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From: Aspirin and multiple sclerosis
Feature
Description
ASA’s effect
Ischemic stroke
MS patients may have an increased risk of stroke [17, 18, 20, 36, 37].
ASA reduces the risk of ischemic stroke in some subjects, for example, those who had a previous stroke [24–26, 79]. ASA decreases platelet activation and aggregation through irreversible inhibition of platelet COX-1, and the resultant decrease in TXA2 production has a cardioprotective effect [57, 64]. It is unknown whether the risk of strokes in MS patients will be reduced in response to ASA.
Thrombosis
MS patients have an increased risk of venous thrombosis [18, 19, 21–23, 39].
ASA lowers the incidence of venous thrombosis in some subjects, for example, orthopedic surgery patients and those who experienced an unprovoked venous thromboembolism [27, 28, 88]. It is not known whether the risk of venous thrombosis is reduced in response to ASA in MS patients, but ASA reduces the risk for first thrombosis in patients with APLAs [107].
A higher percentage of MS patients have APLAs than controls [96–98]. APLAs are a diagnostic feature of APS, which involves thromboses.
Platelets
Platelets are activated in MS and have been implicated in contributing to MS pathogenesis, such as by promoting inflammation [71, 72, 111].
Anticoagulants decreased the severity of EAE [110, 211]. ASA lowers one indicator of platelet activation in MS patients.
ASA may lessen fibrin deposition and induce fibrinolysis [116].
Thrombin
Is thought to promote inflammatory disease states of the CNS [117], and thrombin is associated with multiple pathological features in EAE [118].
ASA may decrease thrombin at microvascular injury sites [119].
Microglia
Activated microglia can have a pro-pathogenic role in MS [3–5].
ASA may reduce production of proinflammatory cytokines and reactive oxygen species (ROS) by microglia [155–157].
Inflammation
Multiple components of inflammation (for example, ROS, proinflammatory cytokines) are thought to contribute to MS pathogenesis.
ASA may promote the resolution of inflammation via the production of lipoxin A4 [158, 159].
Remyelination
Remyelination is incomplete in MS [212].
ASA may increase ciliary neurotrophic factor and promote the differentiation and proliferation of oligodendrocyte precursors [161, 163].
Fatigue
Fatigue is a common symptom of MS.
ASA may reduce fatigue in MS patients via antipyretic effects or by countering proinflammatory cytokines [164, 176, 177].
Depression
Depression is more common in MS than in the general population [180].
ASA usage may lower the risk for major depression, and some evidence shows that ASA in combination with fluoxetine enhances treatment for depression [181, 182, 188]. It is unknown whether ASA would help to reduce depression in MS, but other studies suggest that it can have negative impacts or side effects in depressed patients (see Table 2)
General disease activity
MS patients given calcium aspirin (Solprin) [147, 148] or EAE subjects given sodium salicylate or ASA [149–152]. Studies were performed decades ago.
Overall, the outcome is inconclusive. There was no effect in MS patients [147, 148], but evaluation was done using an outdated measure of disease activity. In EAE, disease onset was delayed and/or disease incidence reduced in 3 out of 4 studies [149, 151, 152]. Treatment after clinical signs appeared resulted in no benefit [149], and in one study disease severity was increased although disease onset was delayed [151].