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Glycine receptor antibodies in PERM: a new channelopathy

Pilar Martinez-Martinez, Peter C. Molenaar, Mario Losen, Marc H. de Baets
DOI: http://dx.doi.org/10.1093/brain/awu153 2115-2116 First published online: 23 July 2014

This scientific commentary refers to ‘Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes’, by Carvajal-González et al. (doi:10.1093/brain/awu142).

Ligand- or voltage-gated ion channels can be affected by mutation or autoimmune attack, leading to so-called channelopathies. A number of CNS disorders, such as limbic encephalitis and certain forms of epilepsy, have been shown to associate with specific serum autoantibodies against ion channels or related proteins (Irani and Lang, 2008). In 2008, the glycine receptor (GlyR) was first recognized as a possible target for autoantibodies in a patient with progressive encephalomyelitis, rigidity and myoclonus (PERM) (Hutchinson et al., 2008). The GlyR is a member of a superfamily of ligand-gated ion channels that also includes N-methyl-d-aspartic acid (NMDA) receptors and nicotinic acetylcholine receptors. GlyRs are present throughout the brain, but are most abundant in the spinal cord and brainstem. The GlyR is also the target of the alkaloid strychnine, which causes generalized muscle spasms and cramps, muscle stiffness and tightness, agitation, heightened awareness and responsiveness, stimulation-evoked seizures, myoclonus, respiratory failure, and sometimes death. For comparison, the symptoms of PERM include muscle spasms, cramps, myoclonus, stimulus-evoked startle and respiratory failure. In this issue of Brain, Carvajal-González et al. (2014) report the presence of antibodies against the GlyR in a relatively large cohort of patients with PERM, and describe the characteristics and clinical features of these patients. Using cellular assays, the authors present strong evidence that GlyR antibodies are …

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