1,646 results on '"STIFF-person syndrome"'
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2. Evaluating Spinal Cord Stimulation for Stiff Person Syndrome
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- 2024
3. Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases
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- 2024
4. Performance Optimization and Injury Mitigation for Air Force Student Fighter Pilots.
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Chayrez, Stephanie E, Acevedo, Anthony, Blake, Jared, Parrott, Christopher, Gerking, Timothy, Guthmann, Deborah, Jilek, Michelle, Dorcheus, Joshua, Zeigler, Zachary, Copeland, Clint, Gill, Haley, Smietana, Andrew, Price-Moore, Carolyn, Nores, Brittaney, and Scott, Ryan M
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HEALTH care teams , *STIFF-person syndrome , *FIGHTER pilots , *AIR bases , *NECK pain - Abstract
Introduction Military fighter aircrew report high rates of cervical pain and injury. There is currently no consensus regarding the best training methods for this population. Eglin Air Force Base (AFB) and Luke AFB have multidisciplinary teams specializing in aircrew training, performance, and injury mitigation. All student pilots (SPs) completing Basic Course training at these locations engage in an 8-week Spine Training Program (STP). The STP originated at Luke AFB in 2020 and was expanded to Eglin AFB in 2022. The primary aim of this study was to assess whether the STP led to significant changes in the performance measure studied, Cervical Endurance Hold (CEH). Further, this study aimed to determine if the CEH training effect was independent of location of STP administration. We hypothesized that SPs would exhibit statistically significant CEH training adaptations irrespective of base location. Materials and Methods Air Force F-16 and F-35 SPs from Luke AFB and Eglin AFB were actively enrolled in the Basic Course and participated in the standardized STP from 2020 to 2023. The CEH test was administered prior to (intake) and following (exit) the 8-week STP. SPSS for Windows version 29 software (IBM, Armonk, NY) was used to retrospectively analyze the data from this study. Participants were excluded if they were unable to perform the CEH test at intake or exit. The study was approved by the Air Force Research Laboratory Institutional Review Board and was performed in accordance with the ethical standards of the Declaration of Helsinki. Results One hundred and ninety-eight SPs (Luke AFB, males n = 170, females n = 12; Eglin AFB, males n = 16) completed the STP program. There was no significant difference between intake and exit concerning age, height, weight, % body fat, and fat-free mass at Luke AFB or Eglin AFB (P < 0.05). Statistically significant improvements in CEH were observed within all groups from intake to exit (P < 0.001). When considering all participants collectively, there was a notable 33.6% increase in CEH from intake to exit (P < 0.001) with an overall effect size of d = 1.14. When analyzing specific subgroups, females from Luke AFB experienced a significant 20.4% increase in CEH (P < 0.001, d = 1.14), males from Luke AFB exhibited a significant 34.5% increase (P < 0.001, d = 1.09), and males from Eglin AFB demonstrated a significant increase of 55.7% in CEH (P < 0.001, d = 1.97). Conclusions This retrospective analysis showed significant improvements in the CEH across all groups following the completion of the STP. Furthermore, CEH results from both bases exhibited a large effect size indicating a meaningful change was found between intake and exit regardless of training location. These preliminary study results should be interpreted with caution as a control group was unable to be established. In the future, a randomized control trial should be performed to test the STP used in this study against other STP programs. This may better inform experts on the best spine training methods for fighter aircrew. [ABSTRACT FROM AUTHOR]
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- 2024
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5. The Role of Chimeric Antigen Receptor T‐Cell Therapy in Immune‐Mediated Neurological Diseases.
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Brittain, Gavin, Roldan, Elisa, Alexander, Tobias, Saccardi, Riccardo, Snowden, John A., Sharrack, Basil, and Greco, Raffaella
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STIFF-person syndrome , *HEMATOPOIETIC stem cells , *CYTOKINE release syndrome , *NEUROLOGICAL disorders , *MYASTHENIA gravis , *NEUROMYELITIS optica - Abstract
Despite the use of 'high efficacy' disease‐modifying therapies, disease activity and clinical progression of different immune‐mediated neurological diseases continue for some patients, resulting in accumulating disability, deteriorating social and mental health, and high economic cost to patients and society. Although autologous hematopoietic stem cell transplant is an effective treatment modality, it is an intensive chemotherapy‐based therapy with a range of short‐ and long‐term side‐effects. Chimeric antigen receptor T‐cell therapy (CAR‐T) has revolutionized the treatment of B‐cell and other hematological malignancies, conferring long‐term remission for otherwise refractory diseases. However, the toxicity of this treatment, particularly cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome, and the complexity of production necessitate the need for a high level of specialization at treating centers. Early‐phase trials of CAR‐T therapies in immune‐mediated B cell driven conditions, such as systemic lupus erythematosus, neuromyelitis optica spectrum disorder and myasthenia gravis, have shown dramatic clinical response with few adverse events. Based on the common physiopathology, CAR‐T therapy in other immune‐mediated neurological disease, including multiple sclerosis, chronic inflammatory polyradiculopathy, autoimmune encephalitis, and stiff person syndrome, might be an effective option for patients, avoiding the need for long‐term immunosuppressant medications. It may prove to be a more selective immunoablative approach than autologous hematopoietic stem cell transplant, with potentially increased efficacy and lower adverse events. In this review, we present the state of the art and future directions of the use of CAR‐T in such conditions. ANN NEUROL 2024;96:441–452 [ABSTRACT FROM AUTHOR]
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- 2024
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6. Efgartigimod as a novel FcRn inhibitor for autoimmune disease.
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Yang, Yun, Shen, Zhengxuan, Shi, Fan, Wang, Fei, and Wen, Ning
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CHRONIC inflammatory demyelinating polyradiculoneuropathy , *STIFF-person syndrome , *FC receptors , *IMMUNOGLOBULIN G , *CLINICAL medicine , *MYASTHENIA gravis , *AUTOIMMUNE diseases - Abstract
Immunoglobulin G (IgG) autoantibodies can lead to the formation of autoimmune diseases through Fab and/or Fc-mediated interactions with host molecules as well as activated T cells. The neonatal Fc receptor (FcRn) binds at acidic pH IgG and albumin, and the mechanism for prolonging serum IgG half-life is making IgG re-entry into circulation by prompting it not to be degraded by lysosomes and back to the cell surface. Given the FcRn receptor's essential role in IgG homeostasis, one of the strategies to promote the quick degradation of endogenous IgG is to suppress the function of FcRn, which is beneficial to the treatment of IgG-driven autoimmune disorders like myasthenia gravis (MG), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), stiff person syndrome, and immune thrombocytopenia (ITP). We elaborately read the literature about efgartigimod and systematically reviewed the research progress and clinical application of this novel FcRn inhibitor in autoimmune diseases. Efgartigimod is the firstly FcRn antagonist developed and was approved on 17 December 2021 by the United States for the therapy of acetylcholine receptor-positive MG. In January 2022, efgartigimod received its second regulatory approval in Japan. In addition, the market authorization application in Europe was submitted and validated in August 2021. China's National Medical Products Administration officially accepted the marketing application of efgartigimod on July 13, 2022. To suppress the function of FcRn, which is beneficial to the treatment of IgG-driven autoimmune disorders like MG, CIDP, ITP, and stiff person syndrome. We review the rationale, clinical evidence, and future perspectives of efgartigimod for the treatment of autoimmune disease. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Machine learning characterization of a rare neurologic disease via electronic health records: a proof-of-principle study on stiff person syndrome.
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Park, Soo Hwan, Song, Seo Ho, Burton III, Frederick, Arsan, Cybèle, Jobst, Barbara, and Feldman, Mary
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STIFF-person syndrome , *NEUROLOGICAL disorders , *ELECTRONIC health records , *SPASMS , *DELAYED diagnosis - Abstract
Background: Despite the frequent diagnostic delays of rare neurologic diseases (RND), it remains difficult to study RNDs and their comorbidities due to their rarity and hence the statistical underpowering. Affecting one to two in a million annually, stiff person syndrome (SPS) is an RND characterized by painful muscle spasms and rigidity. Leveraging underutilized electronic health records (EHR), this study showcased a machine-learning-based framework to identify clinical features that optimally characterize the diagnosis of SPS. Methods: A machine-learning-based feature selection approach was employed on 319 items from the past medical histories of 48 individuals (23 with a diagnosis of SPS and 25 controls) with elevated serum autoantibodies against glutamic-acid-decarboxylase-65 (anti-GAD65) in Dartmouth Health's EHR to determine features with the highest discriminatory power. Each iteration of the algorithm implemented a Support Vector Machine (SVM) model, generating importance scores—SHapley Additive exPlanation (SHAP) values—for each feature and removing one with the least salient. Evaluation metrics were calculated through repeated stratified cross-validation. Results: Depression, hypothyroidism, GERD, and joint pain were the most characteristic features of SPS. Utilizing these features, the SVM model attained precision of 0.817 (95% CI 0.795–0.840), sensitivity of 0.766 (95% CI 0.743–0.790), F-score of 0.761 (95% CI 0.744–0.778), AUC of 0.808 (95% CI 0.791–0.825), and accuracy of 0.775 (95% CI 0.759–0.790). Conclusions: This framework discerned features that, with further research, may help fully characterize the pathologic mechanism of SPS: depression, hypothyroidism, and GERD may respectively represent comorbidities through common inflammatory, genetic, and dysautonomic links. This methodology could address diagnostic challenges in neurology by uncovering latent associations and generating hypotheses for RNDs. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Stiff-person syndrome in association with Hashimoto's thyroiditis: a case report.
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Mingzhu Chen, Zhou Hong, Haicun Shi, Chunmei Wen, and Yuan Shen
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AUTOIMMUNE thyroiditis ,STIFF-person syndrome ,SPASMS ,MUSCLE rigidity ,AUTOIMMUNE diseases - Abstract
Stiff-person syndrome (SPS) is a rare neurological disorder characterized by chronic and progressive axial muscle rigidity and paroxysmal painful muscle spasms. The present case study described an SPS patient (increased anti-GAD65 antibody in serum and cerebrospinal fluid) with co-occurring Hashimoto's thyroiditis and decreased C3 complement levels. The clinical presentation, diagnostic approach, and treatment employed for this unique case were comprehensively described in detail. In this case, we comprehensively presented a case of SPS with co-occurring Hashimoto's thyroiditis and an associated decrease in serum C3 complement, as well as a discussion on the current data on this topic. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Expanding the Understanding of Stiff-Person Syndrome: Insights from 17 Cases in India.
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Jain, Rajendra S., Pemawat, Ashish, Sharma, Pankajkumar, and Nehra, Kuldeep
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THERAPEUTIC use of immunoglobulins , *COMBINATION drug therapy , *BACLOFEN , *THYROXINE , *IMMUNOSUPPRESSIVE agents , *DIAZEPAM , *IMMUNOGLOBULINS , *MYCOPHENOLIC acid , *AUTOANTIBODIES , *RITUXIMAB , *PREDNISOLONE , *ORAL drug administration , *TREATMENT effectiveness , *STIFF-person syndrome , *GABAPENTIN , *DISEASE relapse , *HYPOTHYROIDISM , *IMMUNOSUPPRESSION , *THERAPEUTICS - Abstract
Stiff-person syndrome (SPS) is a rare and complex neurologic disorder characterized by progressive muscle stiffness, painful spasms, and gait difficulties. In this report, we describe a case of SPS who presented with a relapse while on maintenance immunosuppressive treatment. In addition, we review the literature of 16 previously reported cases of SPS from India, highlighting the diverse clinical features, comorbidities, treatment response, and relapse. The occurrence of paraneoplastic SPS emphasizes the need for early recognition and diagnosis. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Clinical features in antiglycine receptor antibody-related disease: a case report and update literature review.
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Xiaoke Wu, Haifeng Zhang, Mengmeng Shi, and Shaokuan Fang
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MOVEMENT disorders ,LITERATURE reviews ,STIFF-person syndrome ,NEURALGIA ,NEUROLOGICAL disorders ,SYMPTOMS - Abstract
Background and objectives: Antiglycine receptor (anti-GlyR) antibody mediates multiple immune-related diseases. This study aimed to summarize the clinical features to enhance our understanding of anti-GlyR antibody-related disease. Methods: By collecting clinical information from admitted patients positive for glycine receptor (GlyR) antibody, the clinical characteristics of a new patient positive for GlyR antibody were reported in this study. To obtain additional information regarding anti-GlyR antibody-linked illness, clinical data and findings on both newly reported instances in this study and previously published cases were merged and analyzed. Results: A new case of anti-GlyR antibody-related progressive encephalomyelitis with rigidity and myoclonus (PERM) was identified in this study. A 20-year-old man with only positive cerebrospinal fluid anti-GlyR antibody had a good prognosis with first-line immunotherapy. The literature review indicated that the common clinical manifestations of anti-GlyR antibody-related disease included PERM or stiff-person syndrome (SPS) (n = 179, 50.1%), epileptic seizure (n = 94, 26.3%), and other neurological disorders (n = 84, 24.5%). Other neurological issues included demyelination, inflammation, cerebellar ataxia and movement disorders, encephalitis, acute psychosis, cognitive impairment or dementia, celiac disease, Parkinson's disease, neuropathic pain and allodynia, steroid-responsive deafness, hemiballism/tics, laryngeal dystonia, and generalized weakness included respiratory muscles. The group of PERM/SPS exhibited a better response to immunotherapy than others. Conclusions: The findings suggest the presence of multiple clinical phenotypes in anti-GlyR antibody-related disease. Common clinical phenotypes include PERM, SPS, epileptic seizure, and paraneoplastic disease. Patients with RERM/SPS respond well to immunotherapy. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Getting to know the real CELINE DION.
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Iley, Chrissy
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STIFF-person syndrome ,VOCAL cords ,MARRIAGE ,MYOCARDIUM ,MULTIPLE pregnancy - Abstract
The article discusses the life and career of Canadian superstar Celine Dion. It highlights her rise to fame, her personal struggles, and her recent battle with a rare disease called stiff-person syndrome (SPS) that has affected her ability to sing and perform. The article also touches on her relationships, including her marriage to her late husband René Angélil, and her role as a mother. Despite her challenges, Celine remains positive and determined to continue pursuing her passion for music. [Extracted from the article]
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- 2024
12. 16 Inspiring, Oh-My-God-Did-That-Just-Happen Moments From the Paris Games.
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Kuzma, Cindy
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WOMEN'S sports ,STIFF-person syndrome ,POSTURAL orthostatic tachycardia syndrome ,HORSE sports ,OLYMPIC medals ,SWIMMERS - Abstract
The 2024 Paris Games were filled with inspiring and unexpected moments for women athletes. Despite personal challenges, the US women's gymnastics team, known as the Golden Girls, won team gold and multiple individual medals. Swimmer Katie Ledecky became the most decorated US female Olympian ever, dominating in long-distance races. Hip-hop stars Snoop Dogg and Flavor Flav brought excitement and unity to the Games, and numerous athletes demonstrated sportsmanship and respect. Historic moments included Lauren Scruggs becoming the first Black American woman to earn an individual Olympic fencing medal, and Sydney McLaughlin-Levrone breaking her own world record in the 400-meter hurdles. Team USA sprinters, including Gabby Thomas, Sha'Carri Richardson, and Melissa Jefferson, achieved success and shared their stories of resilience. Social media provided a behind-the-scenes look at the Games, with athletes sharing their experiences and going viral. The article also highlights the achievements of women athletes such as cyclist Kristen Faulkner, Dutch athlete Sifan Hassan, the US National Women's Soccer Team, the American basketball team, and weightlifter Olivia Reeves. The Games showcased women athletes competing at older ages and athletes managing their health conditions. Overall, women athletes excelled and received significant attention and support. [Extracted from the article]
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- 2024
13. UNDERGROUND TO OLYMPUS.
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Li Wenhan
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OLYMPIC Games , *STIFF-person syndrome , *WEIGHT lifting , *OLYMPIC medals , *ASIAN Games - Abstract
The Paris 2024 Olympic Summer Games opened with a four-hour ceremony that showcased French art and history. Canadian singer Céline Dion made a triumphant return to the stage after a four-year hiatus due to a rare neurological disorder. The opening ceremony took place outside the main stadium, with athletes cruising down the Seine River on boats. Paris 2024 features the Olympic debut of breakdancing and other emerging sports. China has excelled in various sports and has secured 24 medals, including 11 golds, making them the current leader in the medal tally. The Olympics provide a platform for athletes from different countries to come together and promote peace. However, there have been controversies surrounding Chinese athletes, including a food contamination incident and increased anti-doping tests. Despite challenges, the Olympic Games serve as a valuable platform for communication and cross-cultural understanding. [Extracted from the article]
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- 2024
14. Characterization of Anti-GAD65-Associated Neurological Syndromes: Clinical Features and Antibody Titers
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João Moura, Firmina Sambayeta, Ana Paula Sousa, Paula Carneiro, Esmeralda Neves, Raquel Samões, Ana Martins Silva, and Ernestina Santos
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anti-GAD65 ,limbic encephalitis ,epilepsy ,cerebellar ataxia ,stiff-person syndrome ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Introduction: Anti-GAD65 antibodies are associated with several neurological phenotypes. Antibody titers are increasingly recognized as useful in diagnosis and prognosis. Objective: To describe a Portuguese cohort of patients with anti-GAD65-associated neurological syndromes. Methods: Retrospective analysis of all patients with positive anti-GAD65 antibodies and associated neurological syndromes followed in a tertiary referral center. Results: Nineteen anti-GAD65 antibody-positive neurological patients were identified, 62.3% female, with a mean age of onset of 56.0 (SD = 13.3) years. Comorbid autoimmune disorders were present in seven patients. Six patients had limbic encephalitis (31.6%), four had epilepsy (21.1%), four had cerebellar ataxia (21.1%), and three had stiff-person syndrome (15.8%). Two patients presented with isolated cognitive dysfunction (executive and mnesic) in the absence of other neurological symptoms. The mean follow-up time was 24.0 (14.0–42.0) months, at the end of which the mean modified Rankin Scale (mRS) value was 2.0 (1.0–4.0). Screening for malignancies was negative in all patients. Serum quantitative analysis was carried out in 18 patients, 10 of whom showed titers above previously defined cut-off points (>10,000 IU/L for ELISA and >20 mmol/L for RIA). Quantitative CSF analysis was performed in nine patients, with four showing above-threshold titers. There was no association between anti-GAD65 levels and clinical phenotype or the final mRS values. High-dose intravenous methylprednisolone and oral prednisolone were the most common acute and chronic treatment regimens, respectively. Conclusion: Anti-GAD65 antibodies are associated with varied neurological syndromes, and antibody titers alone should not be used to exclude a disease.
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- 2024
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15. Successful use of anti-CD19 CAR T cells in severe treatment-refractory stiff-person syndrome.
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Faissner, Simon, Motte, Jeremias, Sgodzaia, Melissa, Geis, Christian, Haghikia, Aiden, Mougiakakos, Dimitrios, Borie, Dominic, Schroers, Roland, and Gold, Ralf
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STIFF-person syndrome , *T cells , *CYTOKINE release syndrome , *MYASTHENIA gravis , *CHIMERIC antigen receptors , *ELECTROCONVULSIVE therapy , *COMMUNITY mental health services , *AMPUTEES - Abstract
Treatment with autologous chimeric antigen receptor (CAR) T cells has emerged as a highly effective approach in neuroimmunological disorders such as myasthenia gravis. We report a case of successful anti-CD 19 CAR T cell use in treatment-refractory stiff-person syndrome (SPS). To investigate clinical and immunological effects of anti-CD19 CAR T cell use in treatment-refractory SPS, a 69-y-old female with a 9-y history of treatment-refractory SPS with deteriorating episodes of stiffness received an infusion of autologous anti-CD19 CAR T cells (KYV-101) and was monitored clinically and immunologically for more than 6 mo. CAR T cell infusion resulted in reduced leg stiffness, drastic improvement in gait, walking speed increase over 100%, and daily walking distance improvement from less than 50 m to over 6 km within 3 mo. GABAergic medication (benzodiazepines) was reduced by 40%. KYV-101 CAR T cells were well tolerated with only low-grade cytokine release syndrome. This report of successful use of anti-CD19 CAR T cells in treatment-refractory SPS supports continued exploration of this approach in SPS and other B cell--related autoimmune disorders. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Spinal cord stimulation for the symptomatic treatment of rigidity and painful spasm in a case of stiff person syndrome.
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Patel, Janus, Deschler, Emily, and Galang, Enrique
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THERAPEUTIC use of immunoglobulins , *PHYSICAL diagnosis , *ORAL drug administration , *MAGNETIC resonance imaging , *TREATMENT effectiveness , *INTRAVENOUS therapy , *MUSCLE rigidity , *STIFF-person syndrome , *SPINAL fusion , *NEURAL stimulation , *SPASMS , *SERODIAGNOSIS , *SPINAL cord , *DISEASE complications , *SYMPTOMS - Abstract
Background: Stiff person syndrome (SPS) is a rare neuroimmunological disorder characterized by rigidity and painful spasm primarily affecting the truncal and paraspinal musculature due to autoimmune‐mediated neuronal hyperexcitability. Spinal cord stimulation (SCS) is an approved therapy for managing painful neuropathic conditions, including diabetic peripheral neuropathy and refractory angina pectoris. We describe the novel use of SCS for the treatment of spasm and rigidity in a 49‐year‐old man with seropositive stiff person syndrome (SPS). The patient was treated with intravenous immunoglobulin (IVIG) and oral medications over a 13‐month period with minimal improvement, prompting consideration of SCS. To our knowledge, this is the first report of the successful use of SCS in SPS with the demonstration of multifaceted clinical improvement. Methods: Following a successful temporary SCS trial, permanent implantation was performed. Spasm/stiffness (Distribution of Stiffness Index; Heightened Sensitivity Scale; Penn Spasm Frequency Scale, PSFS), disability (Oswestry Disability Index, ODI; Pain Disability Index, PDI), depression (Patient Health Questionnaire‐9, PHQ‐9), sleep (Pittsburgh Sleep Quality Index, PSQI), fatigue (Fatigue Severity Scale, FSS), pain (Numerical Pain Rating Scale, NPRS), quality of life (EuroQoL 5 Dimension 5 Level, EQ‐5D‐5L), and medication usage were assessed at baseline, 6‐month, and 10‐month postimplantation. Results: ODI, PHQ‐9, FSS, NPRS, PSQI, and EQ‐5D‐5L scores showed a notable change from baseline and surpassed the defined minimal clinically important difference (MCID) at 6‐month and 10‐month follow‐up. Oral medication dosages were reduced. Conclusions: The novel use of SCS therapy in seropositive SPS resulted in functional improvement and attenuation of symptoms. We present possible mechanisms by which SCS may produce clinical response in patients with SPS and aim to demonstrate proof‐of‐concept for a future comprehensive pilot study evaluating SCS‐mediated response in SPS. [ABSTRACT FROM AUTHOR]
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- 2024
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17. The Effectiveness of Combining Botulinum Toxin Type A and Therapeutic Exercise in Treating Spasticity in a Patient with Complicated Stiff-Person Syndrome: A Case Report.
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Marvulli, Riccardo, Raele, Maria Vittoria, Riccardi, Mariagrazia, Farì, Giacomo, Ranieri, Maurizio, and Megna, Marisa
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BOTULINUM A toxins ,BOTULINUM toxin ,EXERCISE therapy ,STIFF-person syndrome ,SPASTICITY ,DRUG therapy ,RANGE of motion of joints - Abstract
Stiff-person syndrome is rare and disabling autoimmune condition that most frequently affects women, with no real predisposition by race. Diagnosis is often arduous, which is why patients concomitantly suffer from anxiety and depression. To date, drug therapy is based on the use of benzodiazepines, barbiturates, and baclofen. Refractory cases are treated with intravenous immunoglobulin, plasmapheresis, B lymphocyte depletion with rituximab, and even the implantation of intrathecal baclofen devices. Botulinum toxin injection is frequently used, even if it still has an unclear role in the literature. Our case report aims to demonstrate the efficacy of a combined treatment of botulinum toxin and therapeutic exercise in a 65-year-old patient with biceps brachii muscle hypertonia and diffuse spasms of the axial musculature, using rating scales such as the Numeric Rating Scale (NRS) and Modified Ashworth Scale (MAS), joint range of motion (ROM) measurement, and muscle dynamic stiffness mensuration, which is performed by using the MyotonPro
® . All the assessments were conducted at the first evaluation (T0), soon after the combined treatment with botulin toxin and therapeutic exercise (T1), three months (T2), six months (T3), and eight months after the botulinum toxin injection (T4). The patient demonstrated benefits for more than 6 months with no side effects. The combined therapy of botulinum toxin and therapeutic exercise had an excellent result in our patient. [ABSTRACT FROM AUTHOR]- Published
- 2024
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18. Case 14-2024: A 30-Year-Old Woman with Back Pain, Leg Stiffness, and Falls.
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Doughty, Christopher T., Schaefer, Pamela W., Brizzi, Kate, and Linnoila, Jenny J.
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MOVEMENT disorders , *LEG pain , *BACKACHE , *STIFF-person syndrome - Abstract
The article presents a case study of a 30-year-old woman who sought medical attention due to a constellation of symptoms including back pain, leg stiffness, and recurrent falls. It states that despite previous evaluations by specialists in neurology, rheumatology, and sports medicine, a definitive diagnosis remained elusive, prompting further investigation into potential peripheral nervous system disorders associated with muscle stiffness.
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- 2024
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19. Lessons in clinical reasoning – pitfalls, myths, and pearls: a woman brought to a halt.
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Rezigh, Austin, Rezigh, Alec, and Sherman, Stephanie
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MEDICAL logic , *STIFF-person syndrome , *NERVE conduction studies , *GENERALIZED anxiety disorder , *PHYSICIANS , *JOINT pain , *FIBROMYALGIA - Abstract
Limitations in human cognition commonly result in clinical reasoning failures that can lead to diagnostic errors. A metacognitive structured reflection on what clinical findings fit and/or do not fit with a diagnosis, as well as how discordance of data can help advance the reasoning process, may reduce such errors. A 60-year-old woman with Hashimoto thyroiditis, diabetes, and generalized anxiety disorder presented with diffuse arthralgias and myalgias. She had been evaluated by physicians of various specialties and undergone multiple modalities of imaging, as well as a electromyography/nerve conduction study (EMG/NCS), leading to diagnoses of fibromyalgia, osteoarthritis, and lumbosacral plexopathy. Despite treatment for these conditions, she experienced persistent functional decline. The only definitive alleviation of her symptoms identified was in the few days following intra-articular steroid injections for osteoarthritis. On presentation to our institution, she appeared fit with a normal BMI. She was a long-time athlete and had been training consistently until her symptoms began. Prediabetes had been diagnosed the year prior and her A1c progressed despite lifestyle modifications and 10 pounds of intentional weight loss. She reported fatigue, intermittent nausea without emesis, and reduced appetite. Examination revealed intact strength and range of motion in both the shoulders and hips, though testing elicited pain. She had symmetric hyperreflexia as well as a slowed, rigid gait. Autoantibody testing revealed strongly positive serum GAD-65 antibodies which were confirmed in the CSF. A diagnosis of stiff-person syndrome was made. She had an incomplete response to first-line therapy with high-dose benzodiazepines. IVIg was initiated with excellent response and symptom resolution. Through integrated commentary on the diagnostic reasoning process from clinical reasoning experts, this case underscores the importance of frequent assessment of fit along with explicit explanation of dissonant features in order to avoid misdiagnosis and halt diagnostic inertia. A fishbone diagram is provided to visually demonstrate the major factors that contributed to the diagnostic error. The case discussant demonstrates the power of iterative reasoning, case progression without commitment to a single diagnosis, and the dangers of both explicit and implicit bias. Finally, this case provides clinical teaching points in addition to a pitfall, myth, and pearl specific to overcoming diagnostic inertia. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Expanding clinical profiles and prognostic markers in stiff person syndrome spectrum disorders.
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Wang, Yujie, Hu, Chen, Aljarallah, Salman, Reyes Mantilla, Maria, Mukharesh, Loulwah, Simpson, Alexandra, Roy, Shuvro, Harrison, Kimystian, Shoemaker, Thomas, Comisac, Michael, Balshi, Alexandra, Obando, Danielle, Maldonado, Daniela A. Pimentel, Koshorek, Jacqueline, Snoops, Sarah, Fitzgerald, Kathryn C., and Newsome, Scott D.
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STIFF-person syndrome , *PROGNOSIS , *ORTHOPEDIC apparatus , *ASSISTIVE technology , *AUDITORY neuropathy , *PHENOTYPIC plasticity - Abstract
Objective: To describe the clinical features of a cohort of individuals with stiff person syndrome spectrum disorders (SPSD) and identify potential early predictors of future disability. Background: There is a need to better understand the full spectrum of clinical and paraclinical features and long-term impact of SPSD. Design/Methods: Observational study from 1997 to 2022 at Johns Hopkins. Clinical phenotypes included classic SPS, partial SPS (limb or trunk limited), SPS-plus (classic features plus cerebellar/brainstem involvement), and progressive encephalomyelitis with rigidity and myoclonus (PERM). Outcome measures were modified Rankin scale (mRS) and use of assistive device for ambulation. Multivariate logistic regression was used to assess significant predictors of outcomes. Results: Cohort included 227 individuals with SPSD with mean follow-up of 10 years; 154 classic, 48 SPS-plus, 16 PERM, and 9 partial. Mean age at symptom onset was 42.9 ± 14.1 years, majority were white (69.2%) and female (75.8%). Median time to diagnosis was 36.2 months (longest for SPS-plus and PERM) and 61.2% were initially misdiagnosed. Most had systemic co-morbidities and required assistive devices for ambulation. Female sex (OR 2.08; CI 1.06–4.11) and initial brainstem/cerebellar involvement (OR 4.41; CI 1.63–14.33) predicted worse outcome by mRS. Older age at symptom onset (OR 1.04; CI 1.01–1.06), female sex (OR 1.99; CI 1.01–4.01), Black race (OR 4.14; CI 1.79–10.63), and initial brainstem/cerebellar involvement (OR 2.44; CI 1.04–7.19) predicted worse outcome by use of assistive device. Early implementation of immunotherapy was associated with better outcomes by either mRS (OR 0.45; CI 0.22–0.92) or use of assistive device (OR 0.79; CI 0.66–0.94). Conclusions: We present the expanding phenotypic variability of this rare spectrum of disorders and highlight potential predictors of future disability. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Neurophysiological Analysis of Cortical Myoclonic Tremor and Excessive Startle in ARHGEF9 Deficiency.
- Author
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Pollini, Luca, Greco, Carlo, Novelli, Maria, Mei, Davide, Pisani, Francesco, De Koning‐Tijssen, Marina A.J., Guerrini, Renzo, Leuzzi, Vincenzo, and Galosi, Serena
- Subjects
- *
MYOCLONUS , *TREMOR , *MOVEMENT disorders , *WECHSLER Adult Intelligence Scale , *STIFF-person syndrome - Abstract
This article discusses the neurophysiological analysis of cortical myoclonic tremor and excessive startle in ARHGEF9 deficiency. The study describes the clinical and neurophysiological phenotype of a patient with intellectual disability, cortical myoclonic tremor, and excessive startle due to a de novo variant in ARHGEF9. The patient exhibited symptoms such as jerky movements, intellectual disability, and tremors. Neurophysiological evaluations were conducted, revealing abnormal interactions between hyperexcitable cortical areas and impaired GABAergic and glycinergic neurotransmission. The findings expand the understanding of rare genetic movement disorders and may have implications for diagnosis and treatment. [Extracted from the article]
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- 2024
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22. Paraneoplastic stiff‐leg syndrome: Positive anti‐amphiphysin antibodies associated with breast cancer.
- Author
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Ferreira, Andreia, Cruz, Cristina, Almeida, Marta, Pinto, Joana, and Rocha, Sofia
- Subjects
- *
STIFF-person syndrome , *ANTINEUTROPHIL cytoplasmic antibodies , *CEREBROSPINAL fluid , *PHYSICAL medicine , *SYMPTOMS , *MUSCLE cramps , *SYPHILIS - Abstract
This article discusses a case of paraneoplastic stiff-leg syndrome, a rare immune-mediated disorder associated with breast cancer. The patient, a 45-year-old female, experienced progressive stiffness and painful cramps in her lower extremities, along with other symptoms. After extensive testing, including imaging and electromyography, the patient was diagnosed with paraneoplastic stiff-leg syndrome due to the presence of anti-amphiphysin antibodies. Treatment included chemotherapy, physical rehabilitation, and symptomatic management with medication. The patient showed improvement and remained free of muscular spasms after completing oncological treatment. [Extracted from the article]
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- 2024
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23. Celiac disease with neurological manifestations mimicking stiff‐person syndrome.
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Niu, Jie, Zhao, Huiying, Qin, Xuzhen, Li, Ji, and Li, Jingnan
- Subjects
CELIAC disease ,STIFF-person syndrome ,NEUROLOGICAL disorders ,SYMPTOMS ,MUSCULAR atrophy ,GLUTEN-free diet - Abstract
Celiac disease (CD), a gluten‐related disease, is a multi‐system rare disorder mainly involving the gastrointestinal tract. The clinical signs of CD are exceedingly heterogeneous, which increases the difficulty of clinical differential diagnosis. Neurological manifestations are one of the non‐classical CD symptoms. As some patients present only neurological symptoms at early stages, the diagnosis of CD is always delayed. Correct diagnosis and management could decrease patient morbidity and deaths. A 32‐year‐old male was admitted to the hospital due to progressive muscle atrophy of both lower limbs and lumbar stiffness. Based on positive gluten‐sensitive enteropathy autoantibody profiles and gastroscopy foundation, the diagnosis of CD was established. The patient was instructed to gluten‐free diet. The antibody titer of gluten‐sensitive enteropathy autoantibodies decreased, and the patient's symptoms alleviated. We emphasize the importance of CD screening in patients with neurological disorders of unknown aetiology. [ABSTRACT FROM AUTHOR]
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- 2024
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24. The Power of Céline.
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CHIU, MELODY
- Subjects
- *
STIFF-person syndrome , *SUFFERING , *SPASMS , *SOUND studios - Abstract
Céline Dion, the renowned singer, has been diagnosed with Stiff-Person Syndrome (SPS), a rare autoimmune and neurological disorder. SPS causes muscle rigidity, mobility issues, painful spasms, and shortness of breath. Dion has been privately struggling with these symptoms for years, but she continued to perform and prioritize her career. After her diagnosis, she began a treatment plan involving medication, immune therapy, vocal therapy, and physical rehabilitation. Dion's goal is to get back on stage and raise awareness about SPS while encouraging others to seek help. [Extracted from the article]
- Published
- 2024
25. Book Journeys: FROM IDEA TO PRINTED PAGE, PREPARE TO BE INSPIRED BY THE JOURNEYS OF THESE MAINE AUTHORS.
- Author
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WOOD, ROBIN CLIFFORD
- Subjects
MEMOIRS ,STIFF-person syndrome ,ROMANCE fiction ,SMOKE plumes ,VOYAGES & travels ,AUTHORS ,INDEPENDENT bookstores - Abstract
The article titled "Book Journeys: FROM IDEA TO PRINTED PAGE, PREPARE TO BE INSPIRED BY THE JOURNEYS OF THESE MAINE AUTHORS" explores the journeys of several Maine authors. The authors come from diverse backgrounds and have written a range of books, including fiction, nonfiction, and poetry. The article highlights their experiences, inspirations, and the challenges they faced in the writing and publishing process. The authors' books can be purchased at various local bookstores and online platforms. [Extracted from the article]
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- 2024
26. Glutamic acid decarboxylase antibody-related stiff person syndrome: Two case reports of a child and an adult.
- Author
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Güllü, Gizem, Oguz-Akarsu, Emel, Karlı, Necdet, Okan, Mehmet Sait, and Erer, Sevda
- Subjects
- *
INTRAVENOUS immunoglobulins , *BACLOFEN , *IMMUNOGLOBULINS , *ENZYME-linked immunosorbent assay , *ENZYMES , *PLASMAPHERESIS , *MAGNETIC resonance imaging , *TREATMENT effectiveness , *GLUTAMIC acid , *STIFF-person syndrome , *LORDOSIS , *METHYLPREDNISOLONE , *CLONAZEPAM , *SPASMS , *ELECTROPHYSIOLOGY - Abstract
Stiff person syndrome (SPS) is a disease characterized by rigidity in the extremities, axial muscles, and abdominal muscles, severe and painful spasms, and accompanying gait disturbances. Stiff person syndrome is most common in adults between the ages of 20 to 50 and in female sex. The most frequently reported antibody in patients with SPS is antibodies developed against glutamic acid decarboxylase enzyme. In this article, two SPS cases from different age groups who presented with gait disturbance and painful spasms and were found to have glutamic acid decarboxylase antibody positivity were reported with clinical and electrophysiological findings in the light of the literature. As in our cases, SPS should be considered in the differential diagnosis of patients of all age presenting with muscle stiffness and spasms, specifically those that increase with stimulus. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Neurological gait assessment.
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Mermelstein, Sofia, Barbosa, Pedro, and Kaski, Diego
- Subjects
- *
CHOREA , *ATAXIA , *GAIT disorders , *DIAGNOSIS , *GAIT in humans , *PARKINSON'S disease , *NEUROLOGICAL disorders , *DYSTONIA , *STIFF-person syndrome , *WALKING speed , *GAIT apraxia , *ACCIDENTAL falls - Abstract
Gait disorders are a common feature of neurological disease. The gait examination is an essential part of the neurological clinical assessment, providing valuable clues to a myriad of causes. Understanding how to examine gait is not only essential for neurological diagnosis but also for treatment and prognosis. Here, we review aspects of the clinical history and examination of neurological gait to help guide gait disorder assessment. We focus particularly on how to differentiate between common gait abnormalities and highlight the characteristic features of the more prevalent neurological gait patterns such as ataxia, waddling, steppage, spastic gait, Parkinson's disease and functional gait disorders. We also offer diagnostic clues for some unusual gait presentations, such as dystonic, stiff-person and choreiform gait, along with red flags that help differentiate atypical parkinsonism from Parkinson's disease. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Hypersomnia in anti‐glutamic acid decarboxylase 65 (GAD65) associated neurological syndromes: A pilot study.
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Jeantin, Lina, Gales, Ana, Berzero, Giulia, Leu, Smaranda, Proust, Jérémy, Giry, Marine, Valyraki, Nefeli Eirini, Birzu, Cristina, Alentorn, Agusti, Vidailhet, Marie, Psimaras, Dimitri, and Arnulf, Isabelle
- Subjects
- *
HYPERSOMNIA , *SLEEP duration , *SLEEP latency , *STIFF-person syndrome , *SLEEP disorders , *SYNDROMES - Abstract
Background and purpose: Despite their detrimental impact on the quality of life in autoimmune encephalitis, sleep disorders have not been investigated in anti‐glutamic acid decarboxylase (GAD65) associated neurological syndromes. Methods: Six consecutive adult patients diagnosed with anti‐GAD65‐associated neurological syndromes (four with limbic encephalitis and two with stiff‐person syndrome) and 12 healthy controls were enrolled. Participants underwent sleep interviews and sleep studies including night‐time video‐polysomnography, followed by five daytime multiple sleep latency tests (MSLTs, to assess propensity to fall asleep) and an 18 h bed rest polysomnography (to assess excessive sleep need). Results: Patients reported the need for daily naps and that their cognition and quality of life were altered by sleepiness, but they had normal scores on the Epworth sleepiness scale. Compared with controls, sleep latencies during the MSLT were shorter in the patient group (median 5.8 min, interquartile range [IQR] 4.5, 6.0 vs. 17.7 min, IQR 16.3, 19.7, p = 0.001), and the arousal index was reduced (2.5/h, IQR 2.3, 3.0 vs. 22.3/h, IQR 13.8, 30.0, p = 0.002), although total sleep time was similar between groups (621 min, IQR 464, 651 vs. 542.5 min, IQR 499, 582, p = 0.51). Remarkably, all six patients had MSLT latencies ≤8 min, indicating severe sleepiness. No parasomnia or sleep‐disordered breathing was detected. Conclusion: Central hypersomnia is a relevant characteristic of anti‐GAD65‐associated neurological syndromes. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Autoimmunity Panels: Needs and Implementation in the Underdeveloped Regions and how to Approach the Disparities.
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Bhatia, Kailash and Balint, Bettina
- Subjects
- *
MOVEMENT disorders , *GENERAL practitioners , *PARANEOPLASTIC syndromes , *STIFF-person syndrome , *HEALTH facilities , *MEDICAL education , *AUTOIMMUNITY - Abstract
This article discusses the importance of autoimmunity panels in diagnosing and treating movement disorders caused by autoimmune conditions. The diagnosis of antibody-related movement disorders is based on serum and CSF analysis, and there are various techniques for assessing the presence of antibodies. However, these tests are generally expensive and may only be available in larger centers or referral units. In underdeveloped regions, the availability of autoimmune panels is limited, and the cost and timing of testing can be a barrier to early diagnosis and treatment. The article suggests that widespread education of neurologists is necessary to recognize the classic phenotypes of autoimmune movement disorders and that more funding should be made available for investigations and therapies. [Extracted from the article]
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- 2024
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30. Case report: Approaches to treatment-refractory and super-refractory glutamic acid decarboxylase antibody-spectrum disorders.
- Author
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Rajmohan, Ravi, Baveja, Shivali, Dai Nguyen, Shah, Eshita, Sy, Michael, Attaripour, Sanaz, and Swope, David
- Subjects
GLUTAMATE decarboxylase ,STIFF-person syndrome ,DEEP brain stimulation ,IMMUNOMODULATORS ,HEMATOPOIETIC stem cells - Abstract
Background: Glutamic acid decarboxylase antibody-spectrum disorders (GADSDs) include a group of autoimmune neurological diseases associated with neuronal excitability, most noticeably stiff person syndrome. Immune modulators are the mainstay of treatment, but a significant number of patients remain refractory. Methods: We present our single-center experience of eight cases of GAD-SD, two of which were refractory to immune modulatory treatments. Results: Of the two cases that were refractory to immunomodulation, one showed significant improvement with bilateral globus pallidus interna deep brain stimulation (GPi DBS) placement, and the other showed significant improvement with autologous hematopoietic stem cell transplant (aHSCT). Discussion: To our knowledge, this is the first instance of GPi DBS placement being noted to improve GAD-SD movements. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Efgartigimod beyond myasthenia gravis: the role of FcRn-targeting therapies in stiff-person syndrome.
- Author
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Di Stefano, Vincenzo, Alonge, Paolo, Rini, Nicasio, Militello, Massimiliano, Lupica, Antonino, Torrente, Angelo, and Brighina, Filippo
- Subjects
- *
MYASTHENIA gravis , *STIFF-person syndrome , *GLUTAMATE decarboxylase , *NEUROLOGICAL disorders , *MEDICAL research , *AUTOIMMUNE diseases - Abstract
Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by high titers of antibodies against glutamic acid decarboxylase (GAD) causing impaired GABAergic inhibitory neurotransmission. To date, there is not a defined therapy for such condition, but immunomodulating therapies, such as plasma exchange, intravenous immunoglobulins, and rituximab, have been widely used in clinical practice. However, the efficacy and tolerability of these treatments is not well established. Efgartigimod, a new neonatal Fc receptor (FcRn) blocker, is a human IgG1 antibody Fc fragment engineered with increased affinity for FcRn binding, leading to a reduction in IgGs levels, including pathogenic IgG autoantibody showing promising results in neurological autoimmune disorders and has been approved for the treatment of AChR-seropositive generalized myasthenia gravis (MG). In this study, we report and describe the first data on treatment with efgartigimod in three patients affected by both AChR-seropositive generalized MG and anti-GAD-seropositive SPS. Patients were followed since the start of efgartigimod and for the whole treatment period (12 weeks). MG symptoms were assessed with the "MG activity of daily living score" and the Quantitative Myasthenia Gravis score, while SPS ones were assessed with the "SPS activity of daily living score"; muscle strength was assessed with the Medical Research Council Sum score; the overall disability from MG and SPS was assessed by the modified Rankin Scale. All patients showed an improvement in symptoms of both SPS and MG after 2 cycles of treatment. Our data suggest that efgartigimod may be considered as a candidate drug for SPS and other autoantibody-mediated neurological disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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32. Neuropsychiatric Presentation of Anti‐DPPX Progressive Encephalomyelitis with Rigidity and Myoclonus.
- Author
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Neo, Ray Jen, Mehta, Arpan R., Weston, Mikail, Magrinelli, Francesca, Quattrone, Andrea, Gandhi, Sonia, Joyce, Eileen M., and Bhatia, Kailash P.
- Subjects
- *
MYOCLONUS , *ENCEPHALOMYELITIS , *MEDICAL research , *STIFF-person syndrome , *CHILD mental health services - Abstract
This article discusses a case of progressive encephalomyelitis with rigidity and myoclonus (PERM) associated with anti-DPPX antibodies. PERM is a severe form of stiff-person-syndrome spectrum disorders characterized by brainstem and autonomic involvement, as well as axial and limb rigidity. The patient in this case presented with a neuropsychiatric prodrome, including behavioral changes, weight loss, and movement disorders. The diagnosis was confirmed through positive serum and cerebrospinal fluid DPPX antibodies. Treatment with immunotherapies resulted in significant improvement in symptoms. The document provides a table summarizing the symptoms, CSF findings, and therapy response of patients with PERM associated with different antibodies. The authors emphasize the importance of early recognition and treatment of this condition. [Extracted from the article]
- Published
- 2024
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33. THE UNSINKABLE TITANIQUE.
- Author
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sim, bernardo
- Subjects
- *
UNITED States presidential election, 2016 , *STIFF-person syndrome , *CENTERS for the performing arts - Abstract
Titanique is a queer-coded musical parody that pays homage to the movie Titanic and Céline Dion's music. The show originated from the minds of writer-director Tye Blue and book co-writers Marla Mindelle and Constantine Rousouli. It started as a concert series in Beverly Hills and gained traction, eventually moving to New York City. The show faced challenges in obtaining music licenses when transitioning to a full theater production. Despite these challenges, Titanique had a successful off-Broadway debut and remains popular with audiences. The show has received recognition, including winning the Lucille Lortel Award for Outstanding Musical. The creators of Titanique are fans of Céline Dion and were saddened by her diagnosis of stiff-person syndrome. They hope that she will return to the stage and continue to inspire fans. [Extracted from the article]
- Published
- 2024
34. Case Report: Extraocular muscles paralysis associated with GAD65 antibody: a case series study.
- Author
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Heyu Zhang, Jiajia Yue, Chun Lian, Youming Long, and Dan He
- Subjects
MYASTHENIA gravis ,PARALYSIS ,GLUTAMATE decarboxylase ,STIFF-person syndrome ,CEREBROSPINAL fluid ,MAGNETIC resonance imaging - Abstract
Objective: To explore the clinical manifestations of glutamic acid decarboxylase 65 (GAD65) antibody-positive patients with extraocular symptoms and the possible mechanism. Method: Assays for the presence of GAD65 antibodies were performed on patients' serum and cerebral spinal fluid (CSF). The brain and ocular structures involved in eye movement were assessed via magnetic resonance imaging (MRI). Tests such as electromyography (EMG), particularly repetitive nerve stimulation (RNS), and neostigmine tests were utilized for differential diagnosis. Additionally, the interaction of GAD65 antibodies with muscle tissue was confirmed using immunofluorescence techniques. Result: Each patient exhibited symptoms akin to extraocular myasthenia gravis (MG), with two individuals reporting diplopia and two experiencing ptosis. GAD65 antibodies were detected in either the serum or CSF, which were shown to bind with monkey cerebellum slides and mouse muscle slides. Neuroimaging of the brain and extraocular muscles via MRI showed no abnormalities, and all patients tested negative for the neostigmine test, RNS via EMG, and the presence of MG antibodies. However, thyroid-related antibodies were found to be abnormal in four of the patients. Conclusion: Our results showed that GAD65 antibodies are not only associated with encephalitis, cerebellum ataxia or stiff-person syndrome caused by the decrease of GABAergic transmission but also diplopia and ptosis. Therefore, we should pay more attention to extraocular muscle paralysis patients without pathogenic antibodies directed against the components of neuromuscular junctions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
35. Prevalence of non-neurological autoantibodies and related comorbidities in stiff person spectrum disorders.
- Author
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Balshi, Alexandra, Taylor, Elena, Yishang Huang, Obando, Danielle, Miles, Ashley, Comisac, Michael, Yujie Wang, and Newsome, Scott D.
- Subjects
STIFF-person syndrome ,AUTOANTIBODIES ,TYPE 1 diabetes ,AUTOIMMUNE thyroiditis ,ORTHOPEDIC apparatus ,NON-communicable diseases - Abstract
Background: Stiff Person Syndrome Spectrum Disorders (SPSD) are a group of rare neurological disorders that can present alongside other autoimmune conditions. However, not much is known about the breadth of non-neurological autoantibodies seen in SPSD nor the observed prevalence of co-existing autoimmune comorbidities and their impact on SPSD. Objective: This study aimed to investigate the prevalence of non-neurological autoantibodies and associated conditions in a large cohort of people with SPSD. Methods: A retrospective review of 205 patients with suspected/definitive SPSD seen at Johns Hopkins Hospital from 1997 to 2023 was performed as part of an ongoing, observational study. Relevant demographics, clinical data (e.g., SPSD phenotypes, comorbid conditions, and dates of diagnoses), and laboratory values were collected from electronic medical records. Lab values were excluded if completed within 6 months of receiving intravenous immunoglobin treatment. Summary statistics were performed and assessment for any associations between autoimmune comorbidities and disease burden (modified Rankin score [mRS] and ambulation status) was performed. Results: The majority of participants had classic SPS (66%), followed by SPSplus (18%) and PERM (6%) with less than 5% each of the remaining phenotypes and suspected SPS. The average age at symptom onset in this cohort was 44.1 ± 14.5 years (mean ± standard deviation). The majority of the cohort was white (66%) and female patients (75%). The mean mRS was 2.5, and over 70% required assistive devices for ambulation. The most commonly identified nonneurological autoantibodies were anti-nuclear (ANA) (31%), thyroperoxidase (30%), thyroglobulin (20%), and anti-parietal cell (18%) autoantibodies. The most common comorbid autoimmune conditions were autoimmune thyroiditis (38%), insulin-dependent diabetes mellitus (26%), and pernicious anemia (10%). Having more autoimmune comorbidities was weakly associated with higher mRS and a greater need for ambulatory assistance. Conclusion: The results of this study will hopefully help promote awareness of which autoantibody and medical comorbidity clinicians should be aware of and monitor people with SPSD. Further research is needed to identify if poorly controlled non-neurological autoimmune disorders contribute to disease burden in SPSD and/or if the timing of being diagnosed with one of these conditions plays a role in future disability. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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36. A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review.
- Author
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Tamang Sapana, Wei Li, Fengyan Tian, Wenhao Yan, Binghua Dou, Shuang Hua, and Zhihong Zhuo
- Subjects
ANTI-NMDA receptor encephalitis ,LITERATURE reviews ,STIFF-person syndrome ,GLUTAMATE decarboxylase ,ENCEPHALITIS ,NEUROLOGICAL disorders - Abstract
Background: Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extra limbic encephalitis. While there are few case reports and research on anti-GAD65 antibody-associated encephalitis in adults, such cases are extremely rare in pediatric cases. Methods: For the first time, we report a case of anti-GAD65-positive autoimmune encephalitis associated with autoimmune polyendocrine syndrome (APS) type II. We reviewed previously published pediatric cases of anti-GAD65 autoimmune encephalitis to discuss their clinical features, laboratory tests, imaging findings, EEG patterns, and prognosis. Case presentation: An 8-year-old, male child presented to the outpatient department after experiencing generalized convulsions for twenty days. The child was admitted for epilepsy and had received oral sodium valproate (500 mg/ day) in another center, where investigations such as USG abdomen and MRI brain revealed no abnormalities, however, had abnormal EEG with diffuse mixed activity in the left anterior middle prefrontal temporal region. On the follow-up day, a repeat blood test showed a very low serum drug concentration of sodium valproate hence the dose was increased to 750 mg/day. Then, the child experienced adverse effects including increased sleep, thirst, and poor appetite, prompting the parents to discontinue the medication. A repeat MRI showed increased signals on FLAIR sequences in the right hippocampus hence admitted for further management. The child's past history included a diagnosis of hypothyroidism at the age of 4, and receiving levothyroxine 75 mcg once daily. His parents are healthy with no history of any similar neurological, autoimmune, or genetic diseases, but his uncle had a history of epilepsy. At presentation, hehad uncontrolled blood glucose levels with elevated HbA1c levels. Additionally, the serum and CSF autoantibodies were positive against the anti-GAD65 antibody with the titer of 1:100 and 1:32 respectively. The patient was managed with a mixed type of insulin regimen and received first-line immunotherapy (intravenous immunoglobulin, IVIG) for five consecutive days, followed by oral prednisone and sodium valproate as an antiepileptic drug. Upon achieving a favorable clinical outcome, the patient was discharged with oral medications. Results: Among the 15 pediatric patients reported in this literature, nine presented with limbic encephalitis (LE), three with extralimbic encephalitis (ELE), and three with a combination of limbic and extralimbic encephalitis. Most of these cases exhibited T2-W FLAIR hyperintensities primarily localized to the temporal lobes in the early phase, progressing to hippocampal sclerosis/ atrophy in the later phase on MRI. EEG commonly showed slow or spike waves on frontotemporal lobes with epileptic discharges. Prognostic factors varied among patients, with some experiencing persistent refractory seizures, type-1 diabetes mellitus (T1DM), persistent memory impairment, persistent disability requiring full assistance, and, in severe cases, death. Conclusion: Our findings suggest that anti-GAD65 antibody-positive autoimmune encephalitis patients may concurrently present with other APS. Our unique case presented with multiple endocrine syndromes and represents the first reported occurrence in children. Early diagnosis and timely initiation of immunotherapy are crucial for improving clinical symptoms and reducing the likelihood of relapses or permanent disabilities. Therefore, emphasis should be placed on prompt diagnosis and appropriate treatment implementation to achieve better patient outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
37. Stiff‐person syndrome revealing an occult gray zone lymphoma: A diagnostic challenge.
- Author
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Fakhari, Mohammad Sadegh, Poorsaadat, Leila, Mohammad Talebi, Hooman, and Kosari, Farid
- Subjects
- *
STIFF-person syndrome , *SPASMS , *NEUROLOGICAL disorders , *LYMPHOMAS , *PARANEOPLASTIC syndromes , *OLDER patients - Abstract
Key Clinical Message: Stiff‐Person Syndrome (SPS) can be associated with various malignancies, including lymphomas. Therefore, clinicians should always remain vigilant for the presence of an underlying malignancy, especially in older patients presenting with SPS. Stiff‐person syndrome (SPS) is a rare neurological disorder characterized by painful muscle spasms. It can occur as a paraneoplastic syndrome associated with various malignancies. We present a case of an older male adult with a history of recurrent fever episodes and elevated inflammatory markers for 1 year who subsequently developed neurological symptoms. The presence of positive amphiphysin antibodies led to the diagnosis of SPS, which prompted further investigations revealing an underlying Gray Zone lymphoma (GZL). This case highlights the challenges in diagnosing lymphoma and emphasizes the importance of considering SPS as a paraneoplastic syndrome in guiding toward the final diagnosis. The diagnostic challenge in our case is summarized in Chart 1. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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38. A case of severe paraneoplastic glutamic acid decarboxylase antibody‐spectrum disorder with improvement through prior immunotherapy before surgical intervention.
- Author
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Nozuma, Satoshi, Yuji‐Takeuchi, Mika, Nakamura, Tomonori, Saigo, Ryuji, Masuda, Mirai, Ando, Masahiro, Sakiyama, Yusuke, Miyata, Ryo, Tabata, Kazuhiro, Matsuura, Eiji, and Takashima, Hiroshi
- Subjects
- *
GLUTAMATE decarboxylase , *PARANEOPLASTIC syndromes , *STIFF-person syndrome , *CEREBELLAR ataxia , *IMMUNOTHERAPY , *CEREBROSPINAL fluid - Abstract
Background: Initially associated with stiff‐person syndrome, antibodies to glutamic acid decarboxylase (GAD) antibodies are now recognized as indicators of GAD antibody‐spectrum disorders (GAD‐SD), which encompass cerebellar ataxia, autoimmune epilepsy and limbic encephalitis. Paraneoplastic neurological syndromes associated with GAD‐SD are rare, and optimal timing of surgical intervention and impact on neurological symptoms remain poorly understood. Case Presentation: We present the case of a 65‐year‐old woman who developed overlapping symptoms of cerebellar ataxia and stiff‐person syndrome detected through high‐titer GAD antibodies in both serum and cerebrospinal fluid, alongside the presence of a thymoma. Due to severe dysphagia and gait ataxia that rendered her bedridden on admission, surgical intervention was initially deferred. Instead, she received immunotherapies including intravenous methylprednisolone and intravenous immunoglobulin, which remarkably improved neurological symptoms. However, a decline in symptoms occurred on tapering oral prednisolone. Subsequently, a thoracoscopic thymectomy was carried out 27 months after symptom onset, leading to further neurological improvement and successful reduction of prednisolone. Conclusion: In paraneoplastic GAD‐SD cases with severe symptoms at presentation, prioritizing immunotherapy and considering surgical intervention once the symptoms have stabilized might be advantageous. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
39. The many faces of gastrointestinal dysfunction in stiff person syndrome spectrum disorders.
- Author
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Koshorek, Jacqueline, Yujie Wang, Maldonado, Daniela Pimentel, Reyes-Mantilla, Maria I., Obando, Danielle, Balshi, Alexandra, Comisac, Michael, Pasricha, Pankaj Jay, and Newsome, Scott D.
- Subjects
STIFF-person syndrome ,GASTROINTESTINAL system - Abstract
Introduction: The effect of stiff person syndrome spectrum disorders (SPSD) on the gastrointestinal tract (GIT) is unknown. This case series aims to characterize the prevalence and types of GI dysfunction in individuals with SPSD. Methods: A retrospective chart review included individuals diagnosed with SPSD with descriptors of GI symptoms in their medical records. SPSD phenotypes, type of motility test performed, and dysmotility pattern (upper, lower, or diffuse) were assessed. Descriptive statistics and univariate chi-square analyses were utilized. Results: Of 240 individuals with SPSD, 32% reported GI symptoms, most were female (83.1%), and white (74%), with a median age at time of GI symptom onset of 50 ± 13 years. Most common symptoms reported were dysphagia (45%), constipation (40%), and nausea/vomiting (23%). Most individuals had classic SPS (47%) followed by SPS-plus (29%) and 82.9% were positive for serum antiGAD65 antibodies. Of 36 patients that underwent at least one GI motility test, 26 had evidence of upper, lower, or diffuse GI dysmotility (44.4%, 17%, and 4%, respectively). The group who did not undergo testing had a higher proportion of patients with DM. Discussion: There is a high prevalence of GI symptoms and transit abnormalities in patients with SPSD. Future prospective, longitudinal studies are warranted to further assess GI symptoms in the context of SPSD and to determine if individuals with GI symptoms differ in prognosis or treatment response from those without GI symptoms. In the meantime, there should be a low threshold for motility testing in patients with SPSD. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
40. An update on malignant tumor-related stiff person syndrome spectrum disorders: clinical mechanism, treatment, and outcomes.
- Author
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Yong Peng, Huan Yang, Ya-hui Xue, Quan Chen, Hong Jin, Shu Liu, Shun-yu Yao, and Miao-qiao Du
- Subjects
STIFF-person syndrome ,MYOCLONUS ,CENTRAL nervous system ,LUNG cancer ,CANCER patients ,AUTOANTIGENS - Abstract
Stiff person syndrome (SPS) is a rare central nervous system disorder associated with malignancies. In this review, we retrieved information from PubMed, up until August 2023, using various search terms and their combinations, including SPS, stiff person syndrome spectrum disorders (SPSSDs), paraneoplastic, cancer, and malignant tumor. Data from peer-reviewed journals printed in English were organized to explain the possible relationships between different carcinomas and SPSSD subtypes, as well as related autoantigens. From literature searching, it was revealed that breast cancer was the most prevalent carcinoma linked to SPSSDs, followed by lung cancer and lymphoma. Furthermore, classic SPS was the most common SPSSD subtype, followed by stiff limb syndrome and progressive encephalomyelitis with rigidity and myoclonus. GAD65 was the most common autoantigen in patients with cancer and SPSSDs, followed by amphiphysin and GlyR. Patients with cancer subtypes might have multiple SPSSD subtypes, and conversely, patients with SPSSD subtypes might have multiple carcinoma subtypes. The first aim of this review was to highlight the complex nature of the relationships among cancers, autoantigens, and SPSSDs as new information in this field continues to be generated globally. The adoption of an open-minded approach to updating information on new cancer subtypes, autoantigens, and SPSSDs is recommended to renew our database. The second aim of this review was to discuss SPS animal models, which will help us to understand the mechanisms underlying the pathogenesis of SPS. In future, elucidating the relationship among cancers, autoantigens, and SPSSDs is critical for the early prediction of cancer and discovery of new therapeutic modalities. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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41. Stiff-Leg Syndrome Associated with Autoimmune Retinopathy and Its Treatment with IVIg—A Case Report and Review of the Literature.
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Papadopoulos, Vassilis E., Papadimas, George K., Androudi, Sofia, Anagnostouli, Maria, and Evangelopoulos, Maria-Eleftheria
- Subjects
- *
LITERATURE reviews , *INTRAVENOUS immunoglobulins , *GLUTAMATE decarboxylase , *STIFF-person syndrome , *TYPE 1 diabetes , *AUTOIMMUNE diseases - Abstract
Antibodies to glutamic acid decarboxylase (GAD) have been predominantly associated with stiff-person syndrome (SPS), which is often accompanied by organ-specific autoimmune diseases, such as late-onset type 1 diabetes. Autoimmune retinal pathology in SPS has recently been suggested to coexist in patients suffering from this disease; however, evidence reporting potential treatment options for the neurological and visual symptoms these patients experience remains scarce. We provide a review of the relevant literature, presenting a rare case of a middle-aged woman with autoimmune retinopathy (AIR) followed by stiff-leg syndrome who responded to intravenous immune globulin treatment (IVIg). Our report adds to previously reported data supporting the efficacy of IVIg in SPS spectrum disorders while also proposing the potential effect of IVIg in treating SPS spectrum patients with coexisting AIR. [ABSTRACT FROM AUTHOR]
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- 2023
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42. Diabetes in stiff-person syndrome.
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Heneberg, Petr
- Subjects
- *
STIFF-person syndrome , *TYPE 1 diabetes , *AUTOIMMUNE diseases , *DIABETES - Abstract
Diabetes is common in patients with autoimmune stiff-person syndrome (SPS); 60% of cases represent an organ-specific autoimmune disease. The prevalence of circulating anti-glutamic acid decarboxylase (GAD) antibodies among patients with SPS is approximately 60–98%; 60.5% of anti-GAD-positive patients with SPS develop insulin-dependent diabetes mellitus (IDDM). Frequencies of diabetes-associated antibodies in patients with concomitant SPS and IDDM differ strongly from frequencies known from the general population with type 1 diabetes mellitus. Many patients with SPS manifest diabetes only after being treated with high-dose corticosteroids or progress to dependency on insulin therapy following their treatment with high-dose corticosteroids. IDDM in patients with SPS often has multiple causes, combining autoimmune (anti-GAD antibodies) and toxic (steroid-induced) processes. Anti-glutamic acid decarboxylase (GAD) autoantibodies are a hallmark of stiff-person syndrome (SPS) and insulin-dependent diabetes mellitus (IDDM). However, patients with concurrent IDDM and SPS often manifest insulin resistance, and SPS-associated IDDM probably has heterogeneous causes. Some patients manifest IDDM associated only with high titers of anti-GAD65 caused by SPS. By contrast, other patients develop IDDM only after being treated with high-dose corticosteroids or they progress to insulin dependency following their treatment with high-dose corticosteroids. The profile of autoantibodies differs markedly between type 1 diabetes mellitus (T1DM), late-onset diabetes mellitus, and SPS-associated IDDM. Therefore, as with new-onset diabetes after transplantation (NODAT), SPS-associated IDDM should be classified as a specific diabetes entity, the pathophysiology of which requires increased attention. [ABSTRACT FROM AUTHOR]
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- 2023
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43. Autoimmune Neuromuscular Disorders: Emerging Insights and Future Frontiers.
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Di Stefano, Vincenzo and Brighina, Filippo
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- *
NEUROMUSCULAR diseases , *AUTOIMMUNE diseases , *STIFF-person syndrome , *CHRONIC inflammatory demyelinating polyradiculoneuropathy , *MYASTHENIA gravis , *AMYOTROPHIC lateral sclerosis - Abstract
This document discusses the emerging insights and future frontiers in autoimmune neuromuscular disorders. It highlights the increasing knowledge of the immunology and immunological aspects of these disorders, as well as the development of new target therapies for their treatment. The document also emphasizes the importance of laboratory and instrumental biomarkers for diagnosis and disease progression, as well as the role of specific diagnostic antibody testing in identifying relevant conditions. It concludes by calling for more attention to be given to neuroimmunology in residency programs and the need for further research in this field. [Extracted from the article]
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- 2024
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44. Relapsing remitting encephalomyelitis with glutamic acid decarboxylase antibodies following autologous haematopoietic stem cell transplantation—coincidence or consequence?
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Sequeira, Marta, Lobo, Gonçalo Gama, Ferro, Margarida, and Capela, Carlos
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- *
HEMATOPOIETIC stem cell transplantation , *GLUTAMATE decarboxylase , *ANTI-NMDA receptor encephalitis , *ENCEPHALOMYELITIS , *STIFF-person syndrome , *GRAFT versus host disease , *AUTOIMMUNE diseases - Abstract
This article discusses a case of relapsing remitting encephalomyelitis with glutamic acid decarboxylase (GAD) antibodies following autologous hematopoietic stem cell transplantation (aHSCT). GAD antibodies have been associated with various neurological syndromes, including stiff person syndrome, cerebellar ataxia, limbic encephalitis, and epilepsy. While aHSCT is commonly used to treat autoimmune disorders, the development of new autoimmunity after the procedure is still not well understood. The article highlights the need for further research to understand the mechanisms behind this phenomenon. [Extracted from the article]
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- 2024
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45. The Effectiveness of Combining Botulinum Toxin Type A and Therapeutic Exercise in Treating Spasticity in a Patient with Complicated Stiff-Person Syndrome: A Case Report
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Riccardo Marvulli, Maria Vittoria Raele, Mariagrazia Riccardi, Giacomo Farì, Maurizio Ranieri, and Marisa Megna
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stiff-man syndrome ,stiff-person syndrome ,botulinum toxin type A ,therapeutic exercise ,Medicine - Abstract
Stiff-person syndrome is rare and disabling autoimmune condition that most frequently affects women, with no real predisposition by race. Diagnosis is often arduous, which is why patients concomitantly suffer from anxiety and depression. To date, drug therapy is based on the use of benzodiazepines, barbiturates, and baclofen. Refractory cases are treated with intravenous immunoglobulin, plasmapheresis, B lymphocyte depletion with rituximab, and even the implantation of intrathecal baclofen devices. Botulinum toxin injection is frequently used, even if it still has an unclear role in the literature. Our case report aims to demonstrate the efficacy of a combined treatment of botulinum toxin and therapeutic exercise in a 65-year-old patient with biceps brachii muscle hypertonia and diffuse spasms of the axial musculature, using rating scales such as the Numeric Rating Scale (NRS) and Modified Ashworth Scale (MAS), joint range of motion (ROM) measurement, and muscle dynamic stiffness mensuration, which is performed by using the MyotonPro®. All the assessments were conducted at the first evaluation (T0), soon after the combined treatment with botulin toxin and therapeutic exercise (T1), three months (T2), six months (T3), and eight months after the botulinum toxin injection (T4). The patient demonstrated benefits for more than 6 months with no side effects. The combined therapy of botulinum toxin and therapeutic exercise had an excellent result in our patient.
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- 2024
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46. Stiff‐person syndrome revealing an occult gray zone lymphoma: A diagnostic challenge
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Mohammad Sadegh Fakhari, Leila Poorsaadat, Hooman Mohammad Talebi, and Farid Kosari
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gray zone lymphoma ,paraneoplastic syndrome ,stiff‐person syndrome ,Medicine ,Medicine (General) ,R5-920 - Abstract
Key Clinical Message Stiff‐Person Syndrome (SPS) can be associated with various malignancies, including lymphomas. Therefore, clinicians should always remain vigilant for the presence of an underlying malignancy, especially in older patients presenting with SPS. Abstract Stiff‐person syndrome (SPS) is a rare neurological disorder characterized by painful muscle spasms. It can occur as a paraneoplastic syndrome associated with various malignancies. We present a case of an older male adult with a history of recurrent fever episodes and elevated inflammatory markers for 1 year who subsequently developed neurological symptoms. The presence of positive amphiphysin antibodies led to the diagnosis of SPS, which prompted further investigations revealing an underlying Gray Zone lymphoma (GZL). This case highlights the challenges in diagnosing lymphoma and emphasizes the importance of considering SPS as a paraneoplastic syndrome in guiding toward the final diagnosis. The diagnostic challenge in our case is summarized in Chart 1.
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- 2023
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47. Stiff Person Spectrum Disorders—An Update and Outlook on Clinical, Pathophysiological and Treatment Perspectives.
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Vlad, Benjamin, Wang, Yujie, Newsome, Scott D., and Balint, Bettina
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STIFF-person syndrome ,AUTOIMMUNE diseases ,THERAPEUTICS ,GLUTAMATE decarboxylase ,RARE diseases - Abstract
Stiff person spectrum disorders (SPSD) are paradigm autoimmune movement disorders characterized by stiffness, spasms and hyperekplexia. Though rare, SPSD represent a not-to-miss diagnosis because of the associated disease burden and treatment implications. After decades as an enigmatic orphan disease, major advances in our understanding of the evolving spectrum of diseases have been made along with the identification of multiple associated autoantibodies. However, the most important recent developments relate to the recognition of a wider affection, beyond the classic core motor symptoms, and to further insights into immunomodulatory and symptomatic therapies. In this review, we summarize the recent literature on the clinical and paraclinical spectrum, current pathophysiological understanding, as well as current and possibly future therapeutic strategies. [ABSTRACT FROM AUTHOR]
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- 2023
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48. Relevance of Antibody Testing in Movement Disorders.
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Balint, Bettina
- Subjects
- *
ANTIBODY titer , *MOVEMENT disorders , *ANTI-NMDA receptor encephalitis , *AUTOIMMUNE diseases , *STIFF-person syndrome , *PROGRESSIVE supranuclear palsy , *GLUTAMATE decarboxylase - Abstract
This article explores the role of antibody testing in movement disorders, specifically in autoimmune encephalitis. It highlights the advancements in genetic testing and neuroimmunology that have led to improved diagnosis and understanding of these disorders. Antibody testing is seen as a valuable tool in guiding treatment decisions, but it is important to consider its limitations and use it alongside clinical expertise. The document also serves as a compilation of references and citations related to autoimmune encephalitis and movement disorders, providing a valuable resource for researchers and healthcare professionals. [Extracted from the article]
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- 2023
- Full Text
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49. A loss-of-function variant in canine GLRA1 associates with a neurological disorder resembling human hyperekplexia.
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Heinonen, Tiina, Flegel, Thomas, Müller, Hanna, Kehl, Alexandra, Hundi, Sruthi, Matiasek, Kaspar, Fischer, Andrea, Donner, Jonas, Forman, Oliver P., Lohi, Hannes, and Hytönen, Marjo K.
- Subjects
- *
STIFF-person syndrome , *NEUROLOGICAL disorders , *GLYCINE receptors , *ACOUSTIC reflex , *WHOLE genome sequencing , *STARTLE reaction - Abstract
Hereditary hyperekplexia is a rare neuronal disorder characterized by an exaggerated startle response to sudden tactile or acoustic stimuli. In this study, we present a Miniature Australian Shepherd family showing clinical signs, which have genetic and phenotypic similarities with human hereditary hyperekplexia: episodes of muscle stiffness that could occasionally be triggered by acoustic stimuli. Whole genome sequence data analysis of two affected dogs revealed a 36-bp deletion spanning the exon–intron boundary in the glycine receptor alpha 1 (GLRA1) gene. Further validation in pedigree samples and an additional cohort of 127 Miniature Australian Shepherds, 45 Miniature American Shepherds and 74 Australian Shepherds demonstrated complete segregation of the variant with the disease, according to an autosomal recessive inheritance pattern. The protein encoded by GLRA1 is a subunit of the glycine receptor, which mediates postsynaptic inhibition in the brain stem and spinal cord. The canine GLRA1 deletion is located in the signal peptide and is predicted to cause exon skipping and subsequent premature stop codon resulting in a significant defect in glycine signaling. Variants in GLRA1 are known to cause hereditary hyperekplexia in humans; however, this is the first study to associate a variant in canine GLRA1 with the disorder, establishing a spontaneous large animal disease model for the human condition. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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50. Respiratory symptoms are common in stiff person syndrome spectrum disorders and are associated with number of body regions involved.
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Pimentel Maldonado, Daniela A., Balshi, Alexandra, Hu, Chen, Fitzgerald, Kathryn C., Koshorek, Jacqueline, Reyes‐Mantilla, Maria I., Obando, Danielle, Wang, Yujie, and Newsome, Scott D.
- Subjects
- *
STIFF-person syndrome , *ADULT respiratory distress syndrome , *SPASMS , *SYMPTOMS , *DESCRIPTIVE statistics - Abstract
Background and purpose: Stiff person syndrome (SPS) spectrum disorders (SPSSD) cause spasms and rigidity throughout different body regions and can be associated with apnea and acute respiratory failure. There are limited data on the prevalence and predictors of respiratory symptoms with spasms (RSwS) in SPSSD. We sought to characterize the spirometry patterns and the frequency and predictors of RSwS in a large SPSSD cohort. Methods: Participants were recruited from the Johns Hopkins SPS Center between 1997 and 2021, as part of an ongoing, longitudinal observational study. Medical records were reviewed to assess demographics and clinical characteristics. Data were analyzed using descriptive statistics and multivariable logistic regression models. Results: One‐hundred ninety‐nine participants (mean age = 53.4 ± 13.6 years, median time to diagnosis = 36 [IQR 66] months, 74.9% women, 69.8% White, 62.8% classic SPS phenotype) were included in final analyses; 35.2% of participants reported RSwS, of whom 24.3% underwent spirometry as part of routine clinical care. Obstructive (23.5%) and restrictive (23.5%) patterns were most commonly observed in those with SPSSD. An increasing number of body regions involved predicted the presence of RSwS (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.50–2.53); those with ≥5 body regions involved (vs. ≤4) had higher odds (OR = 6.19, 95% CI = 2.81–13.62) of experiencing RSwS in adjusted models. Two patients died from SPSSD‐associated respiratory compromise. Conclusions: RSwS are common in SPSSD and may be predicted by an increasing number of body regions involved by SPSSD. Close clinical monitoring and having a low threshold to obtain spirometry should be considered in people with SPSSD. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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