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Progressive Large Vessel CNS Vasculitis

P-cPACNS

Progressive large vessel CNS vasculitis (P-cPACNS) is a subtype of primary CNS vasculitis that affects medium-large blood vessels. This subtype often presents as acute ischemic stroke plus diffuse deficits such as cognitive decline, behaviour changes and concentration difficulties. Children with progressive cPACNS often present with proximal and distal vessel segment stenoses on angiography and/or acquire new inflammatory vascular stenoses over time if untreated. 

The following is a list of clinical features, laboratory features, imaging features, and treatment methods associated with P-cPACNS. This is intended for physicians. Parents and family members of suspected children may discuss the following with their physicians.

1. Clinical features:

  • Children with P-cPACNS commonly present with both focal and diffuse neurological deficits. The onset may be acute , subacute or chronic over weeks and months. Children typically develop stroke-like neurological deficits including hemiparesis and/or hemisensory loss. In addition diffuse neurological deficits may be present including headache, cognitive dysfunction, school difficulties and behavioural abnormality. Some children may present with psychiatric symptoms such as hallucinations. Symptoms may wax and wane and are therefore often difficult to capture.
  • Seizures and constitutional symptoms (such as fever, fatigue, malaise, decreased energy, and weight loss) are less commonly present in children with cPACNS.

2. Laboratory tests:

  • Serum markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulin G (IgG) are commonly found to be mildly elevated. Children may have abnormalities in their complete blood counts or differential. Elevated platelet and raised white blood count can be found. 
  • 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 P-cPACNS children.
  • CSF analysis frequently shows mild pleocytosis, raised protein concentrations, and/or raised opening pressure.

3. Neuroimaging and Angiography:

  • Magnetic Resonance Imaging (MRI) is the preferred imaging modality of P-cPACNS. Computed tomography (CT) is not sensitive enough to detect inflammatory lesions, however ischemic lesions may be detected.  MRI may show unilateral or bilateral inflammatory and ischemic lesions in large-vessel territories.
  • Vascular imaging is crucial. Magnetic resonance angiography (MRA) commonly demonstrates proximal and distal vessel segment stenoses in more than one territory. MRA cerebral vessel wall imaging with gadolinium enhancement should be considered. Evidence of wall thickening, edema and contrast wall enhancement can support active wall inflammation. Conventional angiography (CA) may also be required to detect arterial abnormalities in children with suspected cPACNS. 
  • The angiographic diagnosis of  P-cPACNS is made based on either 1) proximal and distal vessel segment stenoses of ≥ one vascular territory on initial angiography ideally supported by contrast wall enhancement or 2) evidence of new inflammatory vascular stenoses at 3 months in children previously diagnosed with NP-cPACNS.  
angiography positive vasculitis image

Figure 1:

(A) Magnetic resonance imaging (MRI) of a 16-year-old patient with P-cPACNS at diagnosis. The arrows point to bilateral proximal vessel stenoses of the middle carotid artery. (B) The corresponding Conventional Angiography (CA) shows proximal (arrow) and distal (open circle) vessel stenoses.
Taken from: Benseler et al., 2006. 

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

4. Treatment:

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

1. Induction Phase (6 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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