Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence‐Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue

Journal of Clinical Apheresis, Journal Year: 2023, Volume and Issue: 38(2), P. 77 - 278

Published: April 1, 2023

The American Society for Apheresis (ASFA) Journal of Clinical (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications the evidence-based use therapeutic apheresis (TA) in human disease. In Ninth Edition, JCA has incorporated systematic review approaches grading evidence categorization to make recommendations on a wide variety diseases conditions. This edition largely maintained general layout concept fact sheet introduced Fourth Edition (2007). Each succinctly summarizes TA specific disease or medical condition. comprises 91 sheets 166 graded categorized indications. includes seven new sheets, nine existing eight changes category seeks continue serve as key resource that guides utilization treatment

Language: Английский

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Therapies in Stiff-Person Syndrome

Neurology Neuroimmunology & Neuroinflammation, Journal Year: 2023, Volume and Issue: 10(3)

Published: April 21, 2023

Among the glutamic acid decarboxylase (GAD)-antibody-spectrum disorders, most common phenotypic subset is stiff-person syndrome (SPS), caused by impaired GABAergic inhibitory neurotransmission and autoimmunity characterized very high titers of GAD antibodies increased GAD-IgG intrathecal synthesis. If not properly treated or untreated because delayed diagnosis, SPS progresses leading to disability; it therefore fundamental apply best therapeutic schemes from outset. This article focused on rationale specific strategies based pathophysiology targeting both reciprocal inhibition symptomatically improve main clinical manifestations stiffness in truncal proximal limb muscles, gait dysfunction, episodic painful muscle spasms enhance improvement slow down disease progression. A practical, step-by-step approach provided, highlighting importance combination therapies with preferred gamma-aminobutyric acid-enhancing antispasmodic drugs, such as baclofen, tizanidine, benzodiazepines, gabapentin, that provide first-line symptomatic therapy, while detailing application current immunotherapies intravenous immunoglobulin (IVIg) plasmapheresis, rituximab. The pitfalls concerns long-term different age groups, including children, women planning pregnancy, especially elderly considering their comorbidities are emphasized, also challenges distinguishing conditioning effects expectations chronically applied objective meaningful benefits. Finally, need for future targeted immunotherapeutic options immunopathogenesis biologic basis autoimmune hyperexcitability discussed, pointing out unique design controlled trials quantifying extend severity stiffness, startle-triggered spasms, task-specific phobias, excitability.

Language: Английский

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Stiff person spectrum disorder diagnosis, misdiagnosis, and suggested diagnostic criteria

Annals of Clinical and Translational Neurology, Journal Year: 2023, Volume and Issue: 10(7), P. 1083 - 1094

Published: May 22, 2023

Abstract Background Stiff person spectrum disorder (SPSD) is heterogeneous, and accurate diagnosis can be challenging. Methods Patients referred for diagnosis/suspicion of SPSD at the Mayo Autoimmune Neurology Clinic from July 01, 2016, to June 30, 2021, were retrospectively identified. was defined as clinical manifestations confirmed by an autoimmune neurologist seropositivity high‐titer GAD65‐IgG (>20.0 nmol/L), glycine‐receptor‐IgG or amphiphysin‐IgG, and/or confirmatory electrodiagnostic studies (essential if seronegative). Clinical presentation, examination, ancillary testing compared differentiate non‐SPSD. Results Of 173 cases, 48 (28%) diagnosed with 125 (72%) Most seropositive (41/48: 28/41, 12/41, amphiphysin‐IgG 2/41). Pain syndromes functional neurologic most common non‐SPSD diagnoses (81/125, 65%). patients more commonly reported exaggerated startle (81% vs. 56%, p = 0.02), unexplained falls (76% 46%, 0.001), other associated autoimmunity (50% 27%, 0.005). often had hypertonia (60% 24%, < hyperreflexia (71% 43%, lumbar hyperlordosis (67% 9%, 0.001) less likely signs (6% 33%, 0.001). frequently abnormalities (74% 17%, least moderate symptomatic improvement benzodiazepines (51% 16%, immunotherapy (45% 13% Only 4/78 who received alternative autoimmunity. Interpretation Misdiagnosis threefold than SPSD. Functional non‐neurologic disorders accounted misdiagnoses. factors reduce misdiagnosis exposure unnecessary treatments. diagnostic criteria are suggested.

Language: Английский

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Stiff Person Syndrome and GAD Antibody–Spectrum Disorders

CONTINUUM Lifelong Learning in Neurology, Journal Year: 2024, Volume and Issue: 30(4), P. 1110 - 1135

Published: Aug. 1, 2024

ABSTRACT OBJECTIVE Antibodies against glutamic acid decarboxylase (GAD), originally associated with stiff person syndrome (SPS), define the GAD antibody–spectrum disorders that also include cerebellar ataxia, autoimmune epilepsy, limbic encephalitis, progressive encephalomyelitis rigidity and myoclonus (PERM), eye movement disorders, all of which are characterized by neuronal excitability. This article elaborates on diagnostic criteria for SPS spectrum highlights disease mimics misdiagnoses, describes electrophysiologic mechanisms underlying autoimmunity stiffness spasms, provides a step-by-step therapeutic scheme. LATEST DEVELOPMENTS Very-high serum antibody titers predict presence antibodies in CSF, increased intrathecal synthesis, reduced CSF γ-aminobutyric (GABA) levels. Low or absence generates challenges require careful distinction patients variety painful spasms stiffness, including functional neurologic disorders. glycine receptors, first found PERM, seen 13% to 15% SPS, whereas amphiphysin gephyrin antibodies, 5% paraneoplastic association. GAD-IgG from different recognizes same dominant intracellular epitope and, although pathogenicity is unclear, an excellent marker. The biological basis muscle related hyperexcitability caused impaired reciprocal acid–mediated (GABA-ergic) inhibition, explains response GABA-enhancing agents immunotherapies. ESSENTIAL POINTS It essential distinguish avoid both overdiagnoses considering treatable if managed correctly outset prevent progression. A step-by-step, combination therapy medications along immunotherapies ensures prolonged clinical benefits.

Language: Английский

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Immunopathology of herpes simplex virus‐associated neuroinflammation: Unveiling the mysteries

Reviews in Medical Virology, Journal Year: 2023, Volume and Issue: 34(1)

Published: Nov. 20, 2023

The immunopathology of herpes simplex virus (HSV)-associated neuroinflammation is a captivating and intricate field study within the scientific community. HSV, renowned for its latent infection capability, gives rise to spectrum neurological expressions, ranging from mild symptoms severe encephalitis. enigmatic interplay between host's immune responses profoundly shapes outcome these infections. This review delves into multifaceted reactions triggered by HSV neural tissues, intricately encompassing innate adaptive immunity. Furthermore, this analysis delicate equilibrium defence potential immunopathology-induced damage. It meticulously dissects roles diverse cells, cytokines, chemokines, unravelling intricacies modulation subsequent effects. By exploring HSV's manipulation exploitation mechanisms, endeavours unveil enigmas surrounding HSV-associated neuroinflammation. comprehensive understanding enhances our grasp viral pathogenesis holds promise pioneering therapeutic strategies designed mitigate ramifications

Language: Английский

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The IVIG treatment response in autoimmune polyendocrine syndromes type 2 with anti-GAD65 antibody-associated stiff person syndrome: a case report and literature review

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

Autoimmune polyendocrine syndromes (APS) is a rare group of disorders caused by impaired function multiple endocrine glands due to disruption immune tolerance. Of which, type 2 (APS-2) the most common. Glutamic acid decarboxylase (GAD) rate-limiting enzyme for synthesis gamma-aminobutyric (GABA). Anti-GAD antibodies are associated with various neurological disorders, including stiff person syndrome (SPS). SPS characterized axial muscle stiffness, rigidity, and intermittent painful spasms, prevalence one two in million, making it an extremely disorder. The comorbidity APS-2 even rarer. Most practicing neurologists encounter only or cases combined anti-GAD65 antibody-associated their careers, resulting underdiagnosis undertreatment, leading severe disability suffering. This case report describes young male who initially exhibited hair loss, vitiligo, previously unreported eosinophilia. Before his diagnosis, he was admitted times, symptoms improving following addition intravenous immunoglobulin (IVIG) therapy poor treatment regimen. paper aims increase physicians' awareness this condition, enhancing likelihood early diagnosis treatment.

Language: Английский

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Neurophysiological Insights into the Pathophysiology of Stiff‐Person Spectrum Disorders

Movement Disorders Clinical Practice, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Abstract Background Stiff Person Spectrum Disorders (SPSD) are classically defined by the presence of muscle stiffness, spasms and hyperactivity central nervous system. There is a notable correlation between neurophysiological features clinical hallmark SPSD, which has greatly encouraged use these techniques for diagnostic purposes. Besides, electrophysiological allow functional evaluation ‘hyperactivity CNS’, thus offering opportunity to clarify mechanisms underlying this disorder. This review delves into current knowledge on aspects highlighting pivotal role various studies in unravelling its pathophysiology. Methods Literature SPSD that included evaluation. Results We first examined abnormal findings across system, from spinal circuit motor cortex. Subsequently, we discussed their pathological implications explored how can be interpreted within framework an immune‐mediated Conclusions Two primary questions remain unanswered: localization abnormality system connection autoimmune basis aspects. Addressing could provide invaluable insights etiology targeted therapeutic strategies.

Language: Английский

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A Rare Case of Stiff Person Syndrome: From Spasms to Bedbound

The American Journal of Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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GAD antibodies in neurological disease: a critical evaluation of the utility and treatment implications of GAD antibodies in clinical practice

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(3)

Published: Feb. 22, 2025

Abstract Background The interpretation of antibodies to glutamic acid decarboxylase 65 (GAD-Abs) in neurological practice is challenging. GAD-Abs are not considered directly pathogenic and immunotherapy guidelines lacking. Methods We undertook a single-center retrospective service evaluation GAD-Abs, documenting clinical features, responses, outcomes 335 patients with positive measured by indirect ELISA between 2012 2020. serum:CSF ratio GAD-Ab values was used as surrogate for intrathecal synthesis. Results 168 (50%) had diagnosed disorders (GAD-ND). Ninety-six often or sometimes associated i.e., stiff person syndrome spectrum (SPS-SD, n = 26), cerebellar ataxia ( 21), epilepsy 19), encephalitis 18), any combination these (“mixed”, 12). Seventy-two other (ONDs) typically GAD-Abs. defined cut-off 10,000 IU/mL priori posteriori NDs, but identified > 21% 11% ONDs diabetes respectively, < 39% classical syndromes, indicating low assay specificity sensitivity. Low serum: CSF ratios were consistent synthesis 12/19 tested; 25/54 oligoclonal bands. 30/50 given adequate immunotherapies partial 17) good 13) particularly those SPS-SD limbic encephalitis. Within the limitations small subgroups routine laboratory titrations, IU/mL, bands, more likely improve than non-inflammatory CSF. Rather, treatment response correlated disease group, principally Conclusions These results suggest caution over-interpreting values. Better biomarkers identifying responsive needed.

Language: Английский

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Espectro del síndrome de persona rígida: serie de casos de un hospital de referencia nacional

Acta neurológica colombiana, Journal Year: 2025, Volume and Issue: 41(1)

Published: March 13, 2025

Introducción: el síndrome de la persona rígida (SPR), enfermedad infrecuente del sistema nervioso central con fisiopatología inmunomediada, está asociado a los anticuerpos anti-GAD (en un 80?%) y otras patologías autoinmunes como diabetes mellitus tipo 2 (DM2) e hipertiroidismo. Clínicamente, este caracterizado por rigidez muscular nivel axial predominantemente periférica, espasmos musculares exacerbados al estímulo táctil o auditivo, además trastornos psiquiátricos. El diagnóstico es desafío, sin embargo, clínico. La respuesta favorable terapéutica benzodiacepinas inmunoglobulinas apoya planteado. Presentación casos: se presentan tres casos mujeres atendidas en hospital referencia Lima, Perú, una edad media 40 años. presentación clínica estuvo caracterizada predominio miembros inferiores, hiperreflexia, dolor limitación funcional marcha musculares. Cuentan antecedentes hipertiroidismo vitíligo, psiquiátricos, sobretodo ansiedad. Todos cumplieron criterios clínicos dos lo hicieron laboratorio anti-GAD65 positivo; además, realizaron diagnósticos diferenciales amplios. pacientes recibieron inmunoglobulina favorable. Discusión: SPR entidad rara inmunomediada inicio subagudo, espasmos, cuales son repentinos precipitados. Los mención presentaron dicho cuadro clínico tratamiento inmunomodulador. Son escasos reportes esta entidad. Conclusiones: presentó serie espectro nacional, donde antiGAD65 característico, adecuado diferencial médico que evidenció Conocer patología tiene gran importancia para mejorar pronóstico calidad vida estos pacientes.

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