Premenstrual Multiple Sclerosis Pseudoexacerbations

Wingerchuk, Dean M.; Rodriguez, Moses

doi:10.1001/archneur.63.7.1005

Cited by 25 publications

(8 citation statements)

References 10 publications

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“…Because of their pharmacological profile NSAIDs have been employed for the management of side effects, when interferon beta is employed for multiple sclerosis treatment. Moreover, the classical COX1 inhibitor aspirin is frequently used to limit the severity of multiple sclerosis related fatigue and premenstrual associated pseudo-exacerbations [ [75] , [76] , [77] ]. Although COX1 in contrast to COX2 may not be considered a classical pro-inflammatory enzyme it contributes to the biosynthesis of pro-inflammatory prostaglandins [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis

2018

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BackgroundAdapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for inflammatory, hyperproliferative and neurodegenerative diseases. Pro-inflammatory eicosanoids have been implicated in the pathogenesis of multiple sclerosis since they augment vascular permeability and induce leukocyte migration into the brain. We explored the impact of ketogenic diets on gene expression of biosynthetic enzymes for pro- (ALOX5, COX1, COX2) and anti-inflammatory (ALOX15) eicosanoids in patients with relapsing-remitting multiple sclerosis.Methods60 adults were prospectively recruited for this six months randomized controlled trial and the impact of dietary treatment on the Multiple Sclerosis Quality of Life-54 index (ClinicalTrials.gov (NCT01538355) has previously been published. Here we explored 24 patients (8 controls, 5 on CR and 11 on AKD). For statistical analysis we combined the two diet groups to a single pooled treatment group.FindingsInter-group comparison indicated that expression of the pro-inflammatory ALOX5 in the pooled treatment group was significantly (p < 0.05) reduced when compared with the control group. Moreover, intra-group comparison (same individuals before and after dietary treatment) suggested significantly impaired expression of other pro-inflammatory enzymes, such as COX1 (p < 0.001) and COX2 (p < 0.05). Finally, pretreatment cross-group analysis revealed a significant positive correlation between expression of pro-inflammatory ALOX5 and COX2 and an inverse correlation of ALOX5 and COX1 expression with the MSQoL-54 index.InterpretationKetogenic diets can reduce the expression of enzymes involved in the biosynthesis of pro-inflammatory eicosanoids. Pharmacological interference with eicosanoid biosynthesis might constitute a strategy supplementing current therapeutic approaches for MS.

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Section: Discussionmentioning

confidence: 99%

Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis

2018

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“…However, relatively little is known about how NSAIDs may limit disease in MS. There are reports of clinical use of NSAIDs for MS in management of side effects associated with IFN therapies [33] and aspirin use for limiting the severity of MS-related fatigue [34] and premenstrual associated pseudoexacerbations [35]. However, these studies were not designed to test the potential for limiting demyelination in disease and there are no other reports of therapeutic effects of NSAIDs for MS.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 expression in oligodendrocytes increases sensitivity to excitotoxic death

Carlson

Rojas

Redd

et al. 2010

J Neuroinflammation

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BackgroundWe previously found that cyclooxygenase 2 (COX-2) was expressed in dying oligodendrocytes at the onset of demyelination in the Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model of multiple sclerosis (MS) (Carlson et al. J.Neuroimmunology 2006, 149:40). This suggests that COX-2 may contribute to death of oligodendrocytes.ObjectiveThe goal of this study was to examine whether COX-2 contributes to excitotoxic death of oligodendrocytes and potentially contributes to demyelination.MethodsThe potential link between COX-2 and oligodendrocyte death was approached using histopathology of MS lesions to examine whether COX-2 was expressed in dying oligodendrocytes. COX-2 inhibitors were examined for their ability to limit demyelination in the TMEV-IDD model of MS and to limit excitotoxic death of oligodendrocytes in vitro. Genetic manipulation of COX-2 expression was used to determine whether COX-2 contributes to excitotoxic death of oligodendrocytes. A transgenic mouse line was generated that overexpressed COX-2 in oligodendrocytes. Oligodendrocyte cultures derived from these transgenic mice were used to examine whether increased expression of COX-2 enhanced the vulnerability of oligodendrocytes to excitotoxic death. Oligodendrocytes derived from COX-2 knockout mice were evaluated to determine if decreased COX-2 expression promotes a greater resistance to excitotoxic death.ResultsCOX-2 was expressed in dying oligodendrocytes in MS lesions. COX-2 inhibitors limited demyelination in the TMEV-IDD model of MS and protected oligodendrocytes against excitotoxic death in vitro. COX-2 expression was increased in wild-type oligodendrocytes following treatment with Kainic acid (KA). Overexpression of COX-2 in oligodendrocytes increased the sensitivity of oligodendrocytes to KA-induced excitotoxic death eight-fold compared to wild-type. Conversely, oligodendrocytes prepared from COX-2 knockout mice showed a significant decrease in sensitivity to KA induced death.ConclusionsCOX-2 expression was associated with dying oligodendrocytes in MS lesions and appeared to increase excitotoxic death of oligodendrocytes in culture. An understanding of how COX-2 expression influences oligodendrocyte death leading to demyelination may have important ramifications for future treatments for MS.

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“…Rarely menstrual-related relapses are described. There may also be pseudo-relapses [68]. A very early study on n = 8 relapsing MS women reported a relationship of progesterone to estradiol ratio during the luteal phase on the number and volume of contrast brain lesions.…”

Section: Mensesmentioning

confidence: 99%