Paraneoplastic Neurological Syndromes Research Articles

Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes: A Nationwide Study on Epidemiology and Antibody Testing Performance.

Autoimmune encephalitis (AIE) and paraneoplastic neurologic syndromes (PNSs) encompass a heterogeneous group of antibody-associated disorders. Both the number of syndromes and commercially available antibody tests have increased considerably over the past decade. High-quality population-based data on epidemiology of these disorders and real-world performance of antibody tests are needed. In this nationwide retrospective cohort study, we identified all serum and CSF samples tested for antibodies against intracellular antigens (IAs: Hu [ANNA1], Yo [PCA1], CV2 [CRMP5], Ri [ANNA2], Ma1, Ma2 [Ta], amphiphysin, GAD65, GFAP, KLHL11, CARP VIII) or extracellular antigens (EAs: NMDAR, LGI1, Caspr2, GABA-B-R, GABA-A-R, AMPAR, DPPX, GlyR, mGluR1, VGCC, IgLON5, Tr [DNER]) between January 2016 and December 2021 in the Netherlands. Nationwide coverage was guaranteed for all antibodies except anti-GAD65 and anti-VGCC. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV); obtained clinical information about patients who tested positive; assigned diagnosis of AIE/PNS according to diagnostic criteria; and calculated incidence rates for IA, EA, and individual antibody-associated syndromes. In the study period, 2,877 (9.5%) of 30,246 samples, belonging to 1,228 patients, tested positive. Sensitivity and specificity were high (>95%) to very high (>99%) for most tests in both serum and CSF. PPVs for several tests were moderate to poor, especially for serum testing of IA antibodies (25%-80%). Clinical data were available for 940 (76.5%) of 1,228 patients. A total of 578 AIE/PNS diagnoses were made. The incidence rate for AIE/PNS (per million person-years) increased from 4.70 (95% CI 3.72-5.85) in 2016 to 5.76 (4.69-7.00) in 2021. Overall, the incidence rate was 5.57 (5.13-6.05), 2.96 (2.64-3.31) for the EA and 2.61 (2.31-2.94) for the IA subgroup. The 4 most common AIE/PNS types were anti-NMDAR, anti-LGI1, anti-Hu, and anti-GAD65, together comprising almost two-thirds of all diagnoses (364/578, 63.0%). Most commercial antibody tests perform well overall, but important pitfalls remain. Although almost all tests had high specificity, PPV was only modest in the setting of these rare diseases and mass testing. We observe trends toward increasing incidence of antibody-associated AIE/PNS.

Paraneoplastic Neurologic Syndromes Associated With Merkel Cell Carcinoma.

To define the clinical and immunologic profile of patients with paraneoplastic neurologic syndromes (PNSs) associated with Merkel cell carcinoma (MCC). Retrospective analysis was conducted on patients with suspected MCC-related PNS assessed at the French Reference Center, and cases were identified by a systematic review of the literature (MEDLINE, Embase) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 17 patients were identified in our center and 30 in the systematic review, resulting in an overall cohort of 47 patients. The median age was 65 years (range 41-90), and 30 of 46 (65%) were men. Lambert-Eaton myasthenic syndrome (LEMS) (14/47, 29%), rapidly progressive cerebellar syndrome (11/47, 23%), and encephalomyelitis (EM) (8/47, 17%) were the most common associated clinical phenotypes. The most frequently associated neural antibodies (Abs) were voltage-gated calcium channel (VGCC)-Abs (14/45, 31%), followed by Hu-Abs (8/45, 17%) and neurofilament (NF)-Abs (8/45, 17%). Patients with NF-Abs only exhibited CNS disorders (8/8, 100%) and often had antibodies against >1 NF subunit (6/8, 75%). At onset, 26 of 43 patients (60%) had no identifiable primary skin tumor but had lymph node metastasis; these patients were more frequently men (21/26, 80%, vs 7/17, 41%; p = 0.007), had more frequently VGCC-Abs (12/26, 46%, vs 2/17, 11%, p = 0.02) predominantly among those with LEMS, and presented reduced mortality than patients with a known primary tumor (5/25, 20%, vs 8/15, 53%; p = 0.02). MCC-related PNSs present as a heterogeneous clinical spectrum including central and/or peripheral nervous system disorders such as LEMS, RCPS, and EM, mainly associated with VGCC-Abs, NF-Abs, and Hu-Abs. NF-Abs were only seen among patients with CNS disorders. At onset, the absence of a primary skin tumor but presence of lymph node metastasis is frequently observed, and this particular clinical presentation is linked to reduced mortality, highlighting distinctive clinical and immunologic features of MCC-related PNS.

Paraneoplastic neurological syndrome and its impact on the treatment outcomes of small-cell lung cancer: A single-center retrospective analysis.

Paraneoplastic neurological syndrome (PNS) is associated with small-cell lung cancer (SCLC). However, the frequency and characteristics of PNS and the efficacy of anticancer treatment for these patients have not been investigated in the Japanese/Asian population previously. Therefore, we aimed to better understand PNS by evaluating real-world data from patients with PNS complicated by SCLC. Patients diagnosed with Stage II-IV SCLC at a single center between August 2007 and April 2021 were retrospectively analyzed. The primary outcome was the incidence of PNS. The secondary outcomes were the change in performance status (PS) after treatment commencement and outcomes following anticancer treatment, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 318 patients were evaluated; PNS was present in 2.8% (n = 9) of the overall population. All patients with PNS exhibited poor Eastern Cooperative Oncology Group PS (≥2); moreover, 78% of patients had a PS score of 3-4. An improvement in PS was observed in 56% (n = 5) of patients. Patients with PNS exhibited treatment efficacies similar to patients without PNS (ORR: 89% vs. 83%, p = 1.0; PFS: 7.6 vs. 5.7 months, p = 0.69; OS: not reached vs. 15.6 months, p = 0.23). A total of 2.8% of patients had SCLC complicated by PNS, with poor PS observed. However, anticancer therapy led to an improvement in PS and comparable ORR, as well as PFS and OS similar to those observed in patients without PNS. Thus, anticancer therapy should be considered in patients with PNS.

Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes with Progressive Supranuclear Palsy-like Manifestations.

Advances in diagnostic procedures have led to an increasing rate of diagnosis of autoimmune encephalitis or paraneoplastic neurological syndrome (AE/PNS) among patients with progressive supranuclear palsy (PSP)-like manifestations. In this narrative review, we first discuss the clinical characteristics of AE/PNS in comparison to those of PSP, followed by a discussion of diagnosis and treatment. The antibodies involved in these conditions include anti-IgLON5, -Ma2, and -Ri antibodies, each of which has a characteristic clinical presentation. The steps in the diagnosis of AE/PNS in patients with PSP-like manifestations include (i) suspicion of AE/PNS based on clinical presentations atypical of PSP and (ii) antibody detection measures. Methods used to identify antibodies include a combination of tissue-based assays and confirmatory tests. The primary confirmatory tests include cell-based assays and immunoblotting. Treatments can be divided into immunotherapy and tumor therapies, the former of which includes acute and maintenance therapies. One of the major challenges of diagnosis is that existing reports on PSP-like patients with AE/PNS include only case reports, with the majority discussing antibodies other than anti-IgLON5 antibody. As such, more patients need to be evaluated to establish the relationship between antibodies and PSP-like manifestations.

Performance Assessment of the New EUROLINE Neurologic Syndrome 15 Ag (IgG) for the Determination of Autoantibodies Associated with Neurological Disorders.

Here, we assess the performance of the new EUROLINE Neurologic Syndrome 15 Ag (IgG) which expands the EUROLINE Paraneoplastic Neurologic Syndrome 12 Ag by adding CDR2L (together with CDR2 targeted by anti-Yo), AK5, and Neurochondrin (NCDN). Many paraneoplastic as well as non-paraneoplastic autoantibodies (AAbs) have been described in neurological disorders in the last decade. By integrating the associated antigens into existing assays, the diagnostic work-up of patients is being improved and diagnostic gaps reduced. Sensitivity of each AAb was analyzed using a total of 194 clinically and diagnostically pre-characterized samples (Table 1). Specificity of each AAb was investigated using a minimum of 100 sera from healthy blood donors. Using the EUROLINE Neurologic Syndrome 15 Ag, autoantibody positivity was confirmed in 89-100% of samples. In particular, all samples for which clinical and tissue-based indirect immunofluorescence assay pre-characterization indicated anti-Yo positivity were anti-CDR2 and -CDR2L double positive. Anti-AK5 was determined in serum and cerebrospinal fluid (CSF) with a sensitivity of 90 and 100%, respectively, and anti-NCDN with a sensitivity of 100%. The individual specificities were ≥99%. This kit is a tool for the qualitative in vitro determination of AAbs against a large panel of 15 different neuronal autoantigens to support the diagnosis of neurologic syndromes. The parallel detection of anti-CDR2 and anti-CDR2L (both anti-Yo) increases the diagnostic significance, as double positivity is strongly related to paraneoplastic cerebellar degeneration.[Table: see text].

Paraneoplastic Neurologic Syndromes Associated with Lymphomas

Paraneoplastic Neurologic Syndromes Associated with Lymphomas

Effectiveness of double-filtration plasmapheresis in reducing immunoglobulin and culprit antibody levels in neuroimmune disorders: A single-center retrospective analysis from China

ObjectiveThis study aims to evaluate the effectiveness of double-filtration plasmapheresis (DFPP) in reducing immunoglobulins and culprit antibodies in neuroimmune disorders. MethodsA retrospective analysis was conducted on 51 patients with neuroimmune diseases treated with DFPP, immunotherapy, and symptomatic treatment. Immunoglobulin and antibody levels were measured pre- and post-treatment, along with neurological function assessments using scales like the modified Rankin Scale (mRS), Expanded Disability Status Scale (EDSS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), and Myasthenia Gravis-specific scales. ResultsThe cohort included patients with neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AIE), myasthenia gravis (MG), anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD), and paraneoplastic neurological syndromes (PNS). DFPP significantly reduced immunoglobulin levels (IgG, IgA, IgM) by ∼70 %. Most patients showed decreased antibody titers and significant neurological improvement. The median mRS score improved from 2 (IQR 2–3) to 1 (IQR 1–2) post-treatment, with further improvement at 90 days. Notable improvements were observed across various scales specific to NMOSD, MOGAD, AIE, and MG. Minor adverse events were reported, with no serious adverse events. ConclusionsDFPP is effective in reducing immunoglobulin and antibody levels, leading to improved neurological function in neuroimmune disorders. Further large-scale studies are warranted to confirm these findings.

Paraneoplastic Syndromes of the Nervous System in Patients Suffering from SCLC. A Review of the Recent Literature

Background. Paraneoplastic Neurological Syndromes (PNS) constitute a heterogeneous cluster of disease manifestations related to various cancers. Small Cell Lung Cancer (SCLC) is strongly related to PNS. This narrative review conducted a survey in the available PubMed literature to highlight the appearance of PNSs in SCLC cases and discuss published research highlights on the subject so that general practitioners can be acquainted with the medical phenomenon present in SCLC patients. Method. A narrative review of the medical literature was conducted as documentary informative research in the PubMed medical database, combined with a survey of the online e-library Google Books. The key words used were: “Paraneoplastic Neurological Syndromes” and “Small Cell Lung Cancer”. Results. Paraneoplastic syndromes are related to the presence of a malignancy and are not secondary to treatment. Paradoxally, both a malignancy and its therapeutic approach may cause a series of PNSs. Paraneoplastic cerebellar degeneration, motor neuron disorders, peripheral neuropathies, hyponatremia, and syndromes such as myasthenic Lambert-Eaton, ectopic Cushing’s, Stiffman, and Opsoclonus-myoclonus syndrome may also appear in SCLC cases. Diagnosis follows specific criteria, and they are caused by tumor-directed antibodies known as onconeural antibodies. Immunosuppressants, intravenous immunoglobulins, plasma exchange, rituximab, cyclophosphamide, azathioprine, and tocilizumab could be considered as treatment agents. Conclusions. Most patients demonstrate poor PNS treatment results with common relapse. The time for beginning treatment of PNS is discussed. A multidisciplinary team is needed for potentially earlier diagnosis and PNS improvement, better prognosis, and increased overall survival and quality of life.

Blood-Brain Barrier Disruption in Neuroimmunological Disease.

The blood-brain barrier (BBB) acts as a structural and functional barrier for brain homeostasis. This review highlights the pathological contribution of BBB dysfunction to neuroimmunological diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AE), and paraneoplastic neurological syndrome (PNS). The transmigration of massive lymphocytes across the BBB caused by the activation of cell adhesion molecules is involved in the early phase of MS, and dysfunction of the cortical BBB is associated with the atrophy of gray matter in the late phase of MS. At the onset of NMOSD, increased permeability of the BBB causes the entry of circulating AQP4 autoantibodies into the central nervous system (CNS). Recent reports have shown the importance of glucose-regulated protein (GRP) autoantibodies as BBB-reactive autoantibodies in NMOSD, which induce antibody-mediated BBB dysfunction. BBB breakdown has also been observed in MOGAD, NPSLE, and AE with anti-NMDAR antibodies. Our recent report demonstrated the presence of GRP78 autoantibodies in patients with MOGAD and the molecular mechanism responsible for GRP78 autoantibody-mediated BBB impairment. Disruption of the BBB may explain the symptoms in the brain and cerebellum in the development of PNS, as it induces the entry of pathogenic autoantibodies or lymphocytes into the CNS through autoimmunity against tumors in the periphery. GRP78 autoantibodies were detected in paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome, and they were associated with cerebellar ataxia with anti-P/Q type voltage-gated calcium channel antibodies. This review reports that therapies affecting the BBB that are currently available for disease-modifying therapies for neuroimmunological diseases have the potential to prevent BBB damage.

Paraneoplastic neurological syndromes associated with anti-Hu antibodies in an ovarian cancer patient: a case report and narrative literature review

Paraneoplastic neurological syndromes associated with anti-Hu antibodies in an ovarian cancer patient: a case report and narrative literature review

Anti-RGS8 paraneoplastic cerebellar ataxia is preferentially associated with a particular subtype of Hodgkin’s lymphoma

Ataxia with anti-regulator of G-protein signaling 8 autoantibodies (RGS8-Abs) is an autoimmune disease recently described in four patients. The present study aimed to identify other patients with RGS8-Abs, describe their clinical features, including the link between RGS8-related autoimmune cerebellar ataxia (ACA) and cancer. Patients with RGS8-Abs were identified retrospectively in the biological collections of the French Reference Center for Paraneoplastic Neurological Syndrome and the University of California San Francisco Center for Encephalitis and Meningitis. Clinical data were collected, and cerebrospinal fluid, serum, and tumor pathological samples were retrieved to characterize the autoantibodies and the associated malignancies. Only three patients with RGS8-Abs were identified. All of them presented with a pure cerebellar ataxia of mild to severe course, unresponsive to current immunotherapy regimens for ACA. Two patients presented with a Hodgkin lymphoma of the rare specific subtype called nodular lymphocyte-predominant Hodgkin lymphoma, with very mild extension. Autoantibodies detected in all patients enriched the same epitope on the RGS8 protein, which is an intracellular protein physiologically expressed in Purkinje cells but also ectopically expressed specifically in lymphoma cells of patients with RGS8-related ACA. The present results and those of the four cases previously described suggest that RGS8-Abs define a new paraneoplastic neurological syndrome of extreme rarity found mostly in middle-aged males that associates pure cerebellar ataxia and a particular lymphoma specifically expressing the RGS8 antigen. As in other paraneoplastic ACA with intracellular antigen, the disease course is severe, and patients tend to exhibit a poor response to immune therapy.

Decoding Multiple Antibody Positivity: Lessons from Paraneoplastic Sensory Ataxia.

Paraneoplastic neurologic syndromes are cancer-associated, immune-mediated neurologic manifestations that may involve any part of the nervous system. They usually present with characteristic neurologic features and should be considered in high-risk phenotypes such as limbic encephalitis, encephalomyelitis, rapidly progressive cerebellar syndrome, opsoclonus-myoclonus, sensory neuronopathy, enteric neuropathy, and Lambert-Eaton myasthenic syndrome. The diagnosis is made by antibody positivity in the serum or cerebrospinal fluid, in the presence of an appropriate clinical phenotype. Findings on antibody testing by immunoblot should always be verified by immunofluorescence. We report a rare case of sensory neuronopathy with triple paraneoplastic antibody positivity (anti-Hu, anti-collapsing response-mediator protein 5, and anti-amphiphysin) on immunoblot but only anti-Hu positivity on immunofluorescence. The presence of lower facial dyskinesias should raise the possibility of an immune-mediated neurologic syndrome in the appropriate clinical context.

Beyond paraneoplastic neurological syndromes: Anti-neuronal antibodies in neuropsychiatric systemic lupus erythematosus.

Anti-neuronal antibodies target antigens produced by tumour cells and cells of nervous system. These antibodies are formed as a result of autoimmune response elicited by the underlying malignancy, when proteins restricted to immune privileged neurons are presented by the tumour. Previous studies have shown presence of anti-neuronal antibodies in systemic lupus erythematosus and neuropsychiatric lupus (NPSLE) but information on individual antibodies and their pathogenic role is lacking. To assess the frequency of anti-neuronal antibodies in our neuropsychiatric lupus cohort and to assess any significant association with specific neurological syndrome and to see if the antibodies were more likely to occur in active rather than inactive neuropsychiatric lupus. This cross-sectional study was conducted in our center from 2019 to 2022. Neuropsychiatric manifestations were defined according to 1999 American College of Rheumatology (ACR) nomenclature and case definitions for neuropsychiatric lupus. Samples were taken from active or inactive NPSLE patients with their informed consent. Testing was done on an anti-neuronal antigen panel which consisted of [Amphiphysin, CV2, GAD 65, PNMA2 (Ma-2/Ta), Ri, Yo, Hu, recoverin, SOX1, titin, Zic, Tr)] by semi-quantitative Line immune assay. Association between the categorical variables and antibody positivity group was established using chi-square/Fisher's exact test as appropriate. 65 patients were recruited, of which 23 (35%) patients had active NPSLE at the time of sample collection. Anti-neuronal antibodies were positive in 13/65 (20%) patients with anti-Gad 65 antibodies having the highest frequency (6.2%) followed by anti CV 2 (3.1%), anti Sox1 (3.1%), anti Amphiphysin (3.1%) anti recoverin (1.5%), anti Yo (1.5%) and anti Zic (1.5%). The panel of anti-neuronal antibodies did not show any specific association with NPSLE features.However, an interesting finding was that, patients with active disease had higher odds of having anti-neuronal antibodies with an OR = 10 (95% CI:2.38 -42) (p < 0.001) than inactive disease. Anti-neuronal antibodies were more likely to be positive in active neuropsychiatric lupus patients, and these antibodies which are commonly used to diagnose paraneoplastic syndromes may have a potential role in the diagnosis of NPSLE.

Paraneoplastic Neurologic Disorders.

This article reviews the clinical presentations, neural antibody associations, and oncologic accompaniments of paraneoplastic neurologic syndromes and neurologic autoimmunity in the context of immune checkpoint inhibitor (ICI) cancer immunotherapy. Neural antibody discovery has improved the diagnosis of paraneoplastic neurologic syndromes. Neural antibodies also delineate the underlying disease pathophysiology and thus inform outcomes and treatments. Neural antibodies specific for extracellular proteins have pathogenic potential, whereas antibodies specific for intracellular targets are biomarkers of a cytotoxic T-cell immune response. A recent update in paraneoplastic neurologic syndrome criteria suggests high- and intermediate-risk phenotypes as well as neural antibodies to improve diagnostic accuracy in patients with paraneoplastic neurologic syndromes; a score was created based on this categorization. The introduction of ICI cancer immunotherapy has led to an increase in cancer-related neurologic autoimmunity with distinct clinical phenotypes. Paraneoplastic neurologic syndromes reflect an ongoing immunologic response to cancer mediated by effector T cells or antibodies. Paraneoplastic neurologic syndromes can present with manifestations at any level of the neuraxis, and neural antibodies aid diagnosis, focus cancer screening, and inform prognosis and therapy. In patients with high clinical suspicion of a paraneoplastic neurologic syndrome, cancer screening and treatment should be undertaken, regardless of the presence of a neural antibody. ICI therapy has led to immune-mediated neurologic complications. Recognition and treatment lead to improved outcomes.

Diagnostic and prognostic biomarkers in immune checkpoint inhibitor-related encephalitis: a retrospective cohort study

Immune checkpoint inhibitor-related encephalitis (ICI-encephalitis) is not well characterised and diagnostic and prognostic biomarkers are lacking. We aimed to comprehensively characterise ICI-encephalitis and identify diagnostic biomarkers and outcome predictors. This retrospective observational study included all patients with ICI-encephalitis studied in the French Reference Centre on Paraneoplastic Neurological Syndromes (PNS) and Autoimmune Encephalitis (2015-2023). ICI encephalitis was considered definite in case of inflammatory findings at paraclinical tests and/or well-characterised neural antibodies. Predictors of immune-related adverse event (irAE) treatment response, defined as a Common Terminology Criteria for Adverse Events v5.0 grade<3at any time after therapeutic intervention, were assessed by logistic regression analysis, and predictors of mortality by Cox regression analysis. Neurofilament light chain (NfL) was measured by enzyme-linked immunosorbent assay. Sixty-seven patients with definite encephalitis were identified (median age, 69 years; 66% male). A focal syndrome was observed in 43/67 patients (64%; limbic encephalitis, cerebellar ataxia, and/or brainstem encephalitis), while 24/67 (36%) had meningoencephalitis, a non-focal syndrome with altered mental status (22/24 patients, 92%) and pleocytosis (24/24 patients, 100%). Patients with focal encephalitis more frequently had abnormal brain MRI (26/42, 62% versus 8/24, 33%, p=0.025), PNS-related antibodies (36/43, 84% versus 1/24, 4%, p<0.001), and neuroendocrine cancers (22/43, 51% versus 1/24, 4%; p<0.001) than patients with meningoencephalitis. Focal encephalitis patients had a lower rate of irAE treatment response (7/39, 18%) and higher mortality (27/43, 63%) compared to meningoencephalitis patients (12/22, 77% and 5/24, 21%, respectively, p<0.001 each). PNS-related antibodies were associated with less irAE treatment response, independently of age, sex, and baseline severity (adjusted OR 0.05; 95%CI [0.01; 0.19]; p<0.001) as well as higher mortality, independently of age and cancer type (adjusted HR 5.07; 95% CI [2.12; 12.12]; p<0.001). Serum NfL discriminated patients with definite ICI-encephalitis (n=27) from cancer-matched controls (n=16; optimal cut-off >273.5pg/mL, sensitivity 81%, specificity 88%, AUC 0.87, 95% CI [0.76; 0.98]) and irAE treatment responders (n=10) from non-responders (n=17, optimal cut-off >645pg/mL, sensitivity 90%, specificity 65%; AUC 0.75, 95% CI [0.55; 0.94]). ICI-encephalitis corresponds to a set of clinically-recognisable syndromes. Patients with focal encephalitis, PNS-related antibodies, and/or higher serum NfL have low irAE treatment response rates. Research is needed on the underlying immunopathogenesis to foster therapeutic innovations. Agence Nationale de la Recherche.

Atypical Presentation of Carcinoma Breast as Paraneoplastic Cerebellar Degeneration on [18F]FDG PET/CT

Paraneoplastic neurological syndrome (PNS) represents a rare group of central nervous system disorders that are unrelated to direct tumor invasion or metastasis but may be triggered by an immune system reaction to a neoplasm or malignant tumor. In many patients, PNS is diagnosed before identifying the primary cancer. In such instances, positron emission tomography/computed tomography scan can assess individuals with suspected PNS enabling the detection of hidden malignancies. We share an interesting image of paraneoplastic cerebellar degeneration in a case of invasive ductal carcinoma breast.

Atypical Presentation of Gall Bladder Adenocarcinoma as Paraneoplastic Myeloneuropathy.

Paraneoplastic neurologic syndromes are a rare, heterogeneous group of complications associated with malignancy, unrelated to direct tumor invasion or metastasis. They are the remote effects of a malignancy owing to immune-mediated reaction toward the antigens that are common to both the malignant and normal cells. Few paraneoplastic syndromes are reported with gall bladder cancer. However, neurological symptoms are infrequent. Here we share an interesting case of adenocarcinoma of gall bladder with initial presentation as a paraneoplastic noncompressing myeloneuropathy.

ПАРАНЕОПЛАСТИЧЕСКИЙ НЕВРОЛОГИЧЕСКИЙ СИНДРОМ У РЕБЕНКА С НЕЙРОБЛАСТОМОЙ: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

Paraneoplastic syndromes are of particular difficulties in establishing a timely diagnosis of a malignant tumor esp. in cases when the decease development is occurred chronologically much earlier than the appearance of its specific symptoms and the neoplasm growth’s first signs. And the clinical manifestation can be represented solely by an isolated clinic of paraneoplastic syndrome, which in its turn is much alike the symptoms of the paraneoplastic neurological syndrome (PNS). Authors represent a clinical case of a severe PNS coupled with the central nervous system (CNS) lesion, mainly the cerebellum, which was manifested clinically by ataxia, tremor, myoclonus, dysartria, cognitive and mental impairment and psychotic disorders, which in its turn had delayed the timely diagnosis of neuroblastoma (left-sided intermixed adrenal ganglioneuroblastoma with metastatic tumors in ipsilateral lymph nodes and paranephric fat, deletion 1q, deletion 1p36 and MYCN amplification - all negative and INSS stage 2B) in a 5 y/o male patient. No ‘classical’ opsoclonus-myoclonus was a matter of diagnosis due to the opsoclonus absence during the whole disease course. This clinical case observation publication is having a practical purpose of pinning attention to paraneoplastic syndromes among practitioners of wide spectrum: neurologists, infectionists and pediatricians.

Paraneoplastic neurological syndromes of small cell lung cancer.

This article reviews the relevant literature on paraneoplastic neurological syndromes of small cell lung cancer and discusses the clinical presentation, pathophysiology, and diagnosis of these syndromes. It also includes a summary of the current treatment options for the management of them. Paraneoplastic syndromes are a group of signs and symptoms that develop due to cancer in a remote site, mainly triggered by an autoantibody produced by the tissues involved or lymphocytes during anti-cancer defense. Among the cancers associated with paraneoplastic syndromes, lung cancers are the most common type, with small cell lung cancer being the most common subtype. The most common antibody associated with paraneoplastic syndromes is anti-Hu. Neurological and neuroendocrine syndromes comprise the majority of small cell lung cancer-related paraneoplastic syndromes. Classical paraneoplastic neurological syndromes include inappropriate antidiuretic hormone secretion, Cushing's syndrome, myasthenia gravis, Lambert-Eaton myasthenic syndrome, limbic encephalitis, paraneoplastic cerebellar degeneration, opsoclonus myoclonus ataxia, sensory neuropathy, and chorea. Antibodies mediate paraneoplastic syndromes, and antibody detection is a crucial part of diagnosing these entities. Managing the underlying tumor is the best treatment approach for most paraneoplastic syndromes. Therefore, early diagnosis of small cell lung cancer may significantly improve the prognosis of paraneoplastic syndromes associated with it.

Paraneoplastic syndromes in childhood neuroblastoma

INTRODUCTION: Neuroblastoma is a malignant tumor primarily affecting infants. Originating from embryonic cells of the sympathetic nervous system, NB commonly arises in the adrenal glands, followed by the abdomen, mediastinum, head, and neck. Clinical presentation varies depending on the tumor's location. General symptoms, if present, include fatigue, weight loss, and fever. The paraneoplastic syndrome refers to symptoms and disorders associated with malignant tumors but not directly caused by the tumor itself or its metastases. Opsoclonus-myoclonus syndrome and diarrhea are the most common paraneoplastic syndromes linked to neuroblastoma. REVIEW METHODS: The article was conducted using PubMed and Google Scholar data concerning paraneoplastic syndromes associated with neuroblastoma. THE STATE OF KNOWLEDGE: Opsoclonus-myoclonus syndrome is a neurological paraneoplastic syndrome that presents itself with characteristic eye movement disorder, short, involuntary, irregular twitches or spasms occurring in a muscle, sleep disturbance, and changes in behavior. Diarrhea resulting in hypokalemia may be also present as a paraneoplastic syndrome associated with neuroblastoma. Cushing’s syndrome is a rare condition in childhood, but it also may be linked to neuroblastoma. CONCLUSIONS: Neuroblastoma is one of the most common childhood cancers, Paraneoplastic syndromes associated with neuroblastoma are rare conditions. Diagnosing chronic diarrhea, OMS, and Cushing's syndrome should always lead to the exclusion of neuroblastoma. Heightened awareness among pediatricians regarding PNS could result in faster diagnosis, timely treatment commencement, and ultimately enhance patient prognosis.