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Pain and spinal cord imaging measures in children with demyelinating disease.

Barakat N, Gorman MP, Benson L, Becerra L, Borsook D - Neuroimage Clin (2015)

Bottom Line: Most of this research has focused on adult populations and patients with traumatic injuries.These techniques may be of potential use for defining the evolution of the disease state, how it may affect specific spinal cord pathways, and contribute to the management of pediatric demyelination syndromes.We also focus on concepts that are essential in developing strategies for the detection, monitoring, treatment and repair of pediatric myelitis.

View Article: PubMed Central - PubMed

Affiliation: Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.

ABSTRACT
Pain is a significant problem in diseases affecting the spinal cord, including demyelinating disease. To date, studies have examined the reliability of clinical measures for assessing and classifying the severity of spinal cord injury (SCI) and also to evaluate SCI-related pain. Most of this research has focused on adult populations and patients with traumatic injuries. Little research exists regarding pediatric spinal cord demyelinating disease. One reason for this is the lack of reliable and useful approaches to measuring spinal cord changes since currently used diagnostic imaging has limited specificity for quantitative measures of demyelination. No single imaging technique demonstrates sufficiently high sensitivity or specificity to myelin, and strong correlation with clinical measures. However, recent advances in diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) measures are considered promising in providing increasingly useful and specific information on spinal cord damage. Findings from these quantitative imaging modalities correlate with the extent of demyelination and remyelination. These techniques may be of potential use for defining the evolution of the disease state, how it may affect specific spinal cord pathways, and contribute to the management of pediatric demyelination syndromes. Since pain is a major presenting symptom in patients with transverse myelitis, the disease is an ideal model to evaluate imaging methods to define these regional changes within the spinal cord. In this review we summarize (1) pediatric demyelinating conditions affecting the spinal cord; (2) their distinguishing features; and (3) current diagnostic and classification methods with particular focus on pain pathways. We also focus on concepts that are essential in developing strategies for the detection, monitoring, treatment and repair of pediatric myelitis.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of the pathogenesis of transverse myelitis affecting pain pathways. Top: macroscopic changes leading to altered spinal cord fiber myelination; in cases that affect the pain pathways (e.g., spinothalamic tracts), pain may be a major symptom in transverse myelitis. Bottom: microscopic changes in the spinal cord. A series of events leading to demyelination are believed to start by exposure to antigens, activation of lymphocytes and immunoglobulins, followed by eosinophils and neutrophils and astrocyte pathology (adapted from Wingerchuk, 2007 and Bukhari, 2012). Macrophages may ‘attack’ astrocytes and myelin, leading to local inflammation, oligodendrocyte death and myelin loss. Exposed axons may thus have abnormal irritability (ectopic firing) and conduction patterns.
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f0015: Schematic diagram of the pathogenesis of transverse myelitis affecting pain pathways. Top: macroscopic changes leading to altered spinal cord fiber myelination; in cases that affect the pain pathways (e.g., spinothalamic tracts), pain may be a major symptom in transverse myelitis. Bottom: microscopic changes in the spinal cord. A series of events leading to demyelination are believed to start by exposure to antigens, activation of lymphocytes and immunoglobulins, followed by eosinophils and neutrophils and astrocyte pathology (adapted from Wingerchuk, 2007 and Bukhari, 2012). Macrophages may ‘attack’ astrocytes and myelin, leading to local inflammation, oligodendrocyte death and myelin loss. Exposed axons may thus have abnormal irritability (ectopic firing) and conduction patterns.

Mentions: Though the mechanisms underlying lesion development and evolution in myelitis remain unknown, the current theory of pathogenesis suggests that when an infection presents in the immune system with an antigen similar to myelin, the resulting antibodies eventually attack myelin (Fig. 3). The cascade of pathological events leading to demyelination include peripheral interactions between activated lymphocytes and immunoglobulins, followed by focal monocyte and lymphocyte infiltrates into the spinal cord perivascular space. The disruption of the blood brain barrier permeability leads to a cellular influx of leukocytes (such as eosinophils and neutrophils) and an activation of astrocytes and glial cells, finally leading to local inflammation, oligodendrocyte death and axonal conducting abnormalities (Kerr and Ayetey, 2002; Krishnan et al., 2004; Bukhari et al., 2012; Wingerchuk, 2007). The inflammatory lesions can occur at the gray matter anterior horns or along the spinothalamic pathway thereby perturbing transmission of pain signals.


Pain and spinal cord imaging measures in children with demyelinating disease.

Barakat N, Gorman MP, Benson L, Becerra L, Borsook D - Neuroimage Clin (2015)

Schematic diagram of the pathogenesis of transverse myelitis affecting pain pathways. Top: macroscopic changes leading to altered spinal cord fiber myelination; in cases that affect the pain pathways (e.g., spinothalamic tracts), pain may be a major symptom in transverse myelitis. Bottom: microscopic changes in the spinal cord. A series of events leading to demyelination are believed to start by exposure to antigens, activation of lymphocytes and immunoglobulins, followed by eosinophils and neutrophils and astrocyte pathology (adapted from Wingerchuk, 2007 and Bukhari, 2012). Macrophages may ‘attack’ astrocytes and myelin, leading to local inflammation, oligodendrocyte death and myelin loss. Exposed axons may thus have abnormal irritability (ectopic firing) and conduction patterns.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588416&req=5

f0015: Schematic diagram of the pathogenesis of transverse myelitis affecting pain pathways. Top: macroscopic changes leading to altered spinal cord fiber myelination; in cases that affect the pain pathways (e.g., spinothalamic tracts), pain may be a major symptom in transverse myelitis. Bottom: microscopic changes in the spinal cord. A series of events leading to demyelination are believed to start by exposure to antigens, activation of lymphocytes and immunoglobulins, followed by eosinophils and neutrophils and astrocyte pathology (adapted from Wingerchuk, 2007 and Bukhari, 2012). Macrophages may ‘attack’ astrocytes and myelin, leading to local inflammation, oligodendrocyte death and myelin loss. Exposed axons may thus have abnormal irritability (ectopic firing) and conduction patterns.
Mentions: Though the mechanisms underlying lesion development and evolution in myelitis remain unknown, the current theory of pathogenesis suggests that when an infection presents in the immune system with an antigen similar to myelin, the resulting antibodies eventually attack myelin (Fig. 3). The cascade of pathological events leading to demyelination include peripheral interactions between activated lymphocytes and immunoglobulins, followed by focal monocyte and lymphocyte infiltrates into the spinal cord perivascular space. The disruption of the blood brain barrier permeability leads to a cellular influx of leukocytes (such as eosinophils and neutrophils) and an activation of astrocytes and glial cells, finally leading to local inflammation, oligodendrocyte death and axonal conducting abnormalities (Kerr and Ayetey, 2002; Krishnan et al., 2004; Bukhari et al., 2012; Wingerchuk, 2007). The inflammatory lesions can occur at the gray matter anterior horns or along the spinothalamic pathway thereby perturbing transmission of pain signals.

Bottom Line: Most of this research has focused on adult populations and patients with traumatic injuries.These techniques may be of potential use for defining the evolution of the disease state, how it may affect specific spinal cord pathways, and contribute to the management of pediatric demyelination syndromes.We also focus on concepts that are essential in developing strategies for the detection, monitoring, treatment and repair of pediatric myelitis.

View Article: PubMed Central - PubMed

Affiliation: Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.

ABSTRACT
Pain is a significant problem in diseases affecting the spinal cord, including demyelinating disease. To date, studies have examined the reliability of clinical measures for assessing and classifying the severity of spinal cord injury (SCI) and also to evaluate SCI-related pain. Most of this research has focused on adult populations and patients with traumatic injuries. Little research exists regarding pediatric spinal cord demyelinating disease. One reason for this is the lack of reliable and useful approaches to measuring spinal cord changes since currently used diagnostic imaging has limited specificity for quantitative measures of demyelination. No single imaging technique demonstrates sufficiently high sensitivity or specificity to myelin, and strong correlation with clinical measures. However, recent advances in diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) measures are considered promising in providing increasingly useful and specific information on spinal cord damage. Findings from these quantitative imaging modalities correlate with the extent of demyelination and remyelination. These techniques may be of potential use for defining the evolution of the disease state, how it may affect specific spinal cord pathways, and contribute to the management of pediatric demyelination syndromes. Since pain is a major presenting symptom in patients with transverse myelitis, the disease is an ideal model to evaluate imaging methods to define these regional changes within the spinal cord. In this review we summarize (1) pediatric demyelinating conditions affecting the spinal cord; (2) their distinguishing features; and (3) current diagnostic and classification methods with particular focus on pain pathways. We also focus on concepts that are essential in developing strategies for the detection, monitoring, treatment and repair of pediatric myelitis.

No MeSH data available.


Related in: MedlinePlus