Abstract
The pathogenesis of the fatal neurodegenerative condition amyotrophic lateral sclerosis (ALS) remains to be fully understood. Blood–brain barrier damage (BBBD) has been implicated as an exacerbating factor in several neurodegenerative conditions, including ALS. Therefore, this cross-sectional study used the novel D50 progression model to assess the clinical relevance of BBBD within a cohort of individuals with either ALS (n = 160) or ALS mimicking conditions (n = 31). Routine laboratory parameters in cerebrospinal fluid (CSF) and blood were measured, and the ratio of CSF to serum albumin levels (Qalb) was used as a proxy measure of BBBD. In the univariate analyses, Qalb levels correlated weakly with disease aggressiveness (as indicated by individual D50 values) and physical function (as measured by ALS Functional Rating Scale). However, after adjustment for cofactors in the elastic net regularization, only having limb-onset disease was associated with BBBD. The results reported here emphasize the clinical heterogeneity of ALS and the need for additional longitudinal and multi-modal studies to fully clarify the extent and effect of BBBD in ALS.
Highlights
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that predominantly affects motor neurons of both the brain and the spinal cord
Within the amyotrophic lateral sclerosis (ALS) subcohort, Blood–brain barrier damage (BBBD) was more frequently noted in patients with limb onset (n = 25, 24.3% vs. n = 4, 7% in bulbar onset; p = 0.007) (Table 2)
The influx of albumin into the cerebrospinal fluid (CSF) is increased resulting in perivascular edema accompanied by obstruction of microcirculation
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that predominantly affects motor neurons of both the brain and the spinal cord. This leads to muscular atrophy and paralysis, with the majority of patients succumbing to respiratory failure 3–4 years from symptom onset. The BBB plays a crucial role in maintaining the internal milieu of the central nervous system (CNS) and the function of neuronal cells. It is a continuous endothelial membrane consisting of non-fenestrated vessels that regulates the transfer of cells, ions, and molecules between the CNS and the blood. Damage to the BBB results in the influx of neurotoxic blood-derived cellular debris and potentially microbial pathogens into the brain,
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