Optical coherence tomography assessment of disease activity in cryopyrin-associated periodic syndrome

E Mulazzani; L Böhm; T Christmann; M Krumbholz; T Kümpfel; J Havla

doi:10.1111/ene.16301

Optical coherence tomography assessment of disease activity in cryopyrin-associated periodic syndrome

Eur J Neurol. 2024 Apr 16:e16301. doi: 10.1111/ene.16301. Online ahead of print.

Authors

E Mulazzani¹, L Böhm¹, T Christmann¹, M Krumbholz^{2

3

4}, T Kümpfel¹, J Havla¹

Affiliations

¹ Institute of Clinical Neuroimmunology, LMU University Hospital, LMU Munich, Munich, Germany.
² Department of Neurology and Pain Treatment, Immanuel Klinik Rüdersdorf, University Hospital of the Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany.
³ Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany.
⁴ Department of Neurology and Stroke, University Hospital of Tübingen, Tübingen, Germany.

PMID: 38628041
DOI: 10.1111/ene.16301

Abstract

Background and purpose: Cryopyrin-associated periodic syndrome is a rare autoinflammatory disease caused by gain-of-function mutations or variants in the NLRP3 gene. Clinically, patients suffer from a broad spectrum of both systemic and neurological symptoms. The aim of this study was to determine whether systemic inflammation demonstrated by serum amyloid A (SAA) elevation is associated with neuroinflammation assessed by optical coherence tomography (OCT).

Methods: Thirty eyes of 15 patients with NLRP3 low penetrance mutations (PwNLRP3) and 20 eyes of 10 age- and sex-matched healthy controls were examined by spectral-domain OCT as part of routine clinical care. All retinal layers and clinical features were evaluated.

Results: At baseline no significant retinal neuroaxonal inflammation or degeneration was observed in all measured retinal layers amongst PwNLRP3 compared with healthy controls. In a pooled analysis of all individual OCT time points a significant difference regarding the macular retinal nerve fibre layer was detected. Increased levels of SAA showed a positive association with averaged combined outer plexiform layer and outer nuclear layer volumes (ρ < 0.0001, r² = 0.35).

Conclusion: In cryopyrin-associated periodic syndrome increased combined outer plexiform layer and outer nuclear layer volumes are mirrored by SAA increase, an acute phase reactant indicating systemic inflammation. Our findings identify OCT as a candidate biomarker to monitor subclinical neuroinflammation and to assess disease activity in PwNLRP3.

Keywords: NLRP3 variants; OCT; autoinflammation.