Paraneoplastic Etiology Research Articles

6712 Intractable Hypoglycemia: A Clue to Tumor Diagnosis

Abstract Disclosure: N. Kharkongor Chengappa: None. E.I. Krug: None. Background: Non-Islet Cell Tumor Hypoglycemia (NICTH) known as Doege-Potter syndrome, is a rare paraneoplastic syndrome of hypo-insulinemic hypoglycemia caused by excessive production of partially processed IGF-II from a solitary fibrous tumor (SFT).We present a case of a patient admitted with intractable hypoglycemia leading to the diagnosis and treatment of a large pelvic SFT. Clinical Case: A 59-year-old male with type 2 Diabetes Mellitus on metformin mono therapy, was admitted after he collapsed at work and was found to have blood glucose (BG) of 22 mg/dl. He was previously in his usual state of health except for an increase in his shoe size over the past year. Physical examination revealed coarse thick skin, large coarse bullous nose, enlarged fingers and a non-tender, firm abdomen with no obvious organomegaly. Laboratory results including CBC, CMP and thyroid function were normal. ACTH stimulation test revealed normal adrenal function. Hypoglycemic drug screen and insulin antibodies were negative. During a hypoglycemic event (BG of 45mg/dl) he had C-peptide level < 0.1ng/ml, beta-hydroxybutyrate levels of <0.05 and insulin level <0.4uIU/ml, indicating non-insulin mediated hypoglycemia. IGF-I and IGF-II levels were ordered. Due to a concern for paraneoplastic etiology of hypoglycemia. CT scan revealed a 20 cm solid mass, filling most of the pelvis and extending into the lower abdomen. Further investigations revealed normal PSA, CEA, CA19-9 and undetectable hCG and AFP levels. MRI confirmed a presence of 23 cm pelvic mass with few areas of central necrosis, extending into the lower abdomen. CT-guided biopsy revealed spindle cell neoplasm consistent with SFT. The patient underwent pelvic mass resection. Postoperatively, hypoglycemia resolved with BG readings of 138mg/dl to 178mg/dl. Surgical pathology results confirmed malignant SFT with positive STAT 6 and CD34 markers. IGF-II level obtained prior to surgery was markedly elevated at 2029 ng/ml (38-267 ng/mL). Conclusion: NICTH was described in 1930 by KW Doege and RP Potter. Less than 5% of patients with SFTs develop NICTH. Diagnosis requires manifestation of Whipple's triad, low insulin, pro-insulin and C-peptide levels, elevated IGF-II levels, or an IGF-I/IGF-II ratio>2, and the identification of the tumor. Positive immunohistochemical stain of the tumor for STAT6 confirms the diagnosis. Management involves resection of the tumor when feasible or debulking. For higher-risk tumors, radiation therapy may be considered. In inoperable cases, glucocorticoids, recombinant hGH and glucagon are recommended for palliation of hypoglycemia. Octreotide and Diazoxide are ineffective in NICTH.

Cancer Frequency in MuSK Myasthenia Gravis and Histological Evidence of Paraneoplastic Etiology.

Cancer frequency in muscle-specific kinase myasthenia gravis (MuSK-MG) has not yet been explored and the mechanisms leading to the formation of MuSK IgG remain elusive. We aimed to explore cancer frequency in MuSK-MG patients and to assess MuSK expression in cancer cells from 2 tumors occurred in this cohort. Immunohistochemistry on tumor specimens revealed the expression of MuSK in the cancer cells from primary mediastinal B cell lymphoma and endometrial carcinoma. Twenty-one males and 73 females were enrolled. Fifteen cancers occurred in 13 of 94 patients (13.8%). Patients with cancer were significantly older at time of MuSK-MG onset. ANN NEUROL 2024;96:1020-1025.

Autoimmune-associated seizure disorders.

With the discovery of an expanding number of neural autoantibodies, autoimmune etiologies of seizures have been increasingly recognized. Clinical phenotypes have been identified in association with specific underlying antibodies, allowing an earlier diagnosis. These phenotypes include faciobrachial dystonic seizures with LGI1 encephalitis, neuropsychiatric presentations associated with movement disorders and seizures in NMDA-receptor encephalitis, and chronic temporal lobe epilepsy in GAD65 neurologic autoimmunity. Prompt recognition of these disorders is important, as some of them are highly responsive to immunotherapy. The response to immunotherapy is highest in patients with encephalitis secondary to antibodies targeting cell surface synaptic antigens. However, the response is less effective in conditions involving antibodies binding intracellular antigens or in Rasmussen syndrome, which are predominantly mediated by cytotoxic T-cell processes that are associated with irreversible cellular destruction. Autoimmune encephalitides also may have a paraneoplastic etiology, further emphasizing the importance of recognizing these disorders. Finally, autoimmune processes and responses to novel immunotherapies have been reported in new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES), warranting their inclusion in any current review of autoimmune-associated seizure disorders.

Evolution of Autoimmune Retinopathy in Stiff Person Syndrome: A Case Report.

To report a case of autoimmune retinopathy (AIR) as the presenting feature of Stiff Person Syndrome (SPS) and assess its evolution. A 35-year-old man presented with progressive, chronic, vision loss. On initial examination, visual acuity measured 20/20 OD and 20/50 OS. Humphrey Visual Field testing (HVF) demonstrated decreased foveal threshold OU. Mild subfoveal ellipsoid zone loss was noted on Optical Coherence Tomography (OCT). Five years later the patient presented with painful lower extremity muscle spasms and stiffness and complained of increasing vision loss with difficulty distinguishing colors. OCT showed marked progression of ellipsoid zone loss. Scotoma were demonstrated on HVF and electroretinography demonstrated reduced responses consistent with bilateral severe maculopathy. Serum testing showed autoantibodies to the glutamic acid decarboxylase 65-kilodalton isoform (GAD65) at a high titer and a diagnosis of AIR in the setting of SPS was made. A systemic workup for malignancy was negative. The patient was treated with IVIG and transitioned to rituximab with improvement in systemic symptoms. and Importance: Unlike previous cases of AIR in the setting of SPS, vision symptoms and OCT changes presented years before the onset of muscle spasms. Etiologies such as SPS should be on the differential of unexplained retinopathy, even in the absence of systemic symptoms, especially when paraneoplastic etiologies are ruled out.

An interesting case of ocular flutter, myoclonus, and ataxia in the postpartum period

Abstract Opsoclonus–myoclonus–ataxia syndrome is a well-established neurologic syndrome with paraneoplastic, postinfectious, immune-mediated, or idiopathic etiology. Ocular flutter and opsoclonus are in the same continuum with a common pathophysiology; however, their phenomenology is distinct. While eye movements in ocular flutter are strictly confined to the horizontal plane, those in opsoclonus are multidirectional. There are few case reports describing the combination of ocular flutter, myoclonus, and ataxia. In this case report, we describe a woman with the abovementioned features in the postpartum period with dramatic response to immunotherapy.

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.

Characteristics of Opsoclonus-Myoclonus Syndrome in Patients of the Largest Pediatric Hospital in Latin America

BackgroundOpsoclonus-myoclonus syndrome (OMS) is a rare neuroinflammatory disorder characterized by ataxia, opsoclonus, and myoclonus. Clinical diagnosis of OMS has been challenging; therefore, we sought to determine the clinical and treatment profiles of patients with OMS at the largest pediatric hospital in Latin America. MethodsWe analyzed the data of patients diagnosed with OMS between 2010 and 2020 at Pequeno Principe Hospital (Brazil) to determine the corresponding clinical profile more accurately. ResultsOf the approximately 50,000 visitors to our pediatric neurology department from 2010 to 2020, 10 patients with OMS were observed. Five nontumor cases included three parainfectious and two idiopathic cases. The median time from symptom onset to diagnosis was 34 days. All patients with diagnostic OMS criteria in the idiopathic, nontumor group underwent whole-exome sequencing, with potentially pathogenic mutations identified in two cases. Nine patients were treated with methylprednisolone pulse, followed by oral steroids; eight received one or more intravenous immunoglobulin treatments; and six received azathioprine and cyclophosphamide. Complete symptomatic recovery was observed in only one patient. ConclusionsOMS diagnosis remains challenging. Diagnostic suspicion is necessary to improve the management of these patients and allow early immunosuppressive treatment. Paraneoplastic etiology is the most prevalent. In idiopathic patients who do not respond to immunosuppressive treatment, tests, such as whole-exome sequencing, may reveal a differential diagnosis. Genetic alterations that increase the risk of tumors may be an important clue to the pathophysiology of OMS.

NCMP-21. AQP4-MOG DOUBLE-POSITIVE PARANEOPLASTIC NEUROLOGICAL SYNDROME IN A PATIENT WITH TRIPLE NEGATIVE BREAST CANCER

Abstract We report a rare case of paraneoplastic neurological syndrome (PNS) with dual seropositivity of anti-aquaporin-4 (AQP-4) and myelin oligodendrocyte glycoprotein (MOG) antibodies in a 40 year-old lady with metastatic triple negative breast cancer with involvement of mediastinal, right axillary, and supraclavicular lymph nodes. She received multiple lines of anti-neoplastic treatment including immunotherapy with pembrolizumab as well as chemotherapy with taxol, carboplatin, gemcitabine, capecitabine, cytoxan, sacituzumab and nevalbine. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis extending from T11-12 that symptomatically improved with high dose intravenous methylprednisolone. One month later she developed left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid (CSF) analysis during both episodes revealed normal glucose, protein, elevated white blood cell count. Cytology was negative for malignancy. CSF was positive for neuromyelitis optica (NMO) IgG antibody APQ-4 and autoimmune myelopathy panel was positive for MOG antibody. Patient had significant clinical and radiographic improvement after completion of plasmapheresis and intravenous immunoglobulin. There was resolution of pleocytosis on repeat CSF testing. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every six months and daily low dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case demonstrates that these antibodies can occur concurrently and cause clinical features like both neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or CSF profile negative for leptomeningeal carcinomatosis.

P16 The wood for the trees

P16 The wood for the trees

Anti-aquaporin-4 immunoglobulin G/anti-myelin oligodendrocyte glycoprotein immunoglobulin G double-positive paraneoplastic neurological syndrome in a patient with triple-negative breast cancer.

We report a rare case of paraneoplastic neurological syndrome with dual seropositivity of anti-aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in a 40 year-old woman with metastatic triple-negative breast cancer. She received multiple lines of anti-neoplastic treatment, including immunotherapy with pembrolizumab, as well as cytotoxic chemotherapy. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis followed by left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid analysis during both episodes showed normal glucose and protein, and elevated white blood cell count. Cytology was negative for malignancy. Cerebrospinal fluid was positive for neuromyelitis optica immunoglobulin G antibody anti-aquaporin-4, and autoimmune myelopathy panel was positive for myelin oligodendrocyte glycoprotein antibody. The patient had significant clinical and radiographic improvement after completion of five cycles of plasmapheresis followed by intravenous immunoglobulin. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every 6 months and daily low-dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case shows that these antibodies can occur concurrently and cause clinical features, such as both neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease, in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or cerebrospinal fluid profile negative for leptomeningeal carcinomatosis.

Predictors of cancer in patients with acute pulmonary embolism

BackgroundAcute pulmonary embolism (PE) can occur as a manifestation of an underlying cancer and be of paraneoplastic aetiology. A previously unknown cancer is sometimes diagnosed after the acute PE diagnosis. The identification of a group of patients with elevated probability of having an occult cancer underlying PE was never performed. We aimed to determine predictors of occult cancer in acute PE. Our hypothesis was that the D-dimer levels would be a predictor of cancer. Patients and methodsWe retrospectively analysed a cohort of patients hospitalized with acute PE. Exclusion criteria: <18 years, venous embolism only of veins other than pulmonary territory or when the embolism was considered chronic, and no image confirmation of acute PE. Patients were grouped according to the timing of cancer diagnosis: 1) known concomitant active cancer, 2) cancer diagnosed during acute PE admission or in the following 2 years and, 3) no known cancer during the 2-year follow-up since PE diagnosis. Predictors of concomitant cancer were determined using a logistic regression analysis. Multivariate models were built. ResultsWe studied 562 patients; median age was 72 years and 219 (39.0 %) were men. In 223 (39.7 %) of the patients the PE was of central arteries and 61.4 % presented with bilateral PE. PE was considered unprovoked at time of discharge in 47.7 %. Median (interquartile range) D-dimer level was 7.98 (3.30–14.99) μg/mL. A total of 126 (22.4 %) patients were in group 1, 47 in group 2 (cancer diagnosed after the diagnosis of acute PE and up to 2 years) and 389 patients were in group 3. Elevated D-dimer levels were independently associated with already known cancer. D-dimer were independent predictors of future cancer diagnosis: OR = 1.07 ((95 % CI: 1.01–1.14) per each 5 ng/mL increase; for patients with D-dimer >15.0 μg/mL the OR of future cancer was 2.10 (1.05–4.18). If only patients with unprovoked PE upon admission (n = 307) were to be considered results were similar considering D-dimer; anaemia also predicted unknown cancer [OR = 2.13 (1.08–4.16)]. ConclusionsPatients with D-dimer >15 μg/mL presented a >2-fold higher risk of being diagnosed with a cancer condition in the upcoming 2 years. D-dimer may help clinicians in identifying which patients are at higher risk of occult cancer.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) associated with anti-glycine receptor antibodies and urothelial carcinoma: a case report

BackgroundProgressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare neurological condition with paraneoplastic etiology in about 20% of cases, usually presenting before or shortly after the oncological diagnosis is established. PERM associated with anti-glycine receptor antibodies is not previously reported in a patient with bladder cancer.Case presentationA 72-years-old Caucasian male was admitted with acute onset of dysarthria, dysphagia and trismus three years after initial surgical treatment for bladder cancer. The condition was initially diagnosed as tetanus and treated accordingly, but the diagnosis was reconsidered because of progression despite adequate treatment. Diagnostic workup on readmission revealed lung and paraaortal metastases from bladder cancer and anti-glycine receptor (anti-GlyR) antibodies both in the cerebrospinal fluid and in serum, which supplemented with the clinical presentation led to the diagnosis of PERM, presumably related to bladder cancer. The patient showed improvement and stabilization after treatment with intravenous immunoglobulin and chemotherapy against metastatic bladder cancer.ConclusionTo the best of our knowledge, this is the first reported case of anti-GlyR antibody positive PERM related to urothelial carcinoma. The symptoms mimicked tetanus, and responded to chemotherapy and immunotherapy.

Paraneoplastic or not? Sirtuin-2 in anti-N-methyl-D-aspartate receptor encephalitis.

NMDAR and LGI1 encephalitis are important types of autoimmune encephalitis (AE) with significant morbidity. In this study, we used a proteomic approach in search for novel clinically relevant biomarkers in these types of encephalitides. Swedish and Czech tertiary neuroimmunology centers collaborated in this retrospective exploratory study. Fifty-eight cerebrospinal fluid samples of 28 patients with AE (14 definite NMDAR, 14 with definite LGI1 encephalitis) and 30 controls were included. CSF samples were analyzed using proximity extension assay technology (Olink® Target 96 Inflammation panel). For each CSF sample, 92 proteins were measured. Clinical variables were retrospectively collected and correlations with protein levels were statistically analyzed. Patients and controls differed significantly in the following 18 biomarkers: TNFRSF9, TNFRSF12, TNFRSF14, TNF-ß, TNF-α, IL7, IL10, IL-12B, IFN-γ, CD5, CD6, CASP-8, MMP-1, CXCL-8, CXCL-10, CXCL-11, IL-20RA, Sirtuin-2 (SIRT2). In LGI1 encephalitis, no clinically useful association was found between biomarkers and clinical variables. In the NMDAR encephalitis group, SIRT2, TNF-ß and CD5 were significantly associated with ovarian teratoma. For SIRT2, this was true even for the first patients' CSF sample (SIRT2 without vs. with tumor [mean ± SD]: 2.2 ± 0.29 vs. 2.88 ± 0.48; p=0.007, 95% CI [-1.15, -0.22]; point-biserial correlation: rpb=0.66, p=0.011). SIRT2 was positively correlated with age (rpb=0.39, p=0.018) and total hospital days (r=0.55, p=<0.001). Sirtuin-2 should be investigated as a biomarker of paraneoplastic etiology in NMDAR encephalitis.

Paraneoplastic and non-paraneoplastic limbic encephalitis: distinguishing features and outcomes (P7-5.031)

Paraneoplastic and non-paraneoplastic limbic encephalitis: distinguishing features and outcomes (P7-5.031)

A Case of Dancing Eyes and Feet (P4-5.006)

<h3>Objective:</h3> To present a case of opsoclonus-myoclonus-ataxia syndrome in an adult patient following Epstein Barr Virus infection. <h3>Background:</h3> Opsoclonus-myoclonus-ataxia syndrome (OMAS), also called disorder of dancing eyes and feet, is a condition that causes opsoclonus along with diffuse or focal body myoclonus and truncal titubation with or without ataxia and other cerebellar signs. It is commonly seen as a paraneoplastic syndrome in children with neuroblastoma; however, there are several associated post-infectious and paraneoplastic etiologies in children and adults. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 26-year-old woman developed generalized malaise, abdominal discomfort, and right upper quadrant abdominal swelling. One week later, she developed blurred vision and gait impairment, for which she presented to the emergency room. On physical exam, she had opsoclonus, left appendicular ataxia, and left hemi-ataxic gait. Brain magnetic resonance imaging was normal. Serologic studies revealed elevated liver function tests and positive Epstein Barr Virus (EBV) IgM and IgG. Evaluation of cerebrospinal fluid revealed normal cells, glucose, and protein, negative oligoclonal bands as well as negative meningitis/encephalitis polymerase chain reaction panel and negative autoimmune encephalopathy panel. Workup for occult neoplasms was unrevealing. She was diagnosed with post-infectious OMAS due to EBV. She was treated with high-dose steroids with taper and intravenous immunoglobulin, which led to further improvement. Gabapentin, clonazepam, and topiramate were used for symptomatic treatment of opsoclonus. <h3>Conclusions:</h3> We describe clinical features, diagnostic workup, and treatment of a case of Epstein Barr Virus-associated post-infectious opsoclonus-myoclonus-ataxia syndrome in an adult. Despite recovery from the viral illness, the patient continued to have symptoms for several weeks which were ultimately improved with steroids and IVIG. <b>Disclosure:</b> Dr. Ahden has nothing to disclose. Dr. George has nothing to disclose. Dr. Samkoff has nothing to disclose.

Chorea as the Initial Manifestation of Antiphospholipid Syndrome (P9-5.020)

<h3>Objective:</h3> To discuss a rare case of chorea presenting as the initial manifestation of autoimmune disease. <h3>Background:</h3> Autoimmune chorea, including paraneoplastic, post-infectious, and idiopathic etiologies, is one of the leading causes of adult-onset chorea behind Huntington’s and vascular diseases.¹ In particular, in primary antiphospholipid syndrome (APS) and systemic lupus erythematosus, chorea is the initial manifestation of disease in 0.9 to 2% of cases.^1,2 <h3>Design/Methods:</h3> Verbal and written consent were obtained from the patient. <h3>Results:</h3> 73-year-old female with PMH of ITP, left MCA ischemic stroke, SDH, and DVT on anticoagulation who presented initially to ED with choreoathetoid movements starting 3 days prior to admission. History was unremarkable for triggering factor. Head imaging was unremarkable for acute intracranial process. B12, folate, TSH, electrolytes, RPR, serum copper, ANA, anti-dsDNA, SS-A, SS-B, Smith, and RNP antibodies negative. Lupus anticoagulant, β2 glycoprotein, and anti-cardiolipin antibodies positive. EEG unremarkable. Pelvic ultrasound negative. Genetic testing for Huntington’s negative. LP normal with exception of positive Coxsackie B1–B6 and A24 antibodies. After five-day course of IVIg, movements improved and she was discharged on no immunosuppression. Five weeks later, patient returned to ED with worsening of choreoathetoid movements. Repeat head CT again negative for acute pathology. Repeated spinal was unremarkable. Patient received Solumedrol 1g for four days with significant improvement in symptoms, and discharged on Prednisone 60 mg daily with recommendation to follow-up with rheumatology and neurology. On follow-up several months later, patient maintained on Prednisone 5 mg daily with no recurrence of choreoathetoid movements. <h3>Conclusions:</h3> While chorea is not the most commonly reported movement disorder in the context of autoimmune disease, it is often a delayed diagnosis, resulting in recurrent admissions and healthcare costs. Laboratory testing for autoimmune disorders should be included in the initial work-up of new-onset chorea to establish the diagnosis and properly treat as to prevent development of fulminant disease. <b>Disclosure:</b> Ms. Alayon has nothing to disclose. Mrs. Goodis has nothing to disclose. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Catalyst. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for eisai. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Feinberg has stock in Amarin. Stuart N. Kieran, MD has nothing to disclose. Dr. Wirkowski has nothing to disclose.

Seronegative Isaac Syndrome Presenting as Focal Limb Stiffness Responsive to Plasma Exchange Therapy (P8-8.015)

<h3>Objective:</h3> N/A <h3>Background:</h3> Isaac syndrome is an autoimmune disorder of peripheral nerve hyperexcitability characterized by neuromyotonia, myokymia, muscles stiffness, pseudomyotonia, and pseudotetany frequently accompanied by dysautonomia and neuropathic pain. Approximately 50% of cases are associated with antibodies against contactin-associated protein-like 2 (CASPR2) or less commonly leucine-rich glioma inactivated protein 1 (LGI1), both components of the voltage-gated potassium channel (VGKC) complex. Paraneoplastic, genetic, and toxic etiologies must be considered. Management includes membrane-stabilizing drugs as well as immunotherapy in more severe cases. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 50-year-old woman presented with one year of left neck, shoulder, and upper extremity pain and stiffness that began one month after an upper respiratory illness. Her exam was notable for anterocollis, left shoulder elevation, impaired left shoulder abduction beyond 35–40 degrees, tonically contracted left biceps, and marked tenderness to palpation of the affected muscles. Symptomatic management with diazepam, lorazepam, baclofen, mexiletine, and trihexyphenidyl was ineffective. EMG demonstrated widespread neuromyotonic discharges throughout the proximal greater than distal left upper extremity, cervical and thoracic paraspinals, and right deltoid. Laboratory studies including CASPR2, LGI1, VGKC, GAD-65, and amphiphysin antibodies were unremarkable. Comprehensive screening for occult malignancy was unrevealing. She received partial benefit from carbamazepine, levetiracetam, cyclobenzaprine, and onabotulinumtoxinA injections, but symptoms remained debilitating. She was treated with IVIg 1g/kg Q2 weeks for three months with symptom progression to the jaw and lower extremities. She was started on plasmapheresis QOD for ten days every four weeks with rapid improvement in symptoms. <h3>Conclusions:</h3> We report a case of seronegative Isaac syndrome initially presenting with focal limb stiffness and dystonic posturing that was exquisitely responsive to plasmapheresis. This case highlights the need to consider peripheral nerve hyperexcitability syndromes in patients presenting with focal limb stiffness or painful dystonia and provides additional support for plasmapheresis as an effective treatment option for patients with debilitating symptoms. <b>Disclosure:</b> Dr. Khalil has received personal compensation in the range of $0-$499 for serving as a Resident and Fellow Council Member with American Association of Neuromuscular &amp; Electrodiagnostic Medicine. Dr. Khalil has received personal compensation in the range of $0-$499 for serving as a MS Mentorship Forum Participant with Foundation of the Consortium of Multiple Sclerosis Centers. Dr. Bradshaw has nothing to disclose.

Anti-IgLON-5 Associated Neurological Disease Presenting with Bilateral Optic Neuritis, Orthostatic Intolerance, Sleep-Related Movements in Setting of Testicular Mass: Expanding Clinical Phenotypes in the Disease. (P5-5.028)

<h3>Objective:</h3> We report a novel presentation of IgLON5-associated neurological disease with possible paraneoplastic phenomena, expanding the clinical phenotypic spectrum of this disorder. <h3>Background:</h3> Anti-IgLON5-associated neurological disease is characterized by neuroinflammatory and neurodegenerative features. Autopsies from advanced cases reveal phospho-tau accumulation in the hypothalamus and brainstem. Clinical features include sleep and movement disorders, bulbar symptoms, dysautonomia and motor neuron disease-like phenotypes. Overlap with progressive supranuclear palsy (PSP-like) is also seen. <h3>Design/Methods:</h3> A fifty-one-year-old man in general good health presented with deficits in visual fields, visual acuity and color vision. Funduscopic examination demonstrated bilateral optic disc edema confirmed by magnetic resonance imaging. Slit-lamp exam demonstrated granular-appearing optic discs and hemorrhagic telangiectasias. Treatment with high-dose steroids with taper was initiated. Early cessation of steroids caused symptom recurrence. New onset disabling orthostatic intolerance, daytime somnolence, sleep apnea, and twitching while sleeping were noted. <h3>Results:</h3> Repeat brain imaging demonstrated partial resolution of optic disc edema. Cerebrospinal fluid evaluation demonstrated normal opening pressure and glucose, 4 nucleated cells, elevated protein (82 mg/dl), and negative neuroinfectious work-up. Cytology showed rare lymphocytes and monocytes. IgLON5 antibodies were identified (1:8 titer). Whole-body PET scan demonstrated FDG-avid lesions in a testicle, with ultrasound demonstrating hypoechogenicity suggestive of infection/trauma vs burned-out tumor, representing a potential paraneoplastic etiology. His treatment regimen was escalated to monthly intravenous Cyclophosphamide infusions over 6 months. <h3>Conclusions:</h3> This patient presented with recurrent bilateral optic neuritis, evolving to develop sleep apnea, daytime hypersomnolence, and involuntary nocturnal movements. IgLON5 antibodies were detected in cerebrospinal fluid. Symptomatic response to immunosuppressive therapy, with symptom relapse on pausing immunosuppression was noted. While oculomotor abnormalities are reported in the disorder, this is a novel presentation of CNII involvement in a patient with IgLON5 antibodies. As understanding of IgLON-5 disease evolves, a low threshold for diagnostic suspicion is emphasized, as treatment may prevent irreversible neuronal damage and subsequent neurodegeneration. <b>Disclosure:</b> Dr. Varma-Doyle has nothing to disclose. Dr. Chwalisz has nothing to disclose. Dr. Linnoila has received research support from NIH/NINDS. Dr. Linnoila has received personal compensation in the range of $10,000-$49,999 for serving as a expert respondent on autoimmune encephalitis with U.S. government/DHHS/vaccine injury compensation program.

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.

Pediatric opsoclonus myoclonus ataxia syndrome in the setting of COVID-19 (P5-9.010)

<h3>Objective:</h3> To describe peri-infectious opsoclonus myoclonus ataxia syndrome (OMAS) in the setting of COVID-19 infection in children. <h3>Background:</h3> OMAS is well described in pediatric patients with peripheral neuroblastic tumors and less defined in the setting of peri-infectious etiologies such as SARS-CoV-19 which is better appreciated in adults. <h3>Design/Methods:</h3> We describe two separate cases of peri-infectious COVID-19 OMAS in pediatric patients at a tertiary Children’s Hospital in 2022, both previously healthy female patients, 2 years and 18 months of age. <h3>Results:</h3> Patient A is a two year-old female who initially presented with ataxia in context of acute COVID-19 infection at 16 months of age and later developed abnormal eye movements, myoclonus and irritability with multiple relapses over a nine month period. Patient B is a 18 month-old female presenting with acute onset abnormal eye movements and ataxia at age 14 months and later developed myoclonic jerks and irritability with sleep disturbance, subsequently found to have COVID-19 antibodies, now with remission of symptoms. Both patients had comprehensive work up for malignancy, toxic-metabolic encephalopathy, structural central nervous system disease, infectious meningoencephalitis and genetic ataxia syndromes. Both were treated with IVIG and high dose steroids. Patient A had subsequent relapses and required escalation of treatment to ACTH. Patient A had a more complicated course which included treatment with acetazolamide and levetiracetam for myoclonus. Her myoclonic jerks demonstrated intermittent electrographic correlates on EEG. <h3>Conclusions:</h3> While OMAS associated with neuroblastic tumors is well described in the pediatric literature, it is less well known in relation to peri-infectious phenomena, particularly SARS-CoV-2 infection in children. Prior published reports of OMAS related to COVID-19 infection in adults indicated a favorable prognosis after initial treatment. However, we present a case with repeated relapses and the need for more aggressive treatment. The present report broadens the phenotypic spectrum for OMAS outside of paraneoplastic etiologies. <b>Disclosure:</b> Dr. Yakir has nothing to disclose. Dr. Most has nothing to disclose. Dr. Hermel has nothing to disclose. Dr. Zimbric has received personal compensation in the range of $0-$499 for serving as a Survey volunteer with Opinionsite. An immediate family member of Dr. Friedman has received personal compensation in the range of $0-$499 for serving as a Consultant for Sinopia Biosciences. An immediate family member of Dr. Friedman has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Pet Dx. Dr. Friedman has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink Neurology. Dr. Friedman has stock in Friedman Bioventure . Dr. Rho has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nutricia. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerecin. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mallinckrodt. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zogenix. Dr. Rho has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Aquestive. The institution of Dr. Rho has received research support from National Institutes of Health. Dr. Rho has received publishing royalties from a publication relating to health care.