Diffuse Leptomeningeal Enhancement Research Articles

Atezolizumab- and bevacizumab -induced encephalitis in a patient with advanced hepatocellular carcinoma: a case report and literature review

Treatment with atezolizumab and bevacizumab is the first-line therapy for unresectable hepatocellular carcinoma. Although immune checkpoint inhibitors are novel and effective treatments, they can induce immune-related adverse events. However, neurological immune-related adverse events have rarely been reported. We report the case of a man in his 40s with hepatocellular carcinoma who developed life-threatening encephalitis after atezolizumab plus bevacizumab was administered. The patient presented with fever, headache, altered mentality, and general epileptic seizures, ten days after administration. Cerebrospinal fluid analysis showed elevated white blood cells and elevated protein levels, but revealed no infection or malignancy. Brain magnetic resonance imaging showed diffuse leptomeningeal enhancement in both the cerebrum and cerebellum. As immune checkpoint inhibitor-induced encephalitis was strongly suspected, steroid pulse therapy was initiated and neurological symptoms quickly improved. The patient was discharged after 66 days of hospitalization, and administration of sorafenib and radiotherapy was started for the hepatocellular carcinoma on an outpatient basis. This case demonstrates the importance of recognizing neurological immune-related adverse events following atezolizumab and bevacizumab treatment for early intervention. We discuss this case in comparison to available literature and previous two cases of Atezolizumab- and bevacizumab- induced encephalitis in hepatocellular carcinoma.

ETMR-21. PRIMARY DIFFUSE LEPTOMENINGEAL MELANOMATOSIS (PDLM) ASSOCIATED WITH INTRACRANIAL BLEEDING AND RAPID PROGRESSION IN A CHILD

Abstract BACKGROUND PDLM is a rare and aggressive disease with limited cases reported worldwide and few cases in the pediatric population. Herein we report on clinical, histologic, and molecular/genetic findings of a young child with PDLM and rapid clinical progression. CASE STUDY A 12-year-old right-handed male presented with two months of intermittent fevers, progressive frontal headaches, lethargy, vomiting, and weight loss, and one month of focal seizures with altered awareness, speech arrest, eye deviation, and tonic posturing. Examination revealed bilateral papilledema and signs of increased intracranial pressure. A brain CT demonstrated increased density of the anterosuperior right frontal lobe and punctate focus of increased density along the left frontal lobe suggestive of hemorrhage. MRI revealed diffuse leptomeningeal thickening and enhancement throughout the brain and spinal cord. At biopsy, the frontal lesion was noted to be grossly abnormal and discolored, and on pathology demonstrated a melanocytic neoplasm infiltrating the subarachnoid space and extending into Virchow-Robin spaces. Tumor cells stained strongly for HMB45, vimentin, Melan-A, and PRAME and were BRAFV600E negative. RNA sequencing was negative for structural variants, Whole exome sequencing revealed a Tier I missense variant in NRAS (c.181C>A) among other copy number variations and loss of heterozygosity. Comprehensive ophthalmologic and dermatologic examinations as well as whole body PET/CT did not reveal any other sites of disease. He was due to commence immunotherapy with combination PD-1/CTLA-4 inhibitors but developed status epilepticus and raised intracranial pressure, warranting ventriculoperitoneal shunt insertion. Three days later, he had further deterioration with altered level of consciousness, hypertension, eye deviation, and vomiting. CT brain revealed large bifrontal hematomas with mass effect and care was redirected to palliation. CONCLUSION PDLM can be challenging to diagnose with a rapidly progressive course. Advanced molecular diagnostics may provide new targets for precision therapy, though overall outcomes remain dismal.

IMMU-04. THE ROLE OF CHECK POINT INHIBITORS IN PEDIATRIC PRIMARY DIFFUSE LEPTOMENINGEAL MELANOMATOSIS: REPORT OF TWO CASES

Abstract BACKGROUND Primary diffuse leptomeningeal melanomatosis (PDLM), a subtype of malignant melanomas of CNS, is rare, especially in children. PDLM is defined by diffuse invasiveness of the leptomeninges with or without nodules. Clinical manifestations of PDLM are nonspecific, mimicking the diagnosis of meningitis. As PDLM is neither sensitive to chemotherapy nor radiotherapy, the prognosis is extremely poor. Recently, some new therapeutic aspects like immunotherapy, especially immune check point inhibitors (ICI) are emerging. Cases report: First case: A 13 years old boy presented with 4 months of weakness, dysphasia and vomiting. MRI demonstrated diffuse leptomeningeal enhancement of the brain and spine. Brain biopsy confirmed the diagnosis of PDLM, with low PDL1 stains in immunohistochemistry, without targetable alterations on NGS. PET FDG normal. Treatment with ICI (Nivolumab 1 mg/kg/dose and Ipilimumab 3 mg/kg/dose, 4 courses every 21 days) was started. He developed severe complications after the 1st course (ICI enterocolitis, pancreatitis) and progressive disease after 2 courses. Craniospinal radiotherapy was delivered at a dose of 30 Gy. The disease continued to progress; the patient died nine months after diagnosis. Second case: A 7-year-old boy presented with diplopia, headache and vomiting. MRI demonstrated a cranial leptomeningeal enhancement and hypo-intense T1 and hyper-intense T2 signal at bilateral medial frontal cortex area. PET FDG normal. Brain biopsy confirmed the diagnosis of PDLM, with TMB 1.9, NRAS mutation and wild type BRAF by NGS. He started combination of ICI therapy. Three weeks after 1st course of Ipilimumab-Nivolumab he was admitted to PICU with prolonged status epilepticus. MRI demonstrated progression of leptomeningeal disease. Trametinib was deferred by parents and the child succumbed a year from diagnosis. CONCLUSIONS We report two cases of pediatric patients with PDLM treated unsuccessfully by immune check point inhibitors, emphasizing the diagnostic and therapeutic challenges in such a rare disease.

Lenalidomide‐induced posterior reversible encephalopathy syndrome: A case report

AbstractPosterior reversible encephalopathy syndrome (PRES) is a disorder of cerebrovascular dysregulation. To our knowledge, we present the first case of lenalidomide‐induced PRES in English. A 59‐year‐old woman with history of multiple myeloma status post stem cell transplant and induction triple therapy 6 months ago with partial remission and subsequent high‐dose melphalan 1 month ago presented with progressive vision loss for 1 week. Her systolic blood pressure was >180 mmHg, and neurological examination demonstrated decreased vision bilaterally. Brain MRI revealed significant T2 hyperintensity restricted to temporal and occipital lobes and left occipital parenchymal hemorrhage and diffuse leptomeningeal enhancement. She had a witnessed generalized tonic–clonic seizure and EEG that captured an electrographic seizure originating from the occipital lobe. Her vision improved rapidly after discontinuing the lenalidomide. She was discharged to rehab with a normal neurological examination. We report the first English case of presumed lenalidomide induced PRES in a patient undergoing multiple myeloma treatment.

Lessons learned from a fatal case of Tuberculosis Meningitis: A case report

BACKGROUND In 2023, 10 million cases of Tuberculosis were reported by the WHO. Tuberculous meningitis (TBM) may be the sole manifestation of Tuberculosis (TB) and does not require prior pulmonary or extrapulmonary disease[1]. Approximately one-half of all TBM infections lead to severe neurological disability with a mortality rate of 30% with death in 6 months and 50% overall[2-4]. Despite being inarguably the most devastating clinical presentation of TB, frequent diagnostic delays are common due to low clinical suspicion or misdiagnosis as current diagnostic tests still have a limited yield[5]. The best way to reduce mortality and morbidity associated with TBM is by maintaining a high index of suspicion, timely diagnosis and initiation of treatment. This case report aims to highlight the clinical presentation, imaging findings, and diagnostic pitfalls in the diagnosis of TBM. CASE PRESENTATION A 36-year-old Indian man with no significant medical, social, or travel history initially sought treatment at a private hospital in Abu Dhabi for fever, intermittent headaches, and confusion. Investigations at the hospital included a negative QuantiFERON TB gold (QTF) test and a negative cerebrospinal fluid (CSF) culture, but the CSF analysis was not included in the provided reports. Consequently, he received acyclovir treatment for suspected viral encephalitis but was discharged without complete symptom resolution. Following discharge, he experienced worsening confusion over three days. Upon presentation to our Emergency Department (ED), he was febrile, disoriented, and difficult to rouse, with a GCS score of 11/15, displaying terminal neck stiffness. There were no signs of lateralization, cranial nerve deficits, or cerebellar abnormalities. A computerized tomography (CT) scan conducted in the ED revealed hydrocephalus with diffuse leptomeningeal enhancement. Laboratory results indicated significant hyponatremia at 121 mmol/L. He was started on broad-spectrum antibiotics and anti-tuberculosis medication empirically based on the clinical scenario and CT findings. During his Intensive Care Unit (ICU) stay, a CSF analysis suggested TB meningitis, and a positive Mycobacterium tuberculosis polymerase chain reaction (MTB-PCR) confirmed the diagnosis. An MRI of the brain showed meningoencephalitis with tuberculoma formation in the left cerebellar hemisphere. Unfortunately, despite treatment, his condition deteriorated, necessitating endotracheal intubation, multiple EVD revisions, and ventriculoperitoneal shunt placement. A follow-up MRI revealed worsening hydrocephalus and cerebral vessel thromboses, ultimately leading to his unfortunate demise in the ICU. CONCLUSION This case highlights that Tuberculous meningitis is a highly lethal, under-recognized disease with characteristic clinical and imaging features in which delay in diagnosis and subsequent treatment can lead to fatal consequences. Emergency Medicine physicians should maintain a high index of suspicion for TBM in patients with fever and vomiting and signs of altered mental status and keep in mind that a normal CXR, negative QuantiFERON test, and the absence of TB exposure history does not exclude TBM from the differential when clinical and Brain imaging findings raise concern. Prompt identification prevents delay in initiation of management and ultimately may lead to better long-term outcomes.

RADT-33. ANALYSIS OF PATIENTS DIAGNOSED WITH ATYPICAL TERATOID RHABDOID TUMOR OF BRAIN AT TERTIARY CARE CENTER

Abstract Atypical Teratoid Rhabdoid Tumor (ATRT) of brain is highly malignant neoplasm with incidence of 1-2% among all pediatric CNS tumors characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5) gene with dismal prognosis of about 6-18 months. On retrospective analysis of patients between 2010-2021 from Medical Record Department, only five cases of ATRT brain were retrieved. All patients were of pediatric age group (6 yr/F, 2yr/M, 6yr/F, 4yr/F, and 1yr/M – Median 4 yrs). On radiological findings, in four patients lesion was primarily in brain and in one patient with diffuse leptomeningeal enhancement. Three patients underwent craniotomy and gross total excision, and, in 2 patients only biopsy was done. In molecular analysis immunohistochemistry (IHC) markers were as follows. In all patients Vimentin and Synaptophysin were positive. EMA was positive in 3 patients, GPAP was positive in 3 patients, CD99 was positive in 2 patients, AE1 was positive in 2 patients. A specific marker for ATRT (INI1 loss) was seen in 3 patients. In other patients INI1 assessment could not be done. In two patients CSF cytology was negative, and, in all patients bone marrow examination was normal. One patient (4yr/F) received local radiotherapy with concurrent Vincristine based chemotherapy and lost to follow up (after 1 year of treatment). One patient (6yr/F) received vincristine based chemotherapy and local palliative radiotherapy and expired (after 1 month of treatment). One patient (6yr/F) received St Jude HR/IRS III protocol chemotherapy and craniospinal irradiation (CSI) and is still on follow up (total follow up period – 9 years). Two patients did not take any kind of treatment in whom one patient expired, another lost to follow up. Looking at rarity of tumors and with the review of literature, multiagent chemotherapy and Craniospinal irradiation seems to be promising approach for treatment of ATRT brain.

Bickerstaff’s brainstem encephalitis: a rare case of neurologic complication in Ulcerative Colitis

Bickerstaff’s brainstem encephalitis is a rare autoimmune disorder that presents with ataxia, ophthalmoplegia, disturbance of consciousness and quadriplegia. A 45-year-old man with a history of ulcerative colitis (UC) taking mesalazine (5-aminosalicylic acid) visited the emergency room presenting with ataxia, ophthalmoplegia and a progressively worsening cognitive impairment. Cerebrospinal fluid analysis showed mild elevation in protein and white blood cell count and increased intracranial pressure. Anti-GQ1b autoantibodies were found positive in the patient’s serum and contrast-enhanced brain magnetic resonance imaging showed diffuse leptomeningeal enhancement and pontine lesions. Based on these findings and the patient’s clinical course and history, he was diagnosed with Bickerstaff’s brainstem encephalitis. Mesalazine was discontinued and high-dose steroid pulse therapy was started, followed by intravenous immunoglobulin, which resulted in gradual improvement of the neurologic symptoms. When an ulcerative colitis patient presents with progressive cognitive impairment, quadriplegia and disturbance of consciousness and gait, Bickerstaff brainstem encephalitis should be considered in the differential diagnosis and prompt immunotherapy may lead to favorable prognosis.

SAT624 Neurosarcoidosis Presenting With Panhypopituitarism

Abstract Disclosure: E.M. Niedzialkowska: None. T. Blazin: None. K. Strubchevska: None. M. Kozyk: None. N. Saini: None. Introduction: Neurosarcoidosis is estimated to occur in approximately 5-15% patients with sarcoidosis. Pituitary involvement may be present in up to 5% of those cases and can manifest as hypothalamus, adenohypophysis dysfunction or arginine vasopressin deficiency (AVP-D) in isolated fashion or variedly combined. Clinical case: 32 year old male presented with chief complaint of worsening bilateral lower extremity weakness, urinary incontinence, polyuria and polydipsia. 9 months prior to admission the patient was diagnosed with neurosarcoidosis. At that time brain MRI showed diffuse leptomeningeal enhancement, chest CT showed hilar lymphadenopathy, lumbar puncture with CSF analysis showed protein 227 mg/dl (N<38), ACE 6 U/l (N <2.5), WBC 10 (N<5) with 88% lymphocytes. Hilar lymph node biopsy was consistent with non-caseating granuloma. The patient was diagnosed with neurosarcoidosis and started on prednisone and methotrexate. The patient was referred to our institution for further evaluation. On examination gait ataxia and gynecomastia were noted. Laboratory results showed urine specific gravity of 1.001, LH 0.4 mIU/ml (N 0.6-1.2), FSH 1.1 mIU/ml (N 1-12), ACTH <5 pg/ml (N 6-46), cortisol 2.1 ug/dl (N 2.9-19.4), prolactin 10.5 ng/ml (N 2-18), total testosterone 4 ng/dl (N 240-1080), free testosterone 0.1 ng/dl (N 4.8-19), TSH 0.58 uIU/ml (N 0.4-4.5), free ft3 1.5 pg/ml (N 1.7-3.7), free ft4 0.6 ng/dl (N 0.7-1.5), IGF-1 52 ng/ml (N 71-234), Copeptin proAVP of <2.8 pmol/l( N>13.2), urine osmolality of 72 mOsmol/kg, blood osmolality of 297 mOsmol/kg (N <295), vit D 25-OH 9 ng/ml (N 30-100), vit D 1,25-OH 57.3 pg/ml (N 19.9-79.3). MRI of the spine showed extensive nodular enhancement of the leptomeninges of the cervical, thoracic spine and lumbar cauda equina nerve roots. Brain MRI was positive for numerous small nodular enhancement involving leptomeninges and pituitary stalk. The patient was started on desmopressin with significant improvement of symptoms and increase in urine osmolality to 709 mOsmol/kg. Due to risk of hypercalcemia and normal vit D 1,25-OH vitamin D supplementation was not initiated. For neurosarcoidosis the patient was started on pulse dose methylprednisolone and infliximab infusion. Upon discharge he was transitioned to oral hydrocortisone and started on levothyroxine and testosterone replacement therapy. Conclusion: We present a case of pituitary neurosarcoidosis presenting with AVP-D, secondary hypothyroidism, secondary adrenal insufficiency, hypogonadism and growth hormone deficiency. Panhypopituitarism with complete anterior and posterior pituitary dysfunction is extremely rare and might be found in up to 13% cases of pituitary sarcoidosis. The diagnosis should be considered in patients with sarcoidosis and endocrine dysfunctions. Presentation: Saturday, June 17, 2023

P16.01.A THE CASE OF AGGRESSIVE DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR IN ADULT TREATED WITH CRANIOSPINAL IRRADIATION AND TEMOZOLOMIDE

Abstract BACKGROUND Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor, which was introduced as a separate entity in the 2016 World Health Organization classification of central nervous system tumors. It is most common in pediatric age, but very rare in adults. Literature demonstrates limited reports regarding treatment strategy in adult. We present a case of young female affected by DLGNT with aggressive behavior. MATERIAL AND METHODS A 28-year-old woman presented with severe headache and vomiting. Brain MRI showed diffuse leptomeningeal enhancement with hydrocephalus. At first, she was under suspicion of tuberculosis meningitis with mild increased protein level in CSF study. Her symptom rapidly improved after ventriculoperitoneal shunt and she started anti-tuberculosis medication. Despite 8-month of medication, her neurological status gradually deteriorated with paraparesis and follow-up MR images showed progression of disease. She underwent open biopsy of superficial brain lesions. RESULTS Intraoperatively, multiple nodular masses were attached inner side of dura mater and diffuse adhesion on subarachnoid space of brain surface. Histological examination revealed small round cells with oligodendroglial-like aspects. Immunohistochemistry showed positivity for Olig2, synaptophysin and S100. Chromosome 1p deletion was confirmed by FISH. Next-generation sequencing profile disclosed mutation of H3K28M, FGFR1 and ATRX. Diagnosis was consistent with DLGNT. She received craniospinal irradiation of 36 Gy in 20 fractions, then started chemotherapy with temozolomide (TMZ) at a dose 200mg/m2/day for 5 days in 4 weeks. After 4 cycles of TMZ, MR images demonstrated stable disease. CONCLUSION DLGNT is a very rare tumor in adult. Diagnosis needed high level of suspicion and histological confirmation. We present a very rare adult DLGNT patient with aggressive clinical features who showed stable state treated with craniospinal irradiation and TMZ chemotherapy.

A New Pattern of Brain and Cord Gadolinium Enhancement in Molybdenum Cofactor Deficiency: A Case Report

Molybdenum cofactor deficiency (MoCD) is a rare and severe autosomal recessive in-born error of metabolism caused by the mutation in MOCS1, MOCS2, MOCS3 or GEPH genes, with an incidence ranging between 1 in 100,000 and 200,000 live births. The clinical presentation with seizures, lethargy and neurologic deficits reflects the neurotoxicity mediated via sulphite accumulation, and it occurs within the first hours or days after birth, often leading to severe neurodegeneration and the patient’s death within days or months. The Imaging of Choice is a brain-specific MRI technique, which is usually performed without contrast and shows typical radiological findings in the early phase, such as diffuse cerebral oedema and infarction affecting the cortex and the basal ganglia and the white matter, as well as in the late phase, such as multicystic encephalomalacia. Our case report represents a novelty in the field, since the patient underwent a contrast-enhanced MRI to exclude a concomitant infectious disease. In the frame of the clinical presentation and laboratory data, we describe the MoCD Imaging findings for MRI morphological and advanced sequences, presenting a new contrast-enhanced MRI pattern characterized by the diffuse and linear leptomeningeal enhancement of brain, cord and spinal roots. The early identification of molybdenum cofactor deficiency is crucial because it may lead to the best multidisciplinary therapy for the patient, which is focused on the prompt and optimal management of the complications.

LGG-24. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR MANAGEMENT AND OUTCOME: A SINGLE CENTER EXPERIENCE

Abstract Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare diagnosis that was first incorporated into the WHO Classification in 2016. DLGNTs are usually low-grade tumors, with no current standard of care. A retrospective review of patients with a histologic diagnosis of DLGNT, from 2010 to 2022, was done with IRB approval. Eight patients were identified with a median age at diagnosis of 5.5 years (range 4 months - 21 years). Imaging findings included diffuse leptomeningeal enhancement and multifocal nodular lesions in the supratentorial and infratentorial locations. One patient had localized pineal disease and 2 patients had isolated spinal cord involvement. Histologically, 6/8 (75%) patients showed low-grade tumor (Ki-67 index = 2-15%). BRAF-KIAA1549 fusion was reported in 3, NTRK fusion in 1, PTPN11 mutation in 1, and FGFR1 mutation in 1 patient. Seven patients (88%) were treated with proton radiation, 3 at diagnosis and 4 upon progression. Chemotherapy was used at diagnosis on 4 patients (temozolomide, carboplatin and vincristine, and vinblastine). Targeted therapy (NTRK or BRAF-inhibitors) was utilized upon progression in four patients, and at diagnosis in one. All patients showed disease progression at a median time of 24 months from diagnosis. The median progression-free survival (PFS) in the group receiving upfront RT was 2.2 years (range = 0.4 – 6.6 years), versus chemotherapy of 1.4 years (range = 0.15 - 2.6 years) The 2 years PFS and OS are 57% and 100%, respectively. At a median follow-up of 4.5 years (range = 3 months to 9 years), 6 patients have stable disease (of whom 2 are off therapy), and 2 patients have progressive disease. DLGNTs are rare tumors with scarce data about radiological and molecular characteristics, and no established standard of care. Our case series emphasizes the need for further studies on molecular profiling and exploring targeted therapies.

Neonatal Salmonella Meningitis With Subdural Empyema: A Case Report.

To the Editors: Salmonella species can cause a variety of neonatal infections which are most prevalent in sub-Saharan Africa. Salmonella meningitis is associated with long-term neurologic sequelae1 including seizures, hydrocephalus, subdural effusions, empyema, ventriculitis, hemorrhage and abscess.2 The present case describes a neonate with Salmonella meningitis with subdural empyema. A 12-day-old full-term female presented to the emergency department for a 1-day history of fever, decreased feeding, and a shorter, gasp-like breathing pattern. The baby was tachycardic and febrile. Per patient’s mother, both she and the infant’s brother were suffering from diarrhea 3 days before onset of the infant’s symptoms. A full sepsis workup was initiated, including blood, urine and cerebrospinal fluid cultures. The patient was empirically started on intravenous ampicillin and gentamicin pending culture results. Additionally, a respiratory pathogen panel via polymerase chain reaction performed on the same day indicated positive results for coronavirus disease 2019 (COVID-19). The patient was admitted for further management of presumed neonatal sepsis and respiratory monitoring of COVID-19 infection. The patient was subsequently found to have positive blood culture and cerebrospinal fluid gram stain for Gram-negative rods. Speciation and sensitivities later grew Salmonella species with sensitivity to ampicillin and ceftriaxone. Magnetic resonance imaging of the brain was significant for diffuse right leptomeningeal enhancement consistent with meningitis and subdural empyema. No neurosurgical intervention was recommended. Ampicillin and gentamicin were discontinued after 3 days of treatment, and ceftazidime was started for treatment of salmonella meningitis. Ceftriaxone was considered as the standard treatment for invasive Salmonella infection, but was inappropriate due to mildly elevated bilirubin on admission (Table 1) and patient’s age. TABLE 1. - Admission Labs Complete blood count With Differential Day 1 of Admission White blood cell count 6.4 × 103/µL Hemoglobin/hematocrit 12.6/37.3 g/dL Platelets 564 × 103/µL Segmented neutrophils 40% Bands 24% Lymphocytes 26% Monocytes 7% Urinalysis Color Dark yellow Specific gravity 1.021 pH 7.0 Protein 2+ Glucose Trace Ketones Negative Bilirubin Negative Blood Negative Nitrites Negative Urobilinogen 0.2 Leukocyte esterase 2+ Urine microscopy White blood cells >50 Red blood cells 11.1 Squamous epithelial 5.3 Bacteria 40 Casts 3.9 Chemistry Sodium 138 mmol/L Potassium 4.1 mmol/L Chloride 107 mmol/L Bicarbonate 22 mmol/L Blood urea nitrogen/creatinine 8/0.37 mg/dL Glucose 108 mg/dL Total bilirubin 9.6 mg/dL Total protein 6.2 g/dL Albumin 3.1 g/dL Alanine transaminase/aspartate transaminase 18/23 Units/L Alkaline phosphatase 143 Units/L Cerebrospinal fluid Color Cloudy White blood cells 667 cu/mm Red blood cells 42,500 cu/mm Segmented neutrophils 90% Lymphocytes 8% Monocytes 1% Eosinophils 1% Basophils 0% Inflammatory markers C-reactive protein (admission) 3.06 mg/dL C reactive protein (hospital day #2) 25 mg/dL On the third day of admission, a repeat respiratory pathogen panel showed the patient to be COVID-19 negative, and it was concluded that the initial positive test was likely a false positive. Repeat blood cultures drawn on day 4 of admission were negative. On day 8 of admission, a peripherally inserted central catheter line was placed for long-term parenteral antibiotics. On day 10 of admission, ceftazidime was discontinued and switched to ceftriaxone after a repeat complete metabolic panel showed normalized bilirubin levels. Ceftriaxone was selected (in lieu of ampicillin) to minimize peripherally inserted central catheter line access thereby reducing probability of central line–associated bacterial infection. Inflammatory markers and bilirubin were trended closely due to use of ceftriaxone. A 6-week course of treatment was completed with no further complications and improvement of radiologic findings. The patient was discharged with no apparent neurological deficits. Her development was ascertained by phone call and the child continues to develop typically. Previous case reports indicate that third generation cephalosporins are ideal for management of salmonella meningitis due to their bactericidal properties.3,4 This case offers a suggested treatment course of neonates with transition from ceftazidime to ceftriaxone showing satisfactory results in the treatment of neonatal Salmonella sepsis and meningitis complicated by empyema. ACKNOWLEDGMENTS The authors thank the patient and family for their participation in this report.

Diffuse Leptomeningeal Glioneuronal Tumor (DLGNT) with Direct Cystic Infiltration of the Optic Chiasm and Tracts (P1-9.003)

<h3>Objective:</h3> N/A <h3>Background:</h3> Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare pediatric neoplasm categorized by the WHO in 2016. It is characterized by communicating hydrocephalus, slow tumor growth, CSF with absence of tumor cells, and MRI showing diffuse leptomeningeal enhancement and cystic changes. Here we present, to our knowledge, the first case in which direct cystic tumor infiltration of the optic apparatus was the initial manifestation. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 3-year-old boy developed emesis, altered mental status, bilateral leg weakness, and decreased visual acuity to 20/125 OD and 20/160 OS. MRI showed hydrocephalus and diffuse leptomeningeal enhancement of the brain and spine. Lumbar puncture showed pleocytosis, elevated protein, positive enterovirus PCR, and opening pressure of 55 cm H2O. VP shunt was placed for presumed enterovirus meningitis. Symptoms of hydrocephalus resolved but vision did not improve. Exam showed optic disc pallor bilaterally and no papilledema. OCT demonstrated retinal nerve fiber layer thinning bilaterally. Visual decline progressed despite normalization of ICP. Repeat MRI brain/orbits showed multiple new subpial cysts along the optic tracts and optic chiasm. Filum biopsy showed rare inflammatory cell. Review of the pathology and radiological findings led to a consensus of DLGNT with cysts compressing and infiltrating optic chiasm and nerves. The patient was started on the MEK inhibitor trametinib, with stabilization of MRI findings and vision, but unfortunately without visual improvement. <h3>Conclusions:</h3> Pathologic confirmation of DLGNT can be difficult as safely obtained biopsy samples are typically small. In this case, bilateral optic neuropathy developed due to infiltration of the optic nerves, chiasm and tracts, while papilledema was never seen. MEK inhibitor therapy was initiated with Trametinib leading to stabilization in disease burden. This diagnosis should be considered in pediatric patients with communicating hydrocephalus, diffuse leptomeningeal enhancement, and elevated CSF protein with otherwise normal profile including absence of tumor cells. <b>Disclosure:</b> Dr. Paddock has nothing to disclose. Dr. Dinkin has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for WILSON ELSER MOSKOWITZ EDELMAN &amp; DICKER LLP. Dr. Dinkin has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Rehabilitation Alternative Services, Inc.. Dr. Dinkin has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for AMFS / Medical Experts Nationwide. Dr. Dinkin has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Bekman, Marder, Hopper, Malarkey &amp; Perlin, L.L.C.. Dr. Dinkin has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Northwestern Mutual. Dr. Dinkin has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Young Conaway Stargatt &amp; Taylor.

Cryptococcal Meningoencephalitis and Immune Reconstitution Inflammatory Syndrome in a patient on Tocilizumab Therapy: A Case Report (P1-10.005)

<h3>Objective:</h3> To describe a case of cryptococcal meningoencephalitis complicated by immune reconstitution inflammatory syndrome (IRIS), vasculitis, ischemic strokes, and hydrocephalus. <h3>Background:</h3> Cryptococcus neoformans is the most common cause of fungal meningitis worldwide and typically affects individuals with defects in cell-mediated immunity. A 71-year-old female with giant cell arteritis on daily prednisone and monthly Tocilizumab infusions presented with worsening headaches for 2 weeks and new-onset confusion for 3 days. Initial workup revealed hyponatremia (sodium 125 mmol/L) and community acquired pneumonia. She was treated with antibiotics, but her mental status rapidly declined necessitating endotracheal intubation. MRI Brain demonstrated multifocal areas of diffusion restriction in the bilateral cerebral and cerebellar hemispheres, basal ganglia, and brainstem with diffuse leptomeningeal enhancement. Cerebrospinal fluid (CSF) studies revealed an elevated opening pressure of 28 cm H₂O, positive CSF cryptococcal antigen, and CSF fungal cultures grew cryptococcus neoformans. She was started on empiric liposomal amphotericin B and flucytosine before the cryptococcal antigen and cultures resulted. Despite treatment, her neurological status continued to decline with repeat MRI showing new ischemic infarctions, subarachnoid hemorrhages, and leptomeningeal and parenchymal enhancement. Digital subtraction angiography revealed cerebral vasospasm and possible vasculitis. Repeat lumbar puncture demonstrated persistently elevated opening pressure, continued pleocytosis, and increased protein. She was continued on antifungal therapy and received IV methylprednisolone for IRIS. She additionally underwent ventriculoperitoneal (VP) shunt placement. Despite these interventions, her clinical status continued to deteriorate and she was palliatively extubated. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> This patient presented with cryptococcal meningoencephalitis in the setting of immune suppression from prednisone and tocilizumab, a monoclonal antibody that targets the IL-6 receptor. Despite early and appropriate treatment, she continued to worsen with multiple complications including IRIS, a dysfunctional inflammatory response to infection precipitated by immune recovery. In patients treated appropriately for cryptococcal meningoencephalitis, a failure to respond should raise concern for complicating conditions. <b>Disclosure:</b> Dr. Navalkar has nothing to disclose. Dr. Sui has nothing to disclose. The institution of Dr. Bashir has received research support from NIH. The institution of Dr. Bashir has received research support from PICORI. The institution of Dr. Bashir has received research support from Sanofi. Dr. Bashir has received research support from GWSP. The institution of Dr. Bashir has received research support from Roche. The institution of Dr. Bashir has received research support from Novartis. The institution of Dr. Bashir has received research support from Hoffmann-La Roche.

All that enhances is not cancer: Cerebral amyloid angiopathy mimicking leptomeningeal enhancement in the two patients with advanced cancer (P14-13.002)

<h3>Objective:</h3> N/A <h3>Background:</h3> Cerebral amyloid angiopathy (CAA) leads to deposition of amyloid-beta-peptide in leptomeninges and cerebral blood vessels. A <i>β</i>-related angiitis (ABRA) is a severe form of CAA characterized by transmural inflammation and/or, granulomatous inflammation. We report two patients with advanced malignancy presenting with leptomeningeal enhancement (LME) concerning for leptomeningeal metastases, with biopsy demonstrating ABRA. <h3>Design/Methods:</h3> 76-year-old man presented with left facial droop, dysarthria and imbalance. MRI head showed acute infarcts in multiple vascular distributions and diffuse LME. CTA showed bilateral cervical lymphadenopathy, without evidence of vasculitis. CSF analysis demonstrated lymphocytic pleocytosis and negative flow cytometry and cytology. Cervical lymph node biopsy revealed a new diagnosis of metastatic papillary thyroid cancer. Repeat MRI brain one month later showed persistent and worsening cortical LME. Prior to surgery for the thyroid cancer, a brain biopsy was performed for staging. Pathology demonstrated fibrinoid necrosis of vessels walls and foci of thrombosis, consistent with CAA. The patient was treated with corticosteroids followed by cyclophosphamide for ABRA. 78-year-old woman with cognitive impairment and stage IV serous endometrial cancer presented after incidental findings of subarachnoid hemorrhage (SAH) with LME on MRI brain. CSF analysis was normal with negative cytology. Head CTA was negative for aneurysm or vascular malformation. A repeat MRI showed new small SAH in the right superior frontal gyrus and multiple new punctate cerebellar infarcts. Brain biopsy revealed amyloid positivity with congo red staining in cerebellar leptomeningeal vessels, consistent with CAA. She received a 5-day course of IVIG (steroids contraindicated) with plan to start immunosuppressive therapy outpatient. <h3>Results:</h3> N/A <h3>Conclusions:</h3> Our patients presented with LME in the setting of newly diagnosed malignancy, which raised concern for leptomeningeal metastases. The presence of SAH and infarcts are uncommon in leptomeningeal metastatic disease. In these cases, pathologic confirmation of CAA on brain biopsy changed the cancer-related prognosis and treatment plan. <b>Disclosure:</b> Dr. Waheed has nothing to disclose. Dr. Seyam has nothing to disclose. Dr. Thomas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roon. The institution of Dr. Thomas has received research support from Novocure. The institution of Dr. Thomas has received research support from Spectrum Pharmaceuticals. The institution of Dr. Thomas has received research support from Ono Pharmaceuticals.

Missing the Mark: CSF CA 19-9 secures diagnosis of rare Pancreatic Leptomeningeal Carcinomatosis (P10-13.005)

<h3>Objective:</h3> - The viewer will appreciate the epidemiology and clinical features of Pancreatic Leptomeningeal Carcinomatosis - The viewer will appreciate radiologic and laboratory findings associated with Leptomeningeal Pancreatic Carcinomatosis <h3>Background:</h3> There exists very few reports of carcinomatosis in patients with pancreatic cancer. Leptomeningeal carcinomatosis (LC) is a rare complication in which there is seeding of the leptomeninges by cancerous cells. LC is estimated to occur in 3% to 8% of solid tumors. It can cause a variety of neurologic complaints including meningitis signs, headache, dizziness, or nausea. Obtaining CSF for pathologic interrogation remains standard for diagnosis, but other avenues such as cell marker evaluation exist. Here, we describe a case of LC confirmed with CSF CA 19-9 and high sensitivity cytology. <h3>Design/Methods:</h3> NA <h3>Results:</h3> <h3>CASE REPORT:</h3> A 55-old male with Stage IV pancreatic adenocarcinoma s/p chemotherapy who presented due to chronic progressive headaches, nausea and vomiting. Initial MRI demonstrated diffuse leptomeningeal enhancement around the brain, cervical and thoracic cord with CSF analysis showing normal chemistry and initial CSF cytology was negative. His symptoms persisted and interval MRI revealed extensive worsening of his leptomeningeal enhancement. After repeated lumbar punctures, his CSF had 15 times the elevated tumor marker CA 19-9 in comparison to serum and high sensitivity cytology revealed KRAS mutation, an exon 2 missense variant. <h3>Conclusions:</h3> LC is an extremely rare complication of pancreatic cancer that unfortunately carries with it high morbidity and mortality. The diagnosis can be challenging as identification of malignant cells in the CSF often requires repeated analyses. Our patient had high levels of tumor marker CA 19-9 in the CSF which may be a useful adjunct to identification when clinical suspicion remains elevated in the setting of negative cytology. <b>Disclosure:</b> Dr. Jones has nothing to disclose.

Postpartum Listeria Meningitis: A Case Report (P2-10.006)

<h3>Objective:</h3> n/a <h3>Background:</h3> Acute bacterial meningitis is a neurological emergency and fatal if left untreated. Here we present a case of bacterial meningitis, highlighting postpartum listeria monocytogenes infection. <h3>Design/Methods:</h3> <h3>Description:</h3> We present a case of 27 years-old woman with past medical history of migraine and hyperthyroidism, brought to the hospital with acute onset of reduced level of consciousness. A day prior to presentation, she woke up with a severe retro-orbital headache of 10/10 intensity along with nausea, vomiting, photophobia and phonophobia. Her symptoms further progressed to worsening confusion/somnolence with agitation. She had an uncomplicated vaginal delivery a month earlier. On admission, vitals were significant for high grade fever, hypotension, tachypnea and tachycardia. On examination, she was restless, combative, was not following any commands. No focal motor deficit. Nuchal rigidity and Babinski were negative. Labs showed mild anemia, leukocytosis, mild hyponatremia and lactic acidosis. MRI Brain showed faint diffuse leptomeningeal enhancement. CSF analysis showed WBC 732/Ul, SEG: 66%, protein&gt; 300mg/dl and CSF glucose &lt;20mg/dl. Meningitis panel and CSF culture were positive for listeria monocytogenes. Post CSF analysis, her broad spectrum antibiotics were deescalated to ampicillin for 21 days and gentamycin for 7 days for synergistic effects. During the initial treatment phase, she developed horizontal binocular diplopia and her exam showed isolated sixth nerve palsy. MRI brain revealed worsening diffuse leptomeningitis, involving the basal cisterns and the ependymal walls of the lateral ventricles. Eventually, she responded to the treatment and her symptoms resolved slowly. <h3>Results:</h3> n/a <h3>Conclusions:</h3> Listeria Monocytogenes can be a possible cause of postpartum meningoencephalitis due to the underlying transient immunosuppressive condition. Return to a normal immune response may take as long as up to one year after childbirth. Treatment should not be delayed in highly suspicion cases to avoid complications like rhombencephalitis, progressive neurological deficits and eventually death. <b>Disclosure:</b> Mr. Tang has nothing to disclose. Dr. Kausar has nothing to disclose. Dr. Rivera has nothing to disclose. The institution of Dr. Cruz-Flores has received research support from University of Texas System. Dr. Yerram has nothing to disclose.

Candida dubliniensis Meningitis in Immunocompetent Adults - case report and review of literature (P10-10.001)

<h3>Objective:</h3> NA <h3>Background:</h3> NA <h3>Design/Methods:</h3> We report a case and review the cases of <i>Candida dubliniensis</i> meningitis in immunocompetent adults. <h3>Results:</h3> 32 years old man with history of intravenous drug use (IVDU) presented with seizures, nuchal rigidity, and papilledema. Head CT showed communicating hydrocephalus and brain and spine MR showed diffuse leptomeningeal enhancement extending to the cauda equina. HIV, syphilis, and quantiferon-gold tests were negative but his CD4 count was 203 (430 – 1185/mm3). Lumbar puncture showed opening pressure of 45 mm H2O, CSF protein &gt; 392 mg/dl (15–45), glucose 5 mg/dL (40–70), nucleated cells 246 (0–5), 83% lymphocytes, red blood cells 1 (0–1). CSF meningitis panel was negative, but encephalitis panel showed NMDA receptor antibody. 1,3-Beta-D-glucan was 79 (&lt;60 pg/mL) in the serum and 295 in the CSF and CSF cultures grew <i>Candida dublinens</i>is. <h3>Conclusions:</h3> Chronic base of the skull meningitis has many causes including inflammatory conditions, malignancies, and infections. Invasive <i>C. dublinensis</i> infection is very rare and usually associated with immunodeficiency (HIV or post-transplant). This is the fourth case of <i>C. dublinensis</i> in an immunocompetent host described in the literature. Like our case, in two of those three reports the infection was associated with IVDU, and this information is not available for the third case. This corroborates the hypothesis that IVDU could be a risk factor for this infection. Regarding his CSF NMDA receptor antibody, he did not have limbic encephalitis, dysautonomia, seizures or psychiatric symptoms. There is a known association of this antibody and ovarian teratomas and herpes simplex encephalitis but no association with <i>Candida sp.</i> is known. Despite his low CD4 count he did not have other opportunistic infections. No etiology was identified for this finding. <b>Disclosure:</b> Dr. Horta has nothing to disclose. Dr. White has nothing to disclose. Dr. Greige has nothing to disclose. Dr. Askari has nothing to disclose. Dr. Cervantes-Arslanian has nothing to disclose.

CNS-Isolated Blast Crisis in A Patient with Chronic Myeloid Leukemia on Dasatinib (P10-13.004)

<h3>Objective:</h3> NA <h3>Background:</h3> Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by increased cellular proliferation of myeloid precursors and mature cells due to formation of the BCR-ABL proto-oncogene. Blast crisis is characterized as a rapid expansion of a population of myeloid or lymphoid blast cells and defined as &gt;20% blasts in bone marrow or blood. Extramedullary blast crises isolated to the central nervous system are extremely rare, limited to few case reports. <h3>Design/Methods:</h3> NA <h3>Results:</h3> We present a 57 year old male with history of CML since October 2020 on dasatinib 70mg daily who presented with complaints of daily occipital headaches for three months. Exam notable for persistent encephalopathy and unsteady gait. Peripheral serology was unrevealing, suggesting complete hematologic response to dasatinib. MRI brain revealed diffuse leptomeningeal enhancement, as well as small regions of parenchymal enhancement in left frontal lobe, right optic nerve, and lower lying tonsils to suggest early tonsillar herniation. Patient subsequently received left frontal open biopsy and CSF drainage. CSF analysis was unremarkable except for atypical cells. Biopsy of the leptomeninges revealed focal areas consistent with aggregation of myeloid blast cells. Peripheral blood RT-PCR showed BCR-ABL positivity in BCR-ABL1 subtype e13a2 (b2a2, p210) at 0.0788%, which is still consistent with major cytogenetic response to dasatinib. Patient was transferred to outside hospital for evaluation of hematopoietic stem cell transplant. <h3>Conclusions:</h3> Isolated CNS blast crises are rare, with a few cases in the hematological literature, reporting occurrence in patients on chronic imatinib or dasatinib therapy. This may be due to poor CNS penetration of these medications. Here, we demonstrate a patient that had complete hematologic response and major cytogenetic response to dasatinib systemically but with extensive CNS involvement. It is therefore important to have appropriate workup for neurological symptoms with patients with CML despite appearing in chronic phase of the hematological illness. <b>Disclosure:</b> Dr. Puccio has nothing to disclose. Dr. Rodriguez Lee has nothing to disclose. Dr. Song has nothing to disclose.

NCMP-15. A CASE OF SYSTEMIC METASTATIC DIFFUSE LEPTOMENINGEAL GLIONEURAL TUMOR

Abstract INTRODUCTION Diffuse leptomeningeal glioneural tumor (DLGT) is a very rare central nervous tumor that has no standard of care for its treatment. This report illustrates a case of DLGT with a unique presentation and a first description of multiple systemic metastasis. Case: 19 year-old male with personal history of hereditary multiple osteochondromas and recent covid-19 infection who on investigation of headaches, progressive cranio-neuropathies, and right-sided weakness was found to have vasospasms resulting in acute infarcts in multiple vascular areas, and diffuse leptomeningeal enhancement in the thoracic spine and cauda equina. Patient underwent meningeal biopsy, after 2 months of first symptoms, which revealed DLGT per two different neuro-oncology centers. Course of disease was complicated with hydrocephalus needing shunt placement soon after diagnosis. Craniospinal radiation concurrent with temozolomide was started one month from diagnosis. Patient developed pancytopenia and chemotherapy was stop in the first weeks during radiation therapy. Metastatic disease to bone marrow was diagnosed in the second adjuvant temozolomide cycle through biopsy. One week after, on investigation of pleural effusion, lung metastasis were discovered on pleural cytology and thoracic computer tomography. Liquid biopsy showed non-actionable mutations on PIK3CA, BRAF and KRAS. Chemotherapy with carboplatin and vincristine was started with markedly improvement of pancytopenia and pleural effusions leading to cessation of frequent transfusions and auxiliary oxygen. Vincristine dose was decreased due to painful neuropathy and tinnitus. At the end of endovenous chemotherapy, worsening of disease was found with metastasis to muscles of the face and brain parenchyma. Patient was then enrolled in hospice, dying weeks after. CONCLUSION DLGT should be considered in the differential diagnosis of vasospasm. DLGT is a primary central nervous system that can metastasize to other organs. Although no standard of care is yet identified, chemotherapy with vincristine and carboplatin can be offered to systemic metastatic disease.