Insight into Elderly ALS Patients in the Emilia Romagna Region: Epidemiological and Clinical Features of Late-Onset ALS in a Prospective, Population-Based Study

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

Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research

Thrombotic microangiopaty associated with parvovirus B19 infection after renal transplantation

Abstract. Human parvovirus B19 is considered an etiologic agent of aplastic anemia in immunosuppressed patients. Microscopic vasculitis, with or without renal involvement, has recently been attributed to this viral infection in immunocompetent patients. This study describes four cases of thrombotic renal graft microangiopathy presumably secondary to B19 infection. Twelve to 50 days after transplantation, four patients presented a renal graft dysfunction with creatinine rising to 360 to 1088 \u3bcmol/L and requiring hemodialysis in three cases. Renal involvement appeared after a systemic illness characterized by fever, fatigue and arthralgia, aplastic anemia (hemoglobin ranged from 5.3 to 7.8 g/dl), and thrombocytopenia. A thrombotic microangiopathy was observed in the renal biopsies, and the parvovirus B19 genome was isolated by PCR from the specimens. All four patients also became IgM-positive for parvovirus. Three of the four renal biopsies taken at the time of transplantation (T0) from the same patients were found positive for the B19 genome. Graft function recovered, with resolution of the aplastic anemia, within 22 to 110 d. Twenty biopsies performed as routine controls or for suspected acute rejection and nine T0 biopsies of patients with no signs of B19 infection were used. The B19 genome was found in two of 20 posttransplant biopsies and in one of nine T0 biopsies. The temporal association between aplastic anemia and the onset of thrombotic graft microangiopathy, isolation of the viral genome in renal specimens, seroconversion, and endothelial tropism of the virus suggests that B19 could be the etiologic agent of thrombotic microangiopathy in these cases. The development of the disease after infection could depend on other detrimental cofactors, which make the patient more susceptible to microthrombi formation in the renal microvasculature. The renal graft could represent the route of B19 transmission

A further Rasch study confirms that ALSFRS-R does not conform to fundamental measurement requirements

View at Publisher| Export | Download | Add to List | More... Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration Volume 16, Issue 5-6, 27 August 2015, Pages 331-337 A further Rasch study confirms that ALSFRS-R does not conform to fundamental measurement requirements (Article) Franchignoni, F.aefghijklmnopqrstuvwx, Mandrioli, J.b , Giordano, A.c, Ferro, S.d, Mandrioli, J.e, Fini, N.e, Georgoulopoulou, E.e, Nichelli, P.e, Biguzzi, S.f, Venturini, E.f, Passarin, M.G.f, Guidi, C.g, Neri, W.g, Sette, E.h, Tugnoli, V.h, Tola, M.R.h, Terlizzi, E.i, Guidetti, D.i, Curro Dossi, M.j, Pasquinelli, M.j, Andruccioli, J.j, Ravasio, A.j, Casmiro, M.k, Rasi, F.k, Salvi, F.l, Bartolomei, I.l, Michelucci, R.l, \ud Avoni, P.m, De Pasqua, S.m, Liguori, R.m, Rizzi, R.n, Canali, E.n, Marcello, N.n, Grassi, A.o, Delay, L.o, Pietrini, V.o, Aiello, M.p, Chierici, E.q, Montanari, E.q, Santangelo, M.r, Amidei, S.r, Greco, G.r, Casetta, I.s, Groppo, E.s, Granieri, E.s, De Massis, P.t, Mussuto, V.t, Borghi, A.u, Gabellini, A.u, Sacquegna, T.u, Rinaldi, R.v, Cirignotta, F.v, Ferro, S.d, D'Alessandro, R.w Hide additional authors a Unit of Occupational Rehabilitation and Ergonomics, Salvatore Maugeri Foundation, Scientific Institute of Veruno (NO), Italy b Department of Neuroscience, University of Modena and Reggio Emilia and Nuovo Ospedale Civile, S. Agostino-Estense di Modena, Via Pietro Giardini n. 1355, Modena, Italy c Unit of Bioengineering, Salvatore Maugeri Foundation, Scientific Institute of Veruno (NO), Italy View additional affiliations View references (25) Abstract Our objective was to verify and expand previous evidence of psychometric inadequacies in the ALSFRS-R, in a different sample of subjects suffering from ALS. Since 2009, a prospective registry records all incident cases of ALS in Emilia Romagna Region, Italy (4.4 million inhabitants) referred to its 17 neurological departments. For each patient, demographic and clinical information is collected by the physician in charge, including compilation of the ALSFRS-R at each clinical follow-up. Results showed that a confirmatory factor analysis on the three-factor model previously found (bulbar, motor, respiratory function) showed a good fit. Rasch analysis on the whole scale showed the need to collapse some rating categories, confirmed the multidimensionality of the ALSFRS-R, and demonstrated the presence of differential item functioning between patients with spinal versus bulbar onset. Moreover, some items included in the three ALSFRS-R subscales showed a problematic fit to the respective construct they were intended to measure. In conclusion, the interpretation of a total raw score of ALSFRS-R is hampered by ambiguities due to the different metric properties of the three domains the scale aggregates, and their content and structure. This study confirms that a refinement of ALSFRS-R is warranted, pointing to the need to revise its whole structure, and providing detailed guidelines for its revision.Our objective was to verify and expand previous evidence of psychometric inadequacies in the ALSFRS-R, in a different sample of subjects suffering from ALS. Since 2009, a prospective registry records all incident cases of ALS in Emilia Romagna Region, Italy (4.4 million inhabitants) referred to its 17 neurological departments. For each patient, demographic and clinical information is collected by the physician in charge, including compilation of the ALSFRS-R at each clinical follow-up. Results showed that a confirmatory factor analysis on the three-factor model previously found (bulbar, motor, respiratory function) showed a good fit. Rasch analysis on the whole scale showed the need to collapse some rating categories, confirmed the multidimensionality of the ALSFRS-R, and demonstrated the presence of differential item functioning between patients with spinal versus bulbar onset. Moreover, some items included in the three ALSFRS-R subscales showed a problematic fit to the respective construct they were intended to measure. In conclusion, the interpretation of a total raw score of ALSFRS-R is hampered by ambiguities due to the different metric properties of the three domains the scale aggregates, and their content and structure. This study confirms that a refinement of ALSFRS-R is warranted, pointing to the need to revise its whole structure, and providing detailed guidelines for its revision