He also reported recently being outside while on a fishing trip. Lumbar puncture (LP) was performed in the Emergency Department; and the patient was started on steroids, Ceftriaxone, Vancomycin and Acyclovir. LP had findings of elevated CSF protein (202.6 mg/dL) and CSF leukocytosis (WBC CSF 288/mm3 with 76% lymphocytes and 24% segs) consistent with meningitis. Initial CBC was remarkable for thrombocytopenia. Meningitis/encephalitis panel, HIV antigen/antibody, CSF culture, blood cultures, and syphilis testing were negative. On day two, the patient developed a petechial rash on bilateral lower extremities that resolved a few days later. The neurology and infectious disease teams were consulted and recommended MRIs of the complete CNS and testing for tick-borne diseases (E. chaffeensis, Anaplasma, Rocky Mountain spotted fever), arboviruses, ANA, complement testing, and CSF autoimmune/ paraneoplastic panel and started Doxycycline. MRI was notable only for leptomeningeal enhancement of the parietal, occipital, and posterior temporal
lobes; and the ordered CSF and serologic testing were unremarkable. Chest, abdominal, and pelvic CTs were performed to rule out malignant and paraneoplastic processes and were also unremarkable. Antibiotic coverage was eventually narrowed to a 7-day course of Doxycycline. The patient’s course was complicated by urinary retention and refractory ileus, thought to be secondary to the ongoing CNS inflammation after workup was negative for other etiologies. The patient also developed worsening hallucinations, nystagmus, tremors, and hyperactive delirium that was difficult to control with antipsychotics. Per recommendations of neurology, he consequently received 5 days of IVIG with gradual improvement. Discussion: While no etiology could be conclusively determined, the patient’s presentation was most consistent with viral or tick-borne meningoencephalitis. This case provides an instance of a patient without a suspected neuroimmunologic cause of his meningoencephalitis for which IVIG therapy was used with clinical improvement.
H2S DONORS AS RADIOSENSITIZERS FOR GLIOBLASTOMA MULTIFORME (GBM) Morni Modi, Camila Weber, QinQin Xu, Kuanling Chen, Ana Cheong, Zachery Nagel, Lynn Harrison; LSU Health - Shreveport School of Medicine, Shreveport, LA.
Introduction: Glioblastoma multiforme (GBM) is an extremely aggressive CNS cancer, resulting in death within 18 months despite maximal treatment. Radiation is a cornerstone therapy but poses high risk of healthy tissue necrosis. The use of radio sensitizing agents is a novel approach to minimizing healthy tissue necrosis by allowing use of lower radiation doses to achieve comparable cytotoxic effects. Our lab has shown that sodium sulfide (Na2S), a hydrogen sulfide (H2S) donor, selectively kills GBM (T98G) cells while sparing normal human brain endothelial (hCMEC/D3) cells. Na2S also selectively radio sensitizes GBM cells and enhances cell killing with photon or proton radiation (Xiao, 2019). Methods/Results: We are currently exploring Diallyl Trisulfide (DATS), another H2S donor and have demonstrated that DATS can kill GBM cells. At a given dose of 2 Gy, radiation alone decreases T98G survival by 10%. With DATS, survival decreases by 70%, suggesting an additive effect. To determine if DATS increases DNA damage mediated cell death, T98G cells were treated with DATS, radiation, or
combined DATS + radiation treatment and then analyzed for γH2AX foci, an indicator of double strand breaks (DSB). Our results show that compared to no treatment, DATS increased the number of γH2AX foci per cell by 1.5-fold, by 3-fold with radiation, and by 4-fold with combined DATS + radiation, an additive response. To elucidate the mechanism of increased DNA damage, a novel fluorescence multiplex host cell reactivation (FM- HCR) reporter system (Piett, 2021) was used to assess repair activity of DSBs in live cells. T98G cells pre- treated with DATS were transfected with reporter plasmids containing site-specific lesions, mimicking radiation-like DNA damage. Repair resulted in expression of a fluorescent reporter protein, which was quantitated using flow cytometry. Our results show that DATS did not alter non-homologous end joining (NHEJ) or homologous repair (HR) activity of DSB. However, DATS did alter base excision repair (BER) activity by decreasing repair of abasic lesions and increasing repair of 8oxoG lesions.
Conclusion: We hypothesize that this attempted
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