Commentary to Merwin SJ, Obis T, Nunez Y, Re DB (2017) Organophosphate neurotoxicity to the voluntary motor system on the trail of environment-caused amyotrophic lateral sclerosis: the known, the misknown, and the unknown. Arch Toxicol [Epub ahead of print]. doi:10.1007/s00204-016-1926-1

Despite an early understanding of amyotrophic lateral sclerosis (ALS) as a disease affecting the motor system, including motoneurons in the motor cortex, brainstem, and spinal cord, today, many cases involving dementia and behavioral disorders are reported. Therefore, we currently divide ALS not only based on genetic predisposition into the most common sporadic variant (90% of cases) and the familial variant (10%), but also based on cognitive and/or behavioral symptoms, with five specific subgroups of clinical manifestation—ALS with cognitive impairment, ALS with behavioral impairment, ALS with combined cognitive and behavioral impairment, the fully developed behavioral variant of frontotemporal dementia in combination with ALS, and comorbid ALS and Alzheimer’s disease (AD). Generally, these cases are referred to as amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD). Clinical behaviors and the presence of the same pathognomonic deposits suggest that FTLD and ALS could be a continuum of one entity. This review was designed primarily to compare neuropathological findings in different types of ALS relative to their characteristic locations as well as the immunoreactivity of the inclusions, and thus, foster a better understanding of the immunoreactivity, distribution, and morphology of the pathological deposits in relation to genetic mutations, which can be useful in specifying the final diagnosis.

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ALS and Frontotemporal Dysfunction: A Review

Neurology Research International ◽

10.1155/2012/806306 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 34

Author(s):

Eugene Y. Achi ◽

Stacy A. Rudnicki

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Executive Function ◽

Frontotemporal Dementia ◽

Cognitive Dysfunction ◽

Noninvasive Ventilation ◽

Motor System ◽

Neuropsychological Testing ◽

Cognitive Changes ◽

Feeding Tubes ◽

Lateral Sclerosis

Though once believed to be a disease that was limited to the motor system, it is now apparent that amyotrophic lateral sclerosis (ALS) may be associated with cognitive changes in some patients. Changes are consistent with frontotemporal dysfunction, and may range from mild abnormalities only recognized with formal neuropsychological testing, to profound frontotemporal dementia (FTD). Executive function, behavior, and language are the most likely areas to be involved. Screening helpful in detecting abnormalities includes verbal or categorical fluency, behavioral inventories filled out by the caregiver, and evaluation for the presence of depression and pseudobulbar affect. Patients with cognitive dysfunction have shortened survival and may be less compliant with recommendations regarding use of feeding tubes and noninvasive ventilation. Evolving knowledge of genetic and pathological links between ALS and FTD has allowed us to better understand the overlapping spectrum of ALS and FTD.

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Selective pattern of motor system damage in gamma-synuclein transgenic mice mirrors the respective pathology in amyotrophic lateral sclerosis

Neurobiology of Disease ◽

10.1016/j.nbd.2012.06.016 ◽

2012 ◽

Vol 48 (1) ◽

pp. 124-131 ◽

Cited By ~ 19

Author(s):

Owen M. Peters ◽

Steven Millership ◽

Tatyana A. Shelkovnikova ◽

Ileana Soto ◽

Lora Keeling ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Transgenic Mice ◽

Motor System ◽

Lateral Sclerosis ◽

Selective Pattern

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How Degeneration of Cells Surrounding Motoneurons Contributes to Amyotrophic Lateral Sclerosis

Cells ◽

10.3390/cells9122550 ◽

2020 ◽

Vol 9 (12) ◽

pp. 2550

Author(s):

Roxane Crabé ◽

Franck Aimond ◽

Philippe Gosset ◽

Frédérique Scamps ◽

Cédric Raoul

Keyword(s):

Spinal Cord ◽

Amyotrophic Lateral Sclerosis ◽

Glial Cells ◽

Neurological Disorder ◽

Cellular Network ◽

Motor System ◽

Progressive Degeneration ◽

Brain And Spinal Cord ◽

The Brain ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by the progressive degeneration of upper and lower motoneurons. Despite motoneuron death being recognized as the cardinal event of the disease, the loss of glial cells and interneurons in the brain and spinal cord accompanies and even precedes motoneuron elimination. In this review, we provide striking evidence that the degeneration of astrocytes and oligodendrocytes, in addition to inhibitory and modulatory interneurons, disrupt the functionally coherent environment of motoneurons. We discuss the extent to which the degeneration of glial cells and interneurons also contributes to the decline of the motor system. This pathogenic cellular network therefore represents a novel strategic field of therapeutic investigation.

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