Anti-GAD65 antibody testing in neurological syndromes
Antibodies against the enzyme glutamic acid decarboxylase (GAD) are associated with a number of neurological syndromes. Stiff-person syndrome (SPS) is the most common and clearly associated condition. It is likely that the circulating antibodies are pathogenic in this condition.
The vast majority of patients with SPS have very high serum titres of anti-GAD antibodies. A small number are negative for anti-GAD but have anti-amphiphysin antibodies. In the anti-amphiphysin positive cases there is often a paraneoplastic cause, most commonly breast cancer in women.
Stiff-limb syndrome (SLS) is similar to SPS but the clinical pattern of stiffness and other clinical features differ and the immunological profile also differs, with more patients with SLS being anti-GAD antibody negative.
Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a more severe, rapidly progressive and fulminant form of SPS that often includes brainstem dysfunction. Some patients are anti-GAD antibody positive but many are not. Other antibodies are also associated with PERM including anti-amphiphysin, anti-glycine and others.
Anti-GAD antibodies have been reported in association with a number of other neurological syndromes including treatment-resistant focal epilepsy, ataxia and others. The relationship between the antibodies and neurological symptoms in these patients is less clear than for SPS.
Lower titres of anti-GAD antibodies are seen in patients with autoimmune diabetes. These recognise an epitope distinct from that recognised by anti-GAD antibodies found in patients with SPS, they are generally not seen in CSF and do not stain cerebellar tissue sections.