Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease and Charcot disease, is a specific disorder that involves the death of neurons.

In the United Kingdom the term motor neurone disease (MND) is commonly used, while others use that term for a group of five conditions of which ALS is the most common.

Numerous intrinsic and extrinsic factors are involved in ALS motor neuron degeneration. One possible effector accelerating motor neuron death in ALS is damage to the blood-Central Nervous System barrier (B-CNS-B), mainly due to endothelial cell (EC) degeneration. Although mechanisms of EC damage in ALS are still unknown, vascular impairment may be initiated by various humoral inflammatory factors and other mediators. Systemic IL-6-mediated inflammation is a possible early extrinsic effector leading to the EC death causing central nervous system (CNS) barrier damage. In this review, we discuss the potential role of humoral factors in triggering EC alterations in ALS. A specific focus was on humoral IL-6 cytokine mediating EC inflammation via the trans-signaling pathway. Our preliminary in vitro studies demonstrated a proof of principle that short term exposure of human bone marrow endothelial cells to plasma from ALS patient leads to cell morphological changes, significantly upregulated IL-6R immunoexpression, and pro-inflammatory cell response. Our in-depth understanding of specific molecular mechanisms of this humoral cytokine in EC degeneration may facilitate an endothelial-IL-6-targeting therapy for restoring cell homeostasis and eventually reestablishing B-CNS-B integrity in ALS 1).

ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscle wasting. This results in difficulty speaking, swallowing, and eventually breathing.

Recording of trapezius Motor evoked potentials (MEPs) is a valuable addition to the limb MEPs study, since it distinguishes ALS from SCM in most patients 2).

Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts.

A large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS 3).

Peripheral nerve imaging is a potentially powerful technique to distinguish multifocal motor neuropathy (MMN) from ALS 4).

Findings suggest that elevated serum neurofilament light chain (NfL) levels in ALS are driven by Upper Motor Neuron degeneration and the disease progression rate and are independently associated with survival at time of diagnosis 5).

Amyotrophic lateral sclerosis treatment.

Garbuzova-Davis S, Ehrhart J, Sanberg PR, Borlongan CV. Potential Role of Humoral IL-6 Cytokine in Mediating Pro-Inflammatory Endothelial Cell Response in Amyotrophic Lateral Sclerosis. Int J Mol Sci. 2018 Jan 31;19(2). pii: E423. doi: 10.3390/ijms19020423. Review. PubMed PMID: 29385088.
Truffert A, Rösler KM, Magistris MR. Amyotrophic lateral sclerosis versus cervical spondylotic myelopathy: a study using transcranial magnetic stimulation with recordings from the trapezius and limb muscles. Clin Neurophysiol. 2000 Jun;111(6):1031-8. PubMed PMID: 10825710.
Müller HP, Turner MR, Grosskreutz J, Abrahams S, Bede P, Govind V, Prudlo J, Ludolph AC, Filippi M, Kassubek J; Neuroimaging Society in ALS (NiSALS) DTI Study Group; Neuroimaging Society in ALS NiSALS DTI Study Group. A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2016 Jan 8. pii: jnnp-2015-311952. doi: 10.1136/jnnp-2015-311952. [Epub ahead of print] PubMed PMID: 26746186.
Jongbloed BA, Haakma W, Goedee HS, Bos JW, Bos C, Hendrikse J, van den Berg LH, van der Pol WL. A comparative study of peripheral nerve MRI and ultrasound in MMN and ALS: Nerve imaging in neuropathies. Muscle Nerve. 2016 Aug 29. doi: 10.1002/mus.25391. [Epub ahead of print] PubMed PMID: 27571543.
Gille B, De Schaepdryver M, Goossens J, Dedeene L, De Vocht J, Oldoni E, Goris A, Van Den Bosch L, Depreitere B, Claeys KG, Tournoy J, Van Damme P, Poesen K. Serum Neurofilament Light Chain Levels as a Marker of Upper Motor Neuron Degeneration in Patients with Amyotrophic Lateral Sclerosis. Neuropathol Appl Neurobiol. 2018 Jun 16. doi: 10.1111/nan.12511. [Epub ahead of print] PubMed PMID: 29908069.
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