Orla Hardiman

Learn More
BACKGROUND Geographical differences in the incidence of amyotrophic lateral sclerosis (ALS) have been reported in the literature but comparisons across previous studies are limited by different methods in case ascertainment and by the relatively small size of the studied populations. To address these issues, the authors undertook a pooled analysis of(More)
BACKGROUND Despite considerable interest, the population-based frequency, clinical characteristics and natural history of cognitive impairment in amyotrophic lateral sclerosis (ALS) are not known. METHODOLOGY The authors undertook a prospective population-based study of cognitive function in 160 incident Irish ALS patients and 110 matched controls.(More)
Mutation in the CHMP2B gene has been implicated in frontotemporal dementia. The authors screened CHMP2B in patients with ALS and several cohorts of control samples. They identified mutations (Q206H; I29V) in two patients with non-SOD1 ALS. Neuropathology of the Q206H case showed lower motor neuron predominant disease with ubiquitylated inclusions in motor(More)
We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide(More)
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that has sporadic and inherited forms. ALS is the most common neurodegenerative disorder of young and middle-aged adults, and few treatments are available. Although the degeneration predominantly affects the motor system, cognitive and behavioural symptoms have been described for over a century,(More)
BACKGROUND The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak. OBJECTIVES To provide evidence-based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel. METHODS All available medical reference systems were searched, and original(More)
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results in progressive loss of bulbar and limb function. Patients typically die from respiratory failure within 3 years of symptom onset. The incidence of ALS in Europe is 2–3 cases per 100,000 individuals in the general population, and the overall lifetime risk of developing the(More)
Mutations in the hypoxia-inducible factor angiogenin (ANG) have been identified in Amyotrophic Lateral Sclerosis (ALS) patients, but the potential role of ANG in ALS pathogenesis was undetermined. Here we show that angiogenin promotes motoneuron survival both in vitro and in vivo. Angiogenin protected cultured motoneurons against excitotoxic injury in a(More)
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease of motor neurons, resulting in worsening weakness of voluntary muscles until death from respiratory failure occurs after about 3 years. Although great advances have been made in our understanding of the genetic causes of ALS, the contribution of environmental factors(More)
We have performed a systematic review to summarize current knowledge concerning factors related to survival in ALS and to evaluate the implications of these data for clinical trials design. The median survival time from onset to death ranges from 20 to 48 months, but 10-20% of ALS patients have a survival longer than 10 years. Older age and bulbar onset are(More)