Clinical Characterization of Definite Autoimmune Limbic Encephalitis: A 30-case Series

Abstract

Objective Limbic encephalitis (LE) is an inflammatory condition of the limbic system that has an acute or subacute onset. Several types of antibodies are related to the onset of LE, including anti-N-methyl Daspartate receptor (NMDAR) antibodies and voltage-gated potassium channel (VGKC)-complex antibodies. However, the characteristics and prevalence of LE remain unclear, especially in Asian cohorts, due to the rarity. We aimed to survey their characteristics. Materials and Methods Data of 30 cases clinically defined as "definite autoimmune LE" (based on the standard criteria) were retrospectively collected. These patients were categorized into four subtypes: NMDAR (+) (n=8), VGKC (+) (n=2), antibodies related to paraneoplastic syndrome (n=2), and an antibody-negative group (uncategorized) (n=18). Results LE is rare in Japan, and affected only 30 of 16,759 hospital patients (0.2%) over a ten-year period. The NMDAR (+) group showed distinctive symptoms, while the other three groups had similar indications. Brain MRI indicated significant medial temporal lobe atrophy at one year follow up after discharge. The prevalence of cognitive dysfunction as a complication was 64% (9/14). First-line immunotherapy resulted in a good outcome. A drastic improvement was seen from 4.0±1.1 to 1.1+ on the modified Rankin Scale. A good treatment outcome was observed in all groups (NMDAR, VGKC, and uncategorized), suggesting the importance of an early clinical diagnosis and the early initiation of treatment. Furthermore, we reviewed 26 cases that were clinically diagnosed as definitive autoimmune LE in previous case reports. Conclusion Our findings show that the establishment of a clinical diagnosis based on the clinical criteria of definitive autoimmune LE is important for the initiation of immunotherapy.

Atypical Association of Autoimmune Limbic Encephalitis with Anti-NMDA Receptor Antibodies in a Young Male Patient: Clinical, Imaging, and Neuropsychological Characteristics

“…Interestingly, a common manifestation in all patients with nonparaneoplastic anti-NMDA receptor ALE was the presence of behavioral changes, which coincides with the clinical manifestations observed in our case [9]. Similarly, in another study, Shojima et al [11] reported 12 cases of anti-NMDA receptor ALE, from which 11 patients were young women with underlying ovarian teratomas and only 1 man that presented with catatonia. Furthermore, only one out of 18 cases reported by Baumgartner et al [8] showed a correlation between anti-NMDA receptor antibodies and mesiotemporal abnormalities in the brain MRI, but the investigators did not provide additional clinical information of the case.…”

“…The cases of this disorder, unlike those with global AE, are commonly associated with antibodies against the onconeuronal antigens Hu and Ma2 [ 3 , 4 ] and cell-surface antibodies like leucine-rich glioma-inactivated 1 [ 5 ], type b gamma-aminobutyric acid receptor [ 6 ], and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor [ 7 ]. Very little evidence exists on the co-occurrence of anti-NMDA receptor antibodies and brain inflammation restricted to the limbic system in patients with AE [ 1 , 8 , 9 , 10 , 11 ]. Indeed, although anti-NMDA receptor encephalitis and ALE have been proposed as different recognizable syndromes [ 2 ], the literature is not clear about the possible overlap between these disorders.…”

Neuropsychiatric Disorders Due to Limbic Encephalitis: Immunologic Aspect

“…Cancers occur in 20–60% of patients with LE [ 11 , 56 ]. LE can be classified as paraneoplastic or nonparaneoplastic, based on the presence or absence of an underlying malignancy [ 57 ].…”

“…In general, LE associated with cell-surface antibodies are more likely to respond to immunotherapy, resulting in good recovery in up to 70–80% of cases [ 56 ]. In PNS caused by onconeural antibodies, the tissue damage is thought to be primarily cell-mediated; therefore, immunotherapy often has only little effect.…”

“…GABA-BR antibody was attributed to the highest mortality rate (23.2%), largely due to tumor progression [ 26 ]. Cognitive dysfunction is a major complication in patients with long-term LE, and some patients are left disabled [ 56 ]. In LE caused by GAD, LGI1, or CASRP2 antibodies, the memory outcomes were poor even after clinical recovery with immunotherapy.…”