Search results for "Amyotrophic Lateral Sclerosis"

Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

2021

ABSTRACTObjectiveTo assess in adult spinal muscular atrophy (SMA) patients the construct validity and responsiveness of several outcome measures.MethodsPatients older than 15 years and followed-up at least for 6 months, between October 2015 and August 2020, with one motor function scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM) in five referral centers were included. Bedside functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) were also collected when available. Correlations and regression models were performed to evaluate the construct validity. The monthly slopes of change were use…

2021

Abstract Strong evidence suggests that endoplasmic reticulum stress plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through altered regulation of proteostasis. Robust preclinical findings demonstrated that guanabenz selectively inhibits endoplasmic reticulum stress-induced eIF2α-phosphatase, allowing misfolded protein clearance, reduces neuronal death and prolongs survival in in vitro and in vivo models. However, its safety and efficacy in patients with ALS are unknown. To address these issues, we conducted a multicentre, randomized, double-blind trial with a futility design. Patients with ALS who had displayed an onset of symptoms within the previous 18 mon…

Sleep–wake problems in patients with amyotrophic lateral sclerosis: implications for patient management

2012

SUMMARY Sleep–wake problems are frequent, although unrecognized, complications of amyotrophic lateral sclerosis (ALS). Sleep disorders such as insomnia, sleep-disordered breathing and restless legs syndrome have all been reported in patients with ALS, despite the limited number of studies and the small populations investigated so far. Sleep disturbances gradually worsen with disease progression, suggesting a relationship between the severity of disease and the neurodegenerative process. However, poor sleep can also be a consequence of several disturbances such as anxiety, depression, pain, choking, sialorrhea, fasciculations, cramps, nocturia and the inability to get comfortable and move f…

Causes and place of death in Italian patients with amyotrophic lateral sclerosis

2010

Objectives - To determine the causes and place of death in a cohort of Italian patients with amyotrophic lateral sclerosis (ALS). A better understanding of the likely causes of death in ALS might improve the palliative care at the end-of-life, whereas knowing the place of death will help to verify the need for highly specialized care services, e.g. hospice and nursing home. Patients and methods - Between 2000 and 2008, 182 ALS patients (onset: spinal, 127; bulbar, 55; M/F: 1.6) were followed in a single ALS Tertiary Centre in Palermo, Sicily, Italy until death. Medical data for each individual patient were recorded in a large database throughout the disease course. Information concerning ca…

Ethical issues: invasive ventilation in amyotrophic lateral sclerosis.

2012

The first man was a school headmaster. By his eye-gaze system he is able to order coins to enlarge his 10-year collection. His grandchildren extort presents from him in exchange for help. The second was a prefect and even now insists that the flowers in the garden represent the national flag. In spite of his gastrostomy, he still likes to sip his espresso from porcelain cups. The ventilation circuit 24/7 has not changed his custom to read the newspapers and listen to classical music in the living room. That girl is a young mum. She is fed by a tube, but she always makes her little child laugh with the dialectal phrases that she writes on the screen. The surgeon, every day in his electric wh…

Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS.

2005

Phosphorylated p38 mitogen-activated protein kinase (p38MAPK), but not activated c-jun-N-terminal kinase (JNK), increases in the motor neurons of transgenic mice overexpressing ALS-linked SOD1 mutants at different stages of the disease. This effect is associated with a selective increase of phosphorylated MKK3-6, MKK4 and ASK1 and a concomitant upregulation of the TNFalpha receptors (TNFR1 and TNFR2), but not IL1beta and Fas receptors. Activation of both p38 MAPK and JNK occurs in the activated microglial cells of SOD1 mutant mice at the advanced stage of the disease; however, this effect is not accompanied by the concomitant activation of the upstream kinases ASK1 and MKK3,4,6, while both …

Genetic analysis of familial Alzheimer’s disease, primary lateral sclerosis and paroxysmal kinesigenic dyskinesia: a tool to uncover common mechanist…

2021

Tesis doctoral 270 p. figuras y tablas

Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial

2022

Background and purpose: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. Methods: This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebul…