The phenotypic variability of amyotrophic lateral sclerosis

@article{Swinnen2014ThePV,
  title={The phenotypic variability of amyotrophic lateral sclerosis},
  author={Bart Swinnen and Wim Robberecht},
  journal={Nature Reviews Neurology},
  year={2014},
  volume={10},
  pages={661-670}
}
Classic textbook neurology teaches that amyotrophic lateral sclerosis (ALS) is a degenerative disease that selectively affects upper and lower motor neurons and is fatal 3–5 years after onset—a description which suggests that the clinical presentation of ALS is very homogenous. However, clinical and postmortem observations, as well as genetic studies, demonstrate that there is considerable variability in the phenotypic expression of ALS. Here, we review the phenotypic variability of ALS and how… Expand
Amyotrophic Lateral Sclerosis 1 and Many Diseases
TLDR
There are clearly common clinical and pathologic features across all of ALS, which suggests that commonality may hold critical keys to understanding ALS. Expand
Emerging understanding of the genotype-phenotype relationship in amyotrophic lateral sclerosis.
TLDR
There are over 100 ALS-associated mutations, and importantly, several genetic mutations, including C9ORF72, SOD1, and TARDBP, have led to mechanistic insight into this complex disease. Expand
Genotypic and Phenotypic Heterogeneity in Amyotrophic Lateral Sclerosis
TLDR
The major genes implicated in the pathogenesis of motor neuron diseases; the clinical, pathological, and genetic links between ALS and frontotemporal dementia; and the vast genotypic and phenotypic heterogeneity of ALS are discussed. Expand
New ALS‐Related Genes Expand the Spectrum Paradigm of Amyotrophic Lateral Sclerosis
TLDR
Considering the increasing number of spectra of ALS, including ALS/Frontotemporal Dementia and ALS/Myopathies spectra as different phenotypes of the same spectrum can help to identify common pathological pathways and consequently new therapeutic targets in these incurable diseases. Expand
Amyotrophic lateral sclerosis: mechanisms and therapeutic strategies
TLDR
The evidence for the involvement of a number of different biological processes that could lead to these new therapeutic strategies and that can be translated into new therapeutic approaches are summarized. Expand
Phenotypic variability and its pathological basis in amyotrophic lateral sclerosis
TLDR
Underlying region‐specific cellular vulnerability may exist in the upper and lower motor neurons and frontotemporal system in patients with ALS, and this vulnerability may be linked to the macroscopic propensities of the sites of onset, and may also determine the direction and rate of progression of the lesions. Expand
Diagnosis and Clinical Management of Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders
TLDR
Although ALS cannot be cured, implementation of appropriate symptomatic treatment is valuable and recognition of suspicious symptoms and the appropriate laboratory evaluation are essential to limit diagnostic delay and avoid unnecessary testing and procedures. Expand
Atypical Familial Amyotrophic Lateral Sclerosis with Slowly Progressing Lower Extremities-predominant Late-onset Muscular Weakness and Atrophy
TLDR
A new atypical fALS family with a benign clinical course is reported and two candidate gene mutations of PLEC and ST3GAL6 linked to this phenotype are identified. Expand
Modelling amyotrophic lateral sclerosis: progress and possibilities
TLDR
The different model systems used to study ALS are reviewed and how they have contributed to the current understanding of the etiology and pathology of this neurodegenerative disease are discussed. Expand
Phenotypic variability in amyotrophic lateral sclerosis.
TLDR
Due to the selective vulnerability among different neuronal systems, lesions are multicentric, region-oriented, and progress at different rates, and may vary from patient to patient, which may be linked to the clinicopathological variability across patients. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 137 REFERENCES
Clinical and genetic heterogeneity of amyotrophic lateral sclerosis
Although clinical picture of amyotrophic lateral sclerosis (ALS) is a stereotypical one, resulting from combination of signs secondary to dysfunction of both upper motor neuron (UMN) and lower motorExpand
The Frontotemporal Syndromes of ALS. Clinicopathological Correlates
TLDR
The contemporary clinical, genetic and neuropathological characteristics of the frontotemporal syndromes of ALS are reviewed and it is proposed that as opposed to being a FTLD in which TDP-43 is the primary disease protein (FTLD-TDP), they represent a hybrid of both T DP-43 and tau pathology. Expand
Autonomic impairment in amyotrophic lateral sclerosis
TLDR
The wide range of autonomic involvement, together with results suggesting cognitive and extrapyramidal dysfunction, supports the view that ALS is a multisystem degenerative disease. Expand
State of play in amyotrophic lateral sclerosis genetics
TLDR
Current literature of the major genes underlying ALS, SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, C9ORF72 and PFN1 are summarized and how each new genetic discovery is broadening the phenotype associated with the clinical entity the authors know as ALS is outlined. Expand
ALS motor phenotype heterogeneity, focality, and spread
TLDR
Heterogeneity of motor phenotypes suggests motor neuron degeneration in ALS is in actuality a very orderly and actively propagating process and that fundamental molecular mechanisms may be uniform and their chief properties deduced. Expand
The epidemiology of ALS: a conspiracy of genes, environment and time
TLDR
The relationship between genetic and environmental risk factors is examined, and a disease model in which ALS is considered to be the result of environmental risks and time acting on a pre-existing genetic load is proposed, followed by an automatic, self-perpetuating decline to death. Expand
Cognitive impairment in amyotrophic lateral sclerosis
TLDR
Understanding of cognitive impairment in ALS will improve care for patients and their families and provide valuable insights into the pathogenesis of neurodegeneration. Expand
Novel FUS deletion in a patient with juvenile amyotrophic lateral sclerosis.
TLDR
This work sequenced the coding exons of SOD1, TARDBP, and FUS in a 19-year-old patient experiencing rapid degeneration of upper and lower motor neurons and confirmed that FUS mutations can lead to an early-onset malignant form of ALS. Expand
The changing scene of amyotrophic lateral sclerosis
TLDR
New findings in ALS research are summarized, what they have taught us about this disease are discussed and issues that are still outstanding are examined. Expand
Clinical genetics of amyotrophic lateral sclerosis: what do we really know?
TLDR
The only clinical feature that distinguishes recognized hereditary from apparently sporadic ALS is a lower mean age of onset in the former, and all the clinical features reported in hereditary cases have also been observed in sporadic cases. Expand
...
1
2
3
4
5
...