Advertisement

Ischemic stroke is a potential complication of uncontrolled inflammation in mevalonate kinase deficiency – A case report

  • Justine Blais
    Affiliations
    Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Canada
    Search for articles by this author
  • Didier Bonneville-Roussy
    Affiliations
    Neurovascular Programme, Division of Neurology, Department of Medicine, Hôpital du Sacré-Coeur de Montréal, 5400 Gouin O. Montreal Québec H4J 1C5, Canada
    Search for articles by this author
  • Hannah Laure Elfassy
    Affiliations
    Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Canada

    Division of Allergy and Immunology, Department of Medicine, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
    Search for articles by this author
  • Sylvain Lanthier
    Correspondence
    Corresponding author: Hôpital du Sacré-Cœur de Montréal, Division of Neurology (Suite C-5075), 5400 Gouin O. Montreal Québec H4J 1C5, Canada.
    Affiliations
    Neurovascular Programme, Division of Neurology, Department of Medicine, Hôpital du Sacré-Coeur de Montréal, 5400 Gouin O. Montreal Québec H4J 1C5, Canada

    Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Canada
    Search for articles by this author

      Highlights

      • Classification criteria help diagnose mevalonate kinase deficiency.
      • Ischemic stroke is a potential complication of mevalonate kinase deficiency.
      • Anti-interleukin-1 therapy prevents recurrent autoinflammatory attacks.

      Abstract

      Objectives

      Mevalonate kinase deficiency (MKD) is an autosomal recessive autoinflammatory disease characterized by recurrent systemic inflammation attacks. Despite interconnections with inflammation, thrombosis is rare or underreported in MKD. Our goal is to report evidence of uncontrolled inflammation as the cause of ischemic stroke.

      Materials and Methods

      Case report.

      Results

      A 39-year-old French-Canadian patient consulted for stroke. He reported a previous diagnosis of familial Mediterranean fever and hospitalizations nearly monthly since birth for recurrent inflammatory attacks despite colchicine prophylaxis. Attacks were triggered by infections or stress, lasted 3-7 days, and included fever up to 41°C, painful lymphadenopathies, abdominal pain, polyarthralgia and maculopapular rash. Stroke culminated his most recent inflammatory attack. Brain MRI confirmed an acute infarct, without chronic ischemic damage. Blood tests documented increased C-reactive protein, amyloid A and immunoglobulin-D. Prothrombotic and autoantibody tests, cervicocephalic CT-angiography, echocardiography, cardiac monitoring, and toxic screen were unremarkable. Infections were excluded. His only sister had similar attacks. In both cases, sequencing of 32 autoinflammatory-associated genes identified two pathogenic mevalonate kinase mutations. Their non-consanguineous parents, half-brother and four children were asymptomatic. Following treatment with anti-interleukin-1beta monoclonal antibodies, he no longer had inflammatory attacks or stroke in >4 years.

      Conclusion

      This MKD patient experienced an ischemic stroke during an attack, attributed to uncontrolled inflammation. Investigations excluded other stroke etiologies. Recurrent febrile attacks starting before age 1 and lasting >3 days, gastrointestinal symptoms, painful lymphadenopathies, maculopapular rash, triggers, aphthous stomatitis, non-Mediterranean ancestry, and ineffectiveness of colchicine prophylaxis are consistent with MKD. Anti-interleukin-1 therapy prevents recurrent autoinflammatory attacks.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Stroke and Cerebrovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Di Donato G
        • d'Angelo DM
        • Breda L
        • et al.
        Monogenic autoinflammatory diseases: state of the art and future perspectives.
        Int J Mol Sci. 2021; 22: 6360https://doi.org/10.3390/ijms22126360
        • Elhani I
        • Hentgen V.
        • Grateau G
        • Georgin-Lavialle S.
        Neurological manifestations in mevalonate kinase deficiency: a systematic review.
        Mol Genet Metab. 2022; 136: 85-93https://doi.org/10.1016/j.ymgme.2022.04.006
        • La Regina M
        • Orlandini F
        • Manna R
        Autoinflammatory diseases: a possible cause of thrombosis?.
        Thromb J. 2015; 13: 19https://doi.org/10.1186/s12959-015-0049-x
        • Simon A.
        • Kremer HPH
        • Wevers RA
        • et al.
        Mevalonate kinase deficiency: evidence for a phenotypic continuum.
        Neurology. 2004; 62: 994-997https://doi.org/10.1212/01.WNL.0000115390.33405.F7
        • Gattorno M
        • Hofer M
        • Federici S
        • et al.
        Classification criteria for autoinflammatory recurrent fevers.
        Ann Rheum Dis. 2019; 78: 1025-1032https://doi.org/10.1136/annrheumdis-2019-215048
        • ter Haar NM
        • Jeyaratnam J
        • Lachmann HJ
        • et al.
        The phenotype and genotype of mevalonate kinase deficiency: a series of 114 cases from the Eurofever Registry.
        Arthritis Rheumatol. 2016; 68: 2795-2805https://doi.org/10.1002/art.39763
        • Boursier C
        • Rittore C
        • Milhavet F
        • et al.
        Mevalonate kinase-associated diseases: hunting for phenotype–genotype correlation.
        J Clin Med. 2021; 10: 1552https://doi.org/10.3390/jcm10081552
        • De Benedetti F
        • Gattorno M
        • Anton J
        • et al.
        Canakinumab for the treatment of autoinflammatory recurrent fever syndromes.
        N Engl J Med. 2018; 378: 1908-1919https://doi.org/10.1056/NEJMoa1706314
        • Hansmann S
        • Lainka E
        • Horneff G
        • et al.
        Consensus protocols for the diagnosis and management of the hereditary autoinflammatory syndromes CAPS, TRAPS and MKD/HIDS: a German PRO-KIND initiative.
        Pediatr Rheumatol Online J. 2020; 18: 17https://doi.org/10.1186/s12969-020-0409-3