Moran Hausman-Kedem1, Shay Menascu2, Yoram Greenstein3, Aviva Fattal-Valevski4. 1. Pediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, P.O.B 39040, Ramat Aviv, Tel Aviv, Israel. Electronic address: moranhk@gmail.com. 2. Sackler Faculty of Medicine, Tel Aviv University, P.O.B 39040, Ramat Aviv, Tel Aviv, Israel; Multiple Sclerosis Center, Sheba Medical Center, Tel-Hasomer, Derech Sheba 2, Ramat Gan, Israel. 3. Zefat Academic College, 11 Jerusalem St, Tsfat, 1320611, Israel; Kibbutzim College, Namir Rd 149, Tel Aviv-Yafo, Israel. 4. Pediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, P.O.B 39040, Ramat Aviv, Tel Aviv, Israel.
Abstract
BACKGROUND: GRIN-related developmental-epileptic encephalopathies are associated with a spectrum of neurodevelopmental disorders, including intellectual disability, epilepsy including continuous spike-and-wave during sleep syndrome (CSWS), or epilepsy-aphasia spectrum phenotypes such as in Landau-Kleffner syndrome. Efficacy of IVIG treatment was recently reported in a patient with LKS related to GRIN2A mutation. AIM AND METHODS: We describe the efficacy of Immunotherapy in 5 consecutive patients (4 males, age range 6 months-13 years) with molecularly confirmed GRIN-related epileptic encephalopathy (4 with GRIN2A- related epilepsy-aphasia spectrum/epileptic encephalopathy with CSWS, accompanied by verbal, communicative and behavioural regression, and one patient with GRIN2D - related infantile developmental-epileptic encephalopathy). All patients had global developmental delay/ intellectual disability in various degrees, and were resistant to anticonvulsants, but none of the patients had frequent clinical seizures. All patients received monthly infusion of IVIG 2 g/ kg for 6 months; 2 patients were also treated with high-dose corticosteroids. RESULTS: Normalization or near normalization of the EEG was noted in 3 patients, from whom 2 had mild improvement in verbal abilities and communication skills. Perceptual/spatial abilities, as well as executive functions and attention span, remained significantly impaired. CONCLUSION: according to this preliminary, open-label study, Immunotherapy may lead to a clinical and electrographic improvement in patients with GRIN-related developmental-epileptic encephalopathies. Further studies to validate the efficacy of immunotherapy and the potential role of autoimmunity in GRIN-related disorders are needed.
BACKGROUND: GRIN-related developmental-epileptic encephalopathies are associated with a spectrum of neurodevelopmental disorders, including intellectual disability, epilepsy including continuous spike-and-wave during sleep syndrome (CSWS), or epilepsy-aphasia spectrum phenotypes such as in Landau-Kleffner syndrome. Efficacy of IVIG treatment was recently reported in a patient with LKS related to GRIN2A mutation. AIM AND METHODS: We describe the efficacy of Immunotherapy in 5 consecutive patients (4 males, age range 6 months-13 years) with molecularly confirmed GRIN-related epileptic encephalopathy (4 with GRIN2A- related epilepsy-aphasia spectrum/epileptic encephalopathy with CSWS, accompanied by verbal, communicative and behavioural regression, and one patient with GRIN2D - related infantile developmental-epileptic encephalopathy). All patients had global developmental delay/ intellectual disability in various degrees, and were resistant to anticonvulsants, but none of the patients had frequent clinical seizures. All patients received monthly infusion of IVIG 2 g/ kg for 6 months; 2 patients were also treated with high-dose corticosteroids. RESULTS: Normalization or near normalization of the EEG was noted in 3 patients, from whom 2 had mild improvement in verbal abilities and communication skills. Perceptual/spatial abilities, as well as executive functions and attention span, remained significantly impaired. CONCLUSION: according to this preliminary, open-label study, Immunotherapy may lead to a clinical and electrographic improvement in patients with GRIN-related developmental-epileptic encephalopathies. Further studies to validate the efficacy of immunotherapy and the potential role of autoimmunity in GRIN-related disorders are needed.
Authors: Eva M M Hoytema van Konijnenburg; Saskia B Wortmann; Marina J Koelewijn; Laura A Tseng; Roderick Houben; Sylvia Stöckler-Ipsiroglu; Carlos R Ferreira; Clara D M van Karnebeek Journal: Orphanet J Rare Dis Date: 2021-04-12 Impact factor: 4.123