REM behavior disorder associated with familial amyotrophic lateral sclerosis

Ebben, Matthew R.; Shahbazi, Mona; Lange, Dale J.; Krieger, Ana C.

doi:10.3109/17482968.2012.673172

Cited by 25 publications

(16 citation statements)

References 6 publications

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“…It is evident that in this family, females had a more severe form of the disease compared to males. It has been reported that, in the 50 affected members with ALS from 10 families from different populations (31)(32)(33)(34)(35)(36)(37) with the L84F substitution (c.255G4C), there was wide variation in age at onset (19-65 years) and duration of the disease (1.5-12 years). Unlike our family, there was no gender bias in the course of the disease.…”

Section: Discussionmentioning

confidence: 98%

Identification of L84F mutation with a novel nucleotide change c.255G > T in the superoxide dismutase gene in a North Indian family with amyotrophic lateral sclerosis

Vats

Gourie-Devi

Verma

et al. 2015

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Mutations in the superoxide dismutase (SOD1) gene account for ∼15% and in the transactive response DNA binding protein (TARDBP) gene for ∼5% of familial amyotrophic lateral sclerosis (FALS) cases. These two genes were analysed in two siblings from North India with ALS and a positive family history. The coding region of SOD1 and TARDBP genes was sequenced in both siblings. Genetic variation identified in SOD1 was typed in unaffected family members (n = 11), sporadic ALS patients (n = 48) and healthy controls (n = 35). Molecular dynamic (MD) simulations were performed on wild-type (WT) and mutant monomers of SOD1 to determine structural changes due to the identified mutation. A novel heterozygous nucleotide variation (c.255G > T) was identified in exon 4 of SOD1 in the two siblings and two asymptomatic family members but not in SALS patients and healthy controls. This variation results in a known non-synonymous substitution from leucine to phenylalanine at position 84 (L84F), making it a triallelic variation. Large conformational changes were observed in the zinc loop and electrostatic loop in an L84F mutant compared to WT SOD1 in MD simulations. In conclusion, this is the first report of mutation in SOD1 associated with FALS in India. Structural perturbations in L84F SOD1 may cause dimer destabilization, with decreased metal affinity leading to oligomerization.

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Section: Discussionmentioning

confidence: 98%

Identification of L84F mutation with a novel nucleotide change c.255G > T in the superoxide dismutase gene in a North Indian family with amyotrophic lateral sclerosis

Vats

Gourie-Devi

Verma

et al. 2015

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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“…It has been often reported that patients with ALS may present difficulties initiating and maintaining sleep, reduced sleep efficiency, increased stage 1 sleep, and shortened duration of rapid eye movement (REM) sleep (6)(7)(8)(9)(10)(11)(12)14). In addition, with the exception of few single cases (14)(15)(16), motor activity during sleep that could be indicative of REM sleep behavior disorder (RBD) and REM sleep without atonia (RSWA), which are highly prevalent in other neurodegenerative disorders with brainstem involvement, has not been assessed. In addition, with the exception of few single cases (14)(15)(16), motor activity during sleep that could be indicative of REM sleep behavior disorder (RBD) and REM sleep without atonia (RSWA), which are highly prevalent in other neurodegenerative disorders with brainstem involvement, has not been assessed.…”

Section: Introductionmentioning

confidence: 99%

REM sleep behavior disorder and periodic leg movements during sleep in ALS

et al. 2016

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“…These conditions, including Parkinson’s disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB)(Gagnon et al 2006, Manni et al 2011), and pure autonomic failure (PAF)(Kaufmann et al 2017) are so named because of the characteristic intracellular protein accumulation of alpha-synuclein, that may be visualized in a subset of synucleinopathies (for example PD and DLB) as Lewy bodies (Figure 1)(Postuma et al 2009, Classen and Schnitzler 2010). It is unclear whether RBD is linked to the alpha-synucleinopathies via aggregated intracellular material, or through a common anatomic pathology(Ebben et al 2012). …”

Section: Introductionmentioning

confidence: 99%

Rapid eye movement sleep behavior disorder and the link to alpha-synucleinopathies

Barone

Henchcliffe

2018

Clinical Neurophysiology

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Rapid eye movement (REM) sleep behavior disorder (RBD) involves REM sleep without atonia in conjunction with a recurrent nocturnal dream enactment behavior, with vocalizations such as shouting and screaming, and motor behaviors such as punching and kicking. Secondary RBD is well described in association with neurological disorders including Parkinson's disease (PD), multiple system atrophy (MSA), and other conditions involving brainstem structures such as tumors. However, RBD alone is now considered to be a potential harbinger of later development of neurodegenerative disorders, in particular PD, MSA, dementia with Lewy bodies (DLB), and pure autonomic failure. These conditions are linked by their underpinning pathology of alpha-synuclein protein aggregation. In RBD, it is therefore important to recognize the potential risk for later development of an alpha-synucleinopathy, and to investigate for other potential causes such as medications. Other signs and symptoms have been described in RBD, such as orthostatic hypotension, or depression. While it is important to recognize these features to improve patient management, they may ultimately provide clinical clues that will lead to risk stratification for phenoconversion. A critical need is to improve our ability to counsel patients, particularly with regard to prognosis. The ability to identify who, of those with RBD, is at high risk for later neurodegenerative disorders will be paramount, and would in addition advance our understanding of the prodromal stages of the alpha-synucleinopathies. Moreover, recognition of at-risk individuals for neurodegenerative disorders may ultimately provide a platform for the testing of possible neuroprotective agents for these neurodegenerative disorders.

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REM behavior disorder associated with familial amyotrophic lateral sclerosis

Cited by 25 publications

References 6 publications

Identification of L84F mutation with a novel nucleotide change c.255G > T in the superoxide dismutase gene in a North Indian family with amyotrophic lateral sclerosis

Identification of L84F mutation with a novel nucleotide change c.255G > T in the superoxide dismutase gene in a North Indian family with amyotrophic lateral sclerosis

REM sleep behavior disorder and periodic leg movements during sleep in ALS

Rapid eye movement sleep behavior disorder and the link to alpha-synucleinopathies

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