Person Syndrome Research Articles

P-NE010. Spectrum of referrals to the ENMG laboratory of BNSRC, the apex Neuro Center in Brunei

Introduction. Neuro-Electrophysiological (NEP) laboratories play an important role in precise characterisation, helping to guide treatment strategies and prognosticating neurological disorder. Brunei Neuroscience, Stroke Rehabilitation Centre (BNSRC) is the tertiary referral neurology centre for Brunei, a country in the South East Asian region with a population of 350,000. The NEP lab does about 700-800 ENMG studies a year and tests were conducted using a Dantec Keypoint. The aim of this study is to examine the spectrum of referrals to the NEP lab of BNSRC from November 2018 to October 2019. Methods . Retrospective descriptive study. The referrals during the study period were retrieved from a computerised database and the records were reviewed. Results. There were a total of 688 referrals; 260 males, 428 females with a mean age of 49.1 years. The commonest referral was Mononeuropathies, predominantly Carpal Tunnel Syndrome at 53% (362) with Polyneuropathy at 12% (77) being the next common. Other mononeuropathies include Bell’s Palsy, Ulnar Neuropathy, Peroneal Neuropathy and Radial Neuropathy made up 8% (55). Guillain-Barre Syndrome and Critical Illness Neuromyopathy made up 1.5% (10) and Myasthenia Gravis accounted for 4.6% (32) of referrals while Inflammatory Myopathies and Muscular Dystrophies accounted for 1.9% (13). Other referrals included conditions such as ALS, Spastic Paraparesis and Stiff Person Syndrome. Conclusion . ENMG Tests play a crucial role as they measure functional anatomy. This study captures the entire spectrum of disorders where the NEP laboratory helps guide the referral doctor. There is a need for protocol based studies, to learn newer techniques and to assist the Neurologist in EMG. The role of the NEP technologist is vital in getting technically robust recordings, even in less conducive surroundings like ICU and vital in developing a ‘State of the Art’ lab.

Quantitative Assessment of Response to Long-Term Treatment with Intravenous Immunoglobulin in Patients with Stiff Person Syndrome.

ABSTRACTBackgroundStiff person syndrome (SPS) is an autoimmune condition involving antibodies against several components of the inhibitory synapse in the spinal cord, with glutamic acid decarboxylase antibodies being the predominant immune marker. SPS affects approximately 1 patient per million population per year. The effect of intravenous immunoglobulin (IVIG) has been established, but studies on the long‐term efficacy of regular IVIG are limited.ObjectivesTo review clinical details and long‐term treatment response using a patient‐reported questionnaire in SPS and related syndromes.MethodsPatients were identified from a tertiary neuroimmunology clinic based on classical clinical symptoms, autoimmune profiles, and neurophysiological changes (Dalakas criteria). They were followed up after treatment to assess the response to IVIG.ResultsA total of 23 patients fulfilled the selection criteria. Patients' demographic profiles and clinical presentations were akin to that reported in literature. There was significant improvement in the functional ability (assessed by the modified Rankin scale [mRS]) and quality of life (QoL) following treatment with IVIG within 4 to 10 weeks (pre‐mRS vs. post‐mRS, P < 0.0001; pre‐QoL vs. post‐QoL, P = 0.0003) and sustained after 5 years of treatment (pre‐mRS vs. present mRS, P = 0.0003; pre‐QoL vs. present QoL, P = 0.0002).ConclusionsThis article describes one of the largest single‐center experiences of 23 patients with SPS and related syndromes and is the first to establish the long‐term efficacy of regular IVIG using a patient‐reported scoring system (Birmingham Response to Immunomodulatory Therapy [BRIT]). Consistent improvement in QoL and functional scores were seen over nearly 5 years after regular use of IVIG. It is recommended to use BRIT scores to assess the initial response as well as to monitor continued improvement to immunomodulation in SPS.

Subcutaneous Immunoglobulin Therapy with IgPro20 in Patients with Stiff Person Syndrome and Primary Immunodeficiency Disease.

Stiff Person Syndrome (SPS), a rare autoimmune neurologic disorder characterized by fluctuating muscle spasms and rigidity, is mediated by autoantibodies to glutamic acid decarboxylase (GAD) antibodies. Symptoms of SPS have been shown to improve after administration of intravenous immunoglobulin (IVIG) however, there is a paucity of information regarding use of SCIg in SPS. Four patients with Stiff Person Syndrome were treated with SCIgPro20 for a period between 31 to 101 months. Most reactions were local and mild. All patients reported improvement in spasticity, and 2 patients reported improvement in seizure frequency. SCIgPro20 was well tolerated in patients with SPS and was associated with improvement in symptoms.

Case Report: Breast cancer-associated paraneoplastic stiff person syndrome: anastrozole monotherapy insufficient for symptom improvement

Stiff person syndrome (SPS) is a rare clinical disorder presenting with progressive muscle stiffness and painful spasms. Its ill-defined mechanism and variable presentation make diagnosis a challenge, though it is associated with a range of specific auto-antibodies. One particular antibody, anti-amphiphysin, is found in the presence of breast or lung malignancy and leads to a disorder termed paraneoplastic SPS (PSPS). Our patient, an 83-year-old woman, presented with bilateral leg weakness, spasms, and left clubfoot over a period of three months. She also reported a lump in her left breast for which she had not sought treatment over the past 10 years. Her ankle radiograph was negative for fractures and dislocations, while an MRI of the left leg was negative for plexopathies. Electromyography was suggestive of an SPS disorder and a positive anti-amphiphysin test indicated a diagnosis of PSPS. Her symptoms were managed with baclofen, diazepam, and five cycles of therapeutic plasma exchange (TPEX) over 10 days. Breast imaging revealed a 4.5-cm left breast lesion, later biopsy-confirmed as invasive ductal carcinoma (ER+, PR+, HER2−). The patient declined definitive surgical management, opting instead for once-daily anastrozole 1 mg as hormonal therapy. This regimen was not sufficient to lead to symptomatic improvement over a period of more than 30 days, and the patient expired less than 45 days after discharge. To our knowledge, this is the first case of PSPS to be treated in this manner. Our report illustrates that conservative management with anastrozole monotherapy was not sufficient to lead to symptomatic improvement in this form of paraneoplastic syndrome, suggesting the need for more aggressive pharmacological or definitive surgical intervention in order to produce symptom improvement and/or resolution.

Stiff Person Syndrome Misdiagnosed as Oxaliplatin Induced Neurotoxicity

Introduction: Stiff person syndrome is characterized by muscle rigidity that waxes and wanes along with concurrent spasms. The symptoms of the stiff-person syndrome were identical to those of oxaliplatin side effects. Methods: This was a case report of a 65-year-old man who was diagnosed with stiff-person syndrome. He experienced pain with bleeding from the rectum. Screening tests were used to check foramphiphysin antibodies and electromyography. FNAC was done from the government hospital which was conclusive of metastasis. He was initiated on Capecitabine and Oxaliplatin protocol. Results: During the hospital stay, he was treated with 1gm Methylprednisolone for 5 days and sequentially with immunoglobulin 2gm per day for 5 days, concomitantly Benzodiazepam was given 10mg three times a day for 3 days but later withdrawn as the patient started experiencing dizziness. He achieved no clinical benefit in neurological status. Eventually developed aspiration pneumonia and succumbed to death after one month of diagnosis of SPS. Conclusion: Further studies should carry out to develop an evidence-based approach to diagnosing and treating SPS patients.

Stiff Person Syndrome Misdiagnosed as Oxaliplatin Induced Neurotoxicity

Introduction: Stiff person syndrome is characterized by muscle rigidity that waxes and wanes along with concurrent spasms. The symptoms of the stiff-person syndrome were identical to those of oxaliplatin side effects. Methods: This was a case report of a 65-year-old man who was diagnosed with stiff-person syndrome. He experienced pain with bleeding from the rectum. Screening tests were used to check foramphiphysin antibodies and electromyography. FNAC was done from the government hospital which was conclusive of metastasis. He was initiated on Capecitabine and Oxaliplatin protocol. Results: During the hospital stay, he was treated with 1gm Methylprednisolone for 5 days and sequentially with immunoglobulin 2gm per day for 5 days, concomitantly Benzodiazepam was given 10mg three times a day for 3 days but later withdrawn as the patient started experiencing dizziness. He achieved no clinical benefit in neurological status. Eventually developed aspiration pneumonia and succumbed to death after one month of diagnosis of SPS. Conclusion: Further studies should carry out to develop an evidence-based approach to diagnosing and treating SPS patients.

P047 An unusual case of dermatomyositis with co-existent anti-GAD and anti-NXP2 antibody positivity

Abstract Background/Aims Dermatomyositis (DM) is a rare disease. We present a case of DM with both anti-nuclear matrix protein 2 antibody (NXP2) as well as anti-glutamic acid decarboxylase antibody (GAD) positivity, the combination of which has yet not been documented in the current literature. Methods The case is described below. Results A 48 year old Caucasian male with no co-morbidities presented with a one-month history of sore throat and lethargy, followed 2 weeks later by muscular pain in his upper arms. On examination, there was erythema to the sun-exposed areas of the face and arms, hoarse voice and Gottron’s papules. He had proximal muscle weakness of 4/5 in his shoulder and hips. His creatinine kinase(CK) was elevated at 2914U/L. He was started on methylprednisolone 1 gram od for 3 days with improvement of his CK to 642U/L. His muscle biopsy showed mild chronic neurogenic changes and upregulation of C5b-9 but no evidence of inflammatory myopathy which was attributed to the steroid use prior to the biopsy. His myositis antibody screen was positive for Anti-Nuclear Matrix Protein antibody 2(NXP2). After 4 days he developed rapid onset dysphagia and a sudden drop in his spirometry readings with a fall in his FEV1from 94% to 85% and a fall in his FVC from 88% to 79%. He became acutely unwell, drowsy with difficulty completing sentences and global weakness. His CK had risen to 1567U/L despite the high dose intravenous methylprednisolone. He was diagnosed with Diabetic ketoacidosis(DKA) with a blood glucose of 32mmol/L , pH of 7.0, and transferred to ITU. Intravenous immunoglobulin (IVIG) was administered with subsequent improvement in all muscle groups. He was then commenced on a subcutaneous insulin regime and pulsed intravenous cyclophosphamide (Eurolupus) as his EMG showed a sensorimotor polyneuropathy as well as an inflammatory myopathy. His serology was negative for infectious aetiology. Malignancy screen including PET scan, oesophagogastroduodenoscopy and colonoscopy were normal however, he was found to be positive for anti-GAD antibody. Conclusion GAD antibodies are known to be associated with many disorders including diabetes and stiff person syndrome and can recognise different epitopes in various diseases. This is the first documented case of GAD occurring in a DM patient, in the presence of NXP2 antibodies. IVIG is used to treat both stiff man syndrome and refractory DM. It is possible that the combination of GAD and NXP2 contributed to the pathogenesis and severity of the clinical presentation in this case. Disclosure K. Beharry: None. G. Barminski: None. D. De Lord: None.

Unanticipated Improvement of Stiff Person Syndrome after severe COVID-19 (2397)

Unanticipated Improvement of Stiff Person Syndrome after severe COVID-19 (2397)

Immunotherapy in Stiff Person Syndrome, is Timing Really Important? (5176)

Immunotherapy in Stiff Person Syndrome, is Timing Really Important? (5176)

Characterization of Spasm-Related Respiratory Impairment in Stiff Person Syndrome Spectrum Disorders (4400)

Characterization of Spasm-Related Respiratory Impairment in Stiff Person Syndrome Spectrum Disorders (4400)

Neuropsychological performance and psychiatric symptoms in stiff person syndrome (2510)

Neuropsychological performance and psychiatric symptoms in stiff person syndrome (2510)

A Rare Combination of Limbic Encephalitis and Stiff Person Syndrome Separated by Several Years in a Patient with Anti-Glutamic Acid Decarboxylase Antibodies (2000)

A Rare Combination of Limbic Encephalitis and Stiff Person Syndrome Separated by Several Years in a Patient with Anti-Glutamic Acid Decarboxylase Antibodies (2000)

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.

Efficacy and safety of therapeutic plasma exchange in stiff person syndrome.

The stiff person syndrome (SPS) is an extremely rare neurological disorder with primarily immune-mediated etiology. The cardinal symptoms are progressive, fluctuating axial/proximal limb muscle stiffness and spasms. The diagnosis is based on the clinical picture, electromyography examination and detection of antibodies to glutamic acid decarboxylase (anti-GAD). Adverse effects of medications might preclude its use or increase in dosing, therefore symptomatic and/or immunomodulatory medical therapy might be ineffective in acute exacerbation of the disease. We present a case of a 49-year-old female with exacerbation of SPS, in whom some standard pharmacotherapy could not be introduced (clonazepam, baclofen used in the past) and doses of existing standard medications could not be increased (diazepam, gabapentin, and levetiracetam) due to adverse effects. Moreover, a newly introduced medication (methylprednisolone) also led to a serious adverse effect (severe hyperglycemia). The patient underwent therapeutic plasma exchange (TPE) with good effect and no complications. We review the literature regarding the efficacy and safety profile of TPE in exacerbation of SPS unresponsive to medical therapy. The procedure seems to have a good safety profile as an adjunct therapy for exacerbation of SPS not responding to standard medical therapy in this patient population.

Use of subcutaneous immunoglobulin in stiff person syndrome: Case series.

Introduction:Intravenous immunoglobulin (IVIG) has been shown to be effective for the treatment of stiff person syndrome (SPS). However, some patients might not tolerate it. We report the tolerability profile of subcutaneous immunoglobulin (SCIg) in patients with SPS who did not tolerate IVIG. To our knowledge, the use of SCIg in SPS has not been reported before in a case series.Patient concerns:The five patients included in this case series presented with various combinations of symptoms of spasms, axial and limb stiffness, and exaggerated responses to outside stimuli. These symptoms often lead to gait and functional impairment.Diagnosis:Patients were diagnosed with classic SPS as they met the clinical criteria, which require the presence of spasms, axial rigidity, and hyperexcitability.Interventions:Subcutaneous immunoglobulin infusion.Outcomes:Five patients were identified that were treated with SCIg. Three tested positive for serum anti-glutamic acid decarboxylase 65 antibodies prior to any treatment. The mean age at SCIg initiation was 33 years (range: 22–47). The mean duration of SPS prior to SCIg initiation was 5.9 years (range: 2.5–7). All patients used IVIG for at least two months (up to 18 months) but switched to SCIg due to IVIG side effects. Duration of SCIg use ranged from 4 months to 6 years (mean, 19.2 months). Upon switching to SCIg, the SPS symptoms remained stable. SCIg was well-tolerated in most as only one patient discontinued SCIg due to side effects.Conclusion:This case series highlights that SCIg could be a treatment option for patients with SPS, especially when IVIG is not feasible. Injection site reactions might be a limiting factor in some patients treated with SCIg. Prospective controlled studies are needed to confirm SCIg treatment durability and efficacy.

GAD antibody-spectrum disorders: progress in clinical phenotypes, immunopathogenesis and therapeutic interventions.

Antibodies against glutamic acid decarboxylase (GAD), originally linked to stiff person syndrome (SPS), now denote the “GAD antibody-spectrum disorders” (GAD-SD) that also include autoimmune epilepsy, limbic encephalitis, cerebellar ataxia and nystagmus with overlapping symptomatology highlighting autoimmune neuronal excitability disorders. The reasons for the clinical heterogeneity among GAD-antibody associated syndromes remain still unsettled, implicating variable susceptibility of GABAergic neurons to anti-GAD or other still unidentified autoantibodies. Although anti-GAD antibody titers do not correlate with clinical severity, very high serum titers, often associated with intrathecal synthesis of anti-GAD-specific IgG, point to in-situ effects of GAD or related autoantibodies within the central nervous system. It remains, however, uncertain what drives these antibodies, why they persist and whether they are disease markers or have pathogenic potential. The review, focused on these concerns, describes the widened clinical manifestations and overlapping features of all GAD-SD; addresses the importance of GAD antibody titers and potential significance of GAD epitopes; summarizes the biologic basis of autoimmune hyperexcitability; highlights the electrophysiological basis of reciprocal inhibition in muscle stiffness; and provides practical guidelines on symptomatic therapies with gamma-aminobutyric acid-enhancing drugs or various immunotherapies.

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.

Defining the Expanding Clinical Spectrum of Pediatric-Onset Stiff Person Syndrome

BackgroundWe aimed to characterize the spectrum of clinical features and examination findings in pediatric-onset stiff person syndrome. MethodsMedical records were reviewed for all patients treated for stiff person syndrome with symptom onset in childhood at a tertiary medical center between March 2001 and February 2019. ResultsOf the 15 individuals who met inclusion criteria, 11 (73%) were female and 13 (87%) were Caucasian. Median age at symptom onset was 14.8 years (range 8.4 to 16.9), and median latency from symptom onset to diagnosis was 6.2 years (range 0.4 to 15.0). Nine individuals (60%) were not diagnosed until adulthood. The most common presenting features were painful spasms (n = 12, 80%), hyper-reflexia (n = 11, 73%), axial rigidity (n = =9, 60%), lower extremity rigidity or spasticity (n = 8, 53%), gait abnormalities (n = 6, 40%), and hyperlordosis (n = 6, 40%). Other noted features included anxiety (n = 5, 33%), dysautonomia (n = 3, 20%), and cranial neuropathies (n = 3, 20%). Personal (n = 9, 60%) and family history (n = 9, 60%) of autoimmune conditions was common. Serum antiglutamate decarboxylase 65 antibodies were found in 13 individuals (87%). Nearly all individuals received immunotherapy (n = 14, 93%), symptomatic medications (n = 15, 100%), and nonpharmacologic therapies (n = 14, 93%). However, most had persistent physical limitations, particularly impaired walking (n = 7, 47%) and inability to carry out previous activities (n = 14, 93%). ConclusionsThere is a wide spectrum of typical and less common features seen in individuals with pediatric-onset stiff person syndrome. Despite symptom onset in childhood, diagnosis is often delayed until adulthood, at which point disability accrual is frequently seen. Early recognition is vital to address symptoms and may potentially limit future disability.

Autologous haematopoietic stem cell transplantation for refractory stiff-person syndrome: the UK experience

Stiff Person Syndrome (SPS) is a rare immune-mediated disabling neurological disorder characterised by muscle spasms and high GAD antibodies. There are only a few case reports of autologous haematopoietic stem cell transplantation (auto-HSCT) as a treatment for SPS.ObjectiveTo describe the UK experience of treating refractory SPS with auto-HSCT.MethodsBetween 2015 and 2019, 10 patients with SPS were referred to our institution for consideration of auto-HSCT. Eight patients were deemed suitable for autograft and four were treated. Of the treated patients, three had classical SPS and one had the progressive encephalomyelitis with rigidity and myoclonus variant. All patients were significantly disabled and had failed conventional immunosuppressive therapy. Patients were mobilised with Cyclophosphamide (Cy) 2 g/m2 + G-CSF and conditioned with Cy 200 mg/kg + ATG followed by auto-HSCT.ResultsDespite their significantly reduced performance status, all patients tolerated the procedure with no unexpected toxicities. Following autograft, all patients improved symptomatically and stopped all forms of immunosuppressive therapies. Two patients were able to ambulate independently from being wheelchair dependent. One patient’s walking distance improved from 300 meters to 5 miles and one patient’s ambulation improved from being confined to a wheelchair to be able to walk with a frame. Two patients became seronegative for anti-GAD antibodies and normalised their neurophysiological abnormalities.ConclusionsAuto-HSCT is an intensive but well tolerated and effective treatment option for patients with SPS refractory to conventional immunotherapy. Further work is warranted to optimise patient selection and establish the efficacy, long-term safety, and cost-effectiveness of this treatment.