Diagnosis Of Stiff Person Syndrome Research Articles

Autoimmune Retinopathy in a Patient with Stiff-Person Syndrome: A Case Report.

To describe a patient who developed retinal degeneration associated with autoimmune retinopathy (AIR) and who was also found to have anti-glutamic acid decarboxylase (GAD65) autoantibodies and the diagnosis of stiff-person syndrome (SPS). Ophthalmologic workup consisted of clinical examination, multi-modality retinal imaging, and electrophysiologic testing. Further neurologic assessment including relevant serum and cerebrospinal fluid studies was also conducted. We highlight the case of a 45-year-old patient who developed subacute, sequential vision loss, along with bilateral lower extremity weakness. On initial presentation, optical coherence tomography (OCT) of the left eye was notable for diffuse attenuation of the outer retinal bands. Fundus autofluorescence demonstrated a ring of hyper-autofluorescence encircling the fovea of the left eye. At fifteen-month follow-up, the right eye also became similarly affected. He was found to have elevated serum and cerebrospinal anti-GAD65 autoantibodies and was diagnosed with both SPS and AIR. There is a potential association of anti-GAD65 autoantibodies with the development of AIR.

THU246 What’s The Importance of GAD Antibodies In Patients With Stiff Person Syndrome

Abstract Disclosure: A. Barnett: None. G. Elshimy: None. Introduction: Stiff Person Syndrome (SPS) has a strong autoimmune component with positive serology for GAD-65 antibody as one of the diagnostic criteria. GAD is an enzyme selectively concentrated in neurons secreting the neurotransmitter gamma-aminobutyric acid (GABA) but is also present in pancreatic beta cells. Hence, insulin-dependent diabetes mellitus (LADA) can develop in patients with SPS. We present two cases that highlight the importance of this association and the difference in the time of onset to ensure appropriate screening. Case: Our first case was a 46-year-old female with systemic sclerosis and SPS that was diagnosed with steroid-induced diabetes in 2012 with HbA1c 8.7% (4.3-6.1%). Her GAD-65 antibody was significantly elevated at 1971 (less than 2nmol/L). For almost 8 years, the patient only required insulin therapy while on high dose steroids, but eventually developed persistent hyperglycemia requiring insulin therapy. Her C-peptide was 0.49 (0.78-5.19ng/mL) with plasma glucose of 201 (74-106mg/dL), consistent with beta-cell dysfunction. The second case was a 60-year-old female with a 20-year history of SPS who was diagnosed with type 2 diabetes in 2014 after receiving high doses of steroids while undergoing chemotherapy for breast cancer. She was initially well-controlled on oral medications until 2 years after her initial diabetes diagnosis where her HbA1c increased rapidly to 8.1% (4.8-5.9%). At that time, she was started on insulin therapy and antibody testing was pursued which showed positive GAD-65 antibody greater than 250 (less than 5IU/mL) consistent with LADA. She had a negative IA-2 antibody undetectable. Due to other autoimmune associations, she was also screened for thyroid disease revealing an elevated TPO-antibody with a normal TSH 4.02 that is being monitored. Discussion: SPS is associated with autoantibodies and other autoimmune disorders including but not limited to type 1 diabetes, anti-thyroglobulin antibodies and anti-parietal cell antibodies. In both cases, the diagnosis of SPS preceded the onset of diabetes then with a latent “honeymoon” phase not requiring long-term insulin therapy for years, most consistent with LADA. However, there are exacerbating factors including high-dose steroids which could be misleading and result in diagnosing these patients with type 2 diabetes initially. It should be taken into consideration that there is variability in the time of onset of beta-cell dysfunction, which varied from 2 to 8 years in our patients. Hence, the recognition of the correlation of autoimmune-mediated diabetes and the variable time course to insulin deficiency is critical for the continued monitoring in patients with SPS. Physicians should be aware of the importance of screening patients with SPS for type 1 diabetes mellitus and differentiate it from steroid-induced type 2 diabetes to avoid developing diabetic ketoacidosis in these patients. Presentation: Thursday, June 15, 2023

THU356 Muscle Pain In A Diabetic: Think Outside The Box

Abstract Disclosure: R. Ellangovan: None. M. Rizk: None. V. Singh MD: None. C. Sherpa: None. Introduction: Stiff person syndrome (SPS) is a rare immunological disorder associated with GAD antibody-spectrum disorders and characterized by rigidity and painful muscle spasms. SPS has a prevalence of 1-2 cases per million and affects females more than men. We present a case of SPS who was admitted for progressive muscle pain and rigidity causing impaired ambulation. Case Presentation: A 60-year-old female with a two-year history of type 2 diabetes, Graves' disease was diagnosed with acral lentiginous melanoma of the left foot. One month after Nivolumab immunotherapy, she converted to type 1 diabetes with low C-peptide and positive GAD antibody. She was admitted with severe muscle pain and spasms in her lower extremities and trunk, debilitating enough to make her bedbound. Her muscle strength and sensory function were intact. MRI of thigh was concerning for myositis versus diabetic myonecrosis. She was initiated on NSAIDs with no improvement. Core muscle biopsy revealed necrosis and granulation tissue with no evidence of malignancy. Extensive work up including myositis panel and myasthenia gravis panel were negative. The presence of GAD antibodies and no improvement to NSAIDs, prompted suspicion for SPS. The patient declined lumbar puncture (LP) for further evaluation. Diazepam showed mild improvement. Due to persistent severe symptoms, she was treated with IVIG for 5 days that resulted in marked improvement. Discussion: There is no gold standard test for definitive diagnosis of SPS. Classic features of SPS include muscle spasms, pain, and rigidity typically involving the trunk and lower extremities. There are GAD antibodies in serum and CSF and glycine receptor or amphiphysin antibodies. EMG study will show continuous motor unit activity in affected muscles. A robust response to muscle relaxants like GABA agonists and exclusion of alternative neurological disorder favors SPS. LP or EMG was not performed on this patient, yet she met other criteria including the presence of other GAD disorders like type 1 diabetes. Current recommended therapy for symptomatic relief includes GABA agonists or baclofen. If no improvement is noted, IVIG can be considered. Plasmapheresis and rituximab have been used with variable efficacy. Prognosis is variable and many patients experience disability despite combining multiple therapies. Hence it is crucial to have a high index of suspicion in GAD spectrum disorders for early recognition and prompt treatment. Presentation: Thursday, June 15, 2023

Prevalence, Clinical Profiles, and Prognosis of Stiff-Person Syndrome in a Japanese Nationwide Survey.

To elucidate current epidemiologic, clinical, and immunologic profiles and treatments of stiff-person syndrome (SPS) in Japan. A nationwide mail survey was conducted using an established method. Data processing sheets were sent to randomly selected departments of internal medicine, neurology, pediatrics, psychiatry, and neurosurgery in hospitals and clinics throughout Japan to identify patients with SPS who were seen between January 2015 and December 2017. Thirty cases were identified as glutamic acid decarboxylase 65 (GAD65)-positive SPS cases on the basis of detailed clinical data of 55 cases. Four patients had α1 subunit of glycine receptor (GlyR) antibodies, and 1 patient had both GAD65 and GlyR antibodies. The total estimated number of patients with GAD65-positive SPS was 140, and the estimated prevalence was 0.11 per 100,000 population. The median age at onset was 51 years (range, 26-83 years), and 23 (76%) were female. Of these, 70% had classic SPS, and 30% had stiff-limb syndrome. The median time from symptom onset to diagnosis was significantly longer in the high-titer GAD65 antibody group than in the low-titer group (13 months vs 2.5 months, p = 0.01). The median modified Rankin Scale (mRS) at baseline was 4, and the median mRS at the last follow-up was 2. Among the 29 GAD65-positive patients with ≥1 year follow-up, 7 received only symptomatic treatment, 9 underwent immunotherapy without long-term immunotherapy, and 13 received long-term immunotherapy such as oral prednisolone. The coexistence of type 1 diabetes mellitus and the lack of long-term immunotherapy were independent risk factors for poor outcome (mRS ≥3) in the GAD65-positive patients (odds ratio, 15.0; 95% CI 2.6-131.6; p = 0.001; odds ratio, 19.8; 95% CI 3.2-191.5; p = 0.001, respectively). This study provides the current epidemiologic and clinical status of SPS in Japan. The symptom onset to the diagnosis of SPS was longer in patients with high-titer GAD65 antibodies than in those with low-titer GAD65 antibodies. The outcome of patients with SPS was generally favorable, but more aggressive immunotherapies are necessary for GAD65-positive patients with SPS.

Stiff Person Syndrome Mimicking as Atypical Parkinson’s Disease - A Diagnostic Dilemma

Stiff person syndrome (SPS) is a rare neurological disorder characterized by stiffness and spasm of the truncal muscles and subsequent postural deformities. In this report, we present a case of a woman in her early 60s who presented to us with muscle stiffness, back pain, and frequent falls. On examination, she was found to have increased muscle tone and mild tremors. Given her age and presentation, a provisional diagnosis of Atypical Parkinson’s was made. Patient was treated with Diazepam. Because of presence of autoimmune co-morbid conditions, anti-glutamic acid decarboxylase (GAD) antibodies were tested, which were positive, and thus, diagnosis of SPS was made. Treatment with Diazepam was continued, and her symptoms significantly improved. Even though SPS is a rare disorder, our case report highlights the need to keep it in differential diagnoses when an elderly patient presents with stiffness and postural instability, as treatment for SPS and atypical Parkinson’s vary considerably.

Abstract #1394329: An Association Between Stiff Person Syndrome and Type 1 Diabetes

Stiff-person syndrome (SPS) is a rare neuromuscular disorder characterized by progressive muscular spasms and rigidity. Anti-glutamic acid decarboxylase (anti-GAD) antibodies are found in type 1 diabetes mellitus (T1DM). Thirty percent of patients diagnosed with SPS have T1DM. This relationship infers that SPS and T1DM share pathogenetic features. We describe a case of a 66-year-old female with a history of SPS who developed T1DM soon after the diagnosis was made. A 66-year-old female with a history of SPS, T1DM, and discoid lupus was referred to our university endocrinology clinic for diabetes management. She had ataxia, loss of balance, and muscle stiffness since 2012. The patient was diagnosed with spinal cerebellar ataxia. She was not treated with any specific agents and continued to have left-sided muscle stiffness with preserved strength. She denied weakness, pain, paresthesia, or muscle atrophy but had difficulty ambulating due to rigidity. The diagnosis of SPS was made based on positive anti-GAD antibodies (normal < 0.02) and positive N-channel antibodies in April 2016. She required hospital admission one month later and received solumedrol and IVIG. Her HbA1c was 6.5% (normal < 5.7% of total Hgb), and glucose levels were between 200-300 mg/dL, which were treated with basal and bolus insulin. She was discharged home in May 2016 with no diabetic medications. The patient developed polyuria and polydipsia with 11 Ibs unintentional weight loss 20 days after hospital discharge. She was referred to the endocrine clinic in June 2016 for further workup. Her HbA1c was 11% with C-peptide less than 0.01 (normal 0.78-5.20 ng/mL). Basal and bolus insulin were initiated, and she remains on an insulin regimen. SPS affects an estimated one person per million per year. Decreased level of gamma amino butyric acid (GABA) in the central nervous system (CNS) in SPS has been implicated, which causes a loss of neural inhibition. Glutamic acid decarboxylase (GAD) is the main enzyme required for the GABA inhibitory pathway. Anti-GAD antibodies decrease inhibitory function within the CNS and cause increased muscle activities and subsequent muscle spasms. While most patients with T1DM do not develop SPS, most with anti-GAD-positive SPS will have or develop T1DM. Either SPS or T1DM may be diagnosed first. Awareness of these associations is essential for early diagnosis and treatment of these disorders.

Development and Validation of Machine Learning and Electronic Medical Records-Based Characterization of Stiff Person Syndrome (P5-8.001)

<h3>Objective:</h3> To develop and validate an objective framework in identifying medical history items that best characterize the diagnosis of Stiff Person Syndrome (SPS). <h3>Background:</h3> SPS is a rare neurologic disorder with characteristic muscle spasms and painful rigidity. While electronic medical records may contain items that can help refine its diagnostic criteria, the rarity of SPS leads to statistical underpowering in conventional tests. A machine learning approach that leverages underutilized electronic medical records may reveal clinical features that are strongly associated with the diagnosis of SPS. <h3>Design/Methods:</h3> This retrospective cohort study assessed 23 patients carrying SPS diagnoses and 25 controls who were all anti-GAD positive and were treated at Dartmouth Hitchcock Medical Center. After binarizing the 319 clinical features, we employed an iterative machine-learning-based feature selection approach (Contribution Selection Algorithm) to identify variables that best discriminate between patients with SPS vs. anti-GAD positive controls. Each iteration generated SHapley Additive exPlanation (SHAP) values for each binarized feature. Classifier accuracy, AUC, and Matthews Correlation Coefficients (MCC) for the Support Vector Machine models were calculated using repeated stratified 4-fold cross-validation. <h3>Results:</h3> The feature selection algorithm identified depression, pain in joint, hypothyroidism, and GERD as the top 4 predictors of SPS, as the SVM model that employed these features achieved the best predictive performance with a binary classification accuracy of 0.775 (95%CI, 0.759–0.790), an AUC of 0.808 (95%CI, 0.791–0.825), and a MCC of 0.565 (95%CI, 0.534–0.597). <h3>Conclusions:</h3> Our machine learning-based architecture identified features that are strongly associated with SPS. By circumventing the limitations of statistical underpowering and focusing on identifying associations through induction, this approach may act as a powerful tool for generating new hypotheses for rare disorders. This framework complements hypothesis-driven investigations, together forming a closed loop approach to aid diagnostic challenges in neurology. <b>Disclosure:</b> Mr. Park has nothing to disclose. Dr. Song has nothing to disclose.

P-NE014. Electromyography in the diagnosis of stiff-person syndrome

Introduction . Stiff-person syndrome (SPS) is a rare autoimmune or paraneoplastic disorder with a wide clinical spectrum but core features of trunk and limb stiffness and muscle spasms. It is commonly associated with glutamic acid decarboxylase (GAD 65) antibody and responds to treatment with benzodiazepines and immunotherapy. We present the details of a patient with SPS and highlight the diagnostic utility of electromyography (EMG). Results . A 58-years-old man developed progressive asymmetric stiffness of both lower limbs and walking difficulty of ten months duration. Superimposed on that, he had painful spasms of lower limb which were triggered by sound or touch. On examination, he was found to have asymmetric hypertonia in both lower limbs and gait difficulty requiring the assistance of two- persons to walk. Serum GAD-65 antibody was strongly positive. He underwent electrophysiological evaluation. Nerve conduction studies were normal. Lower limb surface EMG with recording from quadriceps, hamstrings, tibialis anterior, and lateral head of gastrocnemius on the right side and quadriceps and hamstrings on the left side was performed. It showed continuous motor unit activity in agonist and antagonist muscle groups. After the administration of diazepam, the motor unit activity reduced significantly while stimulation with a loud sound led to an increased in activity. Based on these findings, he was diagnosed with SPS and treated with immunotherapy and symptomatic medications. He had significant improvement and was able to walk independently at four months of follow up. Conclusion . SPS is a rare but treatable neurological illness that can be confused with many other disorders like parkinsonism, dystonia, musculoskeletal, psychogenic, etc. EMG can provide a useful clue to the diagnosis by demonstrating characteristic continuous motor unit activity in agonist and antagonist muscles which triggered by specific stimuli and improved with diazepam.

169-LB: Type 1 Diabetes Mellitus and Stiff-Person Syndrome

Introduction: Type 1 diabetes mellitus (T1DM) is often associated with other autoimmune diseases. One of them is Stiff-Person Syndrome (SPS), a rare neurological disorder characterized by muscle spasms and progressive muscle stiffness, which most often affects females. Glutamic acid decarboxylase antibodies (anti-GAD) are associated with the pathogenesis of this disease as well as T1DM. These antibodies cause a deficit in the synthesis of γ-aminobutyric acid (GABA) that is essential both in the function as neurotransmitter and in the secretion of insulin in pancreatic β cells. Clinical case: We present the case of a 32-year-old female patient diagnosed with T1DM at 18 years old. Currently under intensive functional insulin therapy and flash glucose monitoring (FGM). Since 2019 with subcutaneous insulin infusion system. At the age of 26, the patient reports dystonia in the left lower limb with subsequent involvement of the contralateral lower limb, upper limbs, trunk and face. Collaboration was made with the Neurology department. Among the laboratory findings, of note: positive serum anti-GAD65 (5437 U/mL; &amp;lt;1) and positive cerebrospinal fluid anti-GAD65 (126.23 U /mL; &amp;lt;1). The diagnosis of SPS was made. The patient started human immunoglobulin therapy with progressive clinical improvement. Estimated HbA1c from FGM was 6,8 % at February, 2021. Discussion: The association between T1DM and SPS is frequent. In this case, a patient with a known history of T1DM was presented, but cases of diagnosis of T1DM in patients with SPS have also been described. About 43% of patients have T1DM at the time of diagnosis of SPS. Anti-GAD are involved in the pathophysiology of these two diseases and anti-GAD titers are much higher in cases of association with SPS (about 50 to 100 times). In the treatment of patients with T1DM, physicians should be alert to the onset of other autoimmune diseases and active surveillance is essential for early diagnosis. Disclosure C. A. Araújo: None. C. Baptista: None. I. Paiva: None. A. Morgadinho: None.

A Case of Stiffperson Syndrome

Stiffperson syndrome (SPS) is one of the rarest neurological disorders. It is an autoimmune disease with antibodies against glutamic acid decarboxylase - enzyme needed to produce neurotransmitter GABA. This disease is very debilitating and fatal if not managed in time. A 32-year-old man presented with stiffness of abdominal and thoracolumbar paraspinal muscles first noticed 10 months back. There was history of jerkiness of hands. After excluding other mimicking conditions like multiple sclerosis, parkinsonism and axial dystonia, a diagnosis of Stiffperson syndrome was made. Treatment with IVIG therapy along with anti-spasticity drugs resulted in improved patient outcome. SPS is potentially treatable though cannot be cured. Not one treatment fits all patients with SPS and may have to be tailored according to the clinical manifestations. Increasing awareness in medical doctors and identifying the disease early can help the patients escape the disabling effects of SPS and improve the quality of life.

The Dilemma, Conversion Disorder or Stiff Person Syndrome, a Case Report

The main objectives of this case study are 1. Clinicians facing symptoms that are difficult to interpret should exercise caution in diagnosing conversion disorder. 2. Increasing awareness about rare neurological conditions may appear as psychogenic illnesses. 3. Clinicians be advocate for their patients. Conversion disorder is a mental condition in which a person present with one or more symptoms of altered voluntary motor or sensory function, or other neurologic symptoms that cannot be explained by medical evaluation. Stiff person syndrome (SPS) is a disabling autoimmune central nervous system disorder characterized by progressive muscle rigidity, gait impairment, with superimposed painful spasms. SPS is commonly associated with high anti-glutamic acid decarboxylase (GAD) antibody titers. The dominant antigen recognized by these antibodies is the GABA-synthesizing enzyme GAD. Patient X, a 17-year-old Hispanic American female who presented to the Child and Adolescent Psychiatry Clinic with the complaint of ataxia & aphasia associated with anxiety. Patient was referred by the neurology clinic after they could not establish any organic cause of her ataxia or aphasia. After thorough evaluation at the child psychiatry clinic she was given the diagnosis of anxiety secondary to ataxia and aphasia and r/o Conversion Disorder. She was initiated treatment with sertraline for her anxiety. Her sertraline dose was increased gradually up to 100 mg daily. From the beginning the patient also received counseling & physical therapy. With these combination of treatments, patient's symptoms did not get any better. Her symptoms actually got worse over time. At this point, the Child Psychiatry Clinic sent a message to the neurology clinic for further evaluation of patient due to her progressive gait and speech impairments. The neurology clinic saw the patient again and did further testing. The patient was positive for high titers of anti-glutamic acid decarboxylase antibodies (Anti-GAD). At this point, the patient was given the diagnosis of Stiff Person Syndrome. Patient was admitted to the hospital for further management. She was treated with benzodiazepines, IV immune globulin, & steroid. Soon after discharge from the hospital, the patient was seen at the Child Psychiatric Clinic. The patient's mother reported, after the in-patient treatment, the patient's symptoms improved. It is essential for clinicians to look for neurologic & other general medical conditions while evaluating a patient with possible conversion disorder. A systematic review of 27 studies found that among 1466 patients initially diagnosed with conversion symptoms, the frequency of misdiagnosis was approximately 4 percent.References. BMJ. 2005;331(7523):989. Epub Oct 13. Childhood onset of stiff-man syndrome. JAMA Neurol. 2013;70(12):1531. J Neurol Neurosurg Psychiatry. 2015 Aug; 86(8):840-8. Epub 2014 Dec 15.

Stiff-Person Syndrome and Psychiatric Comorbidities: A Systematic Review.

Stiff-person syndrome (SPS) is a rare autoimmune neurologic disease characterized by painful rigidity and muscle spasms. Patients with SPS may present with psychiatric symptoms, and little is known about the presence of psychiatric comorbidities. The objective of this study was to provide an overview of the association between SPS and psychiatric illnesses. The protocol is registered in PROSPERO (Registration ID CRD42020159354). Peer-reviewed articles on adults with SPS and psychiatric comorbidities published before May 26, 2020, were selected by 2 independent reviewers. Qualitative summary data and relative risk of psychiatric disorders in patients with SPS compared with the general population and multiple sclerosis were calculated. After screening 909 articles, 52 full texts were assessed for eligibility and 27 were ultimately included, 5 of which were selected for quantitative analysis. Although limited by small sample sizes leading to large confidence intervals, the relative risk of any psychiatric comorbidity in SPS was higher than that of the general population, ranging from estimates of 6.09 (95% confidence interval: 4.09, 9.08) to 11.25 (95% confidence interval: 3.27, 38.66). There was no statistically significant difference in the risk of any psychiatric comorbidity between SPS and multiple sclerosis. The review also highlighted delays in SPS diagnosis, often related to misattribution of symptoms as being solely secondary to a psychiatric cause. The higher risk of psychiatric comorbidities emphasizes the important role of psychiatrists in recognizing the symptoms of SPS to reach timely diagnosis and treatment. The presence of psychiatric symptoms should support rather than delay the diagnosis of SPS.

An Appraisal of Electrodiagnostic Studies in Stiff Person Syndrome.

A literature review was performed on the use of electrodiagnostic (EDX) tests including nerve conduction study, electromyography, exteroceptive reflex, blink reflex, and late response in the evaluation of patients with stiff person syndrome (SPS). A web survey was conducted to report the extent of EDX testing usage in the evaluation of SPS among laboratories accredited by the American Academy of Neuromuscular and Electrodiagnostic Medicine. Coactivation of selected agonist and antagonist muscles was performed in 5 healthy subjects to determine its specificity for SPS. Observation of continuous motor unit activity on electromyography and elicitation of exteroceptive reflexes by electric stimulation are informative in assisting a diagnosis of SPS, but further studies focusing on their sensitivities in diagnosing SPS and specificities in differentiating SPS from other movement disorders are needed. The value of EDX testing in SPS lies in ruling out other neuromuscular disorders.

Subcutaneous immunoglobulin for maintenance therapy in stiff-person syndrome: One-year follow-up in two patients

Stiff person syndrome is a rare condition characterised by prolonged stiffness with superimposed muscle spasms. Immunotherapy relies mainly on intravenous immunoglobulin, steroids and plasma exchange. Azathioprine or rituximab are other possible options. We describe two patients who showed a good clinical response with intravenous immunoglobulin and persistence of the clinical improvement after shifting to equivalent dosage of subcutaneous immunoglobulin. Both patients received a diagnosis of stiff person syndrome based on their clinical symptoms (episodes of stiffness and spasms) and presence of antiglutamic acid decarboxylase. Treatment with intravenous immunoglobulin was started with improvement of symptoms as reported by patients and confirmed also by the spasm frequency scale and modified Ashworth scale. After clinical stabilisation in order to avoid the hospitalisation required for intravenous immunoglobulin treatment a switch to subcutaneous immunoglobulins was made. After one year of follow-up from the switch, the patients show clinical stability. Their scores on the modified Ashworth scale, spasm frequency scale and on the 10 Meter Walking Test were also stable. Subcutaneous formulation of immunoglobulin could be as effective as intravenous immunoglobulin in the maintenance treatment of Stiff person syndrome, although studies involving a larger cohort of patients are needed in order to confirm our anecdotal experience.

Association of stiff-person syndrome with autoimmune endocrine diseases.

BACKGROUNDStiff-person syndrome (SPS) and its subtype, stiff limb syndrome (SLS), are rare neurological disorders characterized by progressive muscular rigidity and spasms. Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the production of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter of the central nervous system. SPS is an autoimmune disease triggered by anti-glutamic acid decarboxylase antibody (anti-GAD Ab). Clinically, anti-GAD Ab is associated with SPS, type 1 diabetes mellitus (T1DM), and other autoimmune diseases.AIMTo investigate the link of autoimmune endocrine disorders with anti-GAD Ab in SPS subjects.METHODSThis retrospective study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Taiwan. We collected the patients with SPS from January 2001 to June 2018. By reviewing 14 patients from medical records, we analyzed the clinical findings with coexisting autoimmune diseases, particularly diabetes mellitus and thyroid disease, which are associated with anti-GAD antibody titers or other immunological test results (anti-thyroid peroxidase and anti-nuclear antibodies). We also evaluated malignancies, major complications, and reported treatment to improve symptoms. Anti-GAD antibodies were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). The cut-off values of these tests are < 1 U/mL and < 5 U/mL, respectively.RESULTSThe median age of all patients was 39.3 (range, 28.0-54.0) years with a median follow-up period of 6.0 (2.7-13.3) years. Five (35.7%) patients were female; twelve (85.7%) were diagnosed with classic SPS and two (14.3%) with SLS. The median age of onset of symptoms was 35.0 (26.0-56.0) years with a median follow-up duration of 9.0 (2.1-14.9) years in the classic SPS group; the SLS group had a median age of onset of 46.7 years and a shorter follow-up duration of 4.3 years. Among nine classic SPS patients who underwent the anti-GAD Ab test, three were anti-GAD Ab seropositive and each of these three patients also had T1DM, latent autoimmune diabetes in adults, and autoimmune thyroid disease, respectively. In contrast, other rare autoimmune diseases co-existed in six anti-GAD Ab seronegative SPS patients. None of the SLS patients had additional autoimmune diseases.CONCLUSIONWhile typical clinical symptoms are crucial for the diagnosis of SPS, the presence of anti-GAD autoantibody may consolidate the diagnosis and predict the association with other autoimmune diseases.

SUN-583 Immune Thrombocytopenic Purpura Associated with Stiff Person Syndrome and Polyglandular Autoimmune Syndrome Type 2

Background Idiopathic thrombocytopenic purpura (ITP) is an acquired autoimmune disease caused by antibodies against platelet glycoproteins. Stiff person syndrome (SPS) is a progressive neurological disorder characterized by axial muscle rigidity and involuntary spasms associated with anti-glutamic acid decarboxylase (GAD) antibodies. Polyglandular autoimmune syndrome type 2 (APS-2) is defined by the occurrence of Addison disease with thyroid autoimmune disease and/or Type 1 diabetes mellitus (T1DM). SPS has been associated with APS-2 as well as to T1DM and autoimmune thyroid disease alone. ITP has been linked T1DM in rare cases as well as autoimmune thyroid disease, yet SPS and ITP have not previously been associated. We present the first reported case to our knowledge of a patient with ITP subsequent to Graves disease, SPS and T1DM. Clinical Case The patient is a 35-year-old female evaluated in endocrinology clinic for follow up of Graves disease treated with RAI ablation 5 years prior. She presented with fluctuating muscle rigidity and spasms involving the axial muscles leading to gait disturbance and frequent falls. She displayed the classic “wooden-man” appearance when ambulating first described by Moersch and Wotmann which lead to the name of SPS. She was treated with diazepam due to clinical suspicion for SPS. Neurology was consulted, both the referring physician and neurologist agreed with the diagnosis of SPS. Her symptoms gradually improved yet they have proven to be relapsing and remitting in nature requiring modification of dosing depending on response. 7 years later she was diagnosed with T1DM, presenting to the ED with generalized weakness and fatigue. Initial laboratory work was consistent with DKA. During her hospitalization routine laboratory work showed incidental thrombocytopenia with a platelet count of 15,000. Over the next few days her platelet count dropped to 5,000 prompting diagnostic bone marrow aspiration and biopsy which revealed a hypercellular marrow and adequate megakaryopoiesis. ITP was the working diagnosis and patient was discharged with prednisone. A favorable response to therapy was noted and prednisone was tapered accordingly. 2 years later she presented with a relapse of ITP with a platelet count of 6,000; treatment was initiated with intermittent prednisone and IVIG. At this time T1DM and thyroid disease were well controlled. Serum GAD-antibodies tested after presentation of ITP were >250 IU/ml (0-5.0 IU/ml). Conclusion To our knowledge ITP has not previously been documented in a patient with SPS. Our goal is to create physician awareness regarding the association between these disorders as well as the need for regular monitoring of patients with an endocrine autoimmune disease. SPS has been linked to APS-2; yet is it possible that SPS can independently be associated with ITP?

Improved Gait, Diplopia, Motor Speed, Symptoms, and Cognition in a 60-year-old female Patient with Stiff Person Syndrome

Improved Gait, Diplopia, Motor Speed, Symptoms, and Cognition in a 60-year-old female Patient with Stiff Person Syndrome

F59. Spasmodic reflex myoclonus-an characteristic electrophysiological manifestation for the diagnosis of Stiff-person syndrome

Introduction Stiff person syndrome (SPS) is a rare disease entity and the pivotal clinical features contain progressive course of fluctuating stiffness of the low back and lower limbs. Progressive encephalomyelitis with rigidity and myoclonus (PERM) is one of the unique variants of stiff person syndrome, and it was characterized with rigidity, stimulus-sensitive spasms, myoclonus, autonomic disturbance, and brainstem signs. These features resemble those of hyperekplexia. The accurate diagnosis of SPS is difficult but is crucial for the in time intervention with immunotherapy for life saving. In addition to the detection of responsible antibody, clinical electrophysiological manifestation, spasmodic reflex myoclonus, would be of great help in establishing the diagnosis. Methods Multichannel surface electromyogram (sEMG) and accelerometer recordings were conducted over the lumbar paraspinalis, rectus abdominalis, quadriceps, and hamstring muscles. Stimulus sensitive phenomenon was illustrated with accelerometer tapped over the pinprick. The signals were processed and digitized with CED power1401 with Spike2. The band pass for sEMG was set from 80 Hz to 1000 Hz. Results The results demonstrated that episodes of spontaneous onset of spasm of the low trunk and legs lasted about seconds to minutes. Stimuli with nose tip tapping, would elicit vigorous jerks with dissemination of long lasting muscle spasm of the neck, paraspinal muscle, rectus abdominalis muscle, to quadriceps and hamstring muscles in a descending spreading pattern. The unique electrophysiological manifestations illustrate the characteristic feature of spasmodic reflex myoclonus. The surface EMG recording also showed the phenomena of habituation, in which a trend of amplitude decrescendo from the first toward the third EMG responses were observed during consecutive auditory stimulus. The serum levels of anti-glutamic acid decarboxylase 65 antibodies was 164 IU. Conclusion The unique EMG pattern can help identify SPS. The clinical features of spasmodic reflex myoclonus are similar to hyperekplexia. However, there are some differences between the two phenomena. Unlike hyperekplexia, the spasmodic reflex myoclonus can be habituated after repetitive stimulation in the SPS patient. Furthermore, the initial myoclonic bursts of spasmodic reflex myoclonus were not present in hyperekplexia and the EMG burst duration was much shorter of the hyperekplexia as compared with that of spasmodic reflex myoclonus. These neurophysiological features discern spasmodic reflex myoclonus from hyperekplexia and are helpful in making diagnosis of SPS.

Thymic Abnormalities and Stiff Person Syndrome

SESSION TITLE: Global Case Report Poster - Cardiothoracic Surgery SESSION TYPE: Global Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder characterized by painful muscle spasms and rigidity. It may be seen in association with other autoimmune diseases, and 60% of patients have anti-glutaminic acid decarboxylase (GAD) antibodies. There are limited reports of patients experiencing significant improvement of their symptoms following a thymectomy. We report on 2 patients with SPS who underwent thymectomies at our institution. CASE PRESENTATION: A 39-year-old lady presented with frequent falls associated with lower back pain and stiffness of her lower limbs which led to difficulties with ambulation. A diagnosis of SPS was made based on her symptoms, an electromyogram (EMG) showing continuous motor unit activity and elevated anti-glutamic acid decarboxylase (GAD) antibody levels. Computed tomography (CT) scan of the thorax revealed a large well-circumscribed mediastinal mass (Fig.1 and 2), which was confirmed to be a thymoma after percutaneous biopsy. She underwent surgical resection of the mass and histopathology revealed a Modified Masaoka Stage IIa type B1 thymoma. Post operatively, she made an uneventful recovery and was able to ambulate independently with a walking frame on discharge. Our second patient was a 54-year-old ophthalmologist who presented with intermittent episodes of myoclonic jerks of her trunk, worsened by stress and auditory or tactile stimuli with elevated anti-GAD antibody levels. CT thorax revealed a hyperdense heterogeneity in the anterior superior mediastinal region. She underwent surgery and histopathology showed thymic tissue with reactive lymphoid hyperplasia. Her symptoms improved post-operatively and she was able to resume work. DISCUSSION: SPS associated with thymic abnormalities occurs more frequently in females (66%), and mean age of diagnosis was 55 years. Currently, there are 7 reported cases worldwide of SPS associated with thymoma, with patients reporting a significant improvement of symptoms following thymectomy. Most were World Health Organisation (WHO) type B1/B2 thymomas, with one AB and one invasive carcinoma. Five of the 7 cases had elevated anti-GAD antibody levels, which dropped significantly post-thymectomy. Symptom recurrence occurred spontaneously or following tactile stimuli in 3 of these cases. This was successfully controlled with pyridostigmine, intravenous immunoglobulin (IVIG) or plasmapheresis. All patients remained symptom free on long term follow up. CONCLUSIONS: In conclusion, limited reports suggest that thymectomy can be effective for relieving symptoms of SPS and should be strongly considered when thymomas are discovered in association with this condition. However, all patients should be counselled that symptoms may recur in future and thus remain on long-term follow up with a neurologist. Reference #1: Solimena M, Folli F, Denis-Donini S, Comi GC, Pozza G, De Camilli P, Vicari AM: Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N England J Med. 1988, 318:1012-20. 10.1056/NEJM198804213181602 Reference #2: Gershanik OS: Stiff-person syndrome. Parkinsonism Relat Disord. 2009, 15:S130-S134. 10.1016/S1353-8020(09)70799-0 DISCLOSURE: The following authors have nothing to disclose: Rachel Chen Yanlin, Tousif Kabir, Atasha Asmat, Dokev Basheer Ahmed Aneez No Product/Research Disclosure Information

Efficacy of therapeutic plasma exchange for treatment of stiff‐person syndrome

The efficacy of therapeutic plasma exchange (TPE) in stiff-person syndrome (SPS) is unclear. A retrospective analysis of patients diagnosed with SPS who underwent TPE and a systematic literature review were conducted. Nine patients with the presumptive diagnosis of SPS who underwent TPE were identified. The mean age was 55 years (range, 34-72 years) and 78% (n = 7) were female. Anti-GAD65 was present in 89% (n = 8) of the patients (range, 1.9-40,000 U/mL), and 33% (n = 3) had a history of diabetes. Forty-four percent (n = 4) of patients had previously received immunosuppressive medication and 67% (n = 6) received intravenous immune globulin. The main indication for TPE was worsening of symptoms despite treatment with first-line therapy. Seventy-eight percent of the patients (n = 7) had five TPE procedures. Seventy-eight percent (n = 7) of patients demonstrated at least minimal clinical improvement and 56% (n = 5) had a significant response. Most of the patients who demonstrated a significant response to treatment improved and their symptoms stabilized. Two patients (22%) developed adverse events, including catheter-associated infection and transient hypotension. Eighteen publications were found from the literature review, which resulted in a total of 26 patients diagnosed with SPS. Forty-two percent (n = 11) of patients had a significant symptomatic improvement after TPE treatment, and two patients (8%) developed adverse events. TPE may benefit patients with SPS who are not responsive to first-line therapy, and it is well tolerated.