Xavier Ayrignac1, Radjiv Goulabchand2, Eric Jeziorski2, Patricia Rullier2, Clarissa Carra-Dallière2, Claire Lozano2, Pierre Portales2, Thierry Vincent2, Jean François Viallard2, Nicolas Menjot de Champfleur2, Frédéric Rieux-Laucat2, Caroline Besnard2, Michel Koenig2, Claire Guissart2, Pierre Labauge2, Philippe Guilpain2. 1. From the Department of Neurology (X.A., C.C.-D., P.L.), Montpellier University Hospital, INSERM, Univ Montpellier, Montpellier; Internal Medicine Department (R.G.), Caremeau University Hospital, Nimes; Department of Paediatrics (E.J.), Montpellier University Hospital, INSERM, Univ Montpellier; Médecine interne multi-organes (P.R., P.G.), Montpellier University Hospital, INSERM, Univ Montpellier; Department of Immunology (C.L., P.P., T.V.), Montpellier University Hospital, INSERM, Univ Montpellier; Internal Medicine Department (J.F.V.), Bordeaux University Hospital, Univ Bordeaux; Department of Neuroradiology (N.M.C.), Montpellier University Hospital, INSERM, Univ Montpellier; Université de Paris (F.R.-L., C.B.), Imagine institute, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Paris; and Laboratory of Molecular Genetics (M.K., C.G.), Montpellier University Hospital, INSERM, Univ Montpellier, France. xavier.ayrignac@yahoo.fr. 2. From the Department of Neurology (X.A., C.C.-D., P.L.), Montpellier University Hospital, INSERM, Univ Montpellier, Montpellier; Internal Medicine Department (R.G.), Caremeau University Hospital, Nimes; Department of Paediatrics (E.J.), Montpellier University Hospital, INSERM, Univ Montpellier; Médecine interne multi-organes (P.R., P.G.), Montpellier University Hospital, INSERM, Univ Montpellier; Department of Immunology (C.L., P.P., T.V.), Montpellier University Hospital, INSERM, Univ Montpellier; Internal Medicine Department (J.F.V.), Bordeaux University Hospital, Univ Bordeaux; Department of Neuroradiology (N.M.C.), Montpellier University Hospital, INSERM, Univ Montpellier; Université de Paris (F.R.-L., C.B.), Imagine institute, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Paris; and Laboratory of Molecular Genetics (M.K., C.G.), Montpellier University Hospital, INSERM, Univ Montpellier, France.
Abstract
OBJECTIVE: To describe the clinical and radiologic neurologic characteristics of patients with cytotoxic T-lymphocyte antigen-4 (CTLA4) haploinsufficiency. METHODS: Three patients from 2 families had neurologic manifestations in the context of CTLA4 haploinsufficiency. Their clinical and MRI findings are presented. RESULTS: A 16-year-old boy with a previous diagnosis of combined immunodeficiency presented with severe recurrent episodes of headaches, motor deficit, and seizures associated with waxing and waning gadolinium-enhancing FLAIR cortical/juxtacortical hyperintensities. His sister, who also had combined immunodeficiency, had a brain MRI when she was aged 13 years due to recent headaches and transient right hemianopsia. It revealed a gadolinium-enhancing left occipital white matter hyperintensity. Another 49-year-old woman had progressive visual loss and cerebellar ataxia in the context of recurrent pulmonary infections. All 3 patients were found to have inherited CTLA4 haploinsufficiency. Patient 1's general condition and neurologic manifestations were completely controlled with abatacept (CTLA4-Ig). CONCLUSIONS: These cases suggest that in addition to the variable clinical penetrance and wide spectrum of CTLA4 haploinsufficiency, its neurologic spectrum is broad, ranging from recurrent tumefactive lesions to progressive deficits including cerebellar ataxia and optic atrophy with leukoencephalopathy. These phenotypes must be recognized, and should lead to a complete immunologic workup, because potentially effective targeted immunotherapy exists.
OBJECTIVE: To describe the clinical and radiologic neurologic characteristics of patients with cytotoxic T-lymphocyte antigen-4 (CTLA4) haploinsufficiency. METHODS: Three patients from 2 families had neurologic manifestations in the context of CTLA4haploinsufficiency. Their clinical and MRI findings are presented. RESULTS: A 16-year-old boy with a previous diagnosis of combined immunodeficiency presented with severe recurrent episodes of headaches, motor deficit, and seizures associated with waxing and waning gadolinium-enhancing FLAIR cortical/juxtacortical hyperintensities. His sister, who also had combined immunodeficiency, had a brain MRI when she was aged 13 years due to recent headaches and transient right hemianopsia. It revealed a gadolinium-enhancing left occipital white matter hyperintensity. Another 49-year-old woman had progressive visual loss and cerebellar ataxia in the context of recurrent pulmonary infections. All 3patients were found to have inherited CTLA4haploinsufficiency. Patient 1's general condition and neurologic manifestations were completely controlled with abatacept (CTLA4-Ig). CONCLUSIONS: These cases suggest that in addition to the variable clinical penetrance and wide spectrum of CTLA4haploinsufficiency, its neurologic spectrum is broad, ranging from recurrent tumefactive lesions to progressive deficits including cerebellar ataxia and optic atrophy with leukoencephalopathy. These phenotypes must be recognized, and should lead to a complete immunologic workup, because potentially effective targeted immunotherapy exists.
Authors: M Jamee; S Hosseinzadeh; N Sharifinejad; M Zaki-Dizaji; M Matloubi; M Hasani; S Baris; M Alsabbagh; B Lo; G Azizi Journal: Clin Exp Immunol Date: 2021-05-03 Impact factor: 5.732