A systematic review of Gamma-aminobutyric Acid Receptor Type B autoimmunity

Objective. To review the available research to describe the clinical characteristics and neoplastic associations of patients with gamma-aminobutyric acid receptor type B (GABAB-R) autoantibodies. Methods. Literature was reviewed on PubMed, Mendeley literature search, and the American Academy of Neurology database for articles published from June 2008 to October of 2018 using a variety of key words. These key words include: „gamma-aminobutyric acid seizures,” „gamma-aminobutyric acid limbic encephalitis”, „GABA(B) receptor antibodies,” „autoimmune encephalitis,” „autoimmune epilepsy,” „GABA(B) encephalitis, „ and “GABA paraneoplastic.” With the results, the papers were reviewed in a systematic manner. Results. A total of 10 studies were reviewed. A summary of the demographic, clinical, and serological findings of the cases detailed in the literature are provided. An additional illustrative case is described. In total, 94 patients were reviewed. Conclusions. GABAB-R autoimmune disease is characterized by refractory seizures or status epilepticus and frequent association with small cell lung cancer. Additionally, a substantial minority of patients have non-inflammatory CSF.

Defining the natural history of tumefactive demyelination: A retrospective cohort of 257 patients

Abstract Objective To describe demographic, clinical, and radiographic features of tumefactive demyelination (TD) and identify factors associated with severe attacks and poor outcomes. Methods Retrospective review of TD cases seen at Mayo Clinic, 1990–2021. Results Of 257 patients with TD, 183/257 (71%) fulfilled the 2017 multiple sclerosis (MS) McDonald criteria at the last follow‐up, 12/257 (5%) had myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD), 0 had aquaporin‐4‐IgG seropositive neuromyelitis optic spectrum disorders (AQP4+ NMOSD), and 62/257 (24%) were cryptogenic. Onset before age 18 was present in 18/257 (7%). Female to male ratio was 1.3:1. Cerebrospinal fluid oligoclonal (CSF) bands were present in 95/153 (62%). TD was the first demyelinating attack in 176/257 (69%). At presentation, 59/126 (47%) fulfilled Barkhof criteria for dissemination in space, 59/100 (59%) had apparent diffusion coefficient (ADC) restriction, and 57/126 (45%) had mass effect. Despite aggressive clinical presentation at onset, 181/257 (70%) of patients remained fully ambulatory (Expanded Disability Status Scale [EDSS] ≤4) after a 3.0‐year median follow‐up duration. Severe initial attack‐related disability (EDSS ≥4) was more common in patients with motor symptoms (81/143 vs. 35/106, p < 0.0001), encephalopathy (20/143 vs. 2/106, p < 0.0001) and ADC restriction on initial MRI (42/63 vs. 15/33, p = 0.04). Poor long‐term outcome (EDSS ≥4) was more common in patients with older onset age (41.9 ± 15 vs. 36.8 ± 15.6, p = 0.02) and motor symptoms at onset (49/76 vs. 66/171, p < 0.0001). Interpretation Most TD patients should be considered part of the MS spectrum after excluding MOGAD and NMOSD. Motor symptoms and older age at presentation portend a poor outcome

Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder

Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments. We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy. Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% <18 years), and 59% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74% (14 of 19; ARR 0.67), rituximab 61% (22 of 36; ARR 0.59), azathioprine 59% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5). This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions