Clinical spectrum of anti-glycine receptor antibody-associated disease

Abstract

Anti-glycine receptor (anti-GlyR) antibodies were first reported in 2008 in a case of progressive encephalomyelitis with myoclonus and rigidity (PERM), which is a variant of stiff-person syndrome (SPS). After that, the antibodies have been studied extensively. At least 40 patients have been reported or presented until May 2013. We reviewed 28 patients (median age 47 years, range 1 to 75 years), whose clinical data are available. Seventeen patients (60%) were male. We classified clinical phenotype into PERM (17), classic SPS (5), variant SPS (5), and others (1: progressive optic atrophy). Nine patients (32%) had ant-GAD antibodies. Accompanied diseases included thyroiditis (5), diabetes mellitus (3), thymoma (3), and Addison's disease (2). Twenty-one patients (75%) treated with immunotherapy or thymectomy improved, but two of six patients without immunotherapy died or developed cardiac arrest. The clinical features suggested that antibody-mediated inhibition of the GlyR on the brainstem nuclei or spinal inhibitory interneurons may cause continuous firing of α motor neurons and paroxysmal excessive response to a variety of afferent impulses, leading to increased stiffness, brainstem signs, trismus, myoclonus, painful spasms or hyperekplexia. Phenotype associated with the anti-GlyR antibodies may be broader than previously thought, but among those PERM is the most common phenotype.

Inspiratory laryngeal stridor as the main feature of progressive encephalomyelitis with rigidity and myoclonus: a case report and literature review

“…Antibody-mediated inhibition of the GlyRs on the brainstem nuclei or spinal inhibitory interneurons may cause continuous firing of motor neurons. The excessive and paroxysmal response to various afferent impulses leads to increased stiffness, brainstem signs, trismus, myoclonus, spasms, or hyperekplexia [ 5 ]. GlyR-Abs might disrupt glycinergic inhibition mechanisms, causing an excessive startle reflex.…”

Anti-glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus initially presenting with one-sided stiff face: A case report

“…The glycine receptor is a pentameric ligand-gated chloride channel that is distributed throughout the brainstem and spinal cord. When glycine binds to these ionotropic receptors on a cell's surface, chloride ions flow into the cell, suppressing post-synaptic membrane excitation ( 5 ).…”

“…This indicates excessive excitability of the anterior horn cells of the spinal cord. Iizuka et al reported that trismus was due to muscle stiffness induced by continuous excitation of alpha motor neurons in the brainstem ( 5 ). A summary of published seropositive GlyR antibody-positive PERM cases (including the current case) is provided in Table 1 .…”

"Pediatric Anti-Glyr Antibody-Associated Progressive Encephalomyelitis with Rigidity and Myoclonus: A Case Report and Literature Review"

“…A post-hoc analysis of PERM cases revealed brainstem inflammation. Brainstem involvement can be used to differentiate SPS from PERM [11]. It remains debatable whether PERM belongs to the SPS spectrum and is considered an SPS-plus version of the main syndrome pain.…”