SeXX Matters in Multiple Sclerosis

Gilli, Francesca; DiSano, Krista D.; Pachner, Andrew R.

doi:10.3389/fneur.2020.00616

Cited by 43 publications

(34 citation statements)

References 279 publications

(440 reference statements)

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“…. Men had higher overall disability (PDDS), and worse walking and dexterity scores, which is also consistent with the survey of Chinese MS patients [19] and the literature documenting higher burden of 'spinal' disability and higher load of the destructive, T1-hypointense lesions in men as compared to women (reviewed in [20]).…”

Section: Discussionsupporting

confidence: 85%

“… 15 - 17 Higher anxiety scores among women with MS may reflect a well-known predisposition of women to anxiety disorders. 18 Women also had higher fatigue scores compared with men; similar findings of higher fatigue in women were reported in a recent multicenter study of Chinese patients with MS. 19 Men had higher overall disability (PDDS), and worse walking and dexterity scores, which is also consistent with the survey of Chinese patients with MS 19 and the literature documenting higher burden of spinal disability and higher load of destructive, T1 hypointense lesions in men compared with women (reviewed in reference 20 ).…”

Section: Discussionsupporting

confidence: 82%

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How Multiple Sclerosis Symptoms Vary by Age, Sex, and Race/Ethnicity

2021

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Background:Little is known about how symptom severity in the various neurologic domains commonly affected by MS vary by age, sex and race/ethnicity.Methods:This was a retrospective study of MS patients attending two tertiary centers in the NYC metropolitan area, who self-identified as White, African-American (AA), or Hispanic-American (HA). Disability was rated with Patient-determined Disability steps (PDDS) and symptom severity - with SymptoMScreen (SyMS), a validated battery for assessing symptoms in 12 domains. Analyses comparing race, sex, and age groups were carried out using ANOVA Models and Tukey’s HSD multiple comparison tests to control the overall Type I error. A multivariable model was constructed to predict good self-rated health (SRH) that included demographic variables, PDDS and SyMS domain scores.Results:Sample consisted of 2,622 MS patients (age 46.4 years; 73.6% female; 66.4% White, 21.7% AA, 11.9% HA). Men had higher adjusted PDDS than women (p=0.012), but similar total SyMS score. Women reported higher fatigue and anxiety scores (more botheration), while men had higher walking and dexterity scores. AA and HA had higher symptom domain scores than Whites in each of the 12 domains and worse SRH. In a multivariable logistic model, only pain, walking, depression, fatigue, and global disability (PDDS), but not sex or race/ethnicity predicted good SRH.Conclusions:AA and HA race/ethnicity was associated with higher overall disability, higher symptom severity in each of the 12 domains commonly affected by MS, and worse self-rated health relative to Whites. However, only symptom severity and disability, and not demographic variables, predicted good self-rated health.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 82%

How Multiple Sclerosis Symptoms Vary by Age, Sex, and Race/Ethnicity

2021

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“…Importantly, these sex-specific differences were not observed in spinal cord astrocytes in the same model ( Tassoni et al, 2019 ), highlighting notable regional diversity ( Itoh et al, 2018 ). Further investigation to differentiate plasticity (e.g., hormone effects) from heterogeneity and to elucidate the functional relevance of this observed sex-specific diversity are important goals for future research ( Chowen et al, 2017 ; Gilli et al, 2020 ).…”

Section: Cns Demyelinationmentioning

confidence: 99%

Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

Moulson

Squair

Franklin

et al. 2021

Front. Cell. Neurosci.

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Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as “reactive astrogliosis.” Diversity in astrocyte morphology and gene expression, as revealed by transcriptional analysis, is well-recognized and has been reported in several CNS pathologies, including ischemic stroke, CNS demyelination, and traumatic injury. This diversity appears unique to the specific pathology, with significant variance across temporal, topographical, age, and sex-specific variables. Despite this, there is limited functional data corroborating this diversity. Furthermore, as reactive astrocytes display significant environmental-dependent plasticity and fate-mapping data on astrocyte subsets in the adult CNS is limited, it remains unclear whether this diversity represents heterogeneity or plasticity. As astrocytes are important for neuronal survival and CNS function post-injury, establishing to what extent this diversity reflects distinct established heterogeneous astrocyte subpopulations vs. environmentally dependent plasticity within established astrocyte subsets will be critical for guiding therapeutic development. To that end, we review the current state of knowledge on astrocyte diversity in the context of three representative CNS pathologies: ischemic stroke, demyelination, and traumatic injury, with the goal of identifying key limitations in our current knowledge and suggesting future areas of research needed to address them. We suggest that the majority of identified astrocyte diversity in CNS pathologies to date represents plasticity in response to dynamically changing post-injury environments as opposed to heterogeneity, an important consideration for the understanding of disease pathogenesis and the development of therapeutic interventions.

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“…Sex chromosome-associated genes exhibit disparate expression profiles that arise independent of an individual's hormonal status and therefore represent a significant driver underlying the differences between males and females under normal and pathological conditions of the nervous and immune systems (recently reviewed in [209][210][211][212][213]). This is particularly relevant, given that sex-specific actions of X and Y genes in nociception and analgesia have been shown to occur by the day of birth in mice [214].…”

Section: The Sex Chromosomesmentioning

confidence: 99%

Sex differences in neuro(auto)immunity and chronic sciatic nerve pain

2020

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Chronic pain occurs with greater frequency in women, with a parallel sexually dimorphic trend reported in sufferers of many autoimmune diseases. There is a need to continue examining neuro-immune-endocrine crosstalk in the context of sexual dimorphisms in chronic pain. Several phenomena in particular need to be further explored. In patients, autoantibodies to neural antigens have been associated with sensory pathway hyper-excitability, and the role of self-antigens released by damaged nerves remains to be defined. In addition, specific immune cells release pro-nociceptive cytokines that directly influence neural firing, while T lymphocytes activated by specific antigens secrete factors that either support nerve repair or exacerbate the damage. Modulating specific immune cell populations could therefore be a means to promote nerve recovery, with sex-specific outcomes. Understanding biological sex differences that maintain, or fail to maintain, neuroimmune homeostasis may inform the selection of sex-specific treatment regimens, improving chronic pain management by rebalancing neuroimmune feedback. Given the significance of interactions between nerves and immune cells in the generation and maintenance of neuropathic pain, this review focuses on sex differences and possible links with persistent autoimmune activity using sciatica as an example.

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SeXX Matters in Multiple Sclerosis

Cited by 43 publications

References 279 publications

How Multiple Sclerosis Symptoms Vary by Age, Sex, and Race/Ethnicity

How Multiple Sclerosis Symptoms Vary by Age, Sex, and Race/Ethnicity

Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

Sex differences in neuro(auto)immunity and chronic sciatic nerve pain

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