From the Guidelines
A positive anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody level of 0.05 nmol/L is consistent with a diagnosis of Stiff Person Syndrome (SPS). This finding supports the clinical diagnosis, though the level is relatively low (positive values typically range from 0.02-1.0 nmol/L) 1.
Key Considerations
- The diagnosis of SPS is based on a combination of clinical presentation and laboratory findings, including the presence of anti-GAD65 antibodies 1.
- Treatment should begin with symptomatic management using benzodiazepines, particularly diazepam starting at 5-10mg three times daily and titrating up as needed to control muscle spasms.
- Baclofen (10-25mg three times daily) can be added as a second-line agent.
- For immunomodulatory therapy, consider intravenous immunoglobulin (IVIG) at 2g/kg divided over 2-5 days every 4-6 weeks.
- If symptoms persist, rituximab (1000mg IV given twice, two weeks apart) may be effective.
Management and Monitoring
- Physical therapy is an essential component of treatment to maintain mobility and function.
- Regular monitoring of symptoms and antibody levels is recommended to assess treatment response.
- The presence of anti-GAD65 antibodies indicates an autoimmune process targeting GABAergic neurons, leading to reduced inhibitory neurotransmission and resulting in the characteristic muscle rigidity and spasms of SPS 1.
Treatment Goals
- The primary goal of treatment is to improve symptoms and quality of life, with a focus on reducing muscle rigidity and spasms.
- Treatment should be individualized based on the patient's specific needs and response to therapy.
From the Research
Stiff Person Syndrome and GAD65 Antibodies
- Stiff person syndrome is a disabling central nervous system disorder characterized by muscle rigidity, episodic muscle spasms, and high titers of antibodies against glutamic acid decarboxylase (GAD65) 2.
- A study found that patients with stiff person syndrome and anti-GAD65 antibodies had a significant improvement in symptoms after treatment with intravenous immune globulin 2.
- The presence of anti-GAD65 antibodies is a key diagnostic criterion for stiff person syndrome, and high titers of these antibodies are often associated with the disease 3, 4, 5.
Diagnosis and Treatment
- A diagnosis of stiff person syndrome is typically made based on a combination of clinical symptoms, laboratory tests, and the presence of anti-GAD65 antibodies 3, 5.
- Treatment for stiff person syndrome often involves a combination of symptomatic therapies, such as antispasmodic agents, and immunomodulating therapies, such as intravenous immunoglobulin 2, 5, 6.
- Studies have shown that intravenous immune globulin can be an effective treatment for stiff person syndrome, with significant improvements in symptoms and quality of life 2, 3.
GAD65 Antibody Titers
- High titers of anti-GAD65 antibodies are often associated with stiff person syndrome, and a titer of 0.05 nmol/L is considered positive for the disease 2.
- The presence of high-titer anti-GAD65 antibodies can induce motor dysfunction in rats, suggesting a pathogenic role for these antibodies in stiff person syndrome 4.
- The precise pathogenic mechanism of GAD-antibody-related neurologic disorders is uncertain, but it is thought to involve impaired GABA production and autoimmunity 5, 6.