From the Guidelines
Stiff Person Syndrome (SPS) should be diagnosed based on clinical presentation, electromyography (EMG) findings, and detection of autoantibodies, with a particular focus on glutamic acid decarboxylase (GAD) antibodies, as outlined in recent guidelines and reviews, such as those discussed by Graus et al. 1. The clinical presentation of SPS typically includes progressive muscle stiffness and painful spasms primarily affecting the trunk and proximal limb muscles, with symptoms developing over time and being triggered by emotional stress, sudden movements, or unexpected stimuli. Key diagnostic features include:
- Progressive muscle stiffness
- Painful spasms
- Positive EMG findings showing continuous motor unit activity in affected muscles at rest
- Positive antibody testing, particularly for GAD antibodies, which are present in about 60-80% of cases, as well as other antibodies like amphiphysin and glycine receptor antibodies 1. Other important considerations in the diagnosis of SPS include:
- Lumbar puncture findings, which often reveal elevated protein levels without pleocytosis
- Exclusion of other conditions that might cause similar symptoms
- Screening for associated autoimmune disorders, such as type 1 diabetes, thyroiditis, and pernicious anemia
- Evaluation for underlying malignancies, as SPS can be paraneoplastic in some cases, highlighting the importance of a comprehensive diagnostic approach, as suggested by studies like those reviewed in the Journal of Neurology, Neurosurgery and Psychiatry 1.
From the Research
Presentation of Stiff Person Syndrome
- Stiff person syndrome (SPS) is characterized by progressive rigidity of axial and limb muscles associated with painful spasms 2, 3
- The syndrome can present with stiffness in the limbs and axial muscles, stiff gait with uncontrolled falls, and episodic painful muscle spasms triggered by anxiety, task-specific phobias, and startle responses 4
- Clinical manifestations can also include unusual features such as recurrent vomiting and progressive dysarthria 2
- SPS can be classified into classic SPS, paraneoplastic SPS, and SPS variants, including focal or segmental-SPS, jerking-SPS, and progressive encephalomyelitis with rigidity and myoclonus 2, 3
Diagnosis of Stiff Person Syndrome
- Diagnosis of SPS is often challenging due to its extensive clinical variability and the presence of overlapping glutamic acid decarboxylase (GAD) antibody spectrum disorders 4
- The presence of antibodies against GAD, particularly GAD-65, is a common feature of SPS and can aid in diagnosis 5, 6
- Electromyographic examination can reveal muscle spasms and co-contractions, along with severe rigidity and reactive spasms upon touch 5
- Imaging studies may be necessary to rule out other conditions, such as hypermetabolic lesions or tumors associated with paraneoplastic SPS 5
Diagnostic Findings and Laboratory Tests
- Antibodies against GAD, GABA(A) receptor-associated protein, and the glycine-α1 receptor can be observed in patients with SPS 3
- Paraneoplastic SPS is commonly associated with antiamphiphysin antibodies and breast cancer 3
- Laboratory tests, such as electromyography and imaging studies, can help support the diagnosis of SPS 5