no evidence of tumor, especially no thymoma and no lung cancer were detected. Open in a separate window Fig. a secondary neurological decline after 3C4?weeks, which has recently been attributed to autoimmune encephalitis following HSV encephalitis [4, 5]. So far, antibodies against ON-013100 N-methyl-D-aspartate receptor (NMDAR) have been identified in these patients [4, 5]. Interaction of these antibodies with the NMDAR leads to cerebral dysfunction and a characteristic clinical syndrome [6]. Although there are several other neuronal surface proteins as targets in autoimmune encephalitis, e.g. leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) type 1/2 or gamma-aminobutyric acid-receptor (GABAR) type A/B which frequently cause limbic encephalitis [7], only cases of patients with HSV encephalitis and positive GABAAR antibodies have been reported apart from NMDAR antibodies [5, 8C11]. Here we present a female patient with encephalitis who was tested positive for HSV DNA in CSF as well as for Caspr2 antibodies in serum. Case presentation An 82-year old woman with a pre-morbid modified Rankin Scale (mRS) score of 1 1 was referred to the emergency department due to confusion for two days. Besides breast cancer 41?years ago ON-013100 and herpes zoster skin infection three years ago, the patient suffered from pre-existing hypertension, hyperlipidemia, and hypothyroidism treated with doxazosin, statin, and levothyroxine. The initial clinical examination revealed apart from global aphasia no further neurological deficits. The patient was afebrile (with a body temperature of 36.6?C). Emergency cerebral MRI showed Rabbit Polyclonal to CNTROB a T2-hyperintense swelling in the left temporo-mesial lobe, including cortical and subcortical areas, hippocampus and amygdala. Within these regions partially a diffusion-restriction of the cortex was found; in addition there was a thin contrast-enhancing rim subcortically at the lateral border of the T2-hyperintense swelling (Fig.?1). Electroencephalogram (EEG) revealed continuous bilateral slowing with periodic lateralized discharges. Cerebrospinal fluid (CSF) analysis at admission yielded a mild pleocytosis comprising mononuclear cells (white blood cell [WBC] count of 8/l), a slightly disrupted blood-CSF-barrier (as indicated by elevated CSF total protein of 0.73?g/L and Qalb of 11.3) and an intrathecal IgM synthesis (13%). HSV DNA was detected in CSF by means of polymerase chain reaction and diagnosis of HSV encephalitis was established. Acyclovir treatment (10?mg per kilogram bodyweight every 8?h) was ON-013100 started and the patient was transferred to the neurological intensive care unit. Antiepileptic treatment with Levetiracetam (2000?mg per day) was administered. An appropriate neuropsychological testing at this time was not feasible due to the global aphasia (Mini-Mental State Examination Score [MMSE]: 3). Open ON-013100 in a separate window Fig. 1 Brain MRI in a patient with encephalitis and positive HSV DNA and Caspr2 antibodies. Legend: T2-weighted MRI shows hyperintense lesion in the left temporo-mesial lobe (left) with diffusion restriction on the diffusion-weighted sequences (right) As HSV encephalitis might be associated with secondary autoimmunity [4, 5], we performed further autoimmunity work-up that revealed Caspr2 antibodies in serum (Fig.?2) but not in CSF using a commercially available cell-based assay (Euroimmun, Cat. Nr. FA1439C1005C1; Lbeck, Germany). Antibodies against NMDAR, LGI1, AMPAR type 1/2, GABABR, immunoglobulin-like cell adhesion molecule 5 (IgLON5), dipeptidyl-peptidaseClike protein 6 (DPPX) using a cell-based assay (Euroimmun), Yo, Hu, Ri, CV2, Ma2, Amphiphysin using an immunoblot (Euroimmun), aquaporin-4 (AQP-4) and myelin oligodendrocyte glycoprotein (MOG) using a cell-based assay as previously described [12] were not detected in both CSF and serum. A whole-body 18F-FDG PET/CT revealed no hypermetabolic active lesions, i.e. no evidence of tumor, especially no thymoma and no lung cancer were detected. Open in a separate window Fig. 2 Detection of Caspr2-antibodies by immunofluorescence. Legend: Presence of Caspr2 antibodies was determined by a cell-based immunofluorescence assay. Patients serum sample was added to fixed cells that express Caspr2 protein on their surface (left) as well as to non-transfected cells (right). Reactivity at a serum dilution of??1:100 proves Caspr2 antibodies. The immunofluorescence pattern is shown at a magnification of 10 x (above) and 20 x (below) Acyclovir treatment was maintained for 14?days and corticosteroids were administered additionally for three days. While the clinical course of the patient initially was mainly determined by complications (nasopharyngeal ON-013100 bleeding and subsequent mechanical ventilation, pneumonia), the patient started to improve thereafter. MRI was repeated after.