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Tijdschrift Voor Psychiatrie 2024Anti-NMDA receptor encephalitis is an auto-immune disorder often presenting with non-specific and heterogeneous neuropsychiatric symptoms at onset. This complicates a...
Anti-NMDA receptor encephalitis is an auto-immune disorder often presenting with non-specific and heterogeneous neuropsychiatric symptoms at onset. This complicates a quick and accurate diagnosis. However, a tardy diagnosis has a negative impact on morbidity and mortality. We report about a patient with the clinical presentation of a psychotic depression, who was diagnosed with anti-NMDA receptor encephalitis only after a thorough diagnostic work-up. Neurological symptoms were wrongly attributed to the psychiatric syndrome or considered as side-effects of its treatment. We present an overview of clinical aspects of the disorder, distinctive psychiatric symptoms, diagnostic tools, treatment and prognosis.
Topics: Humans; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Diagnosis, Differential; Prognosis; Female; Delayed Diagnosis; Male
PubMed: 38650533
DOI: No ID Found -
Annals of Clinical and Translational... May 2024To delineate the clinical characteristics of antibody-negative autoimmune encephalitis (AE) and to investigate factors associated with long-term outcomes among...
OBJECTIVE
To delineate the clinical characteristics of antibody-negative autoimmune encephalitis (AE) and to investigate factors associated with long-term outcomes among antibody-negative AE.
METHODS
Patients diagnosed with antibody-negative AE were recruited from January 2016 to December 2022 at the Second Xiangya Hospital of Central South University. The study assessed the long-term outcomes of antibody-negative AE using the modified Rankin scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Predictors influencing long-term outcomes were subsequently analyzed. External validation of RAPID scores (refractory status epilepticus [RSE], age of onset ≥60 years, ANPRA [antibody-negative probable autoimmune encephalitis], infratentorial involvement, and delay of immunotherapy ≥1 month) was performed.
RESULTS
In total, 100 (47 females and 53 males) antibody-negative AE patients were enrolled in this study, with approximately 49 (49%) experiencing unfavorable long-term outcomes (mRS scores ≥3). Antibody-negative AE was subcategorized into ANPRA, autoimmune limbic encephalitis (LE), and acute disseminated encephalomyelitis (ADEM). Psychiatric symptoms were prevalent in LE and ANPRA subtypes, while weakness and gait instability/dystonia were predominant in the ADEM subtype. Higher peak CASE scores (odds ratio [OR] 1.846, 95% confidence interval [CI]: 1.163-2.930, p = 0.009) and initiating immunotherapy within 30 days (OR 0.210, 95% CI: 0.046-0.948, p = 0.042) were correlated with long-term outcomes. Receiver operating characteristic (ROC) analysis returned that the RAPID scores cutoff of 1.5 best discriminated the group with poor long-term outcomes (sensitivity 85.7%, specificity 56.9%).
INTERPRETATION
The ANPRA subtype exhibited poorer long-term outcomes compared to LE and ADEM subtypes, and early immunotherapy was crucial for improving long-term outcomes in antibody-negative AE. The use of RAPID scoring could aid in guiding clinical decision making.
Topics: Humans; Male; Female; Middle Aged; Encephalitis; Adult; Aged; Hashimoto Disease; Autoimmune Diseases of the Nervous System; Young Adult; Autoantibodies; Adolescent; Limbic Encephalitis; Immunotherapy
PubMed: 38644648
DOI: 10.1002/acn3.52049 -
Advances in Therapy Jun 2024Efgartigimod and ravulizumab, both approved for treating acetylcholine receptor auto-antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG), have not been... (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION
Efgartigimod and ravulizumab, both approved for treating acetylcholine receptor auto-antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG), have not been directly compared. This paper assessed comparative effects of efgartigimod vs. ravulizumab for treating adults with AChR-Ab+ gMG using indirect treatment comparison methods.
METHODS
The matching-adjusted indirect comparison used data from two randomized trials of adult men and women. The ADAPT (efgartigimod vs. placebo; individual patient data available) population was reweighted to match the CHAMPION (ravulizumab vs. placebo; index study; aggregate data available) population. The relative effect of efgartigimod versus placebo was estimated in this reweighted population and compared with the observed ravulizumab versus placebo effect to estimate the efgartigimod versus ravulizumab effect. The outcomes were Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG), and Myasthenia Gravis Quality of Life 15-item-revised scale (MG-QoL15r) assessed as cumulative effect (area under the curve; AUC) over 26 weeks (primary) and change from baseline at 4 weeks and time of best response (week 4 for efgartigimod; week 26 for ravulizumab).
RESULTS
For MG-QoL15r, efgartigimod had a statistically significant improvement compared with ravulizumab over 26 weeks [mean difference (95% confidence interval): - 52.6 (- 103.0, - 2.3)], at week 4 [- 4.0 (- 6.6, - 1.4)], and at time of best response [- 3.9 (- 6.5, - 1.3)]. Efgartigimod had a statistically significant improvement over ravulizumab in MG-ADL at week 4 [- 1.9 (- 3.3, - 0.5)] and at time of best response [- 1.4 (- 2.8, 0.0)] and in QMG at week 4 [- 3.2 (- 5.2, - 1.2)] and at time of best response [- 3.0 (- 5.0, - 1.0)]. For AUC over 26 weeks, improvements were not significantly different between efgartigimod and ravulizumab for MG-ADL [- 8.7 (- 36.1, 18.8)] and QMG [- 13.7 (- 50.3, 22.9)].
CONCLUSION
Efgartigimod may provide a faster and greater improvement over 26 weeks in quality of life than ravulizumab in adults with AChR-Ab+ gMG. Efgartigimod showed faster improvements in MG-ADL and QMG than ravulizumab.
Topics: Humans; Myasthenia Gravis; Male; Female; Antibodies, Monoclonal, Humanized; Middle Aged; Receptors, Cholinergic; Adult; Autoantibodies; Treatment Outcome; Aged; Activities of Daily Living; Quality of Life
PubMed: 38642198
DOI: 10.1007/s12325-024-02856-3 -
Cureus Mar 2024Though rare, autoimmune paraneoplastic and non-paraneoplastic chorea can be leading causes of adult-onset acute/subacute chorea. Here, we report a case of acute-onset...
Though rare, autoimmune paraneoplastic and non-paraneoplastic chorea can be leading causes of adult-onset acute/subacute chorea. Here, we report a case of acute-onset chorea with suspected autoimmune-mediated mechanisms in a 79-year-old female who exhibited acute-onset choreiform movements on the right side of her body. She tested positive for anti-centromere antibodies (ACAs) without displaying symptoms of scleroderma. Blood sugar levels, genetic testing for Huntington's disease, and an antibody panel related to paraneoplastic neurological syndrome were unremarkable. Brain magnetic resonance imaging revealed no significant abnormalities. Computed tomography (CT) identified an irregularly shaped nodule in the middle lobe of the right lung. An 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)-CT scan showed an accumulation of radioactivity in the nodule and slight hypermetabolism in the striatum of both hemispheres. Her choreiform movements almost disappeared with a low dose of tiapride alone, without the need for anti-tumor therapy or immunotherapy. In cases of adult-onset acute/subacute chorea, investigating neoplasms and autoimmune diseases as underlying conditions is recommended. Tiapride, due to its good tolerability, is a valuable symptomatic therapy for elderly patients presenting with chorea, even in cases driven by autoimmune mechanisms.
PubMed: 38638733
DOI: 10.7759/cureus.56448 -
Frontiers in Immunology 2024Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs... (Review)
Review
Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against "self". In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients' life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases.
Topics: Adult; Humans; Thymoma; Autoimmunity; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Myasthenia Gravis; Tumor Microenvironment
PubMed: 38629065
DOI: 10.3389/fimmu.2024.1288045 -
Neuromuscular Disorders : NMD May 2024Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as...
Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as second-line choices despite widespread consensus on their efficacy. We aimed to gather real-world data comparing the tolerability and reasons for discontinuation for these agents, by performing a national United Kingdom survey of side effects and reasons for discontinuation of immunosuppressants in myasthenia gravis. Of 235 patients, 166 had taken azathioprine, 102 mycophenolate, and 40 methotrexate. The most common side effects for each agent were liver dysfunction for azathioprine (23 %), diarrhoea for mycophenolate (14 %), and fatigue for methotrexate (18 %). Women were generally more likely to experience side effects of immunosuppressants. Azathioprine was significantly more likely to be discontinued than mycophenolate and methotrexate due to side effects. There was no significant difference in treatment cessation due to lack of efficacy. This study highlights the significant side-effect burden of treatment for myasthenia gravis. Mechanisms to reduce azathioprine toxicity should be utilised, however mycophenolate and methotrexate appear to be good treatment choices if teratogenicity is not a concern. Women are disadvantaged due to higher frequency of side effects and considerations around pregnancy and breastfeeding. Treatments with improved tolerability are needed.
Topics: Humans; Myasthenia Gravis; Methotrexate; Female; Mycophenolic Acid; Azathioprine; Immunosuppressive Agents; Male; Middle Aged; Adult; Aged; United Kingdom
PubMed: 38626662
DOI: 10.1016/j.nmd.2024.03.010 -
Neurology(R) Neuroimmunology &... May 2024To assess the daily function of children with anti-N-methyl-d-aspartate receptor encephalitis (NMDARe) after a minimal follow-up of 5 years.
OBJECTIVES
To assess the daily function of children with anti-N-methyl-d-aspartate receptor encephalitis (NMDARe) after a minimal follow-up of 5 years.
METHODS
Patients 18 years and younger by the time of disease onset, whose serum and CSF were studied in our center between 2013 and 2017, were included in the study. Patients' daily life function was assessed by their physicians using a 15-domain question format (Liverpool Outcome Score).
RESULTS
Of 76 patients, 8 (11%) died and 68 were followed for a mean of 7.1 years (SD 1.5 years, range: 5.0-10.1). Three outcome patterns were identified: full recovery (50; 73%); behavioral and school/working deficits (12; 18%); and multidomain deficits (6; 9%) involving self-care ability, behavioral-cognitive impairment, and seizures. Younger age of disease onset was significantly associated with multidomain deficits (OR 1.6, 95% CI 1.02-2.4, = 0.04), particularly in children younger than 6 years, among whom 8 of 23 (35%) remained sociofamiliar dependent.
DISCUSSION
After a minimal follow-up of 5 years, most children with NMDARe had substantial or full functional recovery, but approximately one-fifth remained with behavioral and school/working deficits. The younger the patient at disease onset, the more probable it was to remain with multidomain deficits and dependent on sociofamiliar support.
Topics: Child; Humans; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Receptors, N-Methyl-D-Aspartate; Seizures; Recovery of Function
PubMed: 38621190
DOI: 10.1212/NXI.0000000000200235 -
Hong Kong Medical Journal = Xianggang... Apr 2024
PubMed: 38618913
DOI: 10.12809/hkmj2210439 -
Cureus Mar 2024Dermatomyositis (DM) is an inflammatory myopathy often paraneoplastic in nature. Patients have characteristic cutaneous findings and possible muscle involvement. In the...
Dermatomyositis (DM) is an inflammatory myopathy often paraneoplastic in nature. Patients have characteristic cutaneous findings and possible muscle involvement. In the latter, muscle enzymes are elevated, and the electromyogram shows varied changes. Muscle or skin biopsy and myositis-specific antibodies confirm the diagnosis. Here, we report the case of an 86-year-old woman with cutaneous lesions, proximal weakness, and sicca symptoms. Muscle enzymes and electromyogram were normal. Antinuclear antibodies were elevated, and anti-TIF1γ and anti-Ro52 antibodies were positive. Muscle biopsy was compatible with the diagnosis of DM, and salivary gland biopsy confirmed Sjögren's syndrome. Malignancy investigation identified a rectal cancer, which was resected. This case illustrates a rare form of cancer presentation - anti-TIF1γ DM with normal muscle enzymes and electromyogram and concomitant secondary Sjögren's syndrome. Malignancy screening and multidisciplinary management were crucial to a successful approach.
PubMed: 38618380
DOI: 10.7759/cureus.55978 -
Pharmacological Research May 2024Kidney cancers comprise about 3% of all new malignancies in the United States. Renal cell carcinomas (RCCs) are the most common type of renal malignancy making up about... (Review)
Review
Kidney cancers comprise about 3% of all new malignancies in the United States. Renal cell carcinomas (RCCs) are the most common type of renal malignancy making up about 85% of kidney cancer cases. Signs and symptoms of renal cell carcinomas can result from local tumor growth, paraneoplastic syndromes, or distant metastases. The classic triad of presentation with flank pain, hematuria, and a palpable abdominal mass occurs in fewer than 10% of patients. Most diagnoses result from incidental imaging findings (ultrasonography or abdominal CT imaging) performed for another reason. Localized disease is treated by partial nephrectomy, total nephrectomy, or ablation (tumor destruction with heat or cold). When the tumors have metastasized, systemic therapy with protein-tyrosine kinase antagonists including sorafenib, sunitinib, pazopanib, and tivozanib that target vascular endothelial, platelet-derived, fibroblast, hepatocyte, and stem cell factor growth factor receptors (VEGFR, PDGFR, FGFR, MET, and Kit) were prescribed after 2005. The monoclonal antibody immune checkpoint inhibitor nivolumab (targeting programed cell death protein 1, PD1) was approved for the treatment of RCCs in 2015. It is usually used now in combination with ipilimumab (targeting CTLA-4) or cabozantinib (a multikinase blocker). Other combination therapies include pembrolizumab (targeting PD1) and axitinib (a VEGFR and PDGFR blocker) or lenvatinib (a multikinase inhibitor). Since the KEYNOTE-426 clinical trial, the use of immune checkpoint inhibitors in combination with protein-tyrosine kinase inhibitors is now the standard of care for most patients with metastatic renal cell carcinomas and monotherapies are used only in those individuals who cannot receive or tolerate immune checkpoint inhibitors.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Animals; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38614375
DOI: 10.1016/j.phrs.2024.107181