved executive functions and a predominant right ATL atrophy with sparing of frontal lobes, should prompt a diagnosis of sbvFTD., (© 2024. The Author(s).)

Background: The present study aimed at deriving equating norms to estimate scores on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) based on those on the ALS Cognitive Behavioral Screen (ALS-CBS™) in an Italian cohort of non-demented ALS patients., Methods: ALS-CBS™ and ECAS scores of 293 ALS patients without frontotemporal dementia were retrospectively retrieved. Concurrent validity of the ALS-CBS™ towards the ECAS was tested by covarying for demographics, disease duration and severity, presence of C9orf72 hexanucleotide repeat expansion and behavioural features. A linear-smoothing equipercentile equating (LSEE) model was employed to derive ALS-CBS™-to-ECAS cross-walks. Gaps in LSEE-based estimation were managed via a linear regression-based equating approach. Equivalence between empirical and derived ECAS scores was tested via a two-one-sided test (TOST) procedure for the dependent sample., Results: The ALS-CBS™ predicted the ECAS (β = 0.75), accounting for the vast majority of its variance (60% out of an R 2  = 0.71). Consistently, a strong, one-to-one linear association between ALS-CBS™ and ECAS scores was detected (r = 0.84; R 2  = 0.73). The LSEE was able to estimate conversions for the full range of the ALS-CBS™, except for raw scores equal to 1 and 6 - for whom a linear equating-based equation was derived. Empirical ECAS scores were equivalent to those derived with both methods., Discussion: Italian practitioners and researchers have been herewith provided with valid, straightforward cross-walks to estimate the ECAS based on ALS-CBS™ scores in non-demented ALS patients. Conversions herewith provided will help avoid cross-sectional/longitudinal inconsistencies in test adoption within research, and possibly clinical, settings., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

To define the presence and type of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS), different screening tools have been created. Currently, the most used screening tests are the Edinburgh cognitive and behavioural ALS screen (ECAS) and the ALS cognitive behavioural screen (ALS-CBS). The objective of this study was to compare the ability of ECAS and ALS-CBS in classifying non-demented ALS patients according to Strong criteria. One-hundred and fifty-four in- and out-patients with an age > 18 and a definite or probable ALS diagnosis were recruited between September 2019 and February 2020 at NeMO Clinical Centre and at Istituto Auxologico Italiano in Milan and underwent the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the ALS Cognitive Behavioural Screen (ALS-CBS). Exclusion criteria involved patients with a diagnosis of FTD, with a severe cognitive deterioration and/or an important behavioural impairment, with a significant psychiatric disorder or with the co-presence of another significant illness. The distribution of patients according to Strong criteria was different for ECAS and ALS-CBS and the degree of agreement between the two tests in terms of Cohen's Kappa coefficient resulted equal to 0.2047 with a 95% confidence limits interval between 0.1122 and 0.2973. This study for the first time compares the ability of ECAS and ALS-CBS in stratifying ALS patients. Further studies will be conducted to better understand the reasons underlying the differences between these two tests in classifying the different subtypes of fronto-temporal dysfunction in ALS., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To comprehensively assess whether neopterin in urine could be a candidate biomarker for determining the neuroinflammatory status in ALS., Methods: We performed an observational, cross-sectional study in 81 pALS, 68 age- and sex-comparable healthy controls (HC), 14 patients affected by MS and 24 OND patients. ALS patients underwent a neurological evaluation to assess the global functional status evaluated by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) and the disease progression rate. Urinary neopterin concentrations were determined by high-performance liquid chromatography method and were recorded at the time of first examination to assess their effect on disease severity and survival., Results: Urinary neopterin was significantly higher in pALS (263.90 [198.71-474.90]) compared to MS (155.28 [131.74-190.38], p =  < .001), OND patients (205.60 [158.96-299.41], p = 0.04) and HC (169.55 [134.91-226.10], p < .001). Moreover, a significant negative correlation was found between neopterin level and the severity of symptoms evaluated by ALSFRS-R total score (r = - 0.46, p < .001) and its subscores (bulbar r = - 0.34, p = 0.002; motor r = - 0.33, p = 0.003; respiratory r = - 0.53, p < .001), also adjusting for the effect of sex, site of onset, age at evaluation and time from onset to evaluation., Conclusions: Our finding indicates that urine neopterin is elevated in ALS, emphasizing the role of the cell-mediated inflammation in the disease. Moreover, whether confirmed in further studies, our results will underline the neopterin's potential use as non-invasive clinical biomarker of ALS, to discriminate patients possibly candidates to clinical interventions aimed to interfere the neuroinflammatory processes.

Introduction: The progression of amyotrophic lateral sclerosis (ALS) leads to a decline of the nutritional status that represents an independent prognostic factor for survival. Recent studies recognize the muscle tissue as an endocrine organ able to release several molecules, called myokines. Among them, irisin seems to be involved in the regulation of metabolism, body weight and development and function of the nervous system., Objectives: (1) To evaluate irisin serum levels in patients with ALS, with comparison to healthy subjects; (2) to assess the possible association of circulating irisin levels of ALS patients with the metabolic status, clinical and biochemical features., Methods: We performed an observational, cross-sectional study in 50 ALS patients and 32 age- and sex-comparable healthy controls. Patients underwent to a complete set of neurological, pulmonary and nutritional evaluations. Serum irisin concentration was measured by enzyme immunoassay. According to indirect calorimetry, ALS patients were divided into a normo-metabolic patient group (n = 24) and a hyper-metabolic patient group (n = 26)., Results: ALS patients showed significantly higher serum irisin levels compared to healthy subjects (51.0 ± 37.8 vs 13.1 ± 2.2 ng/mL, p < 0.0001). Hyper-metabolic ALS patients displayed higher serum irisin levels compared to normo-metabolic ALS patients and healthy controls (p < 0.0009 and p < 0.0001, respectively). Serum irisin levels showed significant association with the ALSFRS-R (β=-1.18, p = 0.042), Forced Vital Capacity (β = - 0.64, p = 0.013), Fat Mass (β=-1.44, p = 0.034), pCO 2 arterial blood levels (β = 2.67, p = 0.003), HCO 3 - arterial blood levels (β = 5.44, p = 0.001) and Free Fat Mass (β = 1.07, p = 0.025) adjusted for sex, age and metabolic status., Conclusions: ALS patients with impaired metabolic status showed higher serum irisin levels compared to normo-metabolic ALS patients and healthy subjects. Irisin levels were also negatively correlated with the extent of functional and respiratory impairment, due to as yet unknown causes, being more elevated in patients with greater disability.

Identifying frontal impairment in ALS is an important goal albeit disease-dedicated tools are still scarce. For this reason, we decided to consider primitive reflexes (PRs), variably regarded as correlates of frontal release and/or of upper motor neuron (UMN) impairment, often in the setting of dementias. Specifically, the aims of this work consisted in assessing the exact prevalence of the combination of seven PRs in ALS, trying to clarify their role as putative proxies of cognitive impairment or of UMN dysfunction. In this cross-sectional study, 50 consecutive ALS outpatients were evaluated for the presence of: palmomental (PM), corneomandibular (CM), glabella tap (MY), rooting, sucking, snout, and grasping reflexes. Cognitive screening was performed by the Frontal Assessment Battery (FAB) and the Weigl's Sorting test (WST); UMN dysfunction was concomitantly evaluated. PM, CM and MY were more frequently detected (62, 52, and 44 % of the ALS sample, respectively), while the other reflexes were under-represented. Patients displaying three or more PRs had significantly lower FAB and WST scores. On the other hand, UMN dysfunction was only moderately associated to PRs. In conclusion, PRs' assessment is a promising complementary tool for screening cognitive impairment in ALS; however, further work will be necessary to establish its added value with respect to already existing ALS-dedicated screening tools for cognition.