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. Author manuscript; available in PMC: 2023 Aug 15.
Published in final edited form as: J Neuroimmunol. 2022 Jun 12;369:577915. doi: 10.1016/j.jneuroim.2022.577915

Table 1.

Examples of Expanded Diagnostic Criteria for Stiff Person Syndrome Spectrum Disorders

Phenotype Classic Partial SPS-plus Pure Cerebellar Ataxia Progressive encephalomyelitis with rigidity and myoclonus (PERM)
Major criteria • Clinical presentation including typical body regions involved (torso and lower extremities > upper extremities)
• Hallmark triggers for spasms/increased rigidity*
• Hallmark exam findings: hyperlordosis, rigidity of torso and/or extremity, paravertebral/abdominal muscle spasm/tightness, spasticity in extremity and/or gait, hyperreflexia with lower extremities > upper extremities
• Presence of serum autoantibody to GAD65 (high titer), glycine receptor, or amphiphysin
• Exclusion of alternative diagnoses and no better explanation for syndrome		 • Clinical presentation including typical body regions involved (isolated to one extremity or torso)
• Hallmark triggers for spasms/increased rigidity*
• Hallmark exam findings: hyperlordosis, rigidity of torso or extremity, paravertebral/abdominal muscle spasm/tightness, spasticity and/or hyperreflexia in affected extremity
• Presence of serum autoantibody to GAD65 (high titer), glycine receptor, or amphiphysin
• Exclusion of alternative diagnoses and no better explanation for syndrome		 • Clinical presentation including typical body regions involved (classic phenotype regions plus brainstem and/or cerebellar symptoms)
• Hallmark triggers for spasms/increased rigidity*
• Hallmark exam findings: classic phenotype exam findings plus brainstem (e.g., ocular motor dysfunction, dysarthria, dysphagia) and/or cerebellar signs (e.g., central nystagmus, appendicular or gait ataxia)
• Presence of serum autoantibody to GAD65 (high titer), glycine receptor, or amphiphysin
• Exclusion of alternative diagnoses and no better explanation for syndrome		 • Clinical presentation including typical body regions involved (e.g., central vertigo, unsteady ambulation, incoordination, poor manual dexterity, etc.)
• Exam findings: scanning speech, ocular motor dysfunction (vertigo nystagmus, sustained gaze evoked nystagmus, overshooting), appendicular dysmetria, and/or gait ataxia
• Presence of serum autoantibody to GAD65 (high titer), glycine receptor, or amphiphysin
• Exclusion of alternative diagnoses and no better explanation for syndrome		 • Clinical presentation including typical body regions involved (neck, torso, extremities, brainstem and/or cerebellar symptoms)
• Hallmark triggers for spasms/increased rigidity*
• Exam findings: admixture of other phenotypes findings plus encephalopathy and severe torso rigidity and/or myoclonus (multifocal or generalized)
• Presence of serum autoantibody to GAD65 (high titer), glycine receptor, or amphiphysin
• EEG (generalized slowing and/or epileptic discharges)
• Exclusion of alternative diagnoses and no better explanation for syndrome
Minor criteria • Presence of CSF autoantibody to GAD65, glycine receptor, or amphiphysin
• CSF-restricted OCB
• Electromyography demonstrating cocontraction of agonist and antagonist muscles and/or continuous motor unit activity in affected muscles (paraspinal/abdominal musculature and/or legs>arms)
• Robust response to muscle relaxers early on; especially GABAergic agonists (e.g., diazepam)		 • Presence of CSF autoantibody to GAD65, glycine receptor, or amphiphysin
• CSF-restricted OCB
• Electromyography demonstrating cocontraction of agonist and antagonist muscles and/or continuous motor unit activity in affected muscles (paraspinal/abdominal musculature or legs/arms)
• Robust response to muscle relaxers early on; especially GABAergic agonists (e.g., diazepam)		 • Presence of CSF autoantibody to GAD65, glycine receptor, or amphiphysin
• CSF-restricted OCB
• Electromyography demonstrating cocontraction of agonist and antagonist muscles and/or continuous motor unit activity in affected muscles (paraspinal/abdominal musculature and/or legs/arms)
• Robust response to muscle relaxers early on; especially GABAergic agonists (e.g., diazepam)		 • Presence of CSF autoantibody to GAD65, glycine receptor, or amphiphysin
• CSF-restricted OCB
• Brain MRI demonstrates cerebellar volume loss/atrophy
• Brain FDG-PET demonstrates hyper-or-
• hypometabolism of the cerebellum		 • Autonomic dysfunction
• Presence of CSF autoantibody to GAD65, glycine receptor, or amphiphysin
• CSF pleocytosis
• CSF-restricted OCB
• Electromyography demonstrating cocontraction of agonist and antagonist muscles and/or continuous motor unit activity in affected muscles (paraspinal/abdominal musculature and/or legs/arms)
• Brain MRI demonstrates T2/contrast-enhancing lesion(s) in brainstem
• Brain FDG-PET demonstrates hyper-or-hypometabolism within cortices

Abbreviations: OCB, oligoclonal bands; FDG-PET, fluorodeoxyglucose (FDG)-positron emission tomography; GAD65, glutamic acid decarboxylase 65-kilodalton isoform; EEG, electroencephalography; MRI, magnetic resonance imaging; CSF, cerebrospinal fluid.

*

abrupt loud noises, cold weather, open spaces, emotional stress (good and bad), and/or tactile stimuli

**

if paraneoplastic, typical cancer seen in SPSD found within 5 years of symptom onset.

***

Primarily upper torso/neck involvement is typical for amphiphysin associated paraneoplastic SPSD.

#

Less typical: involvement of face and neck; epilepsy; normal musculoskeletal and/or neurological exam over time; seronegative; pediatric onset

All Phenotypes (definitive, probable, or possible diagnosis)

Meets all major and minor criteria= Definitive diagnosis

Meets all major criteria and no minor criteria= Definitive diagnosis

Meets 4 major criteria (must include serum autoantibody and exclusion of alternative diagnoses and no better explanation for syndrome) and at least 2 minor criteria= Definitive diagnosis

Meets 3 major criteria (must include serum autoantibody and exclusion of alternative diagnoses and no better explanation for syndrome) and at least 2 minor criteria= Definitive diagnosis

Meets 3 major criteria (must include exclusion of alternative diagnoses and no better explanation for syndrome) and at least 2 minor criteria= Probable

Meets 3 major criteria (must include exclusion of alternative diagnoses and no better explanation for syndrome) and less than 2 minor criteria= Possible

Meets 2 major criteria (must include exclusion of alternative diagnoses and no better explanation for syndrome) and at least 2 minor criteria= Possible