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Primary CNS Vasculitis of Childhood Workup

  • Author: Jefferson R Roberts, MD; Chief Editor: Lawrence K Jung, MD  more...
 
Updated: Jul 06, 2016
 

Laboratory Studies

The goal of the workup in patients with suspected primary CNS vasculitis of childhood should be to rule out other causes of secondary CNS vasculitis and to look for markers of inflammation. Inflammatory changes in the blood are often not present; however, this does not exclude the diagnosis. If the clinical suspicion is high, investigation beyond simple laboratory tests is still indicated.

  • CBC count and differential may reveal mild anemia and elevated WBC count. [9, 16]
  • Erythrocyte sedimentation rate, C-reactive protein levels, and von Willebrand factor antigen levels may be elevated. [9, 16] Nonspecific markers of inflammation may also include elevated complement and immunoglobulin levels.
  • Creatinine and BUN levels should be measured and urine microscopy should be performed to rule out evidence of systemic inflammatory disease that involves the kidney.
  • No specific autoantibody pattern has been identified in isolated CNS vasculitis. However, autoantibody testing should be considered to investigate for underlying connective tissue or systemic vasculitic disease.
  • Infectious and prothrombophilic studies may be indicated to rule out CNS vasculitis secondary to infection or thromboembolic stroke unrelated to inflammatory brain disease. The role of anticardiolipin and lupus anticoagulant have not yet been elucidated in primary CNS vasculitis.
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Imaging Studies

Brain imaging is a crucial stage in investigation of suspected isolated CNS vasculitis. Brain MRI is the first step. MRI sequences in investigation of CNS vasculitis should include the following:

  • Sagittal T1
  • Axial T2, fluid-attenuated inversion recovery (FLAIR), which may reveal areas of signal hyperintensity in both large-medium and small vessel disease
  • Diffusion weighted imaging (DWI), which can identify areas of ischemia in large-medium vessel disease
  • Coronal T2
  • Magnetic resonance angiography to delineate large-medium vessel abnormalities
  • Magnetic resonance venography
  • Postcontrast axial 3-dimensional spoiled gradient recalled (SPGR) and coronal T1 spin echo (T1SE) to reveal abnormal enhancement (if abnormalities are identified on the sequences mentioned above and no contraindications to contrast are noted)

Postcontrast techniques to evaluate vessel wall inflammation are currently under investigation and may prove to be of significant use in identifying active vascular inflammation in large-medium vessel disease.

Conventional angiography is performed in most children with large-medium vessel disease to confirm and further delineate abnormalities seen on magnetic resonance angiography. Conventional angiography may be more sensitive than magnetic resonance angiography in identifying distal lesions that affect small caliber vessels. In patients with suspected small vessel disease, angiography is performed to confirm that no demonstrable large-medium vessel abnormalities are present. By definition, small vessel disease has negative angiography findings.

In large-medium vessel disease, brain MRI classically reveals areas of acute ischemia in a vascular distribution.[17] These lesions may be unilateral in nonprogressive disease and are typically multifocal in progressive disease.[8] They may involve gray and white matter. Magnetic resonance angiography and conventional angiography provide detailed assessment of the vasculature and characteristically reveal beading, tortuosity, stenosis, and occlusion of the vessels.[18]

In small vessel disease, brain MRI reveals lesions that may be bilateral or unilateral, multifocal, and involve both gray and white matter.[9] Unlike the lesions seen in large-medium vessel disease, these lesions do not usually conform to a vascular distribution. Meningeal enhancement can be seen, which may help differentiate this condition from other inflammatory brain diseases such as multiple sclerosis. As mentioned above, by definition, conventional angiography findings are negative.

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Other Tests

Lumbar puncture is an essential part of the diagnostic workup. The results often reveal elevated opening pressure, mildly elevated white cell count, and elevated protein.[8, 15] However, as with serum markers of inflammation, the findings may be within the reference range.

Assessment by an ophthalmologist to look for retinal vasculitis, signs of underlying infection, or signs of other inflammatory disease is important.

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Procedures

Brain biopsy for confirmation of the diagnosis of CNS vasculitis in the case of negative conventional angiography findings has been a useful tool and should be considered in all suspected cases of small vessel disease.[19] Performing a biopsy of a lesion seen on neuroimaging, with tissue samples that capture the leptomeninges, cortex, and white matter, is preferable. Nonlesional biopsy should be considered when the clinical suspicion is high and the lesions identified on imaging are not easily accessible.

Ideally, a biopsy of a peripheral lesion identified on MRI should be performed prior to or at the onset of treatment with corticosteroids. A prolonged course of steroids decreases the sensitivity of the biopsy findings and can lead to indeterminate histology.

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Histologic Findings

A brain biopsy is typically performed to aid in the diagnosis of CNS vasculitis with negative angiography findings, as opposed to large-medium vessel disease, in which confirmation is made using imaging modalities. The biopsy findings characteristically reveal segmental, nongranulomatous, intramural infiltration of arteries, arterioles, capillaries, or venules.[9, 15]

The predominant inflammatory cells involved are T cells. Calcification and pallor of myelin staining may also be observed in the surrounding tissue. Gliosis can be seen in long-standing disease.

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Contributor Information and Disclosures
Author

Jefferson R Roberts, MD Chief of Rheumatology Service, Tripler Army Medical Center; Assistant Clinical Professor of Medicine, Uniformed Services University of the Health Sciences

Jefferson R Roberts, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Society for Simulation in Healthcare

Disclosure: Nothing to disclose.

Coauthor(s)

Phalgoon A Shah, MD Resident Physician, Department of Medicine, Tripler Army Medical Center

Phalgoon A Shah, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

 

Disclosure: Nothing to disclose.

James J Kim, MD Resident Physician, Department of Internal Medicine, Tripler Army Medical Center

James J Kim, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Lawrence K Jung, MD Chief, Division of Pediatric Rheumatology, Children's National Medical Center

Lawrence K Jung, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Rheumatology, Clinical Immunology Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Jayant Deodhar, MD Associate Professor in Pediatrics, BJ Medical College, India; Honorary Consultant, Departments of Pediatrics and Neonatology, King Edward Memorial Hospital, India

Disclosure: Nothing to disclose.

Clare M Hutchinson, MD Lecturer, Part-Time Faculty, Department of Pediatrics, University of Toronto Faculty of Medicine; Pediatrician, Pediatric Education Co-Lead, Department of Child and Teen Health, North York General Hospital, Canada

Disclosure: Nothing to disclose.

Susanne Maria Benseler, MD Pediatric Rheumatologist, Section Chief, Alberta Children's Hospital; Associate Professor, Department of Pediatrics, University of Calgary Faculty of Medicine, Canada

Disclosure: Nothing to disclose.

Acknowledgements

The authors thank Jorina Elbers, William Halliday, Suzanne Laughlin, Helen Branson, Harvey Lim, Robyn Westmacott, and Derek Armstrong for their significant contributions.

References
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  10. Saini AG, Sankhyan N, Bhattad S, Vyas S, Saikia B, Singhi P. CNS vasculitis and stroke in neonatal lupus erythematosus: A case report and review of literature. Eur J Paediatr Neurol. 2014 Jan 25. [Medline].

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  12. [Guideline] Riviello JJ Jr, Ashwal S, Hirtz D, et al. Practice parameter: diagnostic assessment of the child with status epilepticus (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2006 Nov 14. 67(9):1542-50. [Medline].

  13. Hutchinson C, Elbers J, Halliday W, Branson H, Laughlin S, Armstrong D, et al. Treatment of small vessel primary CNS vasculitis in children: an open-label cohort study. Lancet Neurol. 2010 Nov. 9(11):1078-84. [Medline].

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  17. Aviv RI, Benseler SM, Silverman ED, et al. MR imaging and angiography of primary CNS vasculitis of childhood. AJNR Am J Neuroradiol. 2006 Jan. 27(1):192-9. [Medline].

  18. Aviv RI, Benseler SM, DeVeber G, et al. Angiography of primary central nervous system angiitis of childhood: conventional angiography versus magnetic resonance angiography at presentation. AJNR Am J Neuroradiol. 2007 Jan. 28(1):9-15. [Medline].

  19. Torres J, Loomis C, Cucchiara B, Smith M, Messé S. Diagnostic Yield and Safety of Brain Biopsy for Suspected Primary Central Nervous System Angiitis. Stroke. 2016 Jun 28. [Medline].

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