Progressive Encephalomyelitis With Rigidity and Myoclonus With Glycine Receptor Antibodies: Clinical Features and Outcomes

Abstract

Background and objectives: The aim of this study was to describe the clinical features and long-term outcome of patients with glycine receptor (GlyR) antibody-mediated progressive encephalomyelitis with rigidity and myoclonus (PERM), a disease commonly included under the term of stiff-person spectrum disorders (SPSDs).

Methods: We conducted a retrospective analysis of patients with PERM and GlyR antibodies diagnosed in our laboratory and a systematic literature review (following Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] 2020 reporting guideline) of previously reported patients with sufficient clinical information and ≥12 months of follow-up. Neurologic disability was measured with the modified Rankin Scale (mRS). Relapses were defined as any event occurring >6 months after the first episode that required immunotherapy.

Results: Forty-one patients were identified, 22 from our database and 19 from the literature. The median age was 58 years (IQR: 43-66 years), and 36 (88%) were male and 5 female. The median time from symptom onset to admission was 2 weeks (IQR: 1-4 weeks). Predominant presentations included brainstem symptoms, mainly dysphagia and trismus, in 23 patients (56%); muscle stiffness and myoclonus in 9 (22%); dysesthesias or pruritus in 7 (17%); and cacosmia with dysgeusia in 2 (5%). Five patients (12%) never developed muscle stiffness. The median (range) mRS score at nadir was 5 (3-5). All patients received immunotherapy. Eleven patients died, 8 from complications of PERM. There were 12 relapses in 10 (28%) of 36 patients who lived >6 months. All relapses responded to immunotherapy. The functional status at the last visit, median time 24 months (IQR: 18-72 months), was good (mRS score <3) in 23 (70%) of the 33 patients who did not die from PERM. Age (HR: 1.06; 95% CI 1.01-1.11; p = 0.019) and admission to the intensive care unit (HR: 5.26; 95% CI 1.41-19.57, p = 0.013) were independent predictors of bad outcome (mRS score ≥3).

Discussion: GlyR antibody-mediated PERM is a rapidly progressive and severe disease that predominantly affects men and frequently presents with brainstem involvement. Its distinct demographic and clinical features suggest that it should be considered separately from SPSDs, which typically follows a chronic course and is more commonly associated with glutamic acid decarboxylase antibodies.

Figure 1. Flowchart of Patients Included in the Study

Figure 2. Functional Status Evaluated by the Modified Rankin Score (mRS) at Nadir and Last Follow-up

At nadir, 40 patients (97.5%) had a mRS score >3, whereas at the last follow-up, this figure decreased to 14 (34%).