Article type: Original Article
Article title: The limbic and extra-limbic encephalitis associated with glutamic acid decarboxylase (GAD)-65 antibodies: an observational study
Journal: Neurological Sciences
Year: 2024
Authors: Zuying Kuang, José Fidel Baizabal-Carvallo, Marlene Alonso-Juarez, Mohammad Mofatteh, Jamir Pitton Rissardo, Mengqiu Pan, Jinlong Ye, Zhanhang Wang, Yimin Chen
E-mail: jamirrissardo@gmail.com
ABSTRACT
We aimed to define the clinical features and outcomes of encephalitis associated with anti-GAD65 Abs. In addition, we reviewed cases published in the literature with GAD65 encephalitis. We retrospectively studied 482 consecutive patients attending a tertiary care center for evaluation of an autoimmune neurological disorder. Nineteen patients were enrolled (3.94% of the cohort). Twelve (63.16%) patients were females, and the mean age at onset of the cohort was 31.68 ± 13.88 years. The following clinical-neuroimaging syndromes were identified: limbic encephalitis (n = 10), limbic plus extra-limbic encephalitis (n = 6), meningoencephalitis (n = 1), extralimbic encephalitis (n = 1), and unclassified (n = 1). The mesial temporal lobes were the most frequently affected (n = 13, 68.42%) in the brain magnetic resonance imaging (MRI), followed by frontal lobes (21%), and insular lobes (21%). Epileptiform discharges (94.4%), mostly from temporal lobes, were the most common electroencephalogram (EEG) finding. Most patients received immunotherapy and were followed for a mean duration of 21 months. A total of 73 patients, including 54 from the literature and 19 presented from the current series, were analyzed. Limbic encephalitis was the predominant presentation, and most patients received immunotherapy. Outcomes varied considerably. Considering patients from the literature and this series (n = 70), mortality was 5.7%. Also, 82.8% of patients had persistent neurologic manifestations, including seizures and cognitive impairment following immunotherapy. Limbic encephalitis is the most common form of GAD65 encephalitis, while a smaller proportion of patients may have signs of extra-limbic involvement. Most patients have persistent manifestations following combined immunotherapy with a relatively low mortality rate.
Keywords: Gad65; Glutamic acid decarboxylase; Neuronal cell-surface; Paraneoplastic neurologic syndrome; Autoimmune encephalitis; Limbic encephalitis; Extra-limbic encephalitis; Encephalitis; Temporal lobe epilepsy; Neuropsychiatry.
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DOI
Citation
Kuang Z, Baizabal-Carvallo JF, Alonso-Juarez M, Mofatteh M, Rissardo JP, Pan M, Ye J, Wang Z, Chen Y. The limbic and extra-limbic encephalitis associated with glutamic acid decarboxylase (GAD)-65 antibodies: an observational study. Neurol Sci 2025;46(6):2765-2777. doi: 10.1007/s10072-024-07933-7
Figure 1. Diagnostic classification of patients with GAD65-associated encephalitis proposed by Kuang et al. Abbreviations: Abs, antibodies; CSF; cerebrospinal fluid; eLE, extra-limbic encephalitis; GAD65, glutamic acid decarboxylase 65 kDa; HT, hyperintensity; LE, limbic encephalitis; MRI, magnetic resonance imaging; PET, positron emission tomography.
Figure 2. Examples of limbic and extra-limbic encephalitis: A) Case 2 shows hyperintensities in the parietal, insular, and frontal lobes. B) Case 6 shows bilateral insular hyperintensities mainly affecting the subcortical white matter. C) Case 6 also shows bilateral hippocampal hyperintensities. D) In the same patient 3 years later, both temporal lobes have marked atrophy. E) Case 8, there is mild increased signal intensity and volume in both hippocampi. F) Case 17 shows bilateral extensive frontal, insular, cingulate, temporal, parietal, thalamic, and occipital hyperintensities. G) Case 17 also shows bilateral orbitofrontal, hippocampal, and extra-hippocampal temporal hyperintensities. H) Case 17 marked atrophy is observed on MRI 12 months later.
Table 1. Baseline demographic, clinical features, therapeutic, and outcomes.
Table 2. Antibody profile, CSF features, and MRI findings from patients in this study.
Table 3. Summary of demographic, clinical, and neuroimaging features of published cases.
Table 4. Outcomes of patients from the literature review and this current study.