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Current Neurology and Neuroscience... Mar 2023To provide an overview and highlight recent updates in the field of paraneoplastic neurologic disorders. (Review)
Review
PURPOSE OF REVIEW
To provide an overview and highlight recent updates in the field of paraneoplastic neurologic disorders.
RECENT FINDINGS
The prevalence of paraneoplastic neurologic disorders is greater than previously reported and the incidence has been rising over time, due to improved recognition in the era of antibody biomarkers. Updated diagnostic criteria that are broadly inclusive and also contain diagnostic risk for clinical presentations (high and intermediate) and diagnostic antibodies (high, intermediate, and low) have replaced the original 2004 criteria. Antibody biomarkers continue to be characterized (e.g., KLHL-11 associated with seminoma in men with brainstem encephalitis). Some paraneoplastic antibodies also provide insight into likely immunotherapy response and prognosis. The rise of immune checkpoint inhibitors as cancer therapeutics has been associated with newly observed immune-mediated adverse effects including paraneoplastic neurological disorders. The therapeutic approach to paraneoplastic neurologic disorders is centered around cancer care and trials of immune therapy. The field of paraneoplastic neurologic disorders continues to be advanced by the identification of novel antibody biomarkers which have diagnostic utility, and give insight into likely treatment responses and outcomes.
Topics: Male; Humans; Paraneoplastic Syndromes, Nervous System; Autoantibodies; Nervous System Diseases; Encephalitis; Neoplasms
PubMed: 36781586
DOI: 10.1007/s11910-023-01250-w -
The Netherlands Journal of Medicine Dec 2018Hypereosinophilia encompasses a broad differential diagnosis of atopy/allergic reactions, drug reactions, parasitic infections and paraneoplastic syndromes. Although... (Review)
Review
Hypereosinophilia encompasses a broad differential diagnosis of atopy/allergic reactions, drug reactions, parasitic infections and paraneoplastic syndromes. Although mostly of limited clinical significance, hypereosinophilia can also be related to hematological malignancies. One has to be aware of the potential for secondary organ damage for example, in the case of hypereosinophilic syndrome. We present three cases with different underlying mechanisms of hypereosinophilia with a brief overview of causes, diagnostic work-up and treatment options.
Topics: Algorithms; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Eosinophilia; Hematologic Neoplasms; Humans; Paraneoplastic Syndromes; Parasitic Diseases; Patient Care Management
PubMed: 30569889
DOI: No ID Found -
Blood Jul 2014As immune-based therapies for cancer become potent, more effective, and more widely available, optimal management of their unique toxicities becomes increasingly...
As immune-based therapies for cancer become potent, more effective, and more widely available, optimal management of their unique toxicities becomes increasingly important. Cytokine release syndrome (CRS) is a potentially life-threatening toxicity that has been observed following administration of natural and bispecific antibodies and, more recently, following adoptive T-cell therapies for cancer. CRS is associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon γ, and uncontrolled studies demonstrate that immunosuppression using tocilizumab, an anti-IL-6 receptor antibody, with or without corticosteroids, can reverse the syndrome. However, because early and aggressive immunosuppression could limit the efficacy of the immunotherapy, current approaches seek to limit administration of immunosuppressive therapy to patients at risk for life-threatening consequences of the syndrome. This report presents a novel system to grade the severity of CRS in individual patients and a treatment algorithm for management of CRS based on severity. The goal of our approach is to maximize the chance for therapeutic benefit from the immunotherapy while minimizing the risk for life threatening complications of CRS.
Topics: Child; Cytokines; Female; Humans; Immune System Diseases; Leukemia; Paraneoplastic Syndromes; Young Adult
PubMed: 24876563
DOI: 10.1182/blood-2014-05-552729 -
Nutrients Apr 2019Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample... (Review)
Review
Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample biological effects. Omega-3 PUFAs play essential roles in cell signaling and in the cell structure and fluidity of membranes. They participate in the resolution of inflammation and have anti-inflammatory and antinociceptive effects. Additionally, they can act as agonists of G protein-coupled receptors, namely, GPR40/FFA1 and GPR120/FFA4. Cancer patients undergo complications, such as anorexia-cachexia syndrome, pain, depression, and paraneoplastic syndromes. Interestingly, the 2017 European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines for cancer patients only discuss the use of omega-3 PUFAs for cancer-cachexia treatment, leaving aside other cancer-related complications that could potentially be managed by omega-3 PUFA supplementation. This critical review aimed to discuss the effects and the possible underlying mechanisms of omega-3 PUFA supplementation in cancer-related complications. Data compilation in this critical review indicates that further investigation is still required to assess the factual benefits of omega-3 PUFA supplementation in cancer-associated illnesses. Nevertheless, preclinical evidence reveals that omega-3 PUFAs and their metabolites might modulate pivotal pathways underlying complications secondary to cancer, indicating that this is a promising field of knowledge to be explored.
Topics: Anorexia; Depressive Disorder, Major; Fatty Acids, Omega-3; Humans; Neoplasms; Pain; Paraneoplastic Syndromes
PubMed: 31035457
DOI: 10.3390/nu11050945 -
International Journal of Molecular... Mar 2020Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform... (Review)
Review
Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues of internal malignancy may delay diagnosis and treatment of cancer. In this review, we described several paraneoplastic dermatoses and discussed extensively two paradigmatic ones, namely paraneoplastic pemphigus and paraneoplastic dermatomyositis.
Topics: Cytokines; Dermatomyositis; Erythema; Humans; Neoplasms; Paraneoplastic Syndromes; Pemphigus; Pyoderma Gangrenosum; Skin; Skin Diseases; Sweet Syndrome
PubMed: 32245283
DOI: 10.3390/ijms21062178 -
Internal Medicine (Tokyo, Japan) Jun 2019Autoimmune pancreatitis (AIP) is now considered a pancreatic manifestation of a newly proposed disease condition, IgG4-related disease (IgG4-RD). IgG4-RD is... (Review)
Review
Autoimmune pancreatitis (AIP) is now considered a pancreatic manifestation of a newly proposed disease condition, IgG4-related disease (IgG4-RD). IgG4-RD is characterized by enhanced IgG4 antibody responses and multiple organ involvements. Recent epidemiological studies have addressed the incidence of cancer in patients with AIP and/or IgG4-RD. Surprisingly, a significant number of AIP patients were detected with cancer at or within one year of the diagnosis of AIP. Furthermore, around 50% of all cancers detected in AIP patients comprised mainly 3 types (gastric, lung, and prostate cancer). Thus, AIP appears to be associated with cancer of other organs rather than the pancreas itself, which suggests that AIP is not a pre-cancerous condition of the pancreas. Moreover, the simultaneous occurrence of cancer and AIP in many patients has led to the establishment of an attractive concept that AIP might sometimes arise from co-existing cancers as a paraneoplastic syndrome.
Topics: Acute Disease; Autoimmune Diseases; Humans; Immunoglobulin G4-Related Disease; Incidence; Neoplasms; Pancreatitis; Paraneoplastic Syndromes
PubMed: 30713326
DOI: 10.2169/internalmedicine.2210-18 -
Journal of Internal Medicine Mar 2023Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients present with... (Review)
Review
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients present with progressive bone pain, muscle weakness, and fragility fractures. TIO is characterized by hypophosphatemia, excess renal phosphate excretion, and low/inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH) D) levels. Rarity and enigmatic clinical presentation of TIO contribute to limited awareness among the medical community. Accordingly, appropriate diagnostic tests may not be requested, leading to delayed diagnosis and poorer patient outcomes. We have developed a global guidance document to improve the knowledge of TIO in the medical community, enabling the recognition of patients with TIO and appropriate referral. We provide recommendations aiding diagnosis, referral, and treatment, helping promote a global standard of patient management. We reviewed the literature and conducted a three-round Delphi survey of TIO experts. Statements were drafted based on published evidence and expert opinions (≥70% consensus required for final recommendations). Serum phosphate should be measured in patients presenting with chronic muscle pain or weakness, fragility fractures, or bone pain. Physical examination should establish features of myopathy and identify masses that could be causative tumors. Priority laboratory evaluations should include urine/serum phosphate and creatinine to assess renal tubular reabsorption of phosphate and TmP/GFR, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D, 1,25(OH) D, and FGF23. Patients with the clinical/biochemical suspicion of TIO should be referred to a specialist for diagnosis confirmation, and functional imaging should be used to localize causative tumor(s). Recommended treatment is tumor resection or, with unresectable/unidentifiable tumors, phosphate salts plus active vitamin D, or burosumab.
Topics: Humans; Phosphates; Hypophosphatemia; Paraneoplastic Syndromes; Fractures, Bone; Pain; Fibroblast Growth Factors
PubMed: 36511653
DOI: 10.1111/joim.13593 -
The Journal of Thoracic and... Jul 2020
Topics: Humans; Neoplasm Recurrence, Local; Paraneoplastic Syndromes; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 32067787
DOI: 10.1016/j.jtcvs.2020.01.019 -
Continuum (Minneapolis, Minn.) Apr 2015Paraneoplastic disorders are autoimmune diseases associated with risks for specific cancers and marked by specific autoantibodies. They cause diverse clinical syndromes... (Review)
Review
PURPOSE OF REVIEW
Paraneoplastic disorders are autoimmune diseases associated with risks for specific cancers and marked by specific autoantibodies. They cause diverse clinical syndromes of the central and peripheral nervous systems.
RECENT FINDINGS
In the peripheral nervous system, autoimmunity to synaptic or axonal proteins has long been recognized to associate with specific cancers. In these disorders, typified by myasthenia gravis, the antibodies are directly toxic, and recovery with immunotherapy is the rule. In contrast, the classic paraneoplastic syndromes involve a higher risk of cancer, autoantibodies to intracellular proteins (eg, Hu proteins), T-cell-dependent disease mechanisms targeting the CNS or peripheral nervous system, and a poor response to treatment. Following the discovery of N-methyl-D-aspartate (NMDA) receptor antibodies, a new and expanding group of disorders involving autoantibodies to CNS synaptic and neuronal membrane proteins and a favorable response to immunotherapy emerged. A final group of disorders involves antibodies to intracellular synaptic proteins, such as glutamic acid decarboxylase 65 (GAD65), and it is unclear whether these diseases involve antibody or T-cell mechanisms.
SUMMARY
Neurologists should recognize the clinical syndromes associated with paraneoplastic disorders, utilize autoantibody and other testing to confirm the diagnosis, understand the pathologic basis of the diseases, and promptly give appropriate therapies.
Topics: Autoantibodies; DNA-Binding Proteins; Diagnosis, Differential; Glutamate Decarboxylase; Humans; Immunotherapy; Membrane Proteins; Myasthenia Gravis; Neoplasms; Paraneoplastic Syndromes, Nervous System; Receptors, N-Methyl-D-Aspartate; Risk Factors
PubMed: 25837906
DOI: 10.1212/01.CON.0000464180.89580.88 -
Revue Medicale de Liege May 2021Neurological paraneoplastic syndromes are non-metastatic complications of systemic cancers, often resulting from an immune response triggered by the crossed expression...
Neurological paraneoplastic syndromes are non-metastatic complications of systemic cancers, often resulting from an immune response triggered by the crossed expression of neuronal antigens by tumour cells. Several neurological syndromes such as cerebellar degeneration, sensory neuronopathy, limbic encephalitis, encephalomyelitis or the Lambert-Eaton myasthenic syndrome are most often paraneoplastic and require prompt cancer screening, particularly if the patient shows risk factors for cancer. Although there are many exceptions to this rule, a given syndrome is often associated with a particular antibody and the corresponding tumour. A prompt diagnosis of neurological paraneoplastic syndrome is of major importance as it often reveals the underlying tumour. The treatment relies on both the elimination of the neoplasia and the control of the immune response.
Topics: Autoantibodies; Humans; Lambert-Eaton Myasthenic Syndrome; Limbic Encephalitis; Neoplasms; Paraneoplastic Syndromes
PubMed: 34080373
DOI: No ID Found