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- Varicella-zoster virus
- Herpes simplex Virus
- Epstein-Barr Virus
- Post-polio syndrome may represent decades after recovery from initial injury.
- Enterovirus D68: acute flaccid myelitis occurring following respiratory infection (2010s outbreaks)
- HTLV1 (tropical spastic paraparesis, see separate module for details)
- Hepatitis A
- Hepatitis C
- Hepatitis E
- Japanese encephalitis virus (and other arboviruses)
- Inflammation of spinal cord, often immune-mediated. Many cases are idiopathic; infectious driver uncommon but important to recognize.
- Often called transverse myelitis (TM) or interchangeable term, myelopathy.
- Need to define bilateral (not necessarily symmetrical) sensorimotor and autonomic spinal cord dysfunction.
- Acute disease defined as clinical deficits arising between 4h to 21d.
- May be related to infection, idiopathic or associated with existing inflammatory disease, e.g SLE, MS, Sjogren’s, sarcoid.
- Sx: leg weakness, sphincter dysfunction, abnormal DTRs [acutely may be absent, but hyperreflexia the rule].
- Sensory level helps distinguish from polio/Guillain-Barre (GB).
- Ddx: may be confused w/ acute inflammatory demyelinating polyradiculoneuropathy (AIDP) or GB. R/o compressive or vascular explanation, tropical spastic paraparesis (HTLV-I) or vacuolar myelopathy (HIV).
- Dx: MRI with contrast.
- If complete transverse myelitis, obtain neuromyelitis optica (NMO)–immunoglobulin G (IgG) antibodies to assist in determining cause. For complete non-infectious disease recommendations see reference.
- Presence of NMO-IgG antibodies (aquaporin-4–specific antibodies) should be considered useful in determining increased TM recurrence risk.
- Review pathogen list and consider ordering appropriate blood, CSF tests based on risk profile, geography.
- Perform LP including VDRL, AFB and fungal cxs, PCR (HSV, VZV, CMV, EBV, enteroviral).
- Serology: HIV, RPR, HTLV1. Consider polio, West Nile virus, Hepatitis C, Bartonella henselae and others if exposure risks exist.
- Schistosoma: leading parasitic explanation, obtain serology or CSF/ stool O&P if exposure hx exists.
- Transverse Myelitis Consortium Working Group (TMCWG) proposed diagnostic criteria for idiopathic ATM. Patients meeting all diagnostic criteria are considered to have definite idiopathic ATM, whereas those who do not meet the MRI or CSF criteria for inflammation have possible idiopathic ATM.
- Clinical: bilateral sensory, motor, or autonomic dysfunction due to spinal cord process with a clearly defined sensory level that progresses to the nadir over 4 to 21 days from onset.
- MRI used to eliminate structural causes.
- MRI evidence of gadolinium enhancement within the cord.
- CSF findings of pleocytosis or immunoglobulin G (IgG) index elevation.
- Consult w/ neurology. Usual ID consult question is to r/o infectious etiology.
- Cases may be para-infectious, but many idiopathic.
- Idiopathic/inflammatory TM may be treated with steroids, plasma exchange, cyclophosphamide.
- Neurosarcoidsis: myelitis may be part of spectrum of infection.
- If infection diagnosed, consider therapy for specific agent (see specific Pathogen modules). Corticosteroids often considered helping quell inflammation.
- See pathogen-specific module for detailed therapy.
- Common infectious etiologies listed in common pathogen section. Pathogen-specific therapy for some common etiologies listed below.
- Polio may be similar to TM w/ flaccid paralysis, but lack sensory findings.
- Most cases idiopathic or inflammatory; however, need to rule-out infectious etiology, HIV or HTLV1 associated process.
- CSF examination and PCR for viruses helpful. Occasionally, serologies helpful (EBV, schistosomiasis, CMV, HTLV1). Obtain HIV EIA.
- CMV-related myelitis (or radiculopathy) in HIV often associated w/ impressive neutrophilic CSF pleocytosis. Strong consideration should be made to initiating HAART in all HIV CMV myelitis cases.
Pathogen Specific Therapy
Acyclovir 10mg/kg IV q8h x 7d (longer if immune compromised) + prednisone 60-80mg PO qday x 3-5d
Acyclovir 10mg/kg IV q8h x 7d (longer if immune compromised) + prednisone 60-80mg PO qday x 3-5d
Praziquantel 60mg/kg divided in 3 doses x 1 d + steroids (prednisone 60-80mg qday then taper over 6 mos--no uniform guidelines, controversial)
Ceftriaxone 1-2g IV q24h x 28d
Basis for recommendation
- Mihai C, Jubelt B. Infectious myelitis. Curr Neurol Neurosci Rep. 2012;12(6):633-41. [PMID:22927022]
Comment: Helpful review that describes the myelitis universe, but focus on infections which is helpful for the ID consultant.
- Dalton HR, Kamar N, van Eijk JJ, et al. Hepatitis E virus and neurological injury. Nat Rev Neurol. 2016;12(2):77-85. [PMID:26711839]
Comment: HEV has been increasingly described as causing neurologic injury including myelitis as well as Guillian-Barre and encephalitis as well.
- Garg RK, Malhotra HS, Gupta R. Spinal cord involvement in tuberculous meningitis. Spinal Cord. 2015;53(9):649-57. [PMID:25896347]
Comment: Spinal involvement can be seen with tuberculous radiculomyelitis, tuberculoma, myelitis, syringomyelia, vertebral bony infection and very rarely spinal tuberculous abscess. High cerebrospinal fluid protein content is often a risk factor for arachnoiditis. The most important differential diagnosis of tuberculous arachnoiditis is meningeal carcinomatosis.
- Bagnato F, Stern BJ. Neurosarcoidosis: diagnosis, therapy and biomarkers. Expert Rev Neurother. 2015;15(5):533-48. [PMID:25936846]
Comment: Sarcoid can present ~10% of the time with neurological s/s. Myelits is not uncommon along with leptomeningeal enhancement, granulmantous inflammation in brain parenchyma.
- Arslan F, Yilmaz M, Paksoy Y, et al. Cytomegalovirus-associated transverse myelitis: a review of nine well-documented cases. Infect Dis (Lond). 2015;47(1):7-12. [PMID:25390688]
Comment: Review of 12 cases in world literature.
- Verma R, Sahu R, Holla V. Neurological manifestations of dengue infection: a review. J Neurol Sci. 2014;346(1-2):26-34. [PMID:25220113]
Comment: Myelitis along with encephalitis, myelitis, Guillain-Barré syndrome (GBS) and mononeuropathies may be a consequence of Dengue and increasingly recognized.
- Scott TF, Frohman EM, De Seze J, et al. Evidence-based guideline: clinical evaluation and treatment of transverse myelitis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011;77(24):2128-34. [PMID:22156988]
Comment: Evaluation of complete or partial TM with suggestions to obtain antibodies for neuromyelitis optica (NMO)–immunoglobulin G (IgG) antibodies in patients presenting with clinical acute complete transverse myelitis (ACTM) features. The presence of NMO-IgG antibodies (aquaporin-4–specific antibodies) should be considered useful in determining increased TM recurrence risk. Guideline does does not address infectious drivers.
- Bigi S, Aebi C, Nauer C, et al. Acute transverse myelitis in Lyme neuroborreliosis. Infection. 2010;38(5):413-6. [PMID:20505978]
Comment: Report of ATM in a boy of 12 from Europe. This is a rare problem due to Lyme disease. Report also highlights that the CSF/blood index may be negative early in infection, although authors do point out that recent EBV may have been a contributing cause or factor.
- Rafailidis PI, Mourtzoukou EG, Varbobitis IC, et al. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. Virol J. 2008;5:47. [PMID:18371229]
Comment: Review of 290 pts in 89 articles notes that both the GI and CNS are the most common sites of active infection--including transverse myelitis.
- Baylor P, Garoufi A, Karpathios T, et al. Transverse myelitis in 2 patients with Bartonella henselae infection (cat scratch disease). Clin Infect Dis. 2007;45(4):e42-5. [PMID:17638185]
Comment: Cases described in an adolescent and a 46-year old adult. Six cases previously described in the literature. Mechanism unclear as is the case with the much more common Bartonella encephalitis/encephalopathy occuring in acute infection.
- van Baalen A, Muhle H, Straube T, et al. Nonparalytic poliomyelitis in Lyme borreliosis. Arch Dis Child. 2006;91(8):660. [PMID:16861483]
Comment: Case study with images. Pt with Garin-Bujadoux-Bannwarth syndrome and myelitis with strong serological responses to Borrelia. Symptoms resolved with two weeks of cefotaxime therapy.
- de Seze J, Lanctin C, Lebrun C, et al. Idiopathic acute transverse myelitis: application of the recent diagnostic criteria. Neurology. 2005;65(12):1950-3. [PMID:16380618]
Comment: With improved diagnostic techniques including PCR, the number of "idiopathic" cases may be decreasing compared to historical series. This study of 288 patients identified 15.6% as idiopathic.
- Gilden D. Varicella zoster virus and central nervous system syndromes. Herpes. 2004;11 Suppl 2:89A-94A. [PMID:15319095]
Comment: Author reviews The International Herpes Management Forum guidelines suggesting use of CSF PCR for VZV + in highly suspect cases, CSF VZV-specific antibody. Therapy should entail both acyclovir parenterally and corticosteroids to smother inflammation.
- Transverse Myelitis Consortium Working Group. Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology. 2002;59(4):499-505. [PMID:12236201]
Comment: Expert opinion basis for diagnosing idiopathic transverse myelitis.
- Di Rocco A. Diseases of the spinal cord in human immunodeficiency virus infection. Semin Neurol. 1999;19(2):151-5. [PMID:10718535]
Comment: Reasonable review of processes in HIV setting. Vacuolar myelopathy is the most common condition. Vacuolar myelopathy presents usually with slowly progressing spastic paraparesis, accompanied by loss of vibratory and position sense and urinary frequency and urgency (and erectile dysfunction in men). There are other rarer causes of spinal cord disease in AIDS, including a number of infectious myelitis and neoplastic and vascular myelopathies.
- Jeffery DR, Mandler RN, Davis LE. Transverse myelitis. Retrospective analysis of 33 cases, with differentiation of cases associated with multiple sclerosis and parainfectious events. Arch Neurol. 1993;50(5):532-5. [PMID:8489410]
Comment: Small series with 45% of cases categorized as parainfectious, 21% associated with multiple sclerosis, 12% as associated with spinal cord ischemia, and 21% as idiopathic.
- Haribhai HC, Bhigjee AI, Bill PL, et al. Spinal cord schistosomiasis. A clinical, laboratory and radiological study, with a note on therapeutic aspects. Brain. 1991;114 ( Pt 2):709-26. [PMID:2043944]
Comment: All 13 pts had positive schistosomal blood serology. Eight cases improved with either praziquantel, steroids or surgery.
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