PACNS – clinical perspective and first international multidisciplinary guidelines on it

In the last week of October ESO prepared a webinar about changes in the guidelines of the rare vascular disease, a primary angiitis of the central nervous system (PACNS). Dr. Neil Scolding and Prof. Marialuisa Luisa Zedde introduced to us a new ESO guideline on PACNS, where details of diagnostics and therapy were covered.

The term PACNS unifies a group of clinicopathological presentations of vasculitis affecting the vessels of the brain and spinal cord without any overt systemic vasculitis or underlying potential cause (1). Typical clinical features of PACNS may include: confusion and encephalopathy, seizure, headache and strokes. But the features are not always coming together and the disease’s course still remains under-recognized and over-diagnosed, as Prof. Scolding underlined.

Pathophysiologhically PACNS starts from the infiltration of immune cells within CNS blood vessel walls, which leads to destruction and thickening of the vessel walls, stenosis of alternating segments, hence, leading to poor blood circulation. Weakening of vessel walls can lead to its rupture, and hence, to intracranial hemorrhage (2). The gold standard for the PACNS diagnostics is brain biopsy, where inflammation affecting both small and large vessels of the CNS and the blood vessels supplying the brain parenchyma, spinal cord and leptomeninges, and less frequently veins and venules was described (1,2).

ESO recommends (3) using the CSF for the PACNS diagnostics, but the CSF examination should not be limited to determination of the cell count and protein concentration and normal CSF analyses cannot exclude the diagnosis of the PACNS. In PACNS stroke MRI helps to detect infarcts in multiple vascular territories, but according to ESO Guidelines, the presence of leptomeningeal enhancement is not a specific neuroimaging sign (3).

Regarding neuroimaging, ESO experts suggest that digital subtraction angiography (DSA) could be non inferior to magnet-resonance angiography (MRA) if multislice (>128) technique is employed and DSA should be performed if MRA is normal.

As any other vasculitis, PACNS should be treated with glucocorticoid therapy. But what about immunosuppressants? Taking into account that the course of the PACNS is unpredictable and may lead to severe disability ESO experts suggest consideration of adding an immunosuppressant to glucocorticoid therapy in most patients with PACNS (3).

As cytostatics, ESO recommends to use cyclophosphamide per os or iv or mycophenolate mofetil in the induction phase in conjunction with glucocorticoids. Mycophenolate mofetil should be considered for maintenance therapy to reduce the toxicity of long-term treatment with cyclophosphamide and maintenance therapy should be initiated when no recurrent event happened after the induction therapy.

What about antiplatelets? Aspirin is considered to be used in PACNS stroke patients with large/medium vessel occlusion. Its combined antithrombotic and anti-inflammatory effect and its possible complementary action with glucocorticoid therapy may be beneficial.

Thrombolytic therapy for all vessel size occlusion and thrombectomy for large vessel occlusion in absence of contraindications is recommended in ischemic strokes in patients with PACNS.

Concluding, here is the PACNS patient portrait: a young patient with stroke, lacking cerebrovascular risk factors, who is in the fourth decade of his life, who developed confusion not explained by infection or other factors, unexplainable headache and MRI showed multiple ischemic zones.

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References:

1. Pagnoux C. et al. Primary Angiitis of the Central Nervous System: Description of the First Fifty-Two Adults Enrolled in the French Cohort of Patients With Primary Vasculitis of the Central Nervous System https://acrjournals.onlinelibrary.wiley.com/doi/abs/10.1002/art.38340
2. Giannini, C., Salvarani, C., Hunder, G. et al. Primary central nervous system vasculitis: pathology and mechanisms. Acta Neuropathol 123, 759–772 (2012). https://doi.org/10.1007/s00401-012-0973-9
3. Pascarella R, Antonenko K, Boulouis G, De Boysson H, Giannini C, Heldner MR, Kargiotis O, Nguyen TN, Rice CM, Salvarani C, Schmidt-Pogoda A, Strbian D, Hussain S, Zedde M. European Stroke Organisation (ESO) guidelines on Primary Angiitis of the Central Nervous System (PACNS). Eur Stroke J. 2023 Oct 30:23969873231190431. doi: 10.1177/23969873231190431. Epub ahead of print. PMID: 37903069. https://pubmed.ncbi.nlm.nih.gov/37903069/