Childhood multiple sclerosis: A review

Waldman, Amy; O’Connor, Erin E.; Tennekoon, Gihan

doi:10.1002/mrdd.20105

Cited by 14 publications

(16 citation statements)

References 93 publications

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“…Some of the earliest pathological changes in MS lesions are increases in OL apoptosis associated with microglial activation. 102,103 Cytokines released by activated microglia have been shown to trigger OL apoptosis (reviewed in Aktas et al 104 ) and microglia can also trigger excitotoxicity-induced apoptosis in OPCs by releasing glutamate. 46,105,106 Autoantibodies against epitopes within myelin and related proteins have been commonly observed in MS. 107 However, some autoantibodies seem to recognize epitopes, such as NG2, that are expressed only in OPCs.…”

Section: Ols and Diseasementioning

confidence: 99%

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

2008

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Apoptosis plays a crucial role in brain development by ensuring that only appropriately growing, migrating, and synapse-forming neurons and their associated glial cells survive. This process involves an intimate relationship between cell-cell interactions and developmental cues and is further impacted by environmental stress during neurogenesis and disease. Oligodendrocytes (OLs), the major myelin-forming cells in the central nervous system, largely form after this wave of neurogenesis but also show a selective vulnerability to cell death stimuli depending on their stage of development. This can affect not only embryonic and early postnatal brain formation but also the response to demyelinating pathologies. In the present review, we discuss the stagespecific sensitivity of OL lineage cells to damage-induced death and how this might impact myelin survival and regeneration during injury or disease. Apoptosis is a major form of programmed cell death required for the normal development of metazoan tissues, including the brain. 1 During embryonic development of the brain, many more cells than ultimately needed are generated and then selection occurs, resulting in the apoptotic depletion of the surplus cells. The importance of the apoptotic pathway in early brain development has been demonstrated by the targeted deletion in mice of the death-specific cysteine proteases caspase-3 or caspase-9, or of the co-activator Apaf-1, all of which cause severe brain overgrowth and perinatal death. 2,3 In the adult brain, 90% of the cells belong to the glial lineage, which includes oligodendrocytes (OLs), astrocytes and microglia. The glia ensures proper development, function and repair of the neuronal network. This is possible through continuous cross-talk between the glia and neurons mediated by neurotransmitters, cytokines, growth and trophic factor secretion and signaling in a reciprocal manner. [4][5][6][7] In the central nervous system (CNS), OLs are responsible for axon myelination, which insulates the electrical signals transmitted between neurons. OL and neuron development is tightly regulated and the myelin sheath is constructed only when OLs reach maturity and neurons have grown appropriately. In response to injury or during the course of neurological diseases, the neuron-glia network can be replenished to some extent but the degree of repair is dependent on the developmental stage of the OL. This complexity is compounded by the differential sensitivity of OL lineage cells to apoptotic stimuli. In the present review, we will first briefly examine the stages of differentiation of OL cells and then discuss several diseases that are impacted by OL apoptosis, noting how the stage of cell differentiation governs the sensitivity to apoptosis. Defined Stages of OL DevelopmentOligodendrocyte development can be divided into four distinct stages according to the temporal expression of cell surface markers and morphology (Table 1). 8 In the first stage, OL progenitor cells (OPCs) originate from the neuroepithelium of the ventricul...

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Section: Ols and Diseasementioning

confidence: 99%

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

2008

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“…It seems rather difficult to diagnose children with MS. Vague symptoms such as fatigue, tinglings, blurred vision with one eye and clumsy locomotion are not well understood by parents and not mentioned by children [37]. …”

Section: Discussionmentioning

confidence: 99%

Incidence of Multiple Sclerosis in the General Population in the Netherlands, 1996–2008

et al. 2012

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Background: We estimated the multiple sclerosis (MS) incidence in the Netherlands for better active monitoring of potential vaccine safety signals. Methods: A retrospective cohort study (1996–2008) was conducted using a population-based general practice research database containing electronic medical records. Additional information was collected to validate incident probable cases. Results: In the source population (648,656 persons), 146 incident probable MS cases were identified. Overall incidence rate was 6.3/100,000 person years (py; 95% CI, 5.2–7.2). In the subgroup in which MS could be fully validated, the incidence increased from 4/100,000 py (95% CI, 3–5) in 1996–2004 to 9/100,000 py in 2007/8 (95% CI, 6–16). This increase was highest among women, but not statistically significantly different by gender. The median lag time between first recorded symptoms and MS diagnosis decreased from 32 months (<1998) to 2 months (>2005). Conclusions: MS is rare in the Netherlands. In recent years, there was a slight increase in the incidence especially among women during the fertile age. This increase coincided with a decrease in lag time between symptoms and diagnosis, both for men and women. This trend should be taken into account in the interpretation of MS cases occurring in a population where new vaccinations will be introduced shortly.

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“…Firstly, as pediatric onset MS is relatively uncommon, the diagnosis can be delayed due to under-recognition by clinicians 27. Secondly, MS disease-modifying treatments have not been formally approved for pediatric use due to a lack of double-blinded randomized clinical trials in this age group, and long-term safety data is not available.…”

Section: Natural History and Management Issues In Adolescent Multiplementioning

confidence: 99%

Management of multiple sclerosis in adolescents – current treatment options and related adherence issues

Mah

Thannhauser

2010

AHMT

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Multiple sclerosis (MS) is a progressive inflammatory demyelinating disorder of the central nervous system that is increasingly recognized in children and adolescents. This realization comes with additional concerns about existing therapeutic options and the impact of the disease on health-related outcomes of adolescents with MS. This five-part review provides an update on management strategies relevant to the pediatric MS population. The first section gives an overview on the epidemiology and natural history of early onset MS. The second section outlines currently available MS treatments, including medications during acute relapses and long-term immunomodulatory therapies. The third section highlights adherence issues pertaining to MS, including the challenges uniquely faced by adolescents. The fourth section provides a summary of research into quality of life and psychosocial consequences of pediatric onset MS. Attention is drawn to the grief experience of affected adolescents and the importance of peer relationships. Finally, the family resilience framework is presented as a conceptual model to facilitate optimal adaptation of adolescents with MS. Healthcare professionals can promote resilience and treatment adherence by ensuring that these individuals and their families are sufficiently informed about available MS treatments, providing instrumental support for managing potential medication side effects, and addressing age-appropriate developmental needs.

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Childhood multiple sclerosis: A review

Cited by 14 publications

References 93 publications

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

Incidence of Multiple Sclerosis in the General Population in the Netherlands, 1996–2008

Management of multiple sclerosis in adolescents – current treatment options and related adherence issues

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Childhood multiple sclerosis: A review

Cited by 14 publications

References 93 publications

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

Incidence of Multiple Sclerosis in the General Population in the Netherlands, 1996–2008

Management of multiple sclerosis in adolescents &ndash; current treatment options and related adherence issues

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Product

Resources

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Management of multiple sclerosis in adolescents – current treatment options and related adherence issues