Glycine is the major inhibitory neurotransmitter in the spinal cord, brain stem and cerebellum, and is vitally important in the control of movement, and also has sensory functions, including vision and audition. Glycine exerts its inhibitory effects via specific glycine receptors. GlyR (Glycine receptor) autoantibodies were first identified in 2008 in a patient with progressive encephalomyelitis with rigidity and myoclonus (PERM). GlyR dysfunction may be associated with severe muscle spasms, stiffness, agitation, seizures, myoclonus, autonomic instability, and/or respiratory failure.
GlyR antibody encephalitis is seen in both men and women of all ages.
In a study done by Carvajal-González et al., it was found that the most common symptoms include (69%) spasms, often painful, and stiffness and rigidity of the neck, trunk or limb muscles; these were associated with walking difficulties and frequent falls. Excessive startle (42%), and eye movement disorders (40%) or difficulty opening the mouth, swallowing, or speech problems, were all frequent. Non-specific sensory symptoms in the limbs including pain unrelated to muscle spasms, were reported in 22% of patients. In addition, some patients had cognitive disturbance (29%) or seizures (13%).
GlyR antibodies may be detected in both serum and/or the CSF. CSF evaluation may be more sensitive than serum, therefore testing both is recommended. Signs of inflammation may be detected in the CSF, such as increased white cells (lymphocytic pleocytosis)or raised protein, or more rarely oligoclonal bands. However, the CSF examination can also be completely normal. Imaging is typically normal, or shows non-specific abnormalities. EEG may be normal, or show features of focal or generalized seizure activity.
Approximately 10% of patients that present with PERM/SPS, have a tumor (thymoma, lymphoma, breast cancer, leukemia, lung cancer, and melanoma have been described).
Immunotherapies (such as corticosteroids, IVIG, PLEX, cyclophosphamide) are used, sometimes in combination, to treat GlyR antibody encephalitis. If a tumor is detected, treatment of the neurological disorder may depend on successful treatment of the tumor.
Additional treatments are used alongside immunotherapy to control the clinical symptoms. For example motor hyperexcitability and pain may be treated with clonazepam, diazepam, baclofen or gabapentin, and anticonvulsants such as leviteracetam may be used in patients who have seizures.
Eighty percent of patients with GlyR antibodies showed a substantial response to immunotherapy. A minority of patients continue to have sporadic relapses after initial treatment.
Sarah Crisp PhD, MB, BChir, NIHR Clinical Lecturer in Neurology, University of Cambridge, Cambridge, UK