Glycine receptor antibody mediated Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM): a rare but treatable neurological syndrome

Abstract

A 40-year-old man presented with respiratory compromise and was intubated. After tracheostomy, he was found to have ophthalmoplegia, severe limb rigidity, stimulus-sensitive myoclonus and autonomic dysfunction. For 1 week before admission, there had been a prodromal illness with low mood, hallucinations and limb myoclonus. Serum glycine receptor antibodies were strongly positive: we diagnosed progressive encephalomyelitis with rigidity and myoclonus. Despite a relapse, he has done well following immunotherapies. The clinical syndrome of encephalomyelitis with rigidity, described in 1976, often has a severe progressive course. A minority of patients have glutamic acid decarboxylase antibodies. The association with glycine receptor antibody was first reported in 2008, and we briefly review subsequent case reports to illustrate the range of clinical features. The antibody is likely to be disease mediating, although this remains unproven. The spectrum of diagnosable and treatable antibody mediated neurological syndromes is expanding. It is vital to recognise these conditions early to reduce morbidity and mortality.

Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes

“…Retrospectively, the patient’s sera, at onset and peak of disease, contained antibodies that bound to GlyRα1 subunits (now known as GLRA1) expressed on the surface of transfected human embryonic kidney cells, and also immunoprecipitated GlyRα1 (Hutchinson et al , 2008). Since then, further patients with glycine receptor (GlyR) antibodies have been described (Clerinx et al , 2011; Mas et al , 2011; Turner et al , 2011; Iizuka et al , 2012; Peeters et al , 2013; Piotrowicz et al , 2011; Damasio et al , 2013; Stern et al , 2014; Bourke et al , 2014) with combinations of stiffness, rigidity, excessive stimulus-evoked startle, brainstem and autonomic signs. GlyR antibodies have also been found in retrospective cohorts of adults or children (Alexopoulos et al , 2013; Clardy et al , 2013; McKeon et al , 2013), with or without GAD antibodies.…”

Cell‐surface central nervous system autoantibodies: Clinical relevance and emerging paradigms

“…By contrast, the recent discovery of glycine-alpha1–receptor antibodies in PERM and a few cases with SPS,89–91 the association of dipeptidyl peptidase IV–related protein antibodies in 3 patients with a distinctive form of SPS,92 and the recognition that some patients with GABA B R-antibody and AMPAR-antibody LE also harbor GAD antibodies, suggest that potentially pathogenic NGSAbs may also be present in GAD-antibody–positive patients 17–19. Moreover, although classical SPS often responds adequately to benzodiazepines, antibodies to surface epitopes of glycine receptors are now found in a range of PERM and related syndromes,91 with excellent and preferential responses to immunotherapies. It is possible that NGSAbs against other proteins involved in inhibitory neurotransmission are awaiting discovery in several patients with GAD-antibody–associated disorders 19…”

Myoclonus in the critically ill: Diagnosis, management, and clinical impact

“…Encephalitides HSV (Park et al, 2011) EBV West Nile virus (Birlutiu and Birlutiu, 2014;Cooper and Said, 2014) SSPE (Sharma and Biswas, 2013;Shibasaki and Hallett, 2005) Mumps infections (Kang and Kim, 2014) Autoimmune (Balint et al, 2013;DeFelipe-Mimbrera et al, 2014;Ghoreishi et al, 2013;Leigh et al, 1980;Smith et al, 2011;Stern et al, 2014;Uehara et al, 2011) Paraneoplastic (Berger and Mehari, 1999;Kim et al, 2009;Kumar et al, 2005; Spinal cord Traumatic spinal cord injury Calancie (2006) individual has fallen, and it lasts for 1-16 s. The recognition of myoclonus associated with transient cerebral hypoxia is important in the context of critically ill patients, as during intensive care, patients can suddenly develop episodes of severe arterial hypotension that (if detected early) can be treated with vasopressors to avoid hypoxic brain injury. Distinguishing psychogenic from somatic myoclonus is challenging calling for the exclusion of somatic diseases.…”