Differences in epileptic symptoms depending on the type of autoimmune-mediated limbic encephalitis

Abstract

Limbic encephalitis (LE) is an inflammatory disease of the central nervous system that is characterized by the selective involvement of limbic structures. The clinical manifestations of LE include the acute or sub-acute onset of recent memory disorders, mental disorders and seizures. Autoimmune-mediated LE is a major type of non-infectious LE; seizure is a hallmark of this type of LE. The treatment of epilepsy, which is a key factor that affects the prognosis of LE patients, warrants special attention. Understanding the characteristics of epilepsy caused by autoimmune-mediated LE and providing the appropriate treatment will help to improve patients’ outcomes. In this article, we extensively review the literature related to autoimmune-mediated LE epidemiology, mechanisms, characteristics and seizure frequency and onset, and we discuss the possible diagnosis and treatment of this disease.

Keywords:

• autoantibody
• autoimmune
• epilepsy
• limbic encephalitis
• seizures

Financial & competing interests disclosure

This manuscript was supported by the National Natural Science Foundation of China (Project NO. 81471319). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The clinical manifestations of autoimmune-mediated limbic encephalitis (LE) include the acute or sub-acute onset of recent memory disorders, mental disorders and seizures. Seizures and/or status epilepticus are a hallmark of this type of LE.

• The antibodies detected in serum or cerebrospinal fluid (CSF) from patients with LE can be divided into three categories: antibodies against intracellular neuronal antigens or classic anti-onconeuronal antibodies, such as anti-Hu (ANNA-1), anti-Ma2, anti-CV2/CRMP5 and anti-amphiphysin; antibodies against cell membrane antigens, such as anti-NMDAR, anti-VGKC and anti-GABA-B receptor and antibodies against synaptic antigens, such as anti-GAD and anti-amphiphysin.

• The mechanisms by which epilepsy and status epilepticus cause each type of autoimmune-mediated LE differ, and the forms of epileptic seizures, the associated symptoms, and the prognoses vary. The most common types of seizures are generalized seizures, complex seizures, or status epilepticus.

• As a unique type of seizure attack in patients with anti-LGI1 encephalitis, FBDS, which often appears before other symptoms of LE and typically manifests as a transient, frequent and stereotyped attack, should be differentiated from epilepsy.

• GAD-LE can cause chronic epilepsy, but patients with GAD-LE are not sensitive to immunomodulatory therapy or AED treatment. Long-term immunosuppression therapy is likely necessary.

• Cranial magnetic resonance imaging and associated measurements of autoantibodies in serum and CSF have significance to the etiological diagnosis. When a diagnosis of LE has been determined, we must thoroughly examine the patient to search for tumors.

• The role of FDG-PET/CT in LE is evolving. This method can not only detect the equivocal malignancy but also display early functional abnormalities of the brain in the absence of any MRI finding that could indicate therapeutic potential.

• Currently, the selection of AEDs remains primarily based on seizure type, and carbamazepine, oxcarbazepine, valproate, phenytoin, levetiracetam, and lamotrigine are recommended.

• Most cases of autoimmune-mediated LE are sensitive to immunotherapy, but relapse is common. The rate of recurrence correlates with the use of standard immunotherapy and the presence of complicated tumors.