From the Guidelines
Diagnosing stiff person syndrome requires a comprehensive approach involving clinical evaluation, laboratory tests, and electrophysiological studies, with a key focus on detecting anti-glutamic acid decarboxylase (anti-GAD) antibodies, as recommended by recent guidelines 1. The diagnosis begins with recognizing the characteristic symptoms: progressive muscle stiffness and rigidity, primarily in the trunk and abdomen, along with painful muscle spasms triggered by emotional stress, sudden movements, or loud noises.
- Key diagnostic steps include:
- Clinical evaluation to identify characteristic symptoms
- Blood tests to detect anti-GAD antibodies, which are present in approximately 60-80% of cases
- Electromyography (EMG) to demonstrate continuous motor unit activity in affected muscles
- Lumbar puncture to analyze cerebrospinal fluid for elevated protein levels and oligoclonal bands
- Imaging studies like MRI of the brain and spinal cord to exclude other neurological conditions
- According to the study by Graus et al. 1, history of other antibody-mediated disorders or organ-specific autoimmunity, or previous infectious/febrile illness, can also be relevant in the diagnosis of stiff person syndrome.
- Response to benzodiazepines like diazepam can also support the diagnosis, as these medications typically provide symptomatic relief by enhancing GABA neurotransmission, which is impaired in this condition.
- Consultation with a neurologist experienced in movement disorders or autoimmune neurological conditions is strongly recommended for accurate diagnosis, given the rarity and complexity of stiff person syndrome 1.
From the Research
Diagnostic Criteria for Stiff Person Syndrome
To diagnose stiff person syndrome, the following criteria can be considered:
- Muscle rigidity, sporadic muscle spasms, and chronic muscle pain characterize SPS 2
- High titers of antibodies against acid decarboxylase (GAD65) are often found in patients with SPS 2, 3, 4, 5, 6
- Nonmotor symptoms such as phobias, anxiety, and depression may also be present 3
- SPS can be classified into different variants, including classic SPS, focal or segmental-SPS, jerking-SPS, and progressive encephalomyelitis with rigidity and myoclonus 4
Laboratory Tests and Diagnostic Markers
The following laboratory tests and diagnostic markers can be used to support the diagnosis of SPS:
- Presence of antibodies against GAD65 2, 3, 4, 5, 6
- Antibodies against other neuronal proteins, such as glycine receptor, amphiphysin, dipeptidyl-peptidase-like protein 6, gephyrin, and γ-aminobutyric acid receptor A (GABAAR) 3, 4
- Electrophysiological studies, such as electromyography (EMG) and nerve conduction studies (NCS), may also be helpful in supporting the diagnosis 5
Differential Diagnosis
The following conditions should be considered in the differential diagnosis of SPS:
- Other autoimmune disorders, such as multiple sclerosis and rheumatoid arthritis 2
- Neurodegenerative disorders, such as Parkinson's disease and amyotrophic lateral sclerosis 3
- Psychiatric disorders, such as anxiety and depression 3
Diagnostic Challenges
Diagnosing SPS can be challenging due to the following factors: