Intravenous methylprednisolone or immunoglobulin for anti-glutamic acid decarboxylase 65 antibody autoimmune encephalitis: which is better?

Abstract

Background: Patients positive for anti-glutamic acid decarboxylase 65 (GAD65) antibodies have attracted increasing attention. Their clinical manifestations are highly heterogeneous and can be comorbid with tumors. Currently, there is no consensus on the therapeutic regimen for anti-GAD65-associated neurological diseases due to the clinical complexity, rarity and sporadic distribution. We reported six anti-GAD65 autoimmune encephalitis (AE) patients who received intravenous methylprednisolone (IVMP) or immunoglobulin (IVIG) or both. Then, we evaluated the therapeutic effect of both by summarizing results in previous anti-GAD65 AE patients from 70 published references.

Results: Our six patients all achieved clinical improvements in the short term. Unfortunately, there was no significant difference between IVMP and IVIG in terms of therapeutic response according to the previous references, and the effectiveness of IVMP and IVIG was 45.56% and 36.71%, respectively. We further divided the patients into different subgroups according to their prominent clinical manifestations. The response rates of IVMP and IVIG were 42.65% and 32.69%, respectively, in epilepsy patients; 60.00% and 77.78%, respectively, in patients with stiff-person syndrome; and 28.57% and 55.56%, respectively, in cerebellar ataxia patients. Among 29 anti-GAD65 AE patients with tumors, the response rates of IVMP and IVIG were 29.41% and 42.11%, respectively. There was no significant difference in effectiveness between the two regimens among the different subgroups.

Conclusion: Except for stiff-person syndrome, we found that this kind of AE generally has a poor response to IVMP or IVIG. Larger prospective studies enrolling large numbers of patients are required to identify the optimal therapeutic strategy in the future.

Keywords: Autoimmune encephalitis; Glutamic acid decarboxylase 65; Immunoglobulin; Methylprednisolone.

Fig. 1

Axial magnetic resonance imaging (MRI) findings of patient 1 and patient 2 in fluid-attenuated inversion recovery (FLAIR) sequence. a Patient 1, a 35-year-old Chinese female, was diagnosed with typical limbic encephalitis, and MRI showed increased FLAIR signals of the right medial temporal lobe, including the amygdala and hippocampus. b–d Patient 2, a 35-year-old male, was characterized by stiff-person syndrome, cerebellar ataxia and intractable epilepsy. MRI indicated postoperative changes in the left frontal lobe, volume reduction in the left temporal lobe and hippocampus, and encephalatrophy, especially in the bilateral cerebellum

Fig. 2

Interictal phase electroencephalogram of patient 1. There were frequent sharp waves and slow waves in the right temporal regions in the interictal phase

Fig. 3

Ictal phase electroencephalogram of patient 1. One clinical seizure was detected, which presented as a nauseous feeling and oropharyngeal automatism with impaired awareness, and the seizure lasted approximately 50 s second before sudden movement interruption of the patient, EEG showed widespread low voltage in the right leads, followed by rapid rhythmic changes with low amplitude in the right middle-posterior temporal region initially, and spreading to the right middle temporal region 2 s later. The amplitude increased and the frequency decreased gradually and then spread to adjacent leads, accompanied by electromyogram interference and motion artifacts