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Medicina Clinica Mar 2023Stauffer syndrome is a paraneoplastic syndrome (PS) that involves liver disorders; it has been often related to renal tumors, but also to others such as adenocarcinoma... (Review)
Review
Stauffer syndrome is a paraneoplastic syndrome (PS) that involves liver disorders; it has been often related to renal tumors, but also to others such as adenocarcinoma of the prostate (ACP). Our objective was to carry out a systematic review of published cases associated with ACP. A total of 357 articles were accessed, 25 of which met the study's inclusion criteria. All published cases of Stauffer syndrome in patients diagnoses with ACP were in the metastatic stage. The PS resolved in 3 out of 4 patients when ACP-targeted therapy was implemented. The following were identified as poor prognosis factors: the diagnosis of ACP prior to that of SP, non-elevated levels of total bilirubin, and the non-resolution of SP at the start of treatment.
Topics: Male; Humans; Prostate; Jaundice; Kidney Neoplasms; Prostatic Neoplasms; Paraneoplastic Syndromes; Carcinoma
PubMed: 36526448
DOI: 10.1016/j.medcli.2022.11.001 -
Brain and Behavior Jan 2023Myasthenia gravis (MG) people experience adverse psychiatric outcomes, which may impact on their life and disturb their daily activity. Depression and anxiety are... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Myasthenia gravis (MG) people experience adverse psychiatric outcomes, which may impact on their life and disturb their daily activity. Depression and anxiety are identified as significant psychiatric problems that MG people face. However, there is no sufficient epidemiological information about depression and anxiety-based publication. Due to this limitation, the aim of this study was to review the prevalence of depression and anxiety in MG patients.
METHODS
Original and international databases were searched to find papers about the estimation of anxiety and depression. Random-effects analysis was used for calculating the proportions of anxiety and depression. For estimating anxiety and depression based the severity, instruments, type of studies, and study regions, subgroup analysis was performed.
RESULTS
38 studies met inclusion criteria and entered study. The pooling of the prevalence of depression was found at 36%, (95% CI 28% to 45%). Also, prevalence of anxiety was found at 33%, (95% CI 25% to 42%). Prevalence of depression based on mild, moderate, and severe level was 27%, 14%, and 9%, respectively.
CONCLUSIONS
Anxiety and depression are a major concern among MG individuals. The estimation of both anxiety and depression are high even when compared to other autoimmune diseases. It seems depression and anxiety are important issues and more attention needs to be paid to these psychiatric disorders.
Topics: Humans; Depression; Prevalence; Anxiety; Anxiety Disorders; Myasthenia Gravis
PubMed: 36495116
DOI: 10.1002/brb3.2840 -
Cureus Nov 2022Paraneoplastic syndromes (PNS) are uncommon, distinct clinical complications of a primary tumor. Paraneoplastic cerebellar degeneration (PCD) is a PNS that is described... (Review)
Review
Paraneoplastic syndromes (PNS) are uncommon, distinct clinical complications of a primary tumor. Paraneoplastic cerebellar degeneration (PCD) is a PNS that is described as an autoimmune response targeting Purkinje cells in the cerebellum. Ovarian cancer (OC) is one of the most prevalent causes of cancer-related deaths in women. Anti-Yo is the most common onconeural antibody produced in the PCD immune response and is most typically found in ovarian and breast cancer patients. While the current literature highlights the predisposing genetic factors, diagnostic workflows, and treatment options, the pathophysiology of PCD, among other considerations, remains largely unestablished. This review aimed to systematically observe procedural solutions to facilitate an early diagnosis and improve the prognosis of patients with OC-associated PCD. To that end, we examined literature published from 01/01/2015-11/10/2022 indexed in PubMed by using the keywords "paraneoplastic, cerebellar degeneration" combined with "ovarian cancer." Inclusion criteria were met if PCD and OC diagnoses were made and if studies provided adequate patient information. After screening and assessing records for eligibility using the inclusion and exclusion criteria, 18 articles involving 102 patients were included. The typical patient observed in this sample was diagnosed with International Federation of Gynecology and Obstetrics (FIGO) Stage III, high-grade serous carcinoma. The diagnostic workup typically included a clinical evaluation for dysarthria (50%), ataxia (60%), and gait abnormalities (50%), along with multiple imaging modalities and serological findings (90%). Genetic screening for human leukocyte antigen (HLA) haplotype susceptibility for PCD and immune tolerance modulators regulation may also be recommended prior to starting treatment. Findings support the use of corticosteroids (35%) and intravenous immunoglobulin (IVIg) (40%) as viable treatment options for managing PCD in conjunction with systemic therapy for the primary malignancy. A diagnosis of PCD should be considered if a patient has had a malignancy in the past five years with the presence of explicit cerebellar symptoms. This clinical diagnosis can be further supplemented by serologic and radiologic findings. Recognizing PCD symptoms and scheduling genetic and proteomic testing may help with early diagnosis and better prognosis.
PubMed: 36483902
DOI: 10.7759/cureus.31154 -
The Journal of Clinical Endocrinology... Apr 2023Diagnostic accuracy of testing currently used for the differential diagnosis of Cushing disease (CD) vs ectopic adrenocorticotropic hormone secretion (EAS) is difficult... (Meta-Analysis)
Meta-Analysis
CONTEXT
Diagnostic accuracy of testing currently used for the differential diagnosis of Cushing disease (CD) vs ectopic adrenocorticotropic hormone secretion (EAS) is difficult to interpret.
OBJECTIVE
The present study aimed to identify and evaluate the diagnostic accuracy of the corticotropin-releasing hormone (CRH) test, the desmopressin test, and the high-dose dexamethasone suppression test (HDDST) when used to establish a CD or EAS diagnosis.
METHODS
This study is a systematic review of the literature and meta-analysis. MEDLINE, OVID, and Web of Science databases were searched for articles published between 1990 and 2021. Articles included described at least 1 test(s) (CRH, desmopressin, or HDDST) and the diagnostic reference standard(s) (histopathology, petrosal sinus sampling, surgical remission, imaging, and long-term follow-up) used to establish a CD or EAS diagnosis.
RESULTS
Sixty-two studies were included: 43 reported the use of the HDDST; 32, the CRH test; and the 21, the desmopressin test. The CRH test was found to have the highest sensitivity in detecting CD (ACTH 86.9%, 95% CI 82.1-90.6, cortisol 86.2%, 95% CI 78.3-91.5) and the highest specificity in detecting EAS (ACTH 93.9%, 95% CI 87-98.3, cortisol 89.4%, 95% CI 82.8-93.7). This resulted in a high diagnostic odds ratio (58, 95% CI 43.25-77.47), large area under the curve, and a receiver operating characteristic of 0.934. The diagnostic accuracy of the HDDST and desmopressin test was lower than that of the CRH test.
CONCLUSION
The meta-analysis indicates that a patient with a positive ACTH response after a CRH test is highly likely to have CD. Further studies analyzing role of dynamic testing in addition to imaging are needed.
Topics: Humans; Cushing Syndrome; Deamino Arginine Vasopressin; Hydrocortisone; Diagnosis, Differential; ACTH Syndrome, Ectopic; Pituitary ACTH Hypersecretion; Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone
PubMed: 36453141
DOI: 10.1210/clinem/dgac686 -
Neurology(R) Neuroimmunology &... Jan 2023To clinically characterize post-immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders, we analyzed Hu-Ab-positive patients with neurologic...
BACKGROUND AND OBJECTIVES
To clinically characterize post-immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders, we analyzed Hu-Ab-positive patients with neurologic immune-related adverse events (n-irAEs) and compared them with patients with other n-irAEs, ICI-naive patients with Hu-Ab paraneoplastic neurologic syndromes (PNSs) identified in the same study center, and those with Hu-Ab n-irAEs reported elsewhere.
METHODS
Patients whose samples were sent to the French reference center for a suspicion of n-irAE (2015-2021) were identified; those with a final diagnosis of n-irAE and Hu-Ab were included. Control groups included patients with a final diagnosis of n-irAE occurring during the same period as the patients included (2018-2021) but without Hu-Ab, and ICI-naive patients with Hu-Ab PNS diagnosed during the same period; a systematic review was performed to identify previous reports.
RESULTS
Eleven patients with Hu-Ab and n-irAEs were included (median age, 66 years, range 44-76 years; 73% men). Ten patients had small cell lung cancer, and 1 had lung adenocarcinoma. The median follow-up from onset was 3 months (range 0.5-18 months). Compared with those with other n-irAEs (n = 63), Hu-Ab-positive patients had more frequently co-occurring involvement of both central and peripheral nervous systems (36% vs 8%, = 0.02) and limbic (54% vs 14%, < 0.01), brainstem (27% vs 5%, = 0.02), and dorsal root ganglia (45% vs 5%, < 0.01) involvement. The proportion of patients with severe disability (modified Rankin Scale score >3) at diagnosis was higher among Hu-Ab n-irAEs (91% vs 52%, = 0.02). Patients with Hu-Ab had also poorer outcome (100% vs 28%, < 0.01) and higher mortality (91% vs 46%, < 0.01). There was no significant difference in terms of clinical features between Hu-Ab n-irAEs and ICI-naive Hu-Ab PNS (n = 92), but there was a poorer outcome (56/78, 71%, < 0.01) and higher mortality (26%, < 0.01) among the former. No significant difference was found between the patients reported herein and those in the literature.
DISCUSSION
The presence of Hu-Ab identifies a subgroup of n-irAEs that consistently reproduce the phenotypes of Hu-Ab-related PNS, supporting the hypothesis of ICI triggering or unmasking PNS. As these patients show high disability and mortality, further studies are required to investigate the underlying immunopathogenic mechanisms and to improve the outcome of Hu-Ab n-irAEs.
Topics: Humans; Male; Female; Immune Checkpoint Inhibitors; Drug-Related Side Effects and Adverse Reactions; Peripheral Nervous System; Antibodies, Antinuclear; Lung Neoplasms
PubMed: 36446613
DOI: 10.1212/NXI.0000000000200058 -
BMC Neurology Nov 2022Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of...
BACKGROUND
Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of clinical and imaging characteristics as well as of antibody dynamics.
CASE PRESENTATION
We report a 32-year-old male patient who presented with psychosis, decreased consciousness and movement disorders and was tested positive for anti-NMDA receptor antibodies. Forty-four months after symptom onset and diagnosis of autoimmune encephalitis, he suffered from relapse. At this time, the patient developed anti-MOG and anti-Caspr2 antibodies. Treatment with plasmapheresis, steroids and rituximab eventually led to substantial clinical and radiological improvement. Anti-Caspr2 antibodies persisted, anti-NMDA receptor antibodies decreased, while anti-MOG antibodies turned negative again.
CONCLUSION
We provide long-term longitudinal follow-up of a patient with anti-NMDA receptor encephalitis who developed triple antibody positivity at the time of relapse. Antibody dynamics were associated with clinical disease course.
Topics: Male; Humans; Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Myelin-Oligodendrocyte Glycoprotein; Follow-Up Studies; Autoantibodies; Neoplasm Recurrence, Local; Receptors, N-Methyl-D-Aspartate; Demyelinating Diseases
PubMed: 36384491
DOI: 10.1186/s12883-022-02974-x -
Journal of the Neurological Sciences Dec 2022We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the...
INTRODUCTION
We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature.
METHODS
The retrospective observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed.
RESULTS
We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery.
CONCLUSION
Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19.
Topics: Humans; Myelitis, Transverse; Retrospective Studies; COVID-19; Magnetic Resonance Imaging; Multicenter Studies as Topic
PubMed: 36334503
DOI: 10.1016/j.jns.2022.120463 -
Cerebellum (London, England) Dec 2023Current understanding of anti-Yo/PCA1 antibody-associated cerebellar ataxia is based on case reports and small case series. Our goal was to summarize clinical features,... (Review)
Review
Current understanding of anti-Yo/PCA1 antibody-associated cerebellar ataxia is based on case reports and small case series. Our goal was to summarize clinical features, highlighting atypical presentations and gaps of knowledge. Following the PRISMA guidelines, we systematically screened Pubmed/MEDLINE, Embase, Scopus, and Web of Science from inception to April 2022 for all case reports and series concerning anti-Yo antibody-associated cerebellar ataxia. We collected data on clinical presentation, investigation findings, and treatment outcomes. Of 379 included patients, 96% were female with gynecologic cancer (82%). Among men, 87% had an associated tumor, mainly of gastrointestinal origin. The median age was 60 years old. Pancerebellar ataxia was the main clinical feature, but extracerebellar findings were frequent during the disease course. Vertigo and imbalance can be present early in the disease course in about two thirds of patients, as a prodromal phase. Although neuroimaging usually is normal or shows cerebellar atrophy, inflammatory changes may also be present. More than half of the patients reported some improvement after immunotherapy. However, despite treatment, 84% of survivors were unable to walk unassisted on follow-up. Our study provides objective data and advances in current knowledge of anti-Yo antibody-associated cerebellar ataxia such as the description of prodromal symptoms, extracerebellar findings, and its presentations in males.
Topics: Male; Middle Aged; Humans; Female; Cerebellar Ataxia; Paraneoplastic Cerebellar Degeneration; Purkinje Cells; Cerebellar Diseases; Neoplasms; Autoantibodies; Disease Progression
PubMed: 36334195
DOI: 10.1007/s12311-022-01492-3 -
European Journal of Neurology Jan 2023Although myasthenia gravis (MG) is recognized as an immunoglobulin G autoantibody-mediated disease, the relationship between autoantibody levels and disease activity in... (Review)
Review
BACKGROUND AND PURPOSE
Although myasthenia gravis (MG) is recognized as an immunoglobulin G autoantibody-mediated disease, the relationship between autoantibody levels and disease activity in MG is unclear. We sought to evaluate this landscape through systematically assessing the evidence, testing the impact of predefined variables on any relationship, and augmenting with expert opinion.
METHODS
In October 2020, a forum of leading clinicians and researchers in neurology from across Europe (Expert Forum for Rare Autoantibodies in Neurology in Myasthenia Gravis) participated in a series of virtual meetings that took place alongside the conduct of a systematic literature review (SLR).
RESULTS
Forty-two studies were identified meeting inclusion criteria. Of these, 10 reported some correlation between a patient's autoantibody level and disease severity. Generally, decreased autoantibody levels (acetylcholine receptor, muscle-specific kinase, and titin) were positively and significantly correlated with improvements in disease severity (Quantitative Myasthenia Gravis score, Myasthenia Gravis Composite score, Myasthenia Gravis Activities of Daily Living score, Myasthenia Gravis Foundation of America classification). Given the limited evidence, testing the impact of predefined variables was not feasible.
CONCLUSIONS
This first SLR to assess whether a correlation exists between autoantibody levels and disease activity in patients with MG has indicated a potential positive correlation, which could have clinical implications in guiding treatment decisions. However, in light of the limited and variable evidence, we cannot currently recommend routine clinical use of autoantibody level testing in this context. For now, patient's characteristics, clinical disease course, and laboratory data (e.g., autoantibody status, thymus histology) should inform management, alongside patient-reported outcomes. We highlight the need for future studies to reach more definitive conclusions on this relationship.
Topics: Humans; Activities of Daily Living; Myasthenia Gravis; Autoantibodies; Immunoglobulin G; Biomarkers
PubMed: 36094738
DOI: 10.1111/ene.15565 -
International Immunopharmacology Nov 2022Studies have described the role of microRNAs (miRNAs) in thymic function, along with directly observing the altered expression of miRNAs in thymuses of myasthenia gravis...
BACKGROUND
Studies have described the role of microRNAs (miRNAs) in thymic function, along with directly observing the altered expression of miRNAs in thymuses of myasthenia gravis (MG) patients; so, miRNAs became a core component in the pathophysiology of MG. However, because the miRNA analysis results are contradictory, the identification of MG-related miRNAs is daunting.
OBJECTIVE
We did a systematic review of studies analyzing the miRNA expression profile of peripheral blood and mononuclear cells for patients with MG.
METHODS
We ran a database search in PubMed, Scopus, and Web of Science on August 17, 2021. Original articles that analyzed miRNA profiles in peripheral blood (serum, plasma, and whole blood) and peripheral blood mononuclear cells (PBMCs) for patients with MG in comparison with a non-MG or healthy control (HC) group were eligible. The quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).
RESULTS
26 studies were included. The quality of studies was fair (median score, 5). Among 226 different miRNAs that were deregulated in at least one study (range, 1-87), ten miRNAs were significantly deregulated in three or more studies. Five miRNAs (50%) showed the same deregulation: miR-106b-3p and miR-21-5p were consistently upregulated, and miR-20b, miR-15b, and miR-16 were consistently downregulated. Also, there were five miRNAs that were mostly upregulated, miR-150-5p, miR-146a, miR-30e-5p, and miR-338-3p, or downregulated, miR-324-3p, across studies.
CONCLUSION
These miRNAs contribute to different pathways, importantly neural apoptosis and autophagy, inflammation, T regulatory cell development, and T helper cell balance. Prior to being used for diagnostic and therapeutic purposes, it is required to pursue molecular mechanisms these consistently and mostly dysregulated miRNAs specifically use in the context of MG.
Topics: Humans; Gene Expression Profiling; Leukocytes, Mononuclear; MicroRNAs; Myasthenia Gravis; Leukocyte Count
PubMed: 36087508
DOI: 10.1016/j.intimp.2022.109205