8 documents found, page 1 of 1
Utility of cortical inhibitory and facilitatory neuronal circuits in amyotrophi...
Santos Silva, Cláudia; Pavey, Nathan; Calma, Aicee Dawn; Kiernan, Matthew C.; Menon, Parvathi; van den Bos, Mehdi; Vucic, SteveBackground: Cortical hyperexcitability is an early feature of amyotrophic lateral sclerosis (ALS), linked to dysfunction in inhibitory and facilitatory cortical circuits, measurable using paired-pulse transcranial magnetic stimulation (TMS). Short-interval intracortical inhibition (SICI) is a robust biomarker of inhibitory function and an ALS diagnostic marker. Short interval intracortical facilitation (SICF) s...
Novel approaches to diagnosis and management of hereditary transthyretin amyloi...
Carroll, Antonia; Dyck, P. James; Carvalho, Mamede; Kennerson, Marina; Reilly, Mary M.; Kiernan, Matthew C.; Vucic, SteveHereditary transthyretin amyloidosis (ATTRv) is a severe, adult-onset autosomal dominant inherited systemic disease predominantly affecting the peripheral and autonomic nervous system, heart, kidney and the eyes. ATTRv is caused by mutations of the transthyretin (TTR) gene, leading to extracellular deposition of amyloid fibrils in multiple organs including the peripheral nervous system. Typically, the neuropath...
Genome-wide study of DNA methylation shows alterations in metabolic, inflammato...
Hop, Paul J.; Zwamborn, Ramona A. J.; Hannon, Eilis; Shireby, Gemma L.; Nabais, Marta F.; Walker, Emma M.; van Rheenen, Wouter; van Vugt, Joke J. F. A.Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent...
Neurophysiological features of primary lateral sclerosis
Carvalho, Mamede; Kiernan, Matthew C.; Pullman, Seth L; Rezania, Kourosh; Turner, MR; Simmons, ZacharyPrimary lateral sclerosis (PLS) is a motor neuron disease characterized by spinobulbar spasticity, absence of progressive lower motor neuron (LMN) dysfunction and marked by a slow functional decline. Electromyography is essential to exclude significant LMN involvement, particularly in the context of distinguishing PLS from amyotrophic lateral sclerosis (ALS), given that the prognosis is substantially better, an...
Occasional essay: Upper motor neuron syndrome in amyotrophic lateral sclerosis
Swash, Michael; Burke, David; Turner, Martin R.; Grosskreutz, Julian; Leigh, P. Nigel; Carvalho, Mamede; Kiernan, Matthew C.The diagnosis of amyotrophic lateral sclerosis (ALS) requires recognition of both lower motor neuron (LMN) and upper motor neuron (UMN) dysfunction. However, classical UMN signs are frequently difficult to identify in ALS. LMN involvement is sensitively detected by electromyography (EMG), but, as yet, there are no generally accepted markers for monitoring UMN abnormalities, the neurobiology of ALS itself and di...
A proposal for new diagnostic criteria for ALS
Shefner, Jeremy M.; Al-Chalabi, Ammar; Baker, Mark R.; Cui, Li-Ying; Carvalho, Mamede; Eisen, Andrew; Grosskreutz, Julian; Hardiman, OrlaSclerosis (ALS) were initially published in 1994 and revised in 2000. Criteria were established because the ‘‘variety of clinical features which may be present early in the course of ALS makes absolute diagnosis difficult and compromises the certainty of diagnosis for clinical research purposes and therapeutic trials.” The original criteria described 4 categories of disease: Definite, Probable, Possible, and Su...
Fasciculation in amyotrophic lateral sclerosis : origin and pathophysiological ...
Carvalho, Mamede; Kiernan, Matthew C.; Swash, MichaelThis review considers the origin and significance of fasciculations in neurological practice, with an emphasis on fasciculations in amyotrophic lateral sclerosis (ALS), and in benign fasciculation syndromes. Fasciculation represents a brief spontaneous contraction that affects a small number of muscle fibres, causing a flicker of movement under the skin. While an understanding of the role of fasciculation in AL...
Genome-wide association analyses identify new risk variants and the genetic arc...
van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M.; McLaughlin, Russell L.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fin...