Transverse myelitis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]
Overview
- In the pathogenesis of transverse myelitis, a variety of immunological mechanisms may cause pathological substrate and dysfunction of neural cells within the spinal cord.
- Transverse myelitis is the result of progressive demyelination and axonal loss in addition to gray matter involvement, necrosis and cavitation.
- It is understood that infections may cause transverse myelitis by:
- Direct tissue damage
- Immune-mediated infection-triggered tissue damage
- Multiple sclerosis is the other cause to the transverse myelitis and it sometimes transverse myelitis can appear as the first symptom of Multiple sclerosis.
- Acute partial transverse myelitis may be predictive of a subsequent diagnosis of multiple sclerosis in children.
- Invariable histopathological findings of transverse myelitis include:
- Perivascular spread of monocytes
- Focal areas of lymphocytes infiltrating
- Astroglial and microglial activation
- Other histopathological findings of transverse myelitis include:
- Infiltration of CD4+ and CD8+ T-lymphocytes
- Typically preservation of the subpial parenchyma suggesting ischemia as the ultimate cause of the cord lesions in transverse myelitis
Conditions that may cause transverse myelitis include:
- Various infectionsin 30% to 60% of the cases:
- Herpesviridae
- Enteroviruses
- Influenza viruses
- Adenoviruses
- Coxsackieviruses
- Enteric cytopathogenic human orphan (ECHO) virus
- Hepatitis A virus
- Lymphocytic choriomeningitis virus (LCMV)
- Mumps virus
- Measles virus
- Rubella virus
- Poliovirus
- Rubeola virus
- Dengue virus
- Russian spring-summer encephalitis virus
- Varicella virus
- Mycoplasma pneumonia bacteria
- Legionella pneumonia bacteria
- Pulmonary tuberculosis
- Borrelia (Lyme disease)
- Listeria
- Bartonella (cat scratch disease)
- Vaccination
- About 30% of pediatric cases are preceded with immunizations within one month of disease onset
Infections can cause transverse myelitis through two main mechanisms:
- Direct tissue damage
- Immune-mediated infection-triggered tissue damage which may be due to: Molecular mimicry or superantigen effect
- This immune response may be caused either by T-cell mediated immune response or by antibody-mediated immune response.
A non-microbial related immune dysfunction by the presence of autoantibodies has been also proposed in the immunopathogenesis of transverse myelitis.
In the spinal fluid of patients with transverse myelitis, Interleukin 6 (IL-6) levels were also markedly elevated.
Pathophysiology
Physiology
- The lesions in acute transverse myelitis are invariably limited to the spinal cord.[1][2]
- There is no involvement of other structures in the central nervous system.[1]
- The spinal cord involvement in patients with transverse myelitis is usually central, uniform and symmetric but in patients with multiple sclerosis it typically affects the spinal cord in a patchy way and the lesions are usually peripheral.
Pathogenesis
- In the pathogenesis of transverse myelitis, a variety of immunological mechanisms may cause pathological substrate and dysfunction of neural cells within the spinal cord.[3]
- Transverse myelitis is the result of progressive demyelination and axonal loss in addition to gray matter involvement, necrosis and cavitation.[1]
- It is understood that infections may cause transverse myelitis by: [1]
- Direct tissue damage
- Immune-mediated infection-triggered tissue damage
- Multiple sclerosis is the other cause to the transverse myelitis and it sometimes transverse myelitis can appear as the first symptom of Multiple sclerosis.[1]
- Acute partial transverse myelitis may be predictive of a subsequent diagnosis of multiple sclerosis in children.[4]
- Invariable histopathological findings of transverse myelitis include:[1]
- Perivascular spread of monocytes
- Focal areas of lymphocytes infiltrating
- Astroglial and microglial activation
- Other histopathological findings of transverse myelitis include:[1][5]
- Infiltration of CD4+ and CD8+ T-lymphocytes
- Typically preservation of the subpial parenchyma suggesting ischemia as the ultimate cause of the cord lesions in transverse myelitis
Conditions that may cause transverse myelitis include:
- Various infectionsin 30% to 60% of the cases:[1][6][7][8][9][10][11][12][13][14]
- Herpesviridae
- Enteroviruses
- Influenza viruses
- Adenoviruses
- Coxsackieviruses
- Enteric cytopathogenic human orphan (ECHO) virus
- Hepatitis A virus
- Lymphocytic choriomeningitis virus (LCMV)
- Mumps virus
- Measles virus
- Rubella virus
- Poliovirus
- Rubeola virus
- Dengue virus
- Russian spring-summer encephalitis virus
- Varicella virus
- Mycoplasma pneumonia bacteria
- Legionella pneumonia bacteria
- Pulmonary tuberculosis
- Borrelia (Lyme disease)
- Listeria
- Bartonella (cat scratch disease)
- Vaccination[1][15]
- About 30% of pediatric cases are preceded with immunizations within one month of disease onset
Infections can cause transverse myelitis through two main mechanisms:[1][14][16]
- Direct tissue damage
- Immune-mediated infection-triggered tissue damage which may be due to: Molecular mimicry or superantigen effect
- This immune response may be caused either by T-cell mediated immune response or by antibody-mediated immune response.
A non-microbial related immune dysfunction by the presence of autoantibodies has been also proposed in the immunopathogenesis of transverse myelitis.[1][17][18][19]
In the spinal fluid of patients with transverse myelitis, Interleukin 6 (IL-6) levels were also markedly elevated.[1][8][20]
Associated Conditions
Conditions associated with transverse myelitis include:[21][22][1][3][23]
- Various infections
- Systemic autoimmune diseases like:
Microscopic Pathology
Findings on microscopic histopathological analysis of transverse myelitis include:[24][25]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 Awad A, Stüve O (2011). "Idiopathic transverse myelitis and neuromyelitis optica: clinical profiles, pathophysiology and therapeutic choices". Curr Neuropharmacol. 9 (3): 417–28. doi:10.2174/157015911796557948. PMC 3151596. PMID 22379456.
- ↑ Tavasoli A, Tabrizi A (2018). "Acute Transverse Myelitis in Children, Literature Review". Iran J Child Neurol. 12 (2): 7–16. PMC 5904733. PMID 29696041.
- ↑ 3.0 3.1 Kerr DA, Ayetey H (2002). "Immunopathogenesis of acute transverse myelitis". Curr Opin Neurol. 15 (3): 339–47. doi:10.1097/00019052-200206000-00019. PMID 12045735.
- ↑ Meyer P, Leboucq N, Molinari N, Roubertie A, Carneiro M, Walther-Louvier U; et al. (2014). "Partial acute transverse myelitis is a predictor of multiple sclerosis in children". Mult Scler. 20 (11): 1485–93. doi:10.1177/1352458514526943. PMID 24619933.
- ↑ Moulignier A, Lescure FX, Savatovsky J, Campa P (2014). "CD8 transverse myelitis in a patient with HIV-1 infection". BMJ Case Rep. 2014. doi:10.1136/bcr-2013-201073. PMC 3918629. PMID 24503658.
- ↑ Jeffery DR, Mandler RN, Davis LE (1993). "Transverse myelitis. Retrospective analysis of 33 cases, with differentiation of cases associated with multiple sclerosis and parainfectious events". Arch Neurol. 50 (5): 532–5. doi:10.1001/archneur.1993.00540050074019. PMID 8489410.
- ↑ Christensen PB, Wermuth L, Hinge HH, Bømers K (1990). "Clinical course and long-term prognosis of acute transverse myelopathy". Acta Neurol Scand. 81 (5): 431–5. doi:10.1111/j.1600-0404.1990.tb00990.x. PMID 2375246.
- ↑ 8.0 8.1 Krishnan C, Kaplin AI, Deshpande DM, Pardo CA, Kerr DA (2004). "Transverse Myelitis: pathogenesis, diagnosis and treatment". Front Biosci. 9: 1483–99. doi:10.2741/1351. PMID 14977560.
- ↑ PAINE RS, BYERS RK (1953). "Transverse myelopathy in childhood". AMA Am J Dis Child. 85 (2): 151–63. doi:10.1001/archpedi.1953.02050070160004. PMID 13007166.
- ↑ Ropper AH, Poskanzer DC (1978). "The prognosis of acute and subacute transverse myelopathy based on early signs and symptoms". Ann Neurol. 4 (1): 51–9. doi:10.1002/ana.410040110. PMID 697326.
- ↑ Knebusch M, Strassburg HM, Reiners K (1998). "Acute transverse myelitis in childhood: nine cases and review of the literature". Dev Med Child Neurol. 40 (9): 631–9. doi:10.1111/j.1469-8749.1998.tb15430.x. PMID 9766742.
- ↑ ALTROCCHI PH (1963). "ACUTE TRANSVERSE MYELOPATHY". Arch Neurol. 9: 111–9. doi:10.1001/archneur.1963.00460080021002. PMID 14048158.
- ↑ Lerer RJ, Kalavsky SM (1973). "Central nervous system disease associated with Mycoplasma pneumoniae infection: report of five cases and review of the literature". Pediatrics. 52 (5): 658–68. PMID 4598176.
- ↑ 14.0 14.1 Salgado CD, Weisse ME (2000). "Transverse myelitis associated with probable cat-scratch disease in a previously healthy pediatric patient". Clin Infect Dis. 31 (2): 609–11. doi:10.1086/313986. PMID 10987731.
- ↑ Agmon-Levin N, Kivity S, Szyper-Kravitz M, Shoenfeld Y (2009). "Transverse myelitis and vaccines: a multi-analysis". Lupus. 18 (13): 1198–204. doi:10.1177/0961203309345730. PMID 19880568.
- ↑ Giobbia M, Carniato A, Scotton PG, Marchiori GC, Vaglia A (1999). "Cytomegalovirus-associated transverse myelitis in a non-immunocompromised patient". Infection. 27 (3): 228–30. doi:10.1007/bf02561538. PMID 10378139.
- ↑ Tippett DS, Fishman PS, Panitch HS (1991). "Relapsing transverse myelitis". Neurology. 41 (5): 703–6. doi:10.1212/wnl.41.5.703. PMID 2027486.
- ↑ Pandit L, Rao S (1996). "Recurrent myelitis". J Neurol Neurosurg Psychiatry. 60 (3): 336–8. doi:10.1136/jnnp.60.3.336. PMC 1073861. PMID 8609515.
- ↑ Bashir K, Whitaker JN (2000). "Importance of paraclinical and CSF studies in the diagnosis of MS in patients presenting with partial cervical transverse myelopathy and negative cranial MRI". Mult Scler. 6 (5): 312–6. doi:10.1177/135245850000600503. PMID 11064439.
- ↑ Kaplin AI, Deshpande DM, Scott E, Krishnan C, Carmen JS, Shats I; et al. (2005). "IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis". J Clin Invest. 115 (10): 2731–41. doi:10.1172/JCI25141. PMC 1224298. PMID 16184194.
- ↑ Borchers AT, Gershwin ME (2012). "Transverse myelitis". Autoimmun Rev. 11 (3): 231–48. doi:10.1016/j.autrev.2011.05.018. PMID 21621005.
- ↑ Tristano AG (2009). "[Autoimmune diseases associated with transverse myelitis. Review]". Invest Clin. 50 (2): 251–70. PMID 19662820.
- ↑ Cobo Calvo A, Mañé Martínez MA, Alentorn-Palau A, Bruna Escuer J, Romero Pinel L, Martínez-Yélamos S (2013). "Idiopathic acute transverse myelitis: outcome and conversion to multiple sclerosis in a large series". BMC Neurol. 13: 135. doi:10.1186/1471-2377-13-135. PMC 3856522. PMID 24090445.
- ↑ Krishnan C, Kaplin AI, Pardo CA, Kerr DA, Keswani SC (2006). "Demyelinating disorders: update on transverse myelitis". Curr Neurol Neurosci Rep. 6 (3): 236–43. doi:10.1007/s11910-006-0011-1. PMID 16635433.
- ↑ Mirich DR, Kucharczyk W, Keller MA, Deck J (1991). "Subacute necrotizing myelopathy: MR imaging in four pathologically proved cases". AJNR Am J Neuroradiol. 12 (6): 1077–83. PMID 1763730.