anti-Hu Antibodies Research Articles

Evaluation of antineuronal antibodies and 8-OHdG in mothers of children with autism spectrum disorder: a case-control study

Objective The purpose of our study was to investigated the anti-Yo, anti-Hu, anti-Ri, anti-amphiphysin antibody levels and 8-OHdG in mothers of children with autism. Methods This study included 60 participants, 33 of whom were healthy mothers of 3–12-year-old children diagnosed with autism spectrum disorder (ASD) and the 27 others who constituted the control group, were healthy mothers with age-matched healthy children. Two groups were examined for plasma anti-Yo, anti-Hu, anti-amphiphysin and anti-Ri antibodies and, 8-OHdG levels. The participants were asked to accomplish a sociodemographic data form. The severity of ASD symptoms was evaluated according to the Childhood Autism Rating Scale (CARS). Results Anti-amphiphysin antibody levels and anti-Ri antibody positivity were significantly higher in the case group (p = 0.001; p = 0.027, respectively). The two groups did not significantly differ in terms of anti-Yo and anti-Hu antibody levels and in terms of 8-OHdG levels (p = 0.065; p = 0.099; p = 0.490, respectively). The two groups did not significantly differ in terms of sociodemographic data (p > 0.05). Conclusions According to the our study, maternal antineuronal antibodies, such as anti-amphiphysin and anti-Ri, may contribute to the risk of childhood autism. Studies with larger samples are needed. KEY POINTS Maternal factors associated with autism should be investigated in order to create early diagnosis and treatment opportunities for autism. Based on the importance of immunological and cerebellar pathologies in autism aetiology, we aimed to investigate antineuronal antibodies in mothers of children with autism. Maternal antineuronal antibodies, such as anti-amphiphysin and anti-Ri, may contribute to the risk of childhood autism. High anti-amphiphysin antibody levels in mothers of children with autism may also occur against the amphiphysin in the structure of the SrGAP3 gene, which is associated with autism.

Anti Zic4 Paraneoplastic Neurological Syndrome Presenting as Oscillopsia.

Anti Zic4 Paraneoplastic Neurological Syndrome Presenting as Oscillopsia.

Anti-GABA-B receptor encephalitis with small cell lung cancer presenting with septic shock during immunotherapy

Abstract Introduction: Most patients with anti-γ-aminobutyric acid-B (anti-GABA-B) receptor encephalitis present with cancer and have a poor response to immunotherapy. Moreover, septic shock, a subset of sepsis, is rarely reported in these patients during immunotherapy. Patient concerns: A 55-year-old man presented with epileptic seizure and cognitive impairment. He was previously healthy and had no family history of psychiatric disorders but had a history of smoking and emphysema. Diagnoses: Combined with the symptoms and antibody testing, anti-GABA-B encephalitis with anti-Hu antibody was diagnosed. During immunotherapy, he presented with septic shock. Further investigations and pathological examination confirmed the diagnosis of small cell lung cancer. Interventions: The patient was treated with five days of intravenous immunoglobulin (0.4/kg/d), ten days of methylprednisolone (1.0 g once a day and half the dose every three days), plus ten days of oxycarbazepine (0.3 g b.i.d.) and magnesium valproate (0.25 g b.i.d.). He received nine days of conventional treatment for septic shock in addition to meropenem (1 g intravenously every 8 hours) and etimicin (0.3 g intravenously per day). After that, he received one month of prednisone 30 mg with dose reduction 5 mg every two weeks, oxcarbazepine 0.3 g b.i.d. and valproic acid 0.25 g b.i.d. for antiepileptic treatment, olanzapine 5 mg qd + qn for antipsychotic symptoms. Outcomes: He was able to communicate with others normally and also had improved memory and clear thinking. Mini-Mental State Examination and Modified Rankin Scale were 23/30 and 1. At discharge, the titer of anti-GABA-B receptor antibody in serum (1:10) was significantly lower than the titer in serum on the day of admission (1: 100). Conclusion: Anti-GABA-B receptor encephalitis patients with cancer can respond well to immunotherapy. Personalized treatment should be considered to avoid complications like septic shock in anti-GABA-B receptor encephalitis with cancer during immunotherapy.

Paraneoplastic vs. non-paraneoplastic anti-Hu associated dysmotility: a case series and literature review.

This work aimed to report the demographic and clinical characteristics of two new cases with non-paraneoplastic anti-Hu-associated gut motility impairment, and perform a thorough revision covering anti-Hu-associated paraneoplastic (PGID) and non-paraneoplastic (nPGID) gastrointestinal dysmotility. Several case series have clearly established a relationship between certain type of cancers, the development of circulating anti-Hu antibodies, and the concomitant usually severe gastrointestinal dysmotility; in contrast, a few studies focused on anti-Hu-associated nPGID. We searched for studies regarding anti-Hu-associated gastrointestinal manifestations and extracted data concerning clinical characteristics of patients, including specific demographic, oncological, neurological, gastrointestinal, histological, and treatment response features. Forty-nine articles with a total of 59 cases of anti-Hu-associated gastrointestinal dysmotility were analyzed. The patients' age at symptom onset significantly differed between PGID and nPGID (median 61 vs 31years, p < 0.001). Most cancers (95%) in PGID were detected within 24months from the beginning of gastrointestinal symptoms. The impairment of gastrointestinal motility was generalized (i.e., involving the whole gut) in 59.3% of patients, with no significant differences between PGID vs nPGID group. nPGID patients showed a better response to immunomodulatory/immunosuppressive treatment and a longer life expectancy. Anti-Hu-associated gastrointestinal dysmotility covers a wide clinical spectrum. Patients with otherwise unexplained gastrointestinal dysmotility, especially when associated with other neurological symptoms, should be tested for anti-Hu antibodies regardless age of onset and disease duration. Compared to PGID, nPGID occurs in younger patients with a long duration of disease.

Neoplastic Myelopathies.

This article reviews the current classification system of primary spinal cord tumors and explores evolving diagnostic and therapeutic strategies for both primary tumors and metastatic tumors to various compartments of the spinal cord. The 2016 World Health Organization classification system allows for more precise prognostication of and therapy for spinal cord tumors and has identified new entities, such as the diffuse midline glioma, H3 K27M mutant. Whole-exome sequencing reveals that the genetic background of primary glial spinal cord neoplasms differs from that of their intracranial histologic counterparts in ways that can potentially influence therapy. Targeted and immune checkpoint therapies have improved survival for patients with melanoma and lung cancer and have simultaneously produced novel complications by enhancing radiation toxicity in some cases and by facilitating the emergence of novel autoimmune and paraneoplastic syndromes involving the spinal cord, such as neuromyelitis optica spectrum disorder and syndromes associated with anti-Hu and collapsin response mediator protein-5 (CRMP-5) antibodies. These conditions must be distinguished from tumor or infection. Epidural spinal cord compression treatment paradigms have changed with the advent of robotic surgery and advances in radiation therapy. Neoplastic myelopathies subsume a wide spectrum of pathologies. Neoplastic cord involvement may be primary or secondary and may be approached diagnostically by the particular spinal cord compartment localization. Primary spinal cord tumors account for only 2% to 4% of primary central nervous system tumors, ranging from low-grade glial neoplasms to malignant tumors. Metastatic malignancy to the epidural or leptomeningeal spaces is more common than primary cord tumors. Differential diagnoses arising in the course of evaluation for cord tumors include myelopathies related to radiation or chemotherapy and paraneoplastic syndromes, all of which are sources of significant morbidity. Knowledge of genetic syndromes and the biologic behavior of diverse histologies together with selective application of surgery, radiation, and targeted therapies can facilitate diagnosis, minimize surgical morbidity, and prolong quality of life.

A case of IVIg responsive paraneoplastic SOX1 peripheral neuropathy in a male with breast carcinoma

Background and aimsSOX1 antibodies are generally associated with small cell lung cancer and anti-Hu antibody overlap is common. This case demonstrates isolated anti-SOX1 antibodies with an uncommon tumor type, and relapse of a paraneoplastic syndrome with recurrence of tumor. MethodsWe describe a case of a 65-year-old male with a paraneoplastic peripheral neuropathy and anti-SOX1 antibody positivity in the context of a prior male breast Grade 2 ductal carcinoma, in remission at the time of the initial neurological presentation. ResultsTreatment response to intravenous immunoglobulin (IVIg) was demonstrated. After period of clinical stability on IVIg in the context of remission of breast carcinoma, the patient experienced a relapse of his neuropathy. This was associated with tumor recurrence and again responded to tumor excision, radiotherapy and IVIg. InterpretationMale breast carcinoma has not previously been associated with anti-SOX1 antibody positive paraneoplastic neuropathy.

Phase II trial of natalizumab for the treatment of anti-Hu associated paraneoplastic neurological syndromes.

BackgroundParaneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS) have a very poor prognosis: more than half of the patients become bedridden and median survival is less than 12 months. Several lines of evidence suggest a pathogenic T cell-mediated immune response. Therefore, we conducted a prospective open-label phase II trial with natalizumab.MethodsTwenty Hu-PNS patients with progressive disease were treated with a maximum of three monthly natalizumab cycles (300 mg). The primary outcome measure was functional improvement, this was defined as at least one point decrease in modified Rankin Scale (mRS) score at the last treatment visit. In addition, treatment response was assessed wherein a mRS score ≤3 after treatment was defined as treatment responsive.ResultsThe median age at onset was 67.8 years (SD 8.4) with a female predominance (n = 17, 85%). The median time from symptom onset to Hu-PNS diagnosis was 5 months (IQR 2–11). Most patients had subacute sensory neuronopathy (n = 15, 75%), with a median mRS of 4 at baseline. Thirteen patients had a tumor, all small cell lung cancer. After natalizumab treatment, two patients (10%) showed functional improvement. Of the remaining patients, 60% had a stable functional outcome, while 30% showed further deterioration. Treatment response was classified as positive in nine patients (45%).ConclusionsNatalizumab may ameliorate the disease course in Hu-PNS, but no superior effects above other reported immunosuppressive and immunomodulatory were observed. More effective treatment modalities are highly needed.Trial registration https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000675-13/NL

Anti-Hu-related epilepsy diagnosed after surgical management.

Autoimmune epilepsy (AE) refers to epilepsy mediated by autoantibodies or immune cells, and a large proportion of drug-resistant epilepsy cases are classified as AE. AE lacks standardized management guidelines. At present, little research has been conducted on the effectiveness of surgical treatment of AE. This paper reports a patient whose surgical treatment was ineffective before AE was diagnosed and who improved after immunotherapy. A literature review was conducted to examine the progress of surgical treatment of epilepsy, the relationship of temporal lobe epilepsy to neuronal antibodies, surgical and prognostic factors, research progress on the anti-Hu antibody, and treatment of autoimmune encephalitis to provide a clinical reference.

Delayed Diagnosis of Anti-Hu Antibodies in a Young Patient With Cerebellar Atrophy

Delayed Diagnosis of Anti-Hu Antibodies in a Young Patient With Cerebellar Atrophy

Clinical Characteristics of Anti-GABA-B Receptor Encephalitis.

Objective: Anti-GABA-B (gamma aminobutyric acid-B) receptor encephalitis is an autoimmune disease mediated by GABA-B-related antibodies. To fully understand the disease, we collected clinical data from patients with GABA-B receptor encephalitis and conducted an analysis to draw conclusions.Methods: All patients with GABA-B receptor encephalitis from the Neurology Department of Beijing Tiantan Hospital, affiliated with Capital Medical University, from August 2015 to September 2019 were accepted as study subjects. The clinical data of the patients were analyzed retrospectively and included the general demographic characteristics, clinical manifestations, and auxiliary examinations, including laboratory results, electroencephalograms (EEGs), brain magnetic resonance imaging (MRI), and positron emission tomography (PET-CT) results, as well as treatments.Results: From August 2015 to September 2019, 14 cases of anti-GABA-B receptor encephalitis were diagnosed. Among these patients, middle-aged and elderly men were the main demographic, with an average age of 52 years; moreover, the onset of the disease was relatively sudden, and the time from onset to diagnosis was ~1 month. The main clinical symptoms were frequent epileptic seizures, cognitive dysfunction, and mental behavioral disorders. In seven (50%) patients, the leukocyte in cerebrospinal fluid (CSF) were increased. Five (36%) patients had elevated cerebrospinal fluid protein. In most patients, the oligoclonal bands (83%) of CSF were positive, and 24 h IgG levels (92%) were increased. Anti-Hu or anti-Yo antibodies were positive in two (14%) patients. Tumor markers in 10 (71%) patients indicated that neuron-specific enolase, gastrin-releasing precursor, non-small cell lung cancer-related antigen, or carcinoembryonic antigen levels were increased. EEG results often indicated slow waves, sharp waves, or spike waves in temporal areas. Brain MRI always showed high T2 signals in the medial temporal lobe, hippocampus, and amygdala and swelling in the medial temporal lobe and hippocampus. PET-CT scans almost showed abnormal metabolism in the hippocampus and temporal lobe. Three (21%) patients who underwent systemic PET-CT showed hypermetabolism in pulmonary parenchymal nodules and enlargement of mediastinal lymph nodes. All patients underwent high-dose hormone therapy or immunoglobulin immunotherapy. After treatment, the symptoms of epilepsy, cognitive disorders, and mental behavioral disorders improved to varying degrees. However, one patient died of lung cancer.Conclusion: Anti-GABA-B receptor encephalitis mainly occurred in middle-aged and elderly men, and the disease onset was relatively sudden. Before disease onset, some patients experienced fever and non-specific respiratory symptoms, which mainly manifested as frequent epileptic seizures, cognitive dysfunction, and abnormal mental behavior. MRI and PET-CT revealed abnormal signals and local metabolism, respectively, in the temporal lobe. Moreover, the disease has a close relationship with lung cancer, which requires long-term follow-up observation.

Long lasting trigeminal neuropathy, limbic encephalitis and abdominal ganglionitis without primary cancer: An atypical case of Hu-antibody syndrome

ObjectivesAnti-Hu antibodies (Hu-Abs) are the most frequent onconeural antibodies associated with paraneoplastic neurologic syndromes (PNS). PNS include a variety of neurological syndromes, affecting less than 1/10,000 patients with cancer. In the majority of cases, PNS will manifest before the malignancy is diagnosed. We found a case in which PNS was diagnosed without finding a primary malignancy after extensive work-up and even post-mortem autopsy. Patient and methodsWe present a case report of a 58-year-old man. This article includes extensive clinical work-up, full-body autopsy and brain autopsy with classical histochemical and myelin stainings and immunohistochemistry was performed. ResultsThe patient developed a progressive trigeminal neuropathy over a period of 5 years, in combination with cerebellar degeneration, asymmetrical brainstem and limbic encephalitis. Serum showed repeatedly high anti-Hu antibodies. Comprehensive cancer screening could not demonstrate any primary malignancy. Therapy with corticosteroids, plasma exchange, cyclophosphamide and rituximab showed no beneficial effect. He died from the complications of enteric ganglionitis 5 years after onset of the first symptoms. A postmortem autopsy could not detect a primary malignancy either. Brain morphology is described in detail. ConclusionParaneoplastic anti-Hu encephalitis cases associated with SCLC or other primary neoplasms are well known. An adult with a progressive multifocal neurological syndrome in the presence of positive anti-Hu antibodies, but without any primary neoplasm after a follow-up over 5 years is unusual.

Chemiluminescent Immunoassay versus Enzyme Linked Immunosorbent Assays for IgA Anti-Tissue Transglutaminase Antibodies Assessment in Celiac Disease Children

Recent describing of atypical, silent and latent form of celiac disease (CD) increased the preocupation for screening methods.To perform a comparative study of immunoglobulin A (IgA) anti tissue-transglutaminase (tTG) antibodies (Ab) assessment using chemiluminescence versus Enzyme Linked Immunosorbent Assay (ELISA).The study included two lots.The first lot consisted in 35 biopsy confirmed CD children aged between two and 18 years.The control lot included 40 children with normal duodenal morphology on intestinal biopsy that underwent upper digestive endoscopy for different gastrointestinal symptoms.Serum samples were provided from all subjects for IgA measurement, IgA anti tTG and EMA assessment. Immulite 2500 Anti tTG IgA (Siemens Co, LA, USA) and ImmuLisa anti-hu tTG antibody IgA ELISA (Immco Diagnostics Inc, NY, USA) kits were used for tTG-Ab assessment. All children underwent HLA typing for DQ2/DQ8. The sensitivity for IgA tTG assessment was greater for chemiluminescence (93,3%) versus ELISA (86,6%), p[0,05, while specificity, positive and negative predictive value didn�t register significant differences. Statistical comparison of the two tested methods revealed a better sensitivity for chemiluminescence. Diagnosis algorithm optimisation may be obtained by associating IgA anti tTG-Ab assessment using chemiluminescence followed by EMA confirmation by indirect immunofluorescence for CD screening.

Worsening of anti-Hu paraneoplastic neurological syndrome related to anti-PD-1 treatment: Case report and review of literature

We present an illustrative case of a 62-year-old woman with small cell lung cancer who developed progressive worsening of pre-existing anti-Hu antibody associated sensory neuronopathy after treatment with programmed cell death-1 (PD-1) inhibitor, nivolumab. We review the literature and identify 6 reported cases to understand the clinical outcomes of patients with anti-Hu paraneoplastic neurologic syndrome (PNS) treated with anti-PD-1 treatment.The PNS clinical spectrum comprised of encephalitis, a combination of sensory neuronopathy and anti-NMDAR encephalitis, isolated sensory neuronopathy, and encephalomyelitis. Immune checkpoint inhibitor have the potential to worsen pre-existing anti-Hu PNS and may promote the development of anti-Hu PNS.

Paraneoplastic cerebellar degeneration and limbic/brainstem encephalopathy associated with small cell lung cancer with serum positivity for anti-Hu and multiple anti-ganglioside (GM2, GQ1b, GaLNAc-GD1a, GT1a) antibodies: A case report

Paraneoplastic cerebellar degeneration and limbic/brainstem encephalopathy associated with small cell lung cancer with serum positivity for anti-Hu and multiple anti-ganglioside (GM2, GQ1b, GaLNAc-GD1a, GT1a) antibodies: A case report

NCMP-04. OPSOCLONUS-MYOCLONUS SYNDROME ASSOCIATED WITH CONTACTIN-ASSOCIATED PROTEIN-LIKE 2 AUTOANTIBODY IN THE SETTING OF NON-SMALL CELL LUNG CARCINOMA

Abstract INTRODUCTION Opsoclonus–myoclonus syndrome (OMS) is a rare neurological disorder characterized by spontaneous multidirectional saccadic eye movements, myoclonus, and ataxia. It is suspected to be an autoimmune mediated process precipitated by a paraneoplastic or infectious trigger. Among the pediatric population, OMS is often associated with neuroblastoma and anti-Hu antibody. Paraneoplastic syndromes in adults manifesting as OMS are most commonly described in breast, gynecological and small cell lung cancer with associated anti-neuronal antibodies (ANNA-2; anti-Ri). We describe the first case of OMS associated with lung adenocarcinoma and Contactin-associated protein-like 2 (Caspr2) antibody. CASE REPORT: A 46-year-old-woman with history of limited small cell lung cancer (SCLC) status-post chemotherapy with cisplatin and etoposide and prophylactic whole brain radiation, presented with new onset gait instability, nausea, vomiting, vertigo, and opsoclonus. Two months prior to her presentation, a chest computed topography (CT) revealed no evidence of recurrent disease. Brain MRI revealed T2 hyperintensities in the white matter and central pons presumably related to chronic small vessel ischemic changes, unchanged from prior imaging. CSF studies revealed normal cell count, glucose, and protein. Gram stain, culture and meningoencephalitis panel were negative. Her paraneoplastic panel revealed a positive Caspr2 antibody. A repeat CT chest for cancer surveillance revealed a new lung mass. Immunotherapy treatment included plasmapheresis, corticosteroids, and intravenous immunoglobulin therapy. She underwent a biopsy of the new pulmonary lesion and the pathology was consistent with non-small cell lung carcinoma. Her symptoms slowly improved after treatment. Unfortunately, her disease progressed on repeat PET scan despite surgical resection of the lung mass. She ultimately elected for hospice. CONCLUSION We report a novel antibody, Caspr2, occurring in association with paraneoplastic OMS. While SCLC is the most common neoplasm associated with OMS among adults, non-small cell lung carcinoma should be considered. Prompt immunotherapy and neoplasm treatment may result in improvement.

KNOCK KNOCK, HU'S THERE? POSITIVE ANTI-HU ANTIBODY IN EXTRAPULMONARY SMALL CELL CARCINOMA OF LYMPH NODE

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: To date, small cell carcinoma (SCC) has been primarily recognized as a pulmonary malignancy and research has been skewed towards this area. Extrapulmonary SCC is rare, accounting for 2.5% of SCC, out of which lymph node SCC are far and few between. CASE PRESENTATION: A 59-year-old gentleman was initially admitted to neurology for sensory neuropathy and weight loss. He was referred to the respiratory medicine team after imaging revealed subcarinal and left hilar lymphadenopathy. He is a chronic smoker and there was a concern for malignancy. Initial endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) using 22 gauge needle showed lymphoid yield. Serum paraneoplastic panel (Hu, Yo, Ri, CV2, Amphiphysin, PNMA2/Ta, recoverin, SOX1, titin, zic4, GAD65, Tr(DNER)) was performed as part of the diagnostic work up. Anti-Hu antibody was 1:101 (strongly positive); reference titer 1:<10. Fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) scan revealed FDG avid subcarinal (SUVmax:11.1) and left hilar (SUVmax:13.2) nodes. In view of the anti-Hu antibody results and FDG-PET-CT findings, a repeat EBUS-TBNA using 19 gauge needle was performed and histology confirmed SCC. DISCUSSION: Paraneoplastic syndrome was first described by M. Auché in 1890 and is known to affect up to 8% of patients with cancer; most notably small cell lung cancer. Anti-Hu is an onconeural antibody first discovered by F. Grouse in 1985. Its moniker is type I anti-neuronal nuclear antibody (ANNA-1) and has been a signpost for paraneoplastic sensory neuropathy or encephalomyelitis. (Positive anti-Hu antibody titers have a reported specificity of 99% and sensitivity of 82%). It is recognized as a distinct clinical disease, “anti-Hu syndrome”, with characteristic clinical picture and imaging findings. A Dutch study in 2002 found that 85% of patients with positive anti-Hu antibody also have a tumor. Of note, anti-Hu antibodies can also be positive in antecedent inflammatory diseases like systemic lupus erythematosus or Sjogren’s syndrome which can confound the diagnosis. Thus, positive anti-Hu antibody levels should prompt further evaluation and follow up even in absence of concurrent malignancy. Early diagnosis of lymph node SCC has prognostic implications when compared to pulmonary and extrapulmonary SCC, thus making the distinction necessary. CONCLUSIONS: This study highlights the diagnostic implications of an abnormal paraneoplastic panel, emphasizing the role of anti-Hu antibody in its specificity for SCC. The presence of FDG avid thoracic lymph nodes with elevated anti-Hu antibody titers warrants a repeat biopsy. It is imperative for clinicians to identify occult neoplasms in the setting of paraneoplastic syndromes. Reference #1: Koike H, Sobue G. Paraneoplastic neuropathy. Handb Clin Neurol. 2013;115:713-26. Reference #2: Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology. 1985 Apr;35(4):538–43. Sehgal IS, Kaur H, Dhooria S, et al. Extrapulmonary small cell carcinoma of lymph node: Pooled analysis of all reported cases. World J Clin Oncol. 2016;7(3):308-20. Graus F, Keime-Guibert F, Reñe R, Benyahia B, Ribalta T, Ascaso C, Escaramis G, Delattre JY. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain. 2001;124(6):1138-1148. Senties-Madrid H, Vega-Boada F. Paraneoplastic syndromes associated with anti-Hu antibodies. Isr Med Assoc J. 2001 Feb;3(2):94-103. Reference #3: Benyahia B, Amoura Z, Rousseau A, Le Clanche C, Carpentier A, Piette JC, Delattre JY. Paraneoplastic antineuronal antibodies in patients with systemic autoimmune diseases. J Neurooncol. 2003 May;62(3):349-51. Sillevis Smitt P, Grefkens J, de Leeuw B, van den Bent M, van Putten W, Hooijkaas H, Vecht C. Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. J Neurol. 2002 Jun;249(6):745-53. Kim KO, Lee HY, Chun SH, et al. Clinical overview of extrapulmonary small cell carcinoma. J Korean Med Sci. 2006;21(5):833-7. Kannoth S. Paraneoplastic neurologic syndrome: A practical approach. Ann Indian Acad Neurol. 2012;15(1):6-12. DISCLOSURES: No relevant relationships by John Abisheganaden, source=Web Response No relevant relationships by Caroline Choong, source=Web Response No relevant relationships by Sharlene Ho, source=Web Response No relevant relationships by Chuen Peng Lee, source=Web Response No relevant relationships by Ziqin Ng, source=Web Response No relevant relationships by Ser Hon Puah, source=Web Response No relevant relationships by HUIJIA WANG, source=Web Response No relevant relationships by Kim Hoong Yap, source=Web Response

447 Clinical Characteristics of Secondary Achalasia Associated With a Malignancy: A 20-Year Review From a Cancer Hospital

INTRODUCTION: Achalasia is an uncommon neurodegenerative disorder of esophageal motor function with an annual incidence of 1.6:100, 000. Most cases are idiopathic. Achalasia secondary to neoplasia is extremely rare, with an incidence of 1: 750,000. AIM: To evaluate the incidence and characteristics of achalasia in patients with a malignancy at our institution between 1999-2019. METHODS: Electronic medical records were retrospectively reviewed from January 1999 to May 2019 to identify patients with a diagnosis of achalasia and a malignancy. Patiets with direct tumor invasion of the distal esophagus were excluded. We identified 28 patients who had a malignancy and a diagnosis of achalasia. RESULTS: The median age at diagnosis of achalasia was 58 years (19-85). There were 14 (50%) male and 14 (50%) female patients. The most common associated cancer was a hematologic malignancy (N = 9, 32%: lymphoma N = 4, leukemia N = 4, myeloma N = 1), followed by breast cancer, (N = 7, 25%). Other cancers included lung, (N = 3, 11%), carcinoid tumor, (N = 2, 7%), and one each of thymoma, sarcoma, esophagus, stomach, thyroid, larynx, and prostate. The median interval between the diagnosis of cancer and achalasia was 78 months (range 2- 364). In 21 patients, the cancer preceded the diagnosis of achalasia. All patients underwent endoscopy to rule out psuedoachalasia. Where high resolution manometry was done (N = 10/28, 36%), type 2 achalasia was seen in 8/10 patients and type 1 achalasia in 2/10 patients. In seven patients, achalasia was diagnosed before the cancer. The median time interval between diagnosis of achalasia and diagnosis of a primary malignancy in these patients was 72 months (range 12-354 months). Anti-Hu antibodies were present in 2/8 patients who were checked for it, suggestive of a paraneoplastic process. Eight patients underwent endoscopic dilatations, 12 had Botulinum Toxin A injection into the lower esophageal sphincter and 6 had both procedures. 7 patients underwent a Heller myotomy. One is awaiting surgery. Response to treatment was favorable when assessed for improvement in dysphagia and eating ability for 6 months after diagnosis in 24/ 28 patients (85%). CONCLUSION: Malignancy associated secondary achalasia is very rare. In our population heme associated malignancy and breast cancer were the 2 cancers most commonly associated with achalasia. Patients with cancer who develop dysphagia should be screened for achalasia, as response to treatment is favorable.

2638 Intestinal Pseudo-Obstruction Associated With Seropositive Myasthenia Gravis, Thymoma, and Positive CV-2 Antibodies

INTRODUCTION: Intestinal pseudo-obstruction (IPO) is a rare condition characterized by signs and symptoms of bowel obstruction without an identifiable mechanical cause. Antibody-mediated paraneoplastic syndromes and autoimmune diseases have been reported as two potential etiologies. We report a unique case of IPO presenting with thymoma, myasthenia gravis (MG), and positive CV-2 antibodies. CASE DESCRIPTION/METHODS: A 43 year old previously healthy female presented to the ED with abdominal pain, nausea and vomiting. This was her third visit to the ED in the past week for similar symptoms. On admission, laboratory studies were normal. A CT of the abdomen revealed marked gastric and small bowel distention, fecal impaction, and a mediastinal soft tissue density (Figure 1). She was initially managed medically with restriction of oral intake, intravenous fluids, and a nasogastric tube. Since she did not improve after several days, she was taken to the operating room for a diagnostic laparoscopy, which did not show evidence of mechanical obstruction. A CT chest with contrast done to investigate the mediastinal soft tissue density revealed an anterior mediastinal mass.A chest MRI had changes suggestive of a thymoma. This was subsequently confirmed by biopsy. Given the suspicion for a paraneoplastic process, multiple serologic markers were ordered. Acetylcholine receptor (AChR) antibodies and CV-2 antibodies were positive (Table 1). She was diagnosed with paraneoplastic intestinal pseudo-obstruction. The patient was treated with IV methylprednisolone and pyridostigmine with marked improvement in symptoms. DISCUSSION: The association of IPO as a paraneoplastic syndrome of thymoma and myasthenia gravis has been reported in only a few cases. The pathophysiology involves AChR antibodies targeting the neuronal nicotinic acetylcholine receptors present on autonomic ganglia. Our patient had positive AChR antibodies. She had no other symptoms of MG, indicating isolated autonomic dysfunction. IPO has also been associated with malignancies such as small cell lung cancer, which may be mediated by a variety of autoantibodies. Anti-Hu antibody has been most commonly implicated but was negative in this case. Anti-CV2 antibody was positive, which was reported in only one previously published case. In summary, patients with thymomas or MG should have testing for paraneoplastic antibodies; they tend to respond to treatment with immunosuppression and acetylcholinesterase inhibitors.

Paraneoplastic Chorea Associated with Anti-Hu Antibody and Small Cell Lung Carcinoma

Paraneoplastic Chorea Associated with Anti-Hu Antibody and Small Cell Lung Carcinoma

A RARE CASE OF PARANEOPLASTIC NEUROLOGICAL SYNDROME ASSOCIATED WITH ADENOCARCINOMA OF THE LUNG

SESSION TITLE: Lung Cancer 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Paraneoplastic neurologic syndromes (PNS) are rare but clinically important complications of malignancy. These syndromes occur in approximately 0.01% of cancer patients, although more frequently in those with lung cancer, specifically small cell carcinoma. The neurologic syndromes are extensive and may present as encephalomyelitis, cerebellar cortical degeneration, peripheral neuropathy, neuopsoclonus-myoclonus, and retinopathy[1]. CASE PRESENTATION: A 76-year old woman with a recent diagnosis of well differentiated adenocarcinoma, mixed acinar and micropapillary, KRAS p.Gly12Val tumor marker positive, type lung cancer, presented with shortness of breath and altered mental status. According to family she was becoming progressively confused for the prior six weeks, displaying “hyper-somnolence” and speaking “with her eyes closed”. Neurological exam was significant for lethargy, confusion, and incoherent speech. Admission labs showed elevated WBC count 15.7; lactate 0.8. Chest X-ray showed patchy opacities bilaterally, and mild pulmonary congestion. CT scan of her brain was negative for acute pathology. Brain MRI was negative for metastatic disease. Empiric treatment for pneumonia was initiated based on x-ray findings. During her hospital stay, patient remained minimally communicative and unable to follow commands. VEEG was unremarkable. CSF analysis showed 5 WBC, no RBC, with 48% lymphocytes, and 48% monocytes. CSF cytology was negative for malignant cells. Elevated protein was measured at 81 mg/dL. CSF PCR was negative for VZV, HSV, and West Nile Virus. Paraneoplastic encephalitis was suspected due to lack of alternative etiologies for the patient’s symptoms. Treatment with IVIG and high-dose solumedrol was initiated. Ultimately, the paraneoplastic antibody panel resulted with type I anti-neuronal nuclear antibody (ANNA-1) titer of 1:512, Anti-Hu AB titer of 1:32, and anti-recoverin titer of 1:1. DISCUSSION: Paraneoplastic neurologic syndromes are rare clinical syndromes, resulting from the remote effect of a tumor on the nervous system, associated 95% of the time with small cell lung cancer [2]. Our patient’s manifestation of PNS with lung adenocarcinoma is extremely rare. Due to the very low incidence of non-small cell lung cancer associated with PNS, her diagnosis of lung adenocarcinoma was not believed to be contributory to her change in mental status. However, discovery of well characterized onconeural proteins such anti-Hu antibodies in the CSF, made a diagnosis of a PNS highly likely. CONCLUSIONS: Our case demonstrates that lung adenocarcinoma can play a role in the development of paraneoplastic neurologic syndrome and should be considered in the setting of a patient with altered mental status without other cause. Reference #1: Miyamoto, K., et al., A case of paraneoplastic syndrome accompanied by two types of cancer. J Neurol Neurosurg Psychiatry, 2002. 72(3): p. 408-9. Reference #2: Kanaji, N., et al., Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol, 2014. 5(3): p. 197-223. DISCLOSURES: No relevant relationships by Scott Ferrara, source=Web Response No relevant relationships by eman rashed, source=Web Response No relevant relationships by Peter Rattner, source=Web Response No relevant relationships by Michael Silverberg, source=Web Response