Neurophysiology in disorders of glycinergic neurotransmisson
Research type
Research Study
Full title
Pathological Mechanisms in Human Disorders of Glycinergic Neurotransmission
IRAS ID
138058
Contact name
John Rothwell
Contact email
Research summary
Stiff person syndrome is group of rare neurological disorders characterized by progressive stiffness and rigidity. The cause of disease is unknown, but some patients respond to immunosuppressive treatment suggesting that some cases might be autoimmune. Recently some patients with variants of stiff person syndrome, including those which are life-threatening, have been found to make antibodies which bind to glycine receptors on their own nerve cells (autoantibodies). Glycine usually decreases the activity of nerve cells in the brain stem and spinal cord by binding to its receptor. Although patients with antibodies appear to have over-activity of parts of the nervous system, causing stiffness and excessive startling, it has not been shown whether these antibodies reduce activity in inhibitory pathways and are directly responsible for disease. Using non-invasive clinical neurophysiology, we will assess inhibitory pathways in patients with glycine receptor antibodies. By comparing these patients to patients with inherited defects in glycinergic transmission (hereditary hyperekplexia) and normal subjects, we will determine whether patients with glycine receptor antibodies have clear evidence of inhibitory failure in the brain stem and spinal cord.
As well as providing evidence of the disease mechanism, changes in inhibitory reflexes measured using clinical neurophysiology have a number of potential uses in clinical practice. Since autoimmune conditions affecting the central nervous system respond best to early treatment, and testing for antibodies can take several days, clinical neurophysiology might aid in the rapid diagnosis of patients. There is also a group of patients with similar symptoms who respond to immunosuppressive treatment, but do not have glycine receptor antibodies – these patients may have an abnormality of inhibition mediated by antibodies to unknown targets, and clinical neurophysiology could provide supportive evidence of the diagnosis in these patients. Clinical neurophysiology might also provide a useful means of monitoring disease progression and response to treatment.REC name
London - Riverside Research Ethics Committee
REC reference
14/LO/1194
Date of REC Opinion
16 Jul 2014
REC opinion
Favourable Opinion