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Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.76%) out of 1613 patients in incident cases were over 80 years old at diagnosis, with a female predominance (F:M = 1.18). Elderly ALS patients represented 12.02% of patients before 2015 and 15.91% from 2015 onwards (p = 0.024). This group presented with bulbar onset in 38.29% of cases and had worse clinical conditions at diagnosis compared to younger patients, with a lower average BMI (23.12 vs. 24.57 Kg/m2), a higher progression rate (1.43 vs. 0.95 points/month), and a shorter length of survival (a median of 20.77 vs. 36 months). For this subgroup, genetic analyses have seldom been carried out (25% vs. 39.11%) and are generally negative. Finally, elderly patients underwent less frequent nutritional- and respiratory-supporting procedures, and multidisciplinary teams were less involved at follow-up, except for specialist palliative care. The genotypic and phenotypic features of elderly ALS patients could help identify the different environmental and genetic risk factors that determine the age at which disease onset occurs. Since multidisciplinary management can improve a patient's prognosis, it should be more extensively applied to this fragile group of patients. [ABSTRACT FROM AUTHOR]

Introduction: Dopamine agonist (DA) use is considered the main risk factor for impulse control disorder (ICD) development in Parkinson's disease (PD). Besides DAs, personality traits and cognitive features may represent risk factors for ICDs. The primary aim of this study was to investigate differences in DA plasma concentrations in PD patients with and without a positive screening for ICDs according to validated tools. The secondary aim was to compare the psychological profile between ICD positive and negative screened patients. Methods: PD patients receiving chronic DA therapy were screened for ICDs according to the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). Blood samples for measurement of DA (pramipexole, ropinirole, rotigotine) trough plasma concentrations were drawn in the morning, at mean 16–19 h from the last DA dose. Patients' psychological profile was investigated by Millon Clinical Multiaxal Inventory III and Barratt Impulsiveness Scale (BIS-11). Results: One hundred and five PD patients were enrolled. Forty-one patients (39%) were QUIP positive, mainly for binge eating and hobbyism. Median plasma concentrations of pramipexole (n = 71, 66%), ropinirole (n = 21, 19%), and rotigotine (n = 16, 15%) were similar between QUIP positive and negative patients. QUIP positive patients showed higher motor impulsiveness (p = 0.04) and tended to higher total impulsiveness (p = 0.05). Conclusion: This is the first prospective study to evaluate the relationship between DA plasma concentrations and ICDs risk in PD patients. DA plasma levels were overlapping between QUIP positive and negative patients. BIS-11, particularly the motor impulsiveness subscale, might be a useful screening tool in PD patients eligible for DA therapy. [ABSTRACT FROM AUTHOR]

Purpose: Algorithms for the detection of a malignancy in patients with unclear neurologic symptoms of suspicious paraneoplastic origins are not universally applied. Frequently, circulating tumor markers (TMs) are considered a valuable tool for cancer diagnosis in patients with paraneoplastic neurologic syndromes (PNS). Our aim was to extract the recommendations on the use of TMs and onconeural antibodies (Abs) for the diagnosis of malignancies in PNS from clinical practice guidelines and put them forward as evidence in a common framework to facilitate diffusion, dissemination, and implementation. Methods: Systematic literature searches were performed for guidelines on both oncology and PNS published since 2007. Guidelines containing information and recommendations for clinical practice pertaining to the screening and diagnosis of PNS were selected. Information on circulating TMs and onconeural Abs was extracted and synthesized in consecutive steps of increasing simplification. Results: We retrieved 799 eligible guidelines on oncology for the potential presence of information on PNS but only six covered treated diagnosis or the screening of cancer in PNS, which were then selected. Seventy-nine potentially relevant guidelines on PNS were identified as eligible and 15 were selected. Synoptic tables were prepared showing that classical TMs are not recommended for the screening or the diagnosis of a malignancy in patients with a suspected PNS. Neither should onconeural Abs be considered to screen for the presence of a malignancy, although they could be helpful to define the probability of the paraneoplastic origin of a neurologic disorder. Conclusion: The present work of synthesis may be a useful tool in the diffusion, dissemination, and implementation of guideline recommendations, potentially facilitating the decrease of the inappropriate use of circulating biomarkers for cancer screening in the presence of PNS. [ABSTRACT FROM AUTHOR]

The C9orf72 repeat expansion (RE) is one of the most frequent causative mutations of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, it is still unclear how the C9orf72 RE can lead to a heterogeneous phenotype. Several reports have shown the coexistence of mutations in multiple ALS/FTD causative genes in the same family, suggesting an oligogenic etiology for ALS and FTD. Our aim was to investigate this phenomenon in an Italian group of ALS/FTD pedigrees carrying the C9orf72 RE. We included 11 subjects from 11 pedigrees with ALS/FTD and the C9orf72 RE. Mutation screening of FUS, SOD1 and TARDBP genes was performed by direct sequencing. A dementia-specific custom-designed targeted next-generation sequencing panel was used for screening dementia-associated genes mutations. We found genetic variants in additional ALS or dementia-related genes in four pedigrees, including the p.V47A variant in the TYROBP gene. As a group, double mutation carriers displayed a tendency toward a younger age at onset and a higher frequency of positive familiar history and of parkinsonism. Our observation supports the hypothesis that the co-presence of mutations in different genes may be relevant for the clinical expression of ALS/FTD and of their oligogenic nature. [ABSTRACT FROM AUTHOR]