Unilateral Primary Angiitis of the Central Nervous System

Annals of NeurologyVolume 90, Issue 6 p. 999-1000 Neuro-ImagesFree Access Unilateral Primary Angiitis of the Central Nervous System Brendan Santyr MD, Brendan Santyr MD Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, ON, CanadaSearch for more papers by this authorShervin Pejhan MD, Shervin Pejhan MD Department of Pathology and Laboratory Medicine, London Health Sciences Centre, Western University, London, ON, CanadaSearch for more papers by this authorQi Zhang MBBS, PhD, Qi Zhang MBBS, PhD Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, ON, Canada Department of Pathology and Laboratory Medicine, London Health Sciences Centre, Western University, London, ON, CanadaSearch for more papers by this authorAdrian Budhram MD, Corresponding Author Adrian Budhram MD adrian.budhram@lhsc.on.ca orcid.org/0000-0003-4860-0470 Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, ON, Canada Department of Pathology and Laboratory Medicine, London Health Sciences Centre, Western University, London, ON, Canada Address correspondence to E-mail: adrian.budhram@lhsc.on.caSearch for more papers by this author Brendan Santyr MD, Brendan Santyr MD Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, ON, CanadaSearch for more papers by this authorShervin Pejhan MD, Shervin Pejhan MD Department of Pathology and Laboratory Medicine, London Health Sciences Centre, Western University, London, ON, CanadaSearch for more papers by this authorQi Zhang MBBS, PhD, Qi Zhang MBBS, PhD Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, ON, Canada Department of Pathology and Laboratory Medicine, London Health Sciences Centre, Western University, London, ON, CanadaSearch for more papers by this authorAdrian Budhram MD, Corresponding Author Adrian Budhram MD adrian.budhram@lhsc.on.ca orcid.org/0000-0003-4860-0470 Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, ON, Canada Department of Pathology and Laboratory Medicine, London Health Sciences Centre, Western University, London, ON, Canada Address correspondence to E-mail: adrian.budhram@lhsc.on.caSearch for more papers by this author First published: 28 September 2021 https://doi.org/10.1002/ana.26234 The authors have not published, posted, or submitted any part of this manuscript elsewhere. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat A 28-year-old, otherwise healthy female was referred to the neurology clinic after having 3 generalized tonic–clonic seizures over 3 days. Neurologic and general medical examinations were unremarkable. Brain magnetic resonance imaging (MRI) revealed multifocal T2-fluid-attenuated inversion recovery (FLAIR) hyperintense cortical/juxtacortical lesions confined to the left cerebral hemisphere (Fig. 1A, arrows), with enhancement of several lesions on T1-weighted postgadolinium imaging (see Fig. 1B, arrows). Brain magnetic resonance angiography that included vessel wall imaging was unremarkable. Blood work was remarkable only for mildly elevated C-reactive protein of 12.0mg/l (normal <5.0mg/l). Infectious serologies, including human immunodeficiency virus, syphilis, and Lyme disease, were negative. Rheumatologic testing, including antinuclear antibodies, antineutrophil cytoplasmic antibodies, and rheumatoid factor, were negative. Cerebrospinal fluid analysis revealed normal protein, glucose, and white blood cell count, no oligoclonal bands, and negative cytology. Comprehensive serum and cerebrospinal fluid neural antibody testing for autoimmune encephalitis, including myelin oligodendrocyte glycoprotein (MOG)-IgG, was negative. Whole-body positron emission tomography scan was negative for systemic malignancy or inflammatory disease. Brain biopsy was considered, but she was clinically well, and this was therefore deferred. FIGURE FIGUREOpen in figure viewerPowerPoint Neuroimaging and pathological findings in unilateral primary angiitis of the central nervous system. She was maintained on levetiracetam titrated up to 1,250mg p.o. b.i.d. for management of her seizures and monitored. Repeated brain MRIs over 1 year revealed waxing and waning of multifocal enhancing lesions confined to the left cerebral hemisphere, without development of lesions in the right cerebral hemisphere. She had no further generalized tonic–clonic seizures, but 1.5 years into her disease course she developed right leg weakness attributable to her left cerebral pathology that prompted brain biopsy for definitive diagnosis and institution of treatment. Left frontal brain biopsy that included superficial cortex and leptomeninges revealed multiple small vessels with transmural chronic inflammatory cell infiltrates (representative vessel shown in Fig. 1C). Immunostains revealed that the inflammatory cells consisted primarily of T lymphocytes, with a slight predominance of CD8+ T lymphocytes (see Fig. 1D) compared with CD4+ T lymphocytes (see Fig. 1E). Only sparse CD20+ B lymphocytes were observed (see Fig. 1F). Pathological findings were diagnostic of primary angiitis of the central nervous system (PACNS) confined to 1 cerebral hemisphere, termed unilateral PACNS. The patient was referred to the rheumatology clinic and recently received 2 doses of rituximab 1,000mg i.v., 2 weeks apart. Follow-up in 3 months is planned to gauge treatment response. Unilateral PACNS is an exceptionally rare subtype of PACNS, with only sparse reports published in the literature.1 It has been defined as biopsy-proven PACNS with clinical and neuroimaging evidence of disease confined to 1 hemisphere.1 The chronic disease course and the presentation with seizures rather than ischemic stroke or hemorrhage are distinguishing features of unilateral PACNS.1 Differential diagnostic considerations for unihemispheric disease causing seizures include Rasmussen's encephalitis, unilateral cortical FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) and gliomatosis cerebri,2-4 although waxing and waning enhancing cortical/juxtacortical lesions for >1 year confined to 1 hemisphere was most compatible with unilateral PACNS in our patient. Intrinsic asymmetries in immune reactivity between the left and right cerebral hemispheres have been proposed as a possible explanation for striking disease unilaterality.1 Recognition of this unique clinicoradiographic syndrome is important to ensure accurate diagnosis and appropriate treatment. Author Contributions B.S. and A.B. contributed to conception and design of the study; B.S., S.P., Q.Z., and A.B. contributed to acquisition and analysis of the data; B.S., S.P., and A.B. contributed to drafting of the text or preparing the figures. Potential Conflicts of Interest Nothing to report. References 1AbdelRazek MA, Hillis JM, Guo Y, et al. Unilateral relapsing primary angiitis of the CNS: an entity suggesting differences in the immune response between the cerebral hemispheres. Neurol Neuroimmunol Neuroinflamm 2021; 8:E936. CrossrefPubMedWeb of Science®Google Scholar 2Bien CG, Granata T, Antozzi C, et al. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain 2005; 128: 454– 471. CrossrefCASPubMedWeb of Science®Google Scholar 3Budhram A, Mirian A, Le C, et al. Unilateral cortical FLAIR-hyperintense Lesions in Anti-MOG-associated Encephalitis with Seizures (FLAMES): characterization of a distinct clinico-radiographic syndrome. J Neurol 2019; 266: 2481– 2487. CrossrefCASPubMedWeb of Science®Google Scholar 4Ghostine S, Raghavan R, Michelson D, et al. Gliomatosis cerebri mimicking Rasmussen encephalitis. Case report. J Neurosurg 2007; 107: 143– 146. PubMedWeb of Science®Google Scholar Volume90, Issue6December 2021Pages 999-1000 FiguresReferencesRelatedInformation