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Small Vessel CNS Vasculitis

Small vessel CNS Vasculitis (SV-cPACNS) is a subtype of primary CNS vasculitis that affects small blood vessels. It is by definition angiography-negative and is diagnosed by brain biopsy. It has two subtypes:

    1. Small-vessel CNS arteritis predominantly affects the arteries.
    2. Small-vessel CNS venulitis solely affects cerebral veins and venules.
      It appears to have a slowly progressing disease course and is frequently diagnosed with significant delay.

The following is a list of clinical features, laboratory features, imaging features, and treatment methods associated with small-vessel CNS arteritis. This is intended for physicians. Parents and family members of suspected children may print the following and discuss with your physicians.

1. Clinical features:

  • Children with SV-cPACNS present with predominantly diffuse neurological deficits, such as behaviour/mood changes, cognitive decline, worsening school performance, and decreased level of consciousness. 
  • SV-cPACNS children typically report headaches and seizures (including status epilepticus).  
  • SV-cPACNS children may also experience focal neurological deficits (hemiplegia, aphasia, and facial droop), optic neuritis, and myelitis. Constitutional symptoms, such as fever, fatigue, and malaise, have also been reported. 
  • It should be emphasized that previously healthy children can have a sudden onset of the above-mentioned neurological deficits, or these clinical features may evolve slowly and fluctuate over weeks to months.

2. Laboratory tests:

  • Serum markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and C3 complement are commonly elevated. 
  • von-Willebrand-factor antigen, a glycoprotein present in blood serum produced by endothelial cells, may be an additional marker of disease activity. von-Willebrand-factor antigen is commonly found to be elevated in SV-cPACNS children.
  • CSF analysis may show mild pleocytosis, raised CSF protein, and/or raised opening pressure. 
  • Oligoclonal banding may be present in one quarter to one third of the children with SV-cPACNS. 

3. Neuroimaging/Brain biopsy:

  • Magnetic resonance imaging (MRI) is crucial in the diagnosis of SV-cPACNS because it helps to identify the area of the brain to be biopsied. MRI scans commonly reveal MRI multifocal lesions that are not restricted to a large-vessel vascular territory.
  • Conventional angiography and/or magnetic resonance angiography (MRA) is, by definition, normal in children with SV-cPACNS. Angiography is unable to detect abnormalities in small-sized cerebral vessels.
  • Brain biopsy is required for a definitive diagnosis of SV-cPACNS. Lesional biopsy is preferred if lesion identified on MRI is accessible, if not available a non-lesional biopsy can be performed. Non-lesional biopsies are taken from the non-dominant parieto-frontal lobe.
  • The histology of brain biopsy in SV-cPACNS typically reveals a lymphocytic, non-granulomatous vasculitis with a predominant intramural and perivascular T-cell infiltrate of the small muscular arteries, arterioles, capillaries and venules.

*For diagnostic workup, please visit Diagnosing CNS Vasculitis and IBrainD. For diagnostic algorithm, please visit Diagnostic Algorithm for CNS Vasculitis

 

angiography negative vasculitis image

 

 

Figure 1:

MRI of a patient with SV-cPACNS. (A) MRI at diagnosis shows lesion in the frontal lobe, involving both gray and white matter. (B) MRI prior to initiation of treatment; there is extension of frontal lesions and new parietal lesions. (C) MRI at six months after therapy, showing regression of frontal and parietal lesions.
Source: Benseler et al, 2005.

4. Treatment:

Many institutions have adopted the SickKids SV-cPACNS treatment protocol, which consists of a six-month induction and 18-month maintenance phase. 

1. Induction Phase (six months)

Children with P-cPACNS commonly receive three to seven days of IV methyl-prednisolone pulse followed by oral prednisone with a slow monthly taper. IV pulse cyclophosphamide therapy is given monthly for seven doses (six months). 

2. Maintenance Phase (18 months)

After completion of the cyclophosphamide therapy, either mycophenolate mofetil (MMF), Mycophenolic acid (Myfortic), or less commonly azathioprine (AZA) is started along with oral prednisone.

  • The exact treatment protocol for children with progressive cPACNS is constantly evaluated.

 *For suggested Treatment Protocol, please visit Treatment for CNS Vasculitis and IBrainD.

References >

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