Onconeural Antibodies Research Articles

Diaphragmatic Palsy Due to a Paraneoplastic Autoimmune Syndrome Revealed by Checkpoint Inhibitors

Background and Clinical Significance: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but may underlie diverse and potentially life-threatening immune-related adverse events (irAEs). They may cause various conditions leading to respiratory failure, including myasthenic syndromes and myositis. However, diaphragmatic paralysis (DP) has rarely been reported. To describe patients with diaphragmatic paralysis in a pharmacovigilance registry, we searched the prospective REISAMIC registry at the Gustave Roussy Cancer Center (Villejuif, France) for cases of diaphragmatic palsy (DP) occurring from September 2014 to December 2021. Case Presentation: We identified three patients, in whom DP was confirmed by diaphragmatic ultrasonography, pulmonary function tests, and/or diaphragmatic electroneuromyogram. Diaphragmatic palsy was life-threatening in all patients, as it caused respiratory failure requiring mechanical ventilation. In all cases, a pre-existing subclinical paraneoplastic syndrome was detected. Onconeural antibodies (anti-titin and anti-VGCC) were detected in these patients before and after the initiation of ICI therapy, suggesting a mixed paraneoplastic syndrome with features overlapping those of myasthenic syndrome (myasthenia gravis in one patient and Lambert–Eaton syndrome in another) and myositis. Conclusions: Diaphragmatic palsy is a severe irAE potentially resulting from different mechanisms, including myositis and neuromuscular junction involvement (myasthenia gravis, Lambert–Eaton). Antineuronal antibodies associated with such conditions were already present in our patients prior to immunotherapy initiation, suggesting ICIs could trigger flare-ups of pre-existing silent paraneoplastic autoimmune conditions.

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.

AntiSox-1 Limbic Encephalitis: When A Movement Disorder Evolves Oddly And Delirium Just Does Not Feel Right

Abstract Background A 74year old male presented to a Movement Disorder service with a 15year history of a parkinsonian syndrome with asymmetric, akinetic rigidity and prominent axial features. Motor features were stable for almost 13years. Neuropsychiatric features rapidly emerged over several months including: multimodality perceptual hallucinosis, upside down and tilt illusion, akinetopsia, intractable insomnia, emotional incontinence and Othello syndrome. A marked motor, mysaesthenic pattern, deterioration occurred in conjunction with hypoactive delirium, dysphagia, pyrexias, raised inflammatory markers and weight loss, necessitating hospitalisation. Computed tomography (CT) of chest, abdomen and pelvis did not demonstrate infective or neoplastic aetiology. CT brain did not demonstrate cerebellar atrophy. Positron emission tomography did not demonstrate a vasculitis. Drg regimen alterations brought about minor improvements, but he remained very severely frail and discharged to hospice care. Unexpectedly, cognition then markedly improved and neuropsychiatric symptoms resolved over months, and he returned home, albeit now severely frail. There was persistence of hemiparkinsonian symptoms, contralateral to which, dystonia had emerged with new bilateral upper limb ataxia and nystagmus. No mysaesthenic features persisted. Methods Cerebrospinal fluid analysis and electroencephalography were not undertaken. MRI brain was not undertaken. Results Anti Sox-1 positive. Anti Zic-4 and Recoverin were equivocal. Neuronal antibodies were negative. Conclusion Limbic encephalitis as a result of AntiSox-1 onconeural antibodies is most commonly associated with small cell cancer of the lung (prevalence of 36.5% of cases). Lambert-Eaton Mysaesthenic Syndrome is a more common presentation than paraneoplastic cerebellar degeneration. Hindsight raises the possibility of non-convulsive status epilepticus as an explanation for abrupt hypoactive delirium presentation on the background of deteriorating neuropsychiatric features. Oncological or immunotherapeutic intervention was not considered appropriate by respiratory or neurology teams respectively; nor did the patient wish for these to be pursued. Case reports indicate that an underlying neoplasm is not always identified. Non-paraneoplastic autoimmune encephalitis can have a better prognosis.

Link Between Autoimmunity and Epilepsy: Neuronal Autoantibodies

Introduction: Autoimmune epilepsy remains under-recognized, and its true incidence remains uncertain. Objective: This study aimed to determine the prevalence of neuronal autoantibodies in patients with epilepsy of unknown etiology. Materials and Methods: An observational, longitudinal, prospective, and analytical study was conducted to assess the presence of autoantibodies associated with autoimmune encephalitis, glutamic acid decarboxylase-65 (GAD65), and onconeural antibodies in the serum and cerebrospinal fluid of consecutive patients with epilepsy of unknown etiology. Results: Sixty patients and 80 controls (30 healthy individuals, 30 with multiple sclerosis, 10 with systemic lupus erythematosus, and 10 with Sjögren's syndrome) were included to detect neuronal antibodies. Among epilepsy patients, 28 out of 60 (47%) tested positive for antibodies against N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (CASPR2), leucine-rich glioma-inactivated 1 (LGI1), and glutamic acid decarboxylase (GAD), which was significantly higher (p < 0.001) than in the combined control cohort. No onconeural antibodies were detected in epilepsy patients except for 6 cases of epilepsy, 1 case of multiple sclerosis, and 3 cases of lupus with positive GAD by immunofluorescence assay and immunoblotting. There was no significant difference in antibody incidence between male and female epilepsy patients. The incidence of positive autoantibodies was significantly higher in patients with focal epilepsy compared to those with generalized epilepsy (p < 0.01). Conclusions: The findings indicate the presence of antibodies against NMDAR, VGKC-associated proteins (LGI1, CASPR2), and intracellular antigens (GAD65) in the serum and cerebrospinal fluid of patients with epilepsy, suggesting an autoimmune etiology. These results underscore the need for further research to elucidate the role of autoantibodies in epilepsy pathogenesis and to explore immunotherapeutic interventions.

Anti-Hu antibody associated paraneoplastic neurological syndrome in a child with ganglioneuroblastoma: A rare case report and literature review.

Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens. Diagnosis and treatment of Hu-PNS. This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination. The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy. The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence. Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.

Antibody-positive autoimmune encephalitis and paraneoplastic neurological syndrome: A Swedish case series.

This study aimed to explore the clinical characteristics and temporal disease course of patients with autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS) in Sweden. Thirty-seven antibody-positive AE and PNS cases were identified in the Healthcare region Mid Sweden between 2015 and 2019. Clinical data were collected through a retrospective review of electronic health records. Patients were divided into three subgroups based on antibody type: neuronal surface antibodies (NSAbs), onconeural antibodies, and anti-GAD65 antibodies. Nineteen patients had NSAbs, 11 onconeural antibodies, and seven anti-GAD65 antibodies. Anti-LGI1 and anti-NMDAR were the most frequently detected NSAbs, with anti-NMDAR cases having an older-than-expected age distribution (median age 40, range 17-72). Only 11 of 32 (30%) of patients had findings suggesting encephalitis on initial MRI, but 28 of 31 (90%) had pathological findings on initial cerebrospinal fluid analysis. All patients but one had abnormal EEG findings. Median time to immunotherapy was comparable among the three subgroups, whereas patients with anti-LGI1, anti-CASPR2, and anti-IgLON5 had an eightfold longer time to immunotherapy than anti-NMDAR and anti-GABA-B (p=.0016). There was a seasonal variation in onset for patients with non-tumor-related NSAbs and anti-GAD65 antibodies, with most patients (72%) falling ill in spring or summer. Swedish patients with AE and PNS had similar clinical characteristics as previously described cohorts from other geographical regions except for anti-NMDAR encephalitis, with older onset than expected. The onset of non-tumor-related AE occurred predominantly in the warm seasons, and AE with a more insidious onset was associated with delayed treatment initiation.

Neurological Paraneoplastic Syndromes in most Common Cancers in Poland

INTRODUCTION: Paraneoplastic Neurological Syndromes (PNS) represent a heterogeneous group of diseases associated with the presence of neoplasm. The appearance of PNS can precede cancer diagnosis. The estimated frequency amongst cancer patients is about 1%. Malignant tumors represent a serious health problem and are the second leading cause of death in Poland. The aim of this study is to collect information about PNS focusing on cancers mostly diagnosed in Polish adults. REVIEW METHODS: The analysis was conducted based on information regarding PNS gathered from PubMed and Google Scholar within the context of selected cancers. THE STATE OF KNOWLEDGE: PNS develop from an autoimmune reaction in which onconeural antibodies are produced. The recent classification divides PNS to high risk, indicating a likely paraneoplastic origin and intermediate risk, if this association is less evident. Diagnosis is difficult and usually relies on exclusion methods. The symptoms described are non-specific and the diagnostic process may require the involvement of various specialists. The main approaches include cancer treatment, especially tumor removal and immunotherapy, which in certain may prove to be effective. SUMMARY: Although PNS is relatively rare, its detectability has recently increased. Many syndromes are especially associated with lung cancer (mainly small cell carcinoma). Breast and prostate cancers have also shown associations with certain syndromes. They can present with nonspecific symptoms related to different organ systems. Awareness and understanding of this phenomenon can be helpful amongst many specialists.

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.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Isolated Myelopathy in Occult Breast Carcinoma with Negative Paraneoplastic Antibodies: A Case Report of a Rare Condition

Isolated paraneoplastic myelopathy (IPM) is a rare neurological manifestation of systemic cancer and represents an intermediate-risk phenotype of disease according to the diagnostic criteria for Paraneoplastic Neurologic Syndromes (PNS). Here, we present the case of a 47-year-old woman who developed subacute cervical myelopathy and was then diagnosed with breast cancer. Through this lens, we provide a discussion of current literature on IPM. Over four months, our patient developed progressive tetraparesis, hypoesthesia with C3 level, and urinary retention. The first MRI was negative, but a four-month-control MRI showed a T2-hyperintense spinal lesion (C2–C7 and T2–T4). Cerebrospinal fluid (CSF) analysis was normal. Infective and autoimmune screening, including onconeural, anti-MOG, and aquaporin-4 antibodies, was unremarkable. The total-body CT scan was negative, but total-body PET-CT scan evidenced an enlarged axillary lymph node, with the detection of breast cancer cells at fine-needle aspiration. Despite negative mammography, a breast MRI confirmed a mammary nodule, which was removed, and a ductal infiltrating breast carcinoma diagnosis was made. Her neurological condition partially improved after steroid therapy. Our final diagnosis was probable IPM, according to PNS criteria. This rare condition affects most frequently middle-aged women and is often associated with breast and lung cancer, even if two-thirds of patients’ cancer diagnosis is subsequent to the onset of neurological deficits. Clinical presentation is often subtle, and CSF analysis, neuroimaging, and onconeural autoantibodies could be negative or non-specific. However, if the suspect of paraneoplastic disease is strong, cancer should be searched thoroughly since early diagnosis and treatment are associated with a better outcome.

Paraneoplastic Neurological Syndromes: A Single-Center Retrospective Study in Argentina (P9-13.005)

<h3>Objective:</h3> To describe the clinical features, diagnostic approach and treatments in patients diagnosed with paraneoplastic neurological syndromes (PNS). <h3>Background:</h3> PNS are due to an abnormal response of the immune system against the nervous system. In many cases, their identification allows early diagnosis of hidden tumors. Argentina ranks fifth in cancer frequency in Latin America, however data about PNS is lacking. <h3>Design/Methods:</h3> We performed a retrospective study including 42 adult patients with PNS treated between 2010 and 2021 in a referral center of Argentina. <h3>Results:</h3> Mean age at symptom onset was 59.6 years (range 20 to 82). The onset of symptoms was acute in 11 cases (26%), subacute in 25 (59.5%) and chronic in 6 (14.3%). The median time between the onset of symptoms and suspicion of PNS was 16.25 months (SD 16.7). The most frequent symptoms were paresthesias (23.8%) and limb weakness (19%). Classic PNS was found in 6 patients (14.3%) and non-classic PNS were identified in 26 cases (61.9%). An onconeural antibody was identified in 36 patients (85.7%). Primary tumors were found in 14 patients (33.3%). Lung cancer was the most frequent tumor (28.57%). The latency between suspected PNS and tumor diagnosis was 1.89 years (range 0.31 to 4.79). Twenty eight patients (66.7%) received immunological therapy. Nine patients received onco-specific treatment (chemotherapy or radiotherapy) and two patients were treated with tumor resections. Symptoms improved in 21.4% of patients, 57.1% remained stable and 21.4% worsened. Four patients died (9.5%). <h3>Conclusions:</h3> The clinical manifestations were under a non-classical syndrome, had a subacute course and were associated with lung cancer in the majority of cases. The latency between PNS onset and tumor identification was also variable despite the use of appropriate imaging techniques. The absence of antibodies does not rule out an occult tumor, which should not delay immunomodulatory treatment in the suspected cases. <b>Disclosure:</b> Mr. Caiza Zambrano has nothing to disclose. Fabio Gonzalez has nothing to disclose. Dr. Galarza Menoscal has nothing to disclose. Dr. Benetti has nothing to disclose. The institution of Marcela Uribe Roca has received research support from Roche. Dr. Bonardo has nothing to disclose. Manuel Fernandez Pardal has nothing to disclose. Dr. Leon Cejas has nothing to disclose. Dr. Reisin has nothing to disclose.

Clinical Characteristics, Treatment and Outcomes of Patients with Paraneoplastic Neuropathies. A Retrospective Single-Center Study in Argentina. (P14-8.011)

<h3>Objective:</h3> To describe the clinical features, treatments and outcomes in patients diagnosed with Paraneoplastic Neuropathies (PN). <h3>Background:</h3> Peripheral neuropathy represents one of the most common presentations of paraneoplastic neurological disorders. Being a rare entity, clinical suspicion is extremely important. <h3>Design/Methods:</h3> Medical records of PN patients between 2010 and 2021 were reviewed. <h3>Results:</h3> Nineteen patients were included, 68% (13/19) were women, and the mean age at symptom onset was 56.26 years (SD 11.9). In most cases (73.7%) the onset of symptoms was subacute (2 weeks to 3 months). Paresthesias (9/19) and pain (5/19) were the most frequent symptoms. Sensorimotor neuropathy was the most frequent phenotype (8/19). An onconeural antibody was identified in 14 patients (73.7%). Primary tumors were found in 9 patients (47.3%). Lung cancer was the most frequent tumor (33.3%). The latency between PN and the diagnosis of tumors was 27.9 months (SD 18.18). Twelve patients (63.2%) were treated with immunotherapy. In two cases a clinically significant improvement was evidenced (10.5%), 68.4% of patients (13/19) remained stable, 4 patients worsened their symptoms (21%) and three patients died (15%). <h3>Conclusions:</h3> Sensory complaints and a subacute presentation were the most frequent in the majority of cases. The most common phenotype is sensorimotor neuropathy, so this entity should be suspected in patients with these characteristics after proper exclusion of other more frequent causes. <b>Disclosure:</b> Mr. Caiza Zambrano has nothing to disclose. Fabio Gonzalez has nothing to disclose. Dr. Galarza Menoscal has nothing to disclose. Dr. Benetti has nothing to disclose. The institution of Marcela Uribe Roca has received research support from Roche. Dr. Bonardo has nothing to disclose. Manuel Fernandez Pardal has nothing to disclose. Dr. Leon Cejas has nothing to disclose. Dr. Reisin has nothing to disclose.

Paraneoplastic pure motor neuropathy in a 48-year-old male with recently diagnosed DLBCL (P3-8.014)

<h3>Objective:</h3> To report a case of paraneoplastic pure motor neuropathy associated with DLBCL <h3>Background:</h3> Paraneoplastic lower motor neuron disease is a rare clinical entity. Patient’s present with a slow progressive painless asymmetric weakness in the limbs and without upper motor neuron features. Neoplasms that are associated with this syndrome include: lymphoma, ovarian, breast, renal, and lung cancers. Usually, no paraneoplastic antibodies are identified. We report a case of a 48-year-old male with newly diagnosed DLBCL, a non-Hodgkin lymphoma (NHL), who presented with subacute painless asymmetric upper extremity weakness without clear sensory loss prior to initiation of any chemo or radiation therapy. Imaging of the bilateral plexus and cervical spine did not reveal enhancement or infiltration and cerebrospinal fluid studies were unrevealing. Electromyography provided evidence of a primarily demyelinating greater than axonal purely motor polyradiculoneuropathy limited to the arms. Neurological improvement was seen with intravenous immunoglobulin and treatment of malignancy. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> Upon literature review, a case of paraneoplastic purely motor neuron syndrome associated with an NHL such as DLBCL has not been described before. There have been reports of paraneoplastic neurological syndromes associated with NHL none of which were purely motor neuron disease. <i>Flanagan et al</i> reported a similar case of paraneoplastic motor neuron disease associated with a type of Hodgkin’s Lymphoma. Similarly, to their findings, we observed neurological improvement with concurrent IVIG and treatment of the underlying malignancy. This case highlights the continued role for documentation of peripheral neuropathies secondary paraneoplastic etiologies with goals to further characterize novel onconeural antibodies. <b>Disclosure:</b> Dr. Kolli has nothing to disclose. Dr. Ata has nothing to disclose. Dr. Hurst has nothing to disclose.

Paraneoplastic neurological syndromes of the central nervous system: a single institution 7-year case series.

Paraneoplastic neurological syndromes (PNSs) are nonmetastatic complications of malignancy, defined by the presence of onconeural antibodies (ONAs). ONAs may be found in 60% of patients with central nervous system (CNS) involvement, and they are directed against intraneuronal antigens or channels, receptors or associated proteins located at the synaptic or extra-synaptic neuronal cell membrane. Given its rare incidence, there are few epidemiological case series on CNS-PNS. We aim to discuss the variability of CNS-PNSs etiology, clinical features, management and outcome, highlighting the importance of early recognition and appropriate treatment, leading to significant reduction of mortality and morbidity. We retrospectively reviewed our 7-years single-center experience, and specifically discussed the underlying etiology, parenchymal CNS involvement, and the acute treatment response. Only cases fulfilling PNS Euronetwork criteria for definitive PNS were included. A total of 26 probable PNSs cases involving CNS were identified. We reported medical records of eleven (42.3%) illustrative cases, meeting the criteria of definite PNS and presenting variable clinical spectrum and different radiological appearances. Our series has a relative paucity of the most common syndromes and larger portion of clinical diagnosis with ONAs. Well-characterized ONAs had been detected in CSF of six patients. Our case series supports the utmost importance of early recognition of CNS-PNSs. Screening for occult malignancies should not be limited to patients with classical CNS syndrome. Empiric immunomodulatory therapy may be considered before the diagnostic evaluation is completed, in order to prevent unfavorable outcome. Late presentations should not discourage initiation of treatment.

Síndromes paraneoplásicos del sistema nervioso

Paraneoplastic syndromes are clinical manifestations of a tumor that are not related to the direct invasion of the primary tumor or its metastases. Therefore, cerebrovascular, infectious, nutritional metabolic, or toxic complications associated with neoplasms and also treatment-derived complications (surgery, radiotherapy, chemotherapy, or biologic therapies) are excluded. They comprise a heterogeneous group of syndromes that can affect any part of the central nervous system (CNS) or peripheral nervous system (PNS), neuromuscular junction, and muscle and occasionally affect multiple areas in the same patient. They are uncommon, with a general incidence in patients with cancer of less than 1%. Incidence varies according to the type of tumor, with small cell lung cancer (SCLC) being the most commonly involved, with an incidence of 3%. The presence of onconeural antibodies supports the diagnosis of a compatible clinical syndrome. However, they are only present in approximately 50% of cases and therefore its absence does not rule out a diagnosis. As previously stated, paraneoplastic syndrome can occur in patients with an already-diagnosed neoplasm, but it is not apparent in many cases. Therefore, the search for the occult neoplasm is necessary when the syndrome is present. If possible, treatment must be started as soon as possible, given that paraneoplastic syndromes progress in weeks and can cause irreversible damage or even the patient's death.

An Etiological Investigation of Paraneoplastic Cerebellar Degeneration in Ovarian Cancer Patients: A Systematic Review.

Paraneoplastic syndromes (PNS) are uncommon, distinct clinical complications of a primary tumor. Paraneoplastic cerebellar degeneration (PCD) is a PNS that is described asan autoimmune response targeting Purkinje cells in the cerebellum. Ovarian cancer (OC) is one of the most prevalent causes of cancer-related deaths in women. Anti-Yo is the most common onconeural antibody produced in the PCD immune response and is most typically found in ovarian and breast cancer patients. While the current literature highlights the predisposing genetic factors, diagnostic workflows, and treatment options, the pathophysiology of PCD, among other considerations, remains largely unestablished. This review aimed to systematically observe procedural solutions to facilitate an early diagnosis and improve the prognosis of patients with OC-associated PCD.To that end, we examined literature published from 01/01/2015-11/10/2022 indexed in PubMed by using the keywords "paraneoplastic, cerebellar degeneration" combined with "ovarian cancer." Inclusion criteria were met if PCD and OC diagnoses were made and if studies provided adequate patient information. After screening and assessing records for eligibility using the inclusion and exclusion criteria, 18 articles involving102 patients were included. The typical patient observed in this sample was diagnosed with International Federation of Gynecology and Obstetrics (FIGO) Stage III, high-grade serous carcinoma. The diagnostic workup typically included a clinical evaluation for dysarthria (50%), ataxia (60%), and gait abnormalities (50%), along with multiple imaging modalities and serological findings (90%). Genetic screening for human leukocyte antigen (HLA) haplotype susceptibility for PCD and immune tolerance modulators regulation may also be recommended prior to starting treatment. Findings support the use of corticosteroids (35%) and intravenous immunoglobulin (IVIg) (40%) as viable treatment options for managing PCD in conjunction with systemic therapy for the primary malignancy. A diagnosis of PCD should be considered if a patient has had a malignancy in the past five years with the presence of explicit cerebellar symptoms. This clinical diagnosis can be further supplemented by serologic and radiologic findings. Recognizing PCD symptoms and scheduling genetic and proteomic testing may help with early diagnosis and better prognosis.

SOX-1 antibodies in a patient with Crohn’s disease: a case report

BackgroundThe anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohn’s Disease (CD) with ensuing neurological symptoms.Case presentationA Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohn’s Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure; a few days later she died, due to ensuing septic shock and Multiple Organ Failure.ConclusionsOur experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing.

A rare case of paraneoplastic cerebellar ataxia secondary to Gynaecological malignancy

We report on a rare case of paraneoplastic syndrome (PS) that was discovered on completion of diagnostic work up to be a fallopian tube carcinoma. A 65year old female, presented with 1 month history of imbalance, gait instability, incoordination of right upper limb, vertigo and vomiting. Cerebrovascular accident and drug intoxication was excluded. Indicative of further diagnosis of paraneoplastic syndrome was presence of adnexal mass in pelvis with identification of onconeural anti-Yo antibodies, detection of which leads to the confirmation of diagnosis. The anti- Yo (Anti-Purkinje cell) antibodies that specifically damage Purkinje cells of the cerebellum. Anti- Yo related paraneoplastic cerebellar degeneration is most commonly found in women with gynecological and breast cancers.

Whole-body computed tomography as first-line imaging procedure to exclude cancer in patients with neurological suspicion of paraneoplastic syndromes: shall clinical practice adhere to recommendations?

IntroductionTo assess the efficacy of whole-body computed tomography (WB-CT) as imaging procedure to exclude cancer in patients with neurological symptoms and signs at clinical onset. MethodsA retrospective observational study was designed to identify consecutive WB-CT requested by the Neurology Unit with a suspicion of an underlying tumor potentially linked to a paraneoplastic neurological syndrome (PNS) between January 2019 and February 2022. The following data were collected: diagnosis at admission and at discharge, the presence of onconeural antibodies, the scans dose length product (DLP), the estimated effective dose (ED), the total estimated time requested; the PNS-Care-Score was retrospectively calculated only in subjects with available antibodies. ResultsThe total number of patients included was 158. In 13/158 (positive group) a malignant or locally aggressive neoplasm was found while in 145/158 no malignant lesions were found on the WB-CT. Among the positive group, in 7/13 onconeural antibodies were diagnosed, resulting negative in all cases and the most frequent tumor was lung cancer (30.8%). PNS-Care-Score was of 6–7 in 2/7 (probable PNS) and in no case the PNS-Care-Score was ≥8 (definite PNS). The mean DLP for all the scans was 2798 ± 952 mGy cm (average estimated ED of 42 ± 14 mSv). The total estimated time requested for all scans was 11,060 min. ConclusionIf a PNS is suspected, we encourage the prescription of unenhanced chest CT and/or abdomen/testis/female pelvis ultrasound and/or mammography based on clinical picture. The WB-CT using a single portal phase would be appropriate as a second-line technique while magnetic resonance imaging might be indicated for the exclusion of nervous system diseases. Implications for practiceOur suggestion results in saving in terms of radiation exposure, financial resources and time.

P11.49.B MOG antibody positive paraneoplastic brain stem encephalitis associated with cervical cancer: a rare case report

Abstract Background Paraneoplastic neurological syndromes are a rare complication of malignant tumors. Myelin oligodendrocyte glycoprotein (MOG) is an important marker on the surface of oligodendrocytes and is associated with many demyelinating diseases. There are only few reports of MOG antibody positive paraneoplastic syndromes. Here we present the first case of MOG-antibody positive brain stem encephalitis associated with cervical cancer. Material and Methods: Case report. Results A 58-year-old female presented with headache, fever and acute cerebellar signs. 13 months earlier she was diagnosed with cervical cancer and ovarian metastases. Adnexectomy was performed and she received adjuvant chemo- and radiotherapy. At admission cerebrospinal fluid (CSF) analysis showed pleocytosis (90 cells/µl) with a mixed cell profile but no malignant cells could be detected. Protein and lactate were highly elevated. The patient was treated with aciclovir and ceftriaxone until serology and liquor PCR showed no evidence of systemic or cerebral infections. Initial magnetic resonance imaging (MRI) of the brain was unremarkable. The patient was symptomatically treated. CSF two weeks later showed 53 cells/µl, protein and lactate almost normal. Contrary to the mild improvement of CSF parameters, cerebellar symptoms worsened, and the patient complained about impaired vision and diplopia. MRI revealed gadolinium enhancing lesions of the left mesencephalon and the right N. opticus. Visual evoked potentials confirmed a demyelinating lesion of the right N. opticus. We then assumed paraneoplastic brain stem encephalitis and the patient received high dose methylprednisolone and immunoglobulins. Ultimately, lab results came back positive for anti-MOG-antibodies, while paraneoplastic panels were negative. At follow-up three weeks later, CSF analysis showed normal cell count and brain MRI was unremarkable again. MOG-antibodies however remained positive. Since then, the patient has received monthly immunoglobulins leading to a stable neurological status. Unfortunately, the cancer itself is progressive with a local relapse and metastases of liver, lung and bones. Conclusion Our patient had an acute presentation of a rare brain stem encephalitis. However, infectious workup as well as all well-known onconeural antibodies showed negative results. This shows that pleocytosis in patients with a history of malignant disease is highly suggestive for paraneoplastic neurological syndromes even if common antibodies show negative results. Clinicians should be aware of other autoimmune antibodies like anti-MOG-antibodies and should extend workup if necessary. Vice versa it is worth considering tumor workup in patients with neurological symptoms and anti-MOG-positivity. Furthermore, the appearance of paraneoplastic neurological syndromes is always suspicious for progressive disease.