Caspr2 antibody limbic encephalitis is associated with Hashimoto thyroiditis and thymoma Chih-Hong Lee a , Jainn-Jim Lin b,c , Kun-Ju Lin d,e , Bao-Luen Chang a , Hsiang-Yao Hsieh a , Wei-Hsun Chen f , Kuang-Lin Lin b,c,g , Hon-Chung Fung a , Tony Wu a, ⁎ ,1 a Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan b Division of Pediatric Neurology, Chang Gung University, College of Medicine, Taoyuan, Taiwan c Chang Gung Children's Hospital Study Group for Children with Encephalitis/Encephalopathy Related Status Epilepticus and Epilepsy (CHEESE), Taiwan d Molecular Imaging Center and Department of Nuclear Medicine, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan, Taiwan e Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taiwan f Division of Thoracic Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan, Taiwan g Graduate Institute of Clinical Medical Sciences, Chang Gung University, College of Medicine, Taoyuan, Taiwan abstract article info Article history: Received 18 September 2013 Received in revised form 19 March 2014 Accepted 21 March 2014 Available online 29 March 2014 Keywords: Autoimmune encephalitis Thymoma Neuronal surface antibodies Caspr2 VGKC Hashimoto thyroiditis Background: Contactin-associated protein 2 (Caspr2) antibody is a neuronal surface antibody (NSAb) capable of causing disorders involving central and peripheral nervous systems (PNS). Thymoma can be found in patients with Caspr2 antibodies and is most frequently associated with PNS symptoms. Myasthenia gravis can be found in these patients, but Hashimoto thyroiditis (HT) has not been reported. Methods: A 76-year-old woman presented with sub-acute-onset changes in mental status. Further investigations revealed thymoma and HT. The presence of NSAb was tested by immunofluorescence on human embryonic kidney-293 cells. Treatment included corticosteroids, azathioprine, thyroxine, plasmapheresis, and thymectomy. Results: Caspr2 antibody was positive in serum but absent in CSF. Brain magnetic resonance imaging (MRI) showed diffuse cortical atrophy, but did not change significantly after treatments. Brain positron emission tomography (PET) revealed diffuse hypometabolism over the cerebral cortex. The patient's mental status only partially improved. Conclusions: In Caspr2 antibody-associated syndromes, thymoma can occur in patients presenting only with LE, and HT can be an accompanying disease. Brain MRI and PET may not show specific lesions in limbic area. Patients with Caspr2 antibodies and thymoma may not have good prognosis. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Over the past few years, the discovery of several autoimmune disor- ders has solved some problems regarding treatment of patients with “unknown viral encephalitis”. These newly discovered antibodies are the neuronal surface antibodies (NSAbs). Unlike previously known paraneoplastic syndromes associated with intra-cellular or extra-cellular synaptic antigens, NSAbs may cause limbic encephalitis, which is charac- terized by sub-acute-onset short-term memory impairment, behavior change, confusion, psychosis, seizures, and movement disorders, with or without underlying neoplasms [1]. The target antigens include the N methyl d-aspartate receptor (NMDAR), the α amino 3-hydroxy 5- methyl 4-isoxazolepropionic acid receptor (AMPAR), γ aminobutyric acid receptor B (GABA B R), and proteins related to the voltage-gated potassium channels (VGKC) shaker family, such as leucine-rich glioma- inactivated protein 1 (Lgi1) and contactin-associated protein 2 (Caspr2). Caspr2 was first proven to be a target of autoimmune neurologic disorders in 2010 [2]. It is localized at the juxtaparanodes of myelinated axons and is essential for concentrating Kv1.1 and Kv1.2 VGKC sub-units [3]. Patients with Caspr2 antibodies can present with limbic encephalitis (LE), Morvan syndrome (MoS, a collection of neuromyotonia [NMT], dysautonomia, and encephalopathy with marked insomnia), or isolated NMT [2,4–8]. Some patients may have thymoma or myasthenia gravis (MG) [2,9,10]. Herein is a patient with Caspr2 antibodies who has LE, thymoma, and Hashimoto thyroiditis (HT). 2. Materials and methods 2.1. Case A 76-year-old woman was admitted for dizziness and lethargy of one month duration. She had a past medical history of hypertension, Journal of the Neurological Sciences 341 (2014) 36–40 ⁎ Corresponding author at: Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan. Tel.: +886 3 3281200x3944; fax: +886 3 3287226. E-mail address: lysander@cgmh.org.tw (T. Wu). 1 Address: 5, Fuxing Street, Guishan, Taoyuan, Taiwan. http://dx.doi.org/10.1016/j.jns.2014.03.043 0022-510X/© 2014 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns