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Rheumatology (Oxford, England) Jul 2024Paraneoplastic arthritis (PA) is one of the paraneoplastic syndromes. Both laboratory and clinical findings similar to rheumatological diseases can be seen. In this...
OBJECTIVES
Paraneoplastic arthritis (PA) is one of the paraneoplastic syndromes. Both laboratory and clinical findings similar to rheumatological diseases can be seen. In this study we aimed to present the clinical and laboratory findings, malignancy types and pathological diagnoses of patients with paraneoplastic arthritis.
METHODS
In a multicentre retrospective study, 92 patients with PA from the last 10 years were included.
RESULTS
Patients with PA and haematological malignancies exhibited the highest ratio of lymphomas (25.6%). The most common cancer detected in patients with solid malignancy and PA was lung cancer (41.5%). All malignant patients with PA had significant anti-CCP positivity compared with the healthy control group (P = 0.014).
CONCLUSION
Although PA is a rare condition, it can be confused with many rheumatological diseases. The most commonly involved joint is the knee joint, followed by the ankle and hand/wrist. Autoantibody negativity, high lactate dehydrogenase level and arthritis unresponsive to treatment constitute important clues for diagnosis.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Paraneoplastic Syndromes; Arthritis; Aged; Adult; Lung Neoplasms; Neoplasms; Anti-Citrullinated Protein Antibodies; Aged, 80 and over
PubMed: 37738571
DOI: 10.1093/rheumatology/kead500 -
Neurology(R) Neuroimmunology &... May 2024While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABAR-AE) have poor functional outcomes and high... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVES
While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABAR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied.
METHODS
Patients with GABAR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples.
RESULTS
A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases ( = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up ( = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs.
DISCUSSION
Nonparaneoplastic GABAR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABAR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.
Topics: Humans; Female; Male; Middle Aged; Adult; Aged; Receptors, GABA-B; Encephalitis; Hashimoto Disease; Autoantibodies; Retrospective Studies; Young Adult; Paraneoplastic Syndromes, Nervous System; Aged, 80 and over
PubMed: 38657198
DOI: 10.1212/NXI.0000000000200229 -
Der Nervenarzt Apr 2024There is evidence that gender-specific differences can influence the diagnostics, treatment and long-term disease course of myasthenia gravis (MG). In women the... (Review)
Review
BACKGROUND
There is evidence that gender-specific differences can influence the diagnostics, treatment and long-term disease course of myasthenia gravis (MG). In women the diagnosis is often made during childbearing age.
OBJECTIVE
Gender-specific differences in MG and relevant aspects in routine clinical practice are presented. In addition, current studies on family planning, pregnancy and childbirth in MG are highlighted and treatment recommendations are derived.
MATERIAL AND METHODS
Narrative literature review.
RESULTS
In addition to sociodemographic data, gender-specific differences encompass clinical as well as paraclinical factors, such as disease severity and antibody status. With few exceptions pregnancy is possible with good maternal and neonatal outcome. During pregnancy and peripartum, children of MG patients should be closely monitored for early detection and treatment of potential syndromes caused by diaplacental transfer of maternal antibodies.
CONCLUSION
Gender-specific factors can influence the course of MG. Adequate medical counselling and multidisciplinary collaboration are essential for MG patients who wish to have children.
Topics: Pregnancy; Child; Infant, Newborn; Humans; Female; Family Planning Services; Myasthenia Gravis; Autoantibodies; Family; Pregnancy Complications
PubMed: 38499774
DOI: 10.1007/s00115-024-01640-6 -
Brain : a Journal of Neurology Oct 2023In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex...
In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors.
Topics: Pregnancy; Female; Adult; Humans; Immunoglobulins, Intravenous; Receptors, Cholinergic; Myasthenia Gravis; Autoantibodies; Neuromuscular Diseases; Arthrogryposis
PubMed: 37186601
DOI: 10.1093/brain/awad153 -
Journal of Neuroinflammation Jul 2023Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies....
BACKGROUND
Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the central nervous system (CNS). Matrix metalloproteinase-9 (MMP9) and cluster of differentiation (CD44) were measured to evaluate blood‒brain barrier (BBB) permeability in anti-NMDAR encephalitis. The roles of microglial activation and BBB disruption in anti-NMDAR encephalitis are not well known.
FINDINGS
In this work, we detected increased expression levels of CSF sTREM2, CSF and serum CD44, and serum MMP9 in anti-NMDAR encephalitis patients compared with controls. CSF sTREM2 levels were positively related to both CSF CD44 levels (r = 0.702, p < 0.0001) and serum MMP9 levels (r = 0.428, p = 0.021). In addition, CSF sTREM2 levels were related to clinical parameters (modified Rankin Scale scores, r = 0.422, p = 0.023, and Glasgow Coma Scale scores, r = - 0.401, p = 0.031).
CONCLUSION
Increased sTREM2 levels in CSF as well as increased CD44 and MMP9 in serum and CSF reflected activation of microglia and disruption of the BBB in anti-NMDAR encephalitis, expanding the understanding of neuroinflammation in this disease. The factors mentioned above may have potential as novel targets for intervention or novel diagnostic biomarkers.
Topics: Humans; Blood-Brain Barrier; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Matrix Metalloproteinase 9; Microglia; Biomarkers
PubMed: 37481571
DOI: 10.1186/s12974-023-02841-7 -
Bulletin Du Cancer 2024Electrolyte disorders (ED) are common in patients with cancer and in most cases, the etiologies do not differ from the general population. They may also be induced by... (Review)
Review
Electrolyte disorders (ED) are common in patients with cancer and in most cases, the etiologies do not differ from the general population. They may also be induced by the cancer, its therapy or paraneoplastic syndromes. ED are associated with poor outcomes, increased morbidity and mortality in this population. Hyponatremia is the most common disorder, often multifactorial, iatrogenic or secondary to the syndrome of inappropriate antidiuretic hormone secretion, usually due to small cell lung cancer. More rarely, hyponatremia may reveal adrenal insufficiency. Hypokalemia is generally multifactorial and associated with other ED. Cisplatin and ifosfamide induce proximal tubulopathies with hypokalemia and/or hypophosphatemia. Hypomagnesemia is often iatrogenic, related to cisplatin or cetuximab, but can be prevented by supplementation. Hypercalcemia can impair life quality and be life-threatening in the most severe cases. Hypocalcemia is less common and often of iatrogenic origin. Finally, the tumor lysis syndrome is a diagnostic and therapeutic emergency that affects the prognosis of patients. Its incidence tends to increase in solid oncology, related to the improvement of therapies. Prevention and early diagnosis of ED are essential to optimize the overall management of patients with underlying cancer and cancer therapy. The aim of this review is to synthesize most frequent ED and their management.
Topics: Humans; Neoplasms; Hypocalcemia; Water-Electrolyte Imbalance; Hyponatremia; Tumor Lysis Syndrome; Hypokalemia; Hypercalcemia; Hypophosphatemia; Antineoplastic Agents; Paraneoplastic Syndromes; Inappropriate ADH Syndrome; Magnesium Deficiency; Iatrogenic Disease
PubMed: 37208250
DOI: 10.1016/j.bulcan.2023.04.014 -
Brain and Behavior Nov 2023Observational studies have suggested an association between coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG). Here, we aimed to estimate the genetic...
BACKGROUND
Observational studies have suggested an association between coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG). Here, we aimed to estimate the genetic correlation and causal relationship between COVID-19 susceptibility, hospitalization, severity, and MG phenotypes using linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) approach.
METHODS
Summary statistics of COVID-19 susceptibility, hospitalization, and severity were used as instrumental variables for exposure traits. Large-scale genome-wide association study (GWAS) data for MG were used as outcome traits. The inverse variance weighted approach was used for the main MR analysis, complemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analysis was implemented using Cochran's Q test, MR-PRESSO method, and MR-Egger intercept test.
RESULTS
LDSC analysis did not reveal any genetic correlation among COVID-19 susceptibility, hospitalization, severity, and MG phenotypes, including MG, early-onset MG, and late-onset MG (p > .05). Our MR analysis did not provide evidence supporting a causal effect of COVID-19 susceptibility, hospitalization, or severity on MG phenotypes (p > .05). Extensive sensitivity analysis strengthened the robustness and consistency of the MR estimates.
CONCLUSION
Our study did not find evidence of a genetic correlation or causal relationship among COVID-19 susceptibility, hospitalization, severity, and MG. Future studies with more GWAS data are needed to evaluate the association between COVID-19 phenotypes and MG and its subgroups.
Topics: Humans; COVID-19; Genome-Wide Association Study; Mendelian Randomization Analysis; Hospitalization; Myasthenia Gravis
PubMed: 37638499
DOI: 10.1002/brb3.3239 -
Neurology Oct 2023In recent years, neurology and psychiatry journals have been inundated with reports on individual symptoms of autoimmune encephalitis (AE) that are described as distinct...
In recent years, neurology and psychiatry journals have been inundated with reports on individual symptoms of autoimmune encephalitis (AE) that are described as distinct entities such as autoimmune psychosis, obsessive-compulsive disorders, or depression. It is unquestionable that for AE the demonstration of antibodies against neuronal-surface proteins is intrinsically linked to distinct disorders (some defining new diseases) that are usually treatment-responsive and associate with comorbidities that vary according to the antigen. By contrast, for psychiatric diseases, the apparent detection of antibodies has not defined any disorder or affected the diagnosis and treatment of patients. Although these studies frequently use anti-N-methyl-D-aspartate receptor encephalitis to rationalize the findings, they rarely adopt the same rigorous investigations or address the clinical and pathogenic significance of the antibodies or discuss the limitations related to the biological sample or antibody-testing techniques. It is imperative to consider (1) some antibodies (GAD65, TPO) occur in serum of 8%-13% of healthy people; (2) VGKC antibodies are not useful unless LGI1 or CASPR2 are investigated; (3) commercial-clinical testing for Ma2, Zic4, and SOX1 antibodies causes a high number of false-positive results; (4) GlyR antibodies have unclear disease specificity when examined only in serum; and (5) the significance of antibodies against unknown antigens of endothelium, astrocytes, myelin fibers, or granule cells of hippocampus and cerebellum is questioned by the lack of disease specificity and appropriate controls. These limitations and problems are a frequent cause of neurologic consultations. Here we discuss some of these problems, emphasizing the importance of clinical judgment over antibody findings.
Topics: Humans; Nerve Tissue Proteins; Autoantibodies; Mental Disorders; Membrane Proteins; Anti-N-Methyl-D-Aspartate Receptor Encephalitis
PubMed: 37353340
DOI: 10.1212/WNL.0000000000207486 -
Arquivos de Neuro-psiquiatria Dec 2023The nerve terminal and muscle membrane compose the neuromuscular junction. After opening the voltage-gated calcium channels, action potentials from the motor axons... (Review)
Review
The nerve terminal and muscle membrane compose the neuromuscular junction. After opening the voltage-gated calcium channels, action potentials from the motor axons provoke a cascade for the acetylcholine release from synaptic vesicles to the synaptic cleft, where it binds to its receptor at the muscle membrane for depolarization. Low amplitude compound muscle action potential typically presents in presynaptic disorders, increasing by more than 100% after a 10-second effort in the Lambert-Eaton myasthenic syndrome and less in botulism. Needle electromyography may show myopathic motor unit action potentials and morphological instability ("") due to impulse blocking. Low-frequency repetitive nerve stimulation (RNS) is helpful in postsynaptic disorders, such as myasthenia gravis and most congenital myasthenic syndromes, where the number of functioning acetylcholine receptors is reduced. Low-frequency RNS with a decrement >10% is abnormal when comparing the 4th to the first compound muscle action potential amplitude. High-frequency RNS is helpful in presynaptic disorders like Lambert-Eaton myasthenic syndrome, botulism, and some rare congenital myasthenic syndromes. The high-frequency RNS releases more calcium, increasing the acetylcholine with a compound muscle action potential increment. Concentric needle records single-fiber action potentials (spikes). A voluntary activation measures the jitter between spikes from two endplates. An electrical activation measures the jitter of one spike (one endplate). The jitter is the most sensitive test for detecting a neuromuscular junction dysfunction. Most neuromuscular junction disorders are responsive to treatment.
Topics: Humans; Lambert-Eaton Myasthenic Syndrome; Myasthenic Syndromes, Congenital; Botulism; Acetylcholine; Neuromuscular Junction; Electromyography
PubMed: 38157872
DOI: 10.1055/s-0043-1777749 -
Critical Reviews in Oncology/hematology Apr 2024Paraneoplastic neurological syndromes (PNS) are rare neurological disorders arising from malignancy-triggered autoimmunity, yet their association with urothelial... (Review)
Review
Paraneoplastic neurological syndromes (PNS) are rare neurological disorders arising from malignancy-triggered autoimmunity, yet their association with urothelial carcinoma remains unclear. This systematic review intends to explore any connection, alongside patient/clinical features and management. A literature search identified 25 cases of bladder and upper tract carcinoma linked to PNS. Overall, while infrequent, a meaningful association between PNS and urothelial carcinoma was found in that 84% of cases met a 'possible'-or-'higher-likelihood' PNS diagnosis. Most cases presented with high-risk PNS phenotypes, predominantly cerebellar syndromes and encephalomyelitis/sensory neuronopathy, ∼17 months within cancer diagnosis/recurrence. Review findings suggest a female preponderance in suspected PNS despite higher male incidence of urothelial cancer. Main treatments consisted of surgery alongside chemotherapy or immunotherapeutics (IVIG and/or corticosteroids), which improved symptoms for a slight majority (60%). Ultimately, while common PNS-associated neoplasms should always first be excluded in suspected PNS, in the absence of alternative causes, urothelial carcinomas do merit clinical consideration.
Topics: Humans; Male; Female; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Neoplasm Recurrence, Local; Autoimmunity; Paraneoplastic Syndromes
PubMed: 38447785
DOI: 10.1016/j.critrevonc.2024.104314