Seronegative limbic encephalitis

Excerpt

We describe the case of a left-handed 42-year-old woman without relevant diseases, who initially presented with fever (39.5 °C) and headache. This was followed by an acute, severe anterograde and retrograde (working memory) deficit 5 days later, when she was admitted to our hospital. She then started with frequent (up to 10 per day) focal aware non-motor seizures that commenced with an aura characterized by left hemicranial headache followed by bradypsychia, cold sensation and shivering, goosebumps and piloerection of the left limbs, and facial flushing. Brain MRI showed bilateral asymmetric (left more than right) abnormalities in both temporal lobes (edema and hyperintensity of mesial temporal structures and insular cortex) (Fig. 1). Electroencephalography (EEG) monitoring confirmed that previous seizures originated at both temporal lobes with a left predominance; however, subclinical temporal seizures were also recorded. Lumbar puncture showed mild protein increase in cerebrospinal fluid (CSF) (0.68 g/L), mild pleocytosis (6 cells/mm³), normal glucose, and negative PCR for virus and negative cultures. The whole battery of systemic antibodies was negative: antinuclear antibodies (ANA), anti-extractable nuclear antigen antibodies (ENAS) (Sm, RNP, Ro-SSA, La-SSB, Jo-1, Scl-70, PCNA, PM-Scl, ribosomal-P, centromeres), antithyroid peroxidase, antithyroglobulin, anti-transglutaminase, and anti-GAD antibodies. Serological status was negative for acute infection both in serum and CSF, from toxoplasma, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (VHS), varicella zoster virus (VZV), Cryptococcus, hepatitis A, B, and C virus, and human immunodeficiency virus (HIV). No antineuronal antibodies were detected either in CSF (Anti-NMDAR, AMPAR, GABAbR, GABAaR, DPPX, LGI1, CASPR2, mGluR5, mGluR1, neurexin antibodies) or in blood (anti-amphiphysin, CV2/CRMP5, PNMA2/Ma2/Ta, Ri/ANNA2, Yo/PCA1, Hu/ANNA1, Tr/DNER, ZIC, SOX1, GAD antibodies). A negative, whole-body computed tomography (CT) scan study ruled out a hidden tumor; tumor markers were also negative. A whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) scan showed hypermetabolism in the left temporal lobe. Levetiracetam, lacosamide, valproate, carbamazepine, clonazepam, and topiramate were tested without efficacy in seizure control. Furthermore, five pulses of IV methylprednisolone were administered without improvement. Finally, after 5 doses of IV gamma globulin, cognitive alteration started to improve, and seizures were controlled. A brain MRI performed 8 months after the episode showed resolution of the acute alterations and a left hippocampal atrophy without clear sclerosis (Fig. 2). During the follow-up period (26 months), repeated complementary tests (tumor markers, mammography, abdominal and gynecologic ultrasound scans, whole-body CT scans) excluded an underlying tumor. However, a drug-resistant, bi-temporal epilepsy and mild cognitive decline have persisted to the present.

…