Stiff Person Syndrome Masquerading As Multiple Sclerosis

Background: Stiff person syndrome (SPS) is a rare neuroimmunological disorder that typically causes rigidity and spasms in the lower extremities and axial musculature.  Despite ‘classic’ features, SPS can present with a wide variety of signs and symptoms that mimic other neuro-inflammatory diseases.  As such, SPS often goes undiagnosed/misdiagnosed for years. 

Objectives: To describe a case series of patients with a diagnosis of SPS who were previously diagnosed with multiple sclerosis (MS).  

Methods: We performed a chart review of over 100 patients with SPS who were treated at Johns Hopkins Hospital and identified five patients previously diagnosed with MS.   

Results: Patients were female ranging 43-64 years-old. They presented with typical SPS symptoms (gait instability, axial/leg spasms) as well as atypical symptoms (hemiparesis, hemisensory dysfunction, and fine motor impairment) and were all initially given a diagnosis of possible/probable MS.  Brain MRI demonstrated non-enhancing lesions in the subcortical and periventricular white matter in three patients.  Spine MRI was unremarkable for all patients.  CSF analysis revealed normal IgG index and negative oligoclonal bands.  Symptom progression and hyperlordosis on exam prompted anti-glutamic acid decarboxylase (GAD65) antibody testing at 8 months to 15 years following initial symptom onset.  Anti-GAD65 antibody were elevated for each patient, ranging from 3.7 to ~40,000 U/ml.  Two patients were treated with disease-modifying therapy for MS, including one treated with three different therapies, before being diagnosed with SPS.  Following diagnosis with SPS, the patients were treated with varying combinations of benzodiazepines, IVIG, plasmapharesis, mycophenolate, and rituximab.  Four patients had stabilization or improvement of symptoms following initiation of SPS therapy.  

Conclusions: We present five patients with symptoms initially thought to be due to MS who were eventually diagnosed with SPS.  In one case, the patient’s MS therapy was escalated to natalizumab due to “disease progression”.  These cases highlight the challenges in evaluating patients with neurologic symptoms suggestive of MS, and indicate the need for consideration of alternate diagnoses, such as SPS, especially in patients who present with features atypical for MS.