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Journal of the Neurological Sciences Nov 2023Paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis (AIE) are immune-mediated disorders. PNS is linked to cancer, while AIE may not Their clinical... (Review)
Review
INTRODUCTION
Paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis (AIE) are immune-mediated disorders. PNS is linked to cancer, while AIE may not Their clinical manifestations and imaging patterns need further elucidation.
OBJECTIVE/AIMS
To investigate the clinical profiles, antibody associations, neuroimaging patterns, treatments, and outcomes of PNS and AIE.
METHODS
A systematic review of 379 articles published between 2014 and 2023 was conducted. Of the 55 studies screened, 333 patients were diagnosed with either PNS or AIE and tested positive for novel antibodies. Data on demographics, symptoms, imaging, antibodies, cancer associations, treatment, and outcomes were extracted.
RESULTS
The study included 333 patients (mean age 54 years, 67% males) with PNS and AIE positive for various novel antibodies. 84% had central nervous system issues like cognitive impairment (53%), rhombencephalitis (17%), and cerebellar disorders (24%). Neuroimaging revealed distinct patterns with high-risk antibodies associated with brainstem lesions in 98%, cerebellar in 91%, hippocampal in 98%, basal ganglia in 75%, and spinal cord in 91%, while low/intermediate-risk antibodies were associated with medial temporal lobe lesions in 71% and other cortical/subcortical lesions in 55%. High-risk antibodies were associated with younger males, deep brain lesions, and increased mortality of 61%, while low/intermediate-risk antibodies were associated with females, cortical/subcortical lesions, and better outcomes with 39% mortality. Associated cancers included seminomas (23%), lung (19%), ovarian (2%), and breast (2%). Treatments included IVIG, chemotherapy, and plasmapheresis. Overall mortality was 25% in this cohort.
CONCLUSION
PNS and AIE have distinct clinical and radiological patterns based on antibody profiles. High-risk antibodies are associated with increased mortality while low/intermediate-risk antibodies are associated with improved outcomes. Appropriate imaging and antibody testing are critical for accurate diagnosis.
Topics: Male; Female; Humans; Middle Aged; Nervous System Diseases; Paraneoplastic Syndromes, Nervous System; Autoantibodies; Neoplasms; Neuroimaging
PubMed: 37856996
DOI: 10.1016/j.jns.2023.120830 -
Gynecologic Oncology Sep 2017A number of paraneoplastic syndromes have been described with gynecological cancers. These syndromes are induced by substances secreted by the tumor or by an immune... (Review)
Review
A number of paraneoplastic syndromes have been described with gynecological cancers. These syndromes are induced by substances secreted by the tumor or by an immune response triggered by the cancer. Each system of the human body can be affected by different syndromes. Indeed, paraneoplastic syndromes occurring from tumors of the gynecologic tract were found to involve the nervous, ophthalmologic, dermatologic, rheumatologic, endocrine, hematologic and renal systems. These syndromes can manifest before, at the time, or after the diagnosis of cancer. They can also occur at the time of a recurrence. Knowledge about these syndromes is important for physicians caring for patients with cancers, as they can result in severe morbidity and must be treated appropriately. Literature regarding paraneoplastic syndromes associated with tumors of the female genital tract is scattered and the subject has not been reviewed recently. A systematic literature search was thus conducted to identify paraneoplastic syndromes associated with gynecologic cancers. This review focuses on the cancers involved with each paraneoplastic syndrome, and on their pathophysiology, clinical manifestations, possible complications, outcomes, and treatments. As the mainstay of treatment in these conditions is often to address the underlying tumor, it is of upmost importance that physicians be aware of these rare cancer manifestations.
Topics: Female; Genital Neoplasms, Female; Hematologic Diseases; Humans; Kidney Diseases; Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes, Ocular; Rheumatic Diseases; Skin Diseases
PubMed: 28655412
DOI: 10.1016/j.ygyno.2017.06.025 -
Journal of Neurology Jan 2023The link between paraneoplastic neurological syndromes (PNS) and renal cell and bladder cancer (RCC/BC) is rare and uncertain. Our aim was to clinically evaluate, in... (Review)
Review
BACKGROUND
The link between paraneoplastic neurological syndromes (PNS) and renal cell and bladder cancer (RCC/BC) is rare and uncertain. Our aim was to clinically evaluate, in light of the updated PNS criteria, these uncommon associations.
METHODS
Retrospective nationwide cohort chart review study and systematic review of the literature.
RESULTS
After excluding 5 patients due to the diagnosis of another co-occurrent malignancy, 10/18 patients with RCC and 8/18 patients with BC were identified. A total of 31 cases were previously published, yielding an overall series of 27/49 RCC and 22/49 BC patients. There was a predominance of cerebellar syndromes in both cancers (10/27, 37% for RCC; 9/22, 41% for BC), followed by encephalitis in 9/27 (33%) patients with RCC and encephalomyelitis/sensory neuronopathy in 5/22 (23%) patients with BC. The detection of high-risk Abs was more frequent among BC patients (16/19, 84% vs. 3/13, 23% in RCC, p = 0.0009), Ri antibodies being the most frequent thereof. After applying the updated PNS criteria, patients with BC met highest degrees (possible, probable, and definite) of certainty for PNS diagnosis (20/22, 91% vs. 16/27, 59% in RCC, p = 0.021).
CONCLUSION
A second neoplasm should always be ruled out before establishing the diagnosis of PNS in patients with RCC or BC. However, while this association remains dubious for most patients with RCC, a casual role is more probable in patients with BC and high-risk antibodies presenting with cerebellar ataxia, brainstem encephalitis or encephalomyelitis/sensory neuronopathy.
Topics: Humans; Carcinoma, Renal Cell; Retrospective Studies; Paraneoplastic Syndromes; Urinary Bladder Neoplasms; Encephalitis; Encephalomyelitis; Autoantibodies; Kidney Neoplasms; Paraneoplastic Syndromes, Nervous System
PubMed: 36050418
DOI: 10.1007/s00415-022-11356-9 -
Journal of Autoimmunity Jan 2019To perform a systematic review of the current scientific literature in order to identify variables associated with patient prognosis in autoimmune encephalitis. (Review)
Review
OBJECTIVE
To perform a systematic review of the current scientific literature in order to identify variables associated with patient prognosis in autoimmune encephalitis.
METHODS
We performed a systematic literature search using MEDLINE, Embase, PubMed and PsychInfo databases. We selected studies that explored the correlation between early clinical and paraclinical findings, and patient outcomes. Data was extracted, analyzed and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Forty four publications detailing 2823 subjects matched our inclusion criteria. There was considerable heterogeneity in methodology, patient profile, investigation results and clinical outcome measures. Findings were often discrepant for cases of anti-NMDAR encephalitis when compared with other causes of autoimmune encephalitis. Delay in immunotherapy contributed to a variety of worse outcomes for patients with different subsets of autoimmune encephalitis. Altered consciousness, ICU admission and no use of immunotherapy were variables associated with poor prognosis in anti-NMDAR encephalitis. Older age, sex, the presence of status epilepticus, CSF abnormalities and MRI changes were unlikely to have significant prognostic value. The influence of antibody titers, autonomic dysfunction and underlying malignancy was unclear.
CONCLUSIONS
A number of variables were identified to have potential predictive value for outcomes in autoimmune encephalitis. Heterogeneous study design, size and quality were major limiting factors in this review.
Topics: Animals; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Cognition Disorders; Emergency Medical Services; Encephalitis; Hashimoto Disease; Humans; Immunotherapy; Predictive Value of Tests; Prognosis
PubMed: 30595145
DOI: 10.1016/j.jaut.2018.10.014 -
Eye (London, England) Jul 2022Paraneoplastic syndromes affecting the visual system are a group of conditions that arise in the systemic malignancy framework. In this review, we have provided a... (Review)
Review
Paraneoplastic syndromes affecting the visual system are a group of conditions that arise in the systemic malignancy framework. In this review, we have provided a detailed and comprehensive overview of the published literature on the various ophthalmic paraneoplastic manifestations. A systematic review of many databases has been performed to identify ample literature on the paraneoplastic syndromes related to ophthalmology. We have discussed here the clinical features, pathogenesis, and treatment strategies of various ophthalmic paraneoplastic syndromes. It can be challenging to distinguish these disorders from their non-paraneoplastic counterparts and to determine the appropriate systemic assessment for the tumour responsible, to have a proper approach towards the management of the syndrome. METHOD: We searched PubMed, Science Direct and Journal of Ophthalmology for studies published in English between 1995 and April 2020, incorporating the general search term "paraneoplastic ocular syndrome" with connecting terms relevant to subheadings-e.g. Key search terms were cancer-associated retinopathy, (CAR), melanoma-associated retinopathy, (MAR), paraneoplastic retinopathy, autoimmune retinopathy, autoimmune-related retinopathy, and optic neuropathy, (ARRON), acute zonal occult outer retinopathy, (AZOOR), paraneoplastic vitelliform maculopathy, paraneoplastic vitelliform retinopathy, bilateral diffuse uveal melanocytic proliferation, (BDUMP), paraneoplastic optic neuropathy, (PON), polyneuropathy, organomegaly, endocrinopathy, monoclona gammopathy, and skin changes syndrome (POEMS) and various other terms. References from identified studies have been reviewed and included if deemed appropriate, valid, and scientifically important. If referenced in a selected English paper, we contemplated papers in other languages too. We preferentially selected papers that have been published in the last 10 years, but we have included relevant older references.
Topics: Autoantibodies; Autoimmune Diseases; Humans; Optic Nerve Diseases; Paraneoplastic Syndromes, Ocular; Retinal Diseases; Retinal Neoplasms
PubMed: 34345027
DOI: 10.1038/s41433-021-01676-x -
Journal of Cancer 2024There remains a scarcity of published data on the clinical significance of paraneoplastic cutaneous manifestations in hepatocellular carcinoma (HCC). A systematic... (Review)
Review
There remains a scarcity of published data on the clinical significance of paraneoplastic cutaneous manifestations in hepatocellular carcinoma (HCC). A systematic search of MEDLINE was performed in December 2022. Inclusion criteria comprised studies reporting on patients with HCC, who had paraneoplastic cutaneous manifestations. Outcomes of interests comprise survival and response to cancer-directed and/or skin directed therapy. A total of 48 studies comprising 60 HCC patients were included in the analysis. The most frequent reported skin abnormalities were dermatomyositis, pityriasis rotunda, and porphyria. Most patients presented with dermatomyositis had underlying viral hepatitis, while all reported porphyria and acanthosis cases were associated with metabolic causes of HCC, such as steatosis. Paraneoplastic skin changes were more common in patients with metastatic disease. Pityriasis Rotunda was associated with the lowest risk of death, (OR: 0.05, 95% CI: 0.003 to 0.89; p = 0.04), while dermatomyositis had a statistically significant higher risk of death (OR: 3.37, 95% CI: 1.01-12.1; p = 0.03). Most patients showed an improvement in their cutaneous abnormalities, following cancer-directed therapy. Paraneoplastic cutaneous manifestations are reported more frequently in patients with a higher burden of disease, especially presence of metastases. Certain cutaneous manifestations have prognostic implication.
PubMed: 38230223
DOI: 10.7150/jca.88931 -
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 -
Reumatismo Mar 2018Polymyalgia rheumatica (PMR) is the commonest inflammatory rheumatic disease affecting older people. The current mainstay of treatment is long-term oral glucocorticoid... (Review)
Review
Polymyalgia rheumatica (PMR) is the commonest inflammatory rheumatic disease affecting older people. The current mainstay of treatment is long-term oral glucocorticoid therapy. Management of these patients in clinical practice is often complicated by the presence of comorbidity. Comorbidity might be due to shared risk factors such as age, sex, or genetic background; to the presence of the disease itself; or to adverse effects of glucocorticoid therapy. Cardiovascular disease, osteoporosis/fracture, metabolic and ocular comorbidity are of particular interest to clinicians because of their relationship to glucocorticoid therapy and the relevance to clinical treatment decisions regarding glucocorticoid tapering. Patients at high risk of exacerbation of comorbidity by glucocorticoid therapy may be considered for adjunctive steroid-sparing therapies and thus may need specialist management. From a public health perspective, with the ageing population the prevalence of PMR is predicted to increase; accurate data on comorbidity will be needed for planning and delivery of healthcare services.
Topics: Aged; Cardiovascular Diseases; Comorbidity; Eye Diseases; Glucocorticoids; Humans; Metabolic Diseases; Neoplasms; Osteoporosis; Paraneoplastic Syndromes; Polymyalgia Rheumatica; Prevalence; Risk Factors; United Kingdom
PubMed: 29589401
DOI: 10.4081/reumatismo.2018.1039 -
Cerebellum (London, England) Dec 2022Rapidly progressive cerebellar ataxia is a classical paraneoplastic neurological syndrome associated with different autoantibodies and typical demographic... (Review)
Review
Rapidly progressive cerebellar ataxia is a classical paraneoplastic neurological syndrome associated with different autoantibodies and typical demographic characteristics, extracerebellar signs, tumor association, and prognosis. Anti-Tr/anti-Delta/Notch-like epidermal growth factor-related receptor (DNER) antibody is one of the associated antibodies. Given the rarity of this condition, our current knowledge is based on case reports and small case series. In order to improve our understanding of these conditions, we conducted a systematic review of the literature. Our study followed the PRISMA reporting guidelines. Studies of patients with the presence of anti-Tr/DNER antibodies in serum or cerebrospinal fluid (CSF) were included. We extract data information related to study characteristics, demographics, clinical symptoms, tumor association, neuroimaging, and cerebrospinal fluid analysis. Out of 131 records, we analyzed 17 papers, including a total of 85 patients with anti-Tr/DNER antibody-associated cerebellar ataxia. We confirmed that this disease occurred mostly in middle-aged males. Isolated cerebellar ataxia was the most common presentation. Extracerebellar features were rare (8%). Ninety-one percent of the patients presented an associated tumor, being Hodgkin lymphoma the most common. Abnormal neuroimaging patterns included cerebellar atrophy (19%) and cerebellar hypersignal (6%). Cerebrospinal fluid was inflammatory in 64% of the patients. Oncological response was complete in 88%, but neurological prognosis was poor with only 41% of the patients presenting significant neurological improvement at the last follow up. Anti-Tr/DNER antibodies should be tested in rapid progressive cerebellar ataxia. Oncological response is excellent; however, many patients do not improve from their cerebellar ataxia.
Topics: Middle Aged; Male; Humans; Cerebellar Ataxia; Nerve Tissue Proteins; Autoantibodies; Neoplasms; EGF Family of Proteins; Receptors, Cell Surface
PubMed: 34817790
DOI: 10.1007/s12311-021-01346-4 -
Journal of Clinical Neuromuscular... Dec 2023Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle...
OBJECTIVES
Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle twitching, stiffness, hypertrophy, and dysautonomic characteristics, such as hyperhidrosis, are common manifestations. The syndrome can be autoimmune or paraneoplastic, with thymoma being a common cause of paraneoplastic IS. Furthermore, this condition could be handed down from one generation to another. However, there is limited information regarding outcomes, relapses, associated syndromes, associated malignancies (other than thymoma), and treatment options. Despite its rarity, there remains a need for effective management strategies for patients with IS. To address this gap, we conducted a systematic review to summarize the most common and effective treatments of IS in immunomodulatory agents and symptomatic medications, as well as to describe outcomes, relapses, and associated malignancies. Altogether, this review serves to guide clinical practice recommendations for IS and highlight areas for further research.
METHODS
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to conduct a systematic review of cases reposted through the PubMed and Google Scholar databases. The terms "Isaac Syndrome" and "Acquired Neuromyotonia" were used. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the quality of the included studies.
RESULTS
We identified 61 case reports and 4 case series, comprising a total of 70 patients with IS (mean age at onset: 42.5 ± 18 years, and 69% were males). Fourteen cases reported relapses. Thymoma was the most common malignancy associated with IS, followed by lymphoma. Among various serum antibodies, voltage-gated potassium channel-complex antibodies were the most reported antibodies elevated in IS (reported in 38 patients and elevated in 21 patients [55.2%]), followed by acetylcholine ganglionic receptor antibodies, which were reported in 30% of patients (n = 21) and were elevated in 5 cases. The most common electromyography findings were myokymic discharges (n = 22), followed by fasciculations (n = 21) and neuromyotonia (n = 19). For treatment, combining anticonvulsants such as carbamazepine with immunotherapy therapy showed the best results in controlling the symptoms. Among immunotherapy therapies, the combination of plasma exchange plus intravenous high-dose steroids achieved the best results in the acute treatment of IS ([n = 6], with improvement noted in 83.3% [n = 5] of cases). Among the symptomatic treatments with anticonvulsants, carbamazepine was the most efficacious anticonvulsant in treatment of IS, with an average effective dosing of 480 mg/day (carbamazepine was used in 32.3% of acute treatment strategies [n = 23], with improvement noted in 73.9% [n = 17] of cases).
CONCLUSIONS
IS a rare neuromuscular syndrome that tends to affect middle-aged men. These patients should be screened for thymoma and other malignancies such as lymphomas. The management of IS symptoms can be challenging, but based on our review, the combination of multiple immunosuppressives such as IV steroids and plasmapheresis with anticonvulsants such as carbamazepine seems to achieve the best results.
Topics: Male; Middle Aged; Humans; Female; Isaacs Syndrome; Thymoma; Anticonvulsants; Thymus Neoplasms; Autoantibodies; Potassium Channels, Voltage-Gated; Carbamazepine; Receptors, Cholinergic; Steroids; Recurrence
PubMed: 37962197
DOI: 10.1097/CND.0000000000000460