Paraneoplastic Neurological Syndromes Research Articles

Dysautonomia in anti-Hu paraneoplastic neurological syndromes.

Dysautonomia has been associated with paraneoplastic neurological syndrome (PNS)-related mortality in anti-Hu PNS, but its frequency and spectrum remain ill-defined. We describe anti-Hu patients with dysautonomia, estimate its frequency, and compare them to patients without dysautonomia. Patients with anti-Hu antibodies diagnosed in the study centre (1990-2022) were retrospectively reviewed; those with autonomic signs and symptoms were identified. Among 477 anti-Hu patients, 126 (26%) had dysautonomia (the only PNS manifestation in 7/126, 6%); gastrointestinal (82/126, 65%), cardiovascular (64/126, 51%), urogenital (24/126, 19%), pupillomotor/secretomotor (each, 11/126, 9%), and central hypoventilation (10/126, 8%). Patients with isolated CNS involvement less frequently had gastrointestinal dysautonomia than those with peripheral (alone or combined with CNS) involvement (7/23, 30% vs. 31/44, 70% vs. 37/52, 71%; P = 0.002); while more frequently central hypoventilation (7/23, 30% vs. 1/44, 2.3% vs. 2/52, 4%; P < 0.001) and/or cardiovascular alterations (18/23, 78% vs. 20/44, 45% vs. 26/52, 50%; P = 0.055). Median [95% CI] overall survival was not significantly different between patients with (37 [17; 91] months) or without dysautonomia (28 [22; 39] months; P = 0.78). Cardiovascular dysautonomia (HR: 1.57, 95% CI [1.05; 2.36]; P = 0.030) and central hypoventilation (HR: 3.51, 95% CI [1.54; 8.01]; P = 0.003) were associated with a higher risk of death, and secretomotor dysautonomia a lower risk (HR: 0.28, 95% CI [0.09; 0.89]; P = 0.032). Patients with cardiovascular dysautonomia dying ≤ 1year from clinical onset had severe CNS (21/27, 78%), frequently brainstem (13/27, 48%), involvement. Anti-Hu PNS dysautonomia is rarely isolated, frequently gastrointestinal, cardiovascular and urogenital. CNS dysfunction, particularly brainstem, associates with lethal cardiovascular alterations and central hypoventilation, while peripheral involvement preferentially associates with gastrointestinal or secretomotor dysautonomia, being the latest more indolent.

Genetic predisposition to autoimmune encephalitis and paraneoplastic neurological syndromes.

We summarize the recent discoveries on genetic predisposition to autoimmune encephalitis and paraneoplastic neurological syndromes (PNS), emphasizing clinical and pathophysiological implications. The human leukocyte antigen (HLA) is the most studied genetic factor in autoimmune encephalitis and PNS. The HLA haplotype 8.1, which is widely known to be related to systemic autoimmunity, has been only weakly associated with a few types of autoimmune encephalitis and PNS. However, the strongest and most specific associations have been reported in a subgroup of autoimmune encephalitis that comprises antileucine-rich glioma-inactivated 1 (LGI1) limbic encephalitis, associated with DRB1∗07 : 01 , anticontactin-associated protein-like 2 (CASPR2) limbic encephalitis, associated with DRB1∗11 : 01 , and anti-IgLON5 disease, associated with DRB1∗10 : 01∼DQA1∗01∼DQB1∗05 . Non-HLA genes have been poorly investigated so far in autoimmune encephalitis, mainly in those lacking HLA associations such as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, with only a few genome-wide association studies (GWAS) reporting equivocal results principally limited by small sample size. Genetic predisposition seems to be driven mostly by HLA in a group of autoimmune encephalitis characterized by being nonparaneoplastic and having predominantly IgG4 autoantibodies. The contribution of non-HLA genes, especially in those diseases lacking known or strong HLA associations, will require large cohorts enabling GWAS to be powerful enough to render meaningful results.

Central nervous system adverse events of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICI) may trigger immune-related adverse events which rarely affect the central nervous system (CNS-irAEs). Over the past few years, cumulative data have led to the characterization of well defined syndromes with distinct cancer and antibody associations as well as different outcomes. The most frequent CNS-irAE is encephalitis, which includes three main groups: meningoencephalitis, a nonfocal syndrome usually responsive to corticosteroids; limbic encephalitis, associated with high-risk paraneoplastic neurological syndromes (PNS) antibodies (e.g. anti-Hu, anti-Ma2) and neuroendocrine cancers, characterized by poor treatment response and outcomes; and cerebellar ataxia, with variable outcomes (worse when high-risk PNS antibodies are detected). Additionally, a diffuse encephalopathy without inflammatory findings, with poor response to corticosteroids and high mortality has been described. The spectrum of CNS-irAEs also includes meningitis, myelitis, and rarer presentations. A subset of CNS-irAEs (i.e. limbic encephalitis and/or rapidly progressive cerebellar ataxia) is undistinguishable from ICI-naïve PNS. The clinical and outcomes diversity of CNS-irAEs suggests different pathogenic mechanisms, which need to be understood to establish more effective and specific treatment modalities. It is crucial to identify biomarkers able to predict which patients will experience severe CNS-irAEs, to anticipate their diagnosis, and to predict long-term outcomes.

Paraneoplastic neurological syndromes: upgraded approaches to diagnosis

Paraneoplastic neurological syndromes (PNNS) are neurological disorders due to autoimmune attack on the nervous system, induced by a tumor remote from these structures. The existence of relatively stable associations between the neurological syndrome, the type of antineuronal antibodies (Ab) and the nature of tumor has been proven. At the same time, there are no pathognomonic combinations of this kind: the same antibodies can be detected in diff erent types of tumors and in diff erent syndromes. In addition, level of reliability of the diagnosis of PNNS is considered, taking into account the phenotype of the neurological disorder, the presence of certain antibodies in the blood serum, the verifi cation of oncopathology and the duration of the observation for the patient.

Neurological autoimmunity in melanoma patients: a comparison between those exposed and non-exposed to immune checkpoint inhibitors.

The clinical spectrum of melanoma-associated neurological autoimmunity, whether melanoma-associated paraneoplastic neurological syndromes (PNS) or induced by immune checkpoint inhibitors (ICI), is not well characterized. We aim to describe the clinical spectrum of melanoma-associated neurological autoimmunity. A systematic review of the literature combined with patients from French databases of paraneoplastic neurological syndromes was conducted. All melanoma patients with a possible immune-mediated neurologic syndrome were included and classified according to whether they had previously been exposed to ICI (ICI-neurotoxicity) or not (ICI-naïve) at first neurological symptoms. Seventy ICI-naïve (literature: n = 61) and 241 ICI-neurotoxicity patients (literature: n = 180) were identified. Neuromuscular manifestations predominated in both groups, but peripheral neuropathies were more frequent in ICI-neurotoxicity patients (39.4% vs 21.4%, p = 0.005) whereas myositis was more frequent in ICI-naïve patients (42.9% vs 18.7%, p < 0.001). ICI-naïve patients had also more frequent central nervous system (CNS) involvement (35.7% vs 23.7%, p = 0.045), classical paraneoplastic syndrome (25.7% vs 5.8%, p < 0.001), and more frequently positive for anti-neuron antibodies (24/32, 75.0% vs 38/90, 42.2%, p = 0.001). Although more ICI-neurotoxicity patients died during the acute phase (22/202, 10.9% vs 1/51, 2.0%, p = 0.047), mostly myositis patients (14/22, 63.6%), mortality during follow-up was higher in ICI-naïve patients (58.5% vs 29.8%, p < 0.001). There was no significant difference in the frequency of life independence (mRS ≤ 2) in the surviving patients in both groups (95.5% vs 91.0%, p = 0.437). Melanoma-associated PNS appear remarkably rare. The clinical similarities observed in neurological autoimmunity between ICI-treated and ICI-naïve patients, characterized predominantly by demyelinating polyradiculoneuropathy and myositis, suggest a potential prior immunization against melanoma antigens contributing to ICI-related neurotoxicity.

Seroprevalence of neuronal antibodies in diseases mimicking autoimmune encephalitis

Detection of neuronal antibodies for autoimmune encephalitis and paraneoplastic neurological syndromes relies on commercially available cell-based assays and lineblots. However, lineblots may reveal the presence of neuronal antibodies in patients with various non-autoimmune etiologies. Herein we describe patients with non-autoimmune etiologies (cohort B) and detectable neuronal antibodies and compare them to definite cases of autoimmune encephalitis (cohort A) for differences in clinical data. All patients positive for at least one neuronal antibody were retrospectively evaluated for autoimmune encephalitis and/or paraneoplastic neurological syndrome between 2016 and 2022. 39 cases in cohort B and 23 in cohort A were identified. In cohort B, most common diagnoses were neurodegenerative disorders in 9/39 (23.1%), brain tumors in 6/39 (15.4%) while most common detected antibodies were anti–titin (N10), anti-recoverin (N11), anti-Yo (N8) and all were detected in serum only. Differential aspects between cohort A and B were CSF pleocytosis (14/23 (60.8%) vs 11/35 (31.4%), p = 0.042, respectively), MRI features suggestive of encephalitis (6/23 (26.1%) vs 0 (0%), p = 0.002, respectively) and epilepsy restricted to temporal lobes (14/23 (60.9%) vs 2/30 (6.7%), p = 0.0003, respectively). A large proportion of lineblot results were non-specific when only serum was tested and were frequently found in non-autoimmune neurological conditions.

New-onset seizures misdiagnosed as psychogenic non-epileptic seizures: a case of paraneoplastic limbic encephalitis with primary testicular cancer

BackgroundBehavioral psychiatric symptoms can be the only warning signs of more serious conditions such as paraneoplastic limbic encephalitis. Differentiating between primary psychiatric disorders and paraneoplastic neurological syndromes is crucial as they require distinct treatment approaches. In this case report, we provide an overview of paraneoplastic encephalitis and introduce a unique case that showcases a misdiagnosis of psychogenic non-epileptic seizures (PNES) in a male as the primary symptom of paraneoplastic encephalitis due to pure seminoma. This case highlights the underlying pathophysiology of antibody-mediated paraneoplastic encephalitis and its significance.Case presentationA 31-year-old male with no known past medical history presented due to recurrent seizures. There was no prior history of epilepsy or exposure to seizure-triggering agents. Imaging and electroencephalogram findings during his initial hospitalizations pointed to a potential diagnosis of PNES. The patient continued to experience seizures following discharge, leading to repeat hospitalizations. During the fourth hospitalization, the patient received mood-stabilizing anti-seizure medications and benzodiazepines, but he deteriorated and required intubation. It was during this time that the patient was transferred to our facility. Magnetic resonance imaging of the brain revealed multifocal areas of hyperintensity and restricted diffusion with avid enhancement. Immunotherapy was initiated with improvement of non-epileptic spells and encephalopathy. Outpatient workup uncovered malignant pure seminoma with metastases to the retroperitoneum. The authors theorize that paraneoplastic neurological disorders stemming from testicular cancer led to the neurological symptoms seen in this case.ConclusionThis report highlights a rare occurrence of paraneoplastic limbic encephalitis associated with pure testicular seminoma, clinically manifested as PNES. The diagnostic challenge posed by variability of presenting symptoms in paraneoplastic encephalitis emphasizes the importance of accurate differentiation from conditions such as autoimmune encephalitis. Current diagnostic approaches for paraneoplastic and autoimmune etiologies involve detection of known antibodies, as well as brain imaging. Notable antibodies associated with psychogenic non-epileptic seizures symptoms include anti-GAD-65, anti-Ma2, KLH11-antibodies, anti-Hu, and NMDA receptor antibodies. Recognizing paraneoplastic limbic encephalitis symptoms is challenging and often leads to misdiagnosis or overlooking of malignancies highlighting the need for awareness, comprehensive evaluation and timely treatment. Through this comprehensive case analysis, we enhance the understanding of underlying mechanisms, associated symptoms, and treatment options.

Paraneoplastic neurological syndrome associated with onconeural autoantibodies: report of two cases

Paraneoplastic neurological syndromes (PNS) are rare and often severe neurological complications of malignancies, significantly impacting patient prognosis and quality of life. They are characterized by a diverse range of onconeural autoantibodies, with further discoveries likely due to ongoing research. Among these, high-risk autoantibodies primarily target intracellular neural cell antigens. We present cases of lung cancer patients who developed limbic encephalitis and seizures at diagnosis, suggestive of PNS. Each case demonstrated distinct autoantibody profiles. Recognition of these potentially life-altering neurological sequelae, as paraneoplastic manifestations of malignancies, is crucial for physicians. PNS may precede primary cancer diagnosis and substantially affect patient presentation and overall outcome. We provide in detail the diagnostic work-up and available treatment options for these complex cases.

Asymptomatic giant thymoma

Thymomas are tumours that originate from epithelial cells of the thymus gland. Most patients, estimated to be two thirds, remain asymptomatic and are often diagnosed following routine examinations. Symptomatic patients may present with neurological paraneoplastic syndromes as well as compression symptoms. Asymptomatic patients are usually found incidentally. In this article, we present a case of a giant thymoma that was discovered incidental/perioperatively in the light of the existing literature.

Paraneoplastic Neurological Syndromes as Initial Presentation of Tumors: An Eight-Year Single-Center Experience

Background: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue. Methods: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria. Results: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR (n = 4), anti-P/Q-VGCC (n = 3), anti-Hu (n = 3), anti-Yo (n = 1), anti-Ma (n = 1), anti-titin (n = 1), anti-IgLON5 (n = 1), and anti-GAD65 (n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively. Conclusions: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes.

PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome

The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. We show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits.

Mononeuritis multiplex following immune checkpoint inhibitors in malignant pleural mesothelioma

IntroductionMononeuritis multiplex is frequently related to vasculitic neuropathy and has been reported only sporadically as an adverse event of immune checkpoint inhibitors.MethodsCase series of three patients with mononeuritis multiplex—all with mesothelioma—identified in the databases of two French clinical networks (French Reference Center for Paraneoplastic Neurological Syndromes, Lyon; OncoNeuroTox, Paris; January 2015–October 2022) set up to collect and investigate n-irAEs on a nationwide level.ResultsThree patients (male; median age 86 years; range 72–88 years) had pleural mesothelioma and received 10, 4, and 6 cycles, respectively, of first-line nivolumab plus ipilimumab combined therapy. In patient 1, the neurological symptoms involved the median nerves, and in the other two patients, there was a more diffuse distribution; the symptoms were severe (common terminology criteria for adverse events, CTCAE grade 3) in all patients. Nerve conduction studies indicated mononeuritis multiplex in all patients. Peripheral nerve biopsy demonstrated necrotizing vasculitis in patients 1 and 3 and marked IgA deposition without inflammatory lesions in patient 2. Immune checkpoint inhibitors were permanently withdrawn, and corticosteroids were administered to all patients, leading to complete symptom regression (CTCAE grade 0, patient 2) or partial improvement (CTCAE grade 2, patients 1 and 3). During steroid tapering, patient 1 experienced symptom recurrence and spreading to other nerve territories (CTCAE grade 3); he improved 3 months after rituximab and cyclophosphamide administration.DiscussionWe report the occurrence of mononeuritis multiplex, a very rare adverse event of immune checkpoint inhibitors, in the three patients with mesothelioma. Clinicians must be aware of this severe, yet treatable adverse event.

Clinicopathologic Findings in Patients With Paraneoplastic Neuropathies and Antibodies Strongly Associated With Cancer.

Pathologic descriptions of peripheral nerve involvement in paraneoplastic neuropathies are sparse, mostly from autopsies focusing on CNS and dorsal root ganglia tissues. Here, we describe the clinicopathologic features of peripheral nerve biopsies in patients with paraneoplastic neurologic syndromes to expand the currently limited knowledge. Retrospective review of the Mayo Clinic electronic medical record from 1995 to 2022 for patients identified to have subacute onset neuropathy with paraneoplastic antibodies identified in our neuroimmunology laboratory having available nerve biopsies performed at the time of diagnosis. Patients with another cause of neuropathy not linked to their subacute onset were excluded. Nineteen patients met inclusion criteria: 4 with amphiphysin antibodies, 6 with antineuronal nuclear antibody (ANNA)-1 only, 3 with both ANNA-1 and collapsin response-mediator protein 5 (CRMP-5), 2 with ANNA-2, and 4 with CRMP-5 antibodies only. Fifteen biopsies had reduced the density of myelinated nerve fibers-4 with multifocality. Subperineurial edema was present in 17 biopsies. Prominent epineurial perivascular inflammation was present in 3 biopsies, all belonging to patients with a lumbosacral radiculoplexus neuropathy (LRPN) phenotype. Axonal loss, subperineurial edema, and an absence of prominent inflammation are the most common findings in nerve biopsies of patients with paraneoplastic antibodies strongly associated with cancer. The LRPN phenotype was the only subset with inflammatory collections. Paraneoplastic autoantibody testing should be considered in patients with subacute onset neuropathies, with or without interstitial inflammatory findings.

Updates in the Management of Paraneoplastic Syndrome.

Paraneoplastic neurological syndromes (PNS) are defined as remote neurologic immune-mediated effects triggered by underlying systemic tumors. While recognizing specific syndromes can aid early cancer detection, overutilization of paraneoplastic assays in the absence of a classic syndrome can precipitate overdiagnosis and overtreatment. PNS involve autoantibodies targeting intracellular or extracellular antigens, with variable immunotherapy responses based on antigen type. Diagnosing PNS is challenging, requiring exclusion of other differential diagnoses. New diagnostic criteria classify PNS into high-risk and intermediate-risk phenotypes based on clinical phenotype, neuronal antibodies, and cancer presence. Patients with cell surface antibodies respond better to immunotherapies compared to those with intracellular antigen targets. Understanding PNS syndromes, serological markers, and oncological features guides management, which facilitates initiation of immunosuppression for PNS alongside treatment of the underlying neoplasm, thereby improving neurologic and oncologic outcomes. Initial treatments often include intravenous methylprednisolone, plasma exchange, or intravenous immunoglobulins. Second-line immunosuppressants like rituximab or cyclophosphamide may be necessary if initial treatments fail. Specific therapies vary based on antibody target. Here, we summarize the current approach to the investigation, diagnosis, and treatment of patients with suspected PNS.

Management of Paraneoplastic Syndromes in the Era of Immune Checkpoint Inhibitors.

Our understanding of paraneoplastic neurologic syndromes (PNS) has blossomed over the past few decades. Clinicians have access to more robust diagnostic criteria and have a heightened index of suspicion for these disorders. Nonetheless, treatment, which typically includes immunosuppression, and response to treatment, varies. Due to persistent difficulty in making a definitive diagnosis, we favor empiric treatment when a possible diagnosis of PNS is suspected, and other alternative causes have substantially been excluded (e.g., infections, toxic-metabolic derangements, metastasis, or leptomeningeal disease). Treatment of the underlying cancer, if identified, is the first therapeutic step and can prevent disease worsening and in rare cases, can reverse neurologic symptoms. In addition to anti-cancer treatment, first line immunotherapies, which include corticosteroids, intravenous immunoglobulins (IVIG), or plasma exchange (PLEX) are typically used. If partial or no benefit is seen, second line immunotherapeutic agents such as rituximab are considered. Additionally, the severity of the initial presentation and possible risk for relapse influences the use of the latter agents. Symptomatic management is also an important component in our practice and will depend on the syndrome being treated. One of the more novel entities we are facing currently is the management of immune checkpoint (ICI)-induced PNS. In those cases, current American Society of Clinical Oncology (ASCO) guidelines are followed.

Paraneoplastic syndromes in patients with melanoma.

Paraneoplastic syndromes are a group of rare clinical conditions characterized by a diverse array of systemic manifestations that arise in association with malignant tumours, often due to the production of bioactive substances by the tumour or an autoimmune response to the tumour. Melanoma, a malignant skin neoplasm originating from melanocytes, has been associated with various paraneoplastic syndromes. This paper provides an overview of the key paraneoplastic syndromes observed in patients with melanoma. Paraneoplastic syndromes in melanoma can manifest with neurological, dermatological, endocrine, haematological, and rheumatological symptoms, among others. Melanoma-associated retinopathy was the most reported paraneoplastic syndrome; this entity is characterized by a spectrum of retinal abnormalities. Paraneoplastic neurological syndromes, such as paraneoplastic encephalitis and paraneoplastic cerebellar degeneration, are among the most frequently reported. The pathophysiology of paraneoplastic syndromes often involves the production of autoantibodies against neuronal or tumour antigens, immune-mediated reactions, or the release of cytokines and growth factors from the tumour. Management strategies for paraneoplastic syndromes associated with melanoma primarily focus on treating the underlying malignancy, which may lead to resolution or improvement of the paraneoplastic manifestations. Immune-modulating therapies, including corticosteroids, intravenous immunoglobulins, and plasmapheresis, may be considered in selected cases to ameliorate symptoms and suppress the autoimmune response. In conclusion, paraneoplastic syndromes in patients with melanoma are a complex and diverse group of clinical entities with a broad range of presentations. Further research is needed to enhance our understanding of the mechanisms and therapeutic options for paraneoplastic syndromes associated with melanoma.

Cancer-associated neuromyelitis optica spectrum disorder: a case report with literature review.

Neuromyelitis optica spectrum disorders (NMOSD) is one of autoimmune inflammatory diseases and is characterized by area postrema syndrome, brainstem syndrome, optic neuritis, and/or myelitis. Typical myelitis is longitudinally extended transverse myelitis (LETM) which extends over three vertebral bodies. Several previous case reports have suggested association between cancer and NMOSD. A 50-year-old woman had breast cancer and underwent mastectomy and, 10 months later, she had developed acutely progressive dysbasia. Spine MRI showed LETM in 13 vertebrae length and blood test revealed positive anti-aquaporin 4 (anti-AQP4) antibody based on enzyme-linked immunosorbent assay with index of over 40. She was treated by intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulin, followed by oral prednisolone. The condition had mostly recovered after the treatment. A small population of NMOSD has the aspect of paraneoplastic neurological syndrome. The age of onset in patients with cancer-associated NMOSD tends to be higher than that in individuals with NMOSD due to any causes of NMOSD.

Evaluation of potential prevalence of onconeural antibodies in women with breast cancer.

Aim: To analyse onconeural antibodies in the blood serum of breast cancer patients without neurological symptoms.. Materials and Methods: The study included 48 women with breast cancer. Paraneoplastic Neurologic Syndromes 12 Ag (IgG) Euroline by EUROIMMUN test was used to determine onconeural antibodies: anti-Hu, anti-Yo, anti-Ri, anti-CV2, anti-Ma/anti-Ta, anti-amphiphysin, anti-recoverin, anti-SOX1, anti-tytin, anti-zic4, anti-GAD65 and anti-Tr (DNER). Results: The conducted analysis revealed the presence of onconeural antibodies such as: anti-recoverin, anti-CV2, anti-Zic4, anti-SOX1, anti-MA2/Ta and antititin in blood serum of women with breast cancer. Conclusions: Further analysis may allow the assessment of the possible clinical usefulness of these determinations.

Paraneoplastic Neurological Syndrome as an Initial Presentation of Occult Breast Cancer: A Case Report

Paraneoplastic Neurological Syndrome as an Initial Presentation of Occult Breast Cancer: A Case Report

Paraneoplastic Neurologic Syndromes.

Progress is ongoing in understanding paraneoplastic neurologic disorders, with new syndromes and antibodies being described and more detailed evidence available to guide workup for diagnosis and treatment to improve outcomes. Many excellent reviews have summarized the molecular features of different antibodies, but this article emphasizes the clinical features of each syndrome that may help guide initial diagnosis and treatment, which often should occur before an antibody or cancer is found to confirm the diagnosis. Recent findings include updated diagnostic criteria with validated sensitivity and specificity, discovery of novel antibodies, and clinical findings that increase the likelihood of an underlying paraneoplastic disorder. Suggestive syndromes that have been recently identified include faciobrachial dystonic seizures and pilomotor auras in anti-leucine-rich glioma inactivated protein 1 encephalitis, extreme delta brush on EEG in N-methyl-d-aspartate (NMDA)-receptor encephalitis, déjà vu aura in anti-glutamic acid decarboxylase 65 (GAD65) encephalitis, and sleep disturbances in several disorders. In addition, there is confirmed utility of brain positron emission tomography (PET) and CSF markers, including carcinoembryonic antigen and oligoclonal bands, as well as improved tests for the presence of leptomeningeal cancer cells in CSF. Associations of cancer immunotherapies with paraneoplastic syndromes and herpes simplex virus encephalitis (and COVID-19) with NMDA-receptor encephalitis have been described. All neurologists should be aware of advances regarding paraneoplastic neurologic syndromes, as patients can present with a wide variety of neurologic symptoms and earlier diagnosis and treatment can improve outcomes.