Stiff Person Syndrome Masquerading as

Joseph J. Sabatino, Jr., MD/PhD1, Scott D. Newsome, DO1 1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Introduction Results Results • Stiff person syndrome (SPS) is a rare Table 1. Background information of patients included in study Figure 1. Severe lumbar hyperlordosis. autoimmune or paraneoplastic disorder that Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 classically causes rigidity and of the proximal and axial muscles and gait dysfunction Gender Female Female Female Female Female • It is typically associated wi th auto-antibodies against glutamic acid decarboxylase (GA D)65 and Ethnicity Afric an-Americ an Caucasian Afric an-Americ an Caucasian Caucasian with EMG findings revealing co-contraction of agonist and antagonist muscles and/or Medical history HTN, OSA, Migraine HTN, HLD DM, HTN, HLD, HTN, HLD, degenerative spine ulcerative colitis, intrac ranial continuous motor unit activity1,2. • disease neuropathy stenosis, psoriasis, Despite these ‘classic’ features, SPS is an melanoma enigmatic disease that can present with a wide Symptoms Gait instability, axial Poor memory recall, Foot tingling, leg Atypical leg sensory Gait instability, variety of , su ch as ataxi a and leg spasms and , hemi- stiffness, gait symptoms, leg balance 3,4 and encephalomyelitis that can mimic various rigidity, dysphagia, sensory defic its, instability, gait spasms, fine motor impairment, neuro-inflammatory diseases. dysarthria axial rigidity and dysfunction, limb impairment, dysarthria, fine spasms, leg and arm and axial rigidity, abdominal/back motor impairment, Objective , anxiety urinary urgency spasms, intermittent attacks urinary urgency, diplopia • We describe a case series of patients with a headache diagnosis of SPS who were previously diagnosed Abbreviations: HTN = hypertension, HLD = hyperlipidemia, DM = diabetes mellitus, OSA = obstructive sleep apnea. with multiple sclerosis (MS). Table 2. Patient exam findings, results, and treatment history Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Methods Exam findings Hypomimia, Lumbar Hypometric Bilateral upper Lumbar • We performed a retrospective chart review of dysarthria, axial hyperlordosis, T11- horizontal saccades, extremity hyperlordosis, left- over 100 patients with SPS who were treated at rigidity, 12 sensory level, lumbar , sided , bradykinesia, mild positive Romberg hyperlordosis, axial reduced vibration bilateral upper Johns Hopkins Hospital from 1996 to 2015 and proximal left-sided sign, spastic gait rigidity, lower sensation hands and extremity identified five patients previously diagnosed weakness and extremity feet, hyperreflexia, Conclusions with MS. dysmetria, slow hyperreflexia, left without or bilateral lower • SPS is a rare disease that is difficult to diagnose unsteady gait hemi-sensory instability extremity spasticity, • All review was done in accordance with the IRB- in its early presentation and it is often deficits, slow wide-based approved protocol. Detailed pertinent misdiagnosed. demographic and medical findings are outlined , unsteady gait impaired tandem • Each of the patients possessed a number of in Ta b l e s 1 a n d 2 . walking features that shared similarities between MS MRI findings Non-spec ific non- Non-spec ific non- Non-spec ific non- Numerous non- Minimal non- and SPS: strong female predominance, white Results enhancing enhancing enhancing enhancing spec ific non- matter abnormalities on MRI, as well as certain subc ortic al T2+ subc ortic al and subc ortic al and subc ortic al and enhancing signs/symptoms including gait and balance • Patients were female with an average age of 53 lesions, normal periventricular T2+ periventricular T2+ periventricular T2+ subc ortic al T2+ instability, progressive myelopathy, and bladder years old (range; 43-64). Average time to SPS spinal c ord lesions, lesions, normal lesions, normal lesions, normal issues. More importantly, each patient had diagnosis was 5.5 years for this cohort. questionable T2+ spinal c ord spinal c ord spinal c ord lesion at C6 features that were atypical of MS, including axial • Patients presented with typical SPS symptoms rigidity, prominent leg spasms, lack of MRI lesion CSF Results Not tested Normal Normal Normal Normal (axial/leg spasms, torso rigidity, gait instability) formation over time, lack of spine lesions, and as well as atypical symptoms (hemiparesis, EMG Results Normal Normal Not tested Normal Normal negative CSF oligoclonal bands. hemi-sensory dysfunction, and fine motor • These cases demonstrate the need to consider impairment) and were all initially given a Anti-GAD65 (U/ml) >40,000 130.7 18,420 2.4 19,580 less common neuroimmunological disorders, diagnosis of MS. such as SPS, especially in patients with atypical Age at Diagnosis 49 43 61 47 64 • Exam findings typical of SPS included axial features for MS. rigidity, lumbar hyperlordosis (figure 1), References spasticity, and slow unsteady gait. Time until SPS 8 months 6 years 3 years 3 years 15 years Diagnosis References • SPS diagnosis was supported by GAD65 Prior MS Therapy None Avonex , Copax one, None None Avonex 1.Ciccotto, G., Blaya, M. & K elley, R. E. Stiff Person Syndrome. Neurol. Clin . 31, antibodies in each patient at 8 months to 15 Tysabri 319–328 (2013). years after initial symptom onset. SPS Treatment BZD, anti- IVIG, BZD, anti- IVIG, BZD, anti- BZD, anti- BZD, anti- 2. Martinez-Hernandez, E. et al. Clinical and immunological investigations in 121 patients with stiff-per s on s pect r um d is ord er. JAMA Neurol.In p ress, 1–7 (2016). spasmodic s, PL EX, spasmodic s, spasmodic s, spasmodic s, spasmodic s, I VI G, • Two patients were previously treated with 3.Shaw, P. J . Stiff-man syndrome and its variants Radiological assessment of hip CellCept, Ritux imab, PLEX, CellCept, osteoarthritis. Lancet353,86–87 ( 199 9). disease-modifying therapies for MS, including RItuximab 4.Dalakas, M. C., Fujii, M., Li, M. & McElroy, B. The clinical spectrum of anti-GA D one treated with three different therapies, an t ib o d y-positive patients with stiff-person syndrome. Neu rology 55,15 31–1535 Treatment Worsening gait Improved Stabilized Improved Stabilized (2000). before being diagnosed with SPS. Response instability 5.Andreadou, E., K attoulas, E., Sf agos, C. & Vassilopoulos, D. Stif f person BZD = b en zo d iazep ine, IV IG = in tr aveno us immun oglob ulin, P LEX = p lasma exchan ge. *No rmal < 1 .0 U/ml. syndrome: avoiding misdiagnosis. Neu rol. Sci. 28, 35–7 ( 2007 ).