Initial Lumbar Puncture Research Articles

Miliary TB in children and adolescents: a scoping review.

<sec><title>OBJECTIVE</title>To summarise the available literature regarding clinical presentation, immunological and microbiological diagnosis, treatment, and outcomes of miliary TB in children and adolescents.</sec><sec><title>METHODS</title>Four databases were searched from 1 January 1950 to 31 January 2023. "Miliary" and "disseminated" TB were the main search concepts.</sec><sec><title>FINDINGS</title>Of 257 studies, 1,883 patients with miliary TB were included. Bacille Calmette-Guérin (BCG) vaccination was confirmed in 223/549 (40.6%) children. Central nervous system (CNS) involvement was reported in 367/924 (39.7%) cases; many of them had no neurological symptoms despite also having abnormal brain imaging. Of 1,112 children with known outcomes, 341 (30.6%) died; mortality was higher in publications before 1995 (41.5%) and in children with CNS involvement (31.9%). TB microbiological confirmation (55.8%) and sensitivity of tuberculin skin test (46.9%) and QuantiFERON Gold (72.4%) were overall low.</sec><sec><title>CONCLUSIONS</title>Evidence is lacking to support best practices for paediatric miliary TB. Whether lumbar puncture (LP) and brain imaging should both be routinely done in miliary TB children, or a step-by-step approach based on initial LP findings, remains unclear. This study should inform policymakers and funding agencies about current significant gaps that need to be addressed by future high-quality studies.</sec>.

Severe Neuropathic Back Pain as the Initial Presentation in Angiostrongylus cantonensis Infection: The Role of ICU Management in Overcoming Diagnostic and Analgosedation Challenges

Introduction: Angiostrongylus cantonensis is a parasitic nematode that typically inhabits the pulmonary arteries of rats but can also reside in the central nervous systems of rats and mollusks. Humans can become infected with A. cantonensis by eating infected hosts or consuming contaminated food, especially if it is raw or undercooked. This infection can lead to various neurological symptoms, including neuropathic pain, which is often an early indication of the condition. In this report, we present a case in which the patient experienced neuropathic pain as the initial clinical manifestation of A. cantonensis infection. Case Presentation: We present a rare case of a 27-year-old female who required intensive care unit (ICU) monitoring due to heavy sedation after receiving high doses of sedative-analgesics for back pain. The patient reported experiencing severe, slow-progressing low back pain radiating to her arms and legs. The pain was described as sharp, tingling, and numbing, severely limiting her movements. To manage the pain, a combination of morphine, intermittent fentanyl, ketamine, dexmedetomidine, duloxetine, and pregabalin was administered. Consequently, the patient had to be intubated due to the effects of the analgesics. During the first two weeks in the ICU, diagnosis proved challenging as the MRI was normal and the initial lumbar puncture revealed only an eosinophilic infection. However, during a follow-up lumbar puncture, multiple parasites were discovered in the cerebrospinal fluid, which were identified as A. cantonensis. The patient remains on a ventilator as the infection has affected the spinal nerve roots, cord, meninges, and brain. We explore the crucial role of ICU care in providing both supportive and definitive treatment for this patient. Conclusions: This report underscores the critical role of the ICU in providing care for a patient with a progressively deteriorating condition without an initial definitive diagnosis. The ICU's ability to deliver optimal pain relief and sedation, advanced monitoring, and prompt therapy for deteriorating symptoms was of utmost significance. Furthermore, the multidisciplinary team in the ICU was instrumental in managing the continuum of care for the patient.

NeuroBehcet’s-related intracranial hypertension without cerebral venous thrombosis: case report and review of literature

BackgroundWe present a rare case of NeuroBehcet’s-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of NeuroBehcet’s. In addition, we describe the novel use of subcutaneous tocilizumab for this indication. This is followed by a review of the literature on this topic.CaseThe patient was a 28-year-old lady of Southern Chinese origin with a known history of Behcet’s disease with oral ulcers and ocular findings for which she was on mycophenolate mofetil and adalimumab. She presented with a headache and bilateral disc swelling associated with an intracranial pressure (ICP) of > 40cmH20. There were no structural lesions or cerebral venous thrombosis (CVT) on imaging. Initial lumbar puncture had raised leucocytes and protein. We discuss diagnostic challenges given persistently elevated ICP despite subsequent non-inflammatory cerebrospinal fluid (CSF) profiles and non-response to acetazolamide. She eventually showed a response to immunosuppressant therapy in the form of pulsed methylprednisolone, cyclophosphamide and subsequently subcutaneous tocilizumab, supporting the diagnosis of NBrIHwCVT. Complete normalization of ICP remains challenging. Her disease course was severe, unusual for her ethnicity.Literature reviewWe identified 34 patients (including ours) from 14 publications. We found that the majority of NBrIHwCVT patients were young (average age of 34 years), with a slight female preponderance. Of the 17 cases in the literature with available data on CSF profile, none had raised leucocytes whilst one patient had elevated protein. Patients were generally treated with steroids and occasionally azathioprine, in line with the suspected autoimmune pathophysiology. Of 22 patients with data on outcome, six (27%) were noted to have recurrence of symptoms generally occurring a few months later.ConclusionAs demonstrated by this case, NBrIHwCVT can present with BD with raised ICP even if there is no prior history of NB, central Asian ethnicity, cerebral venous thrombosis or features of inflammation on the CSF. We demonstrated how novel use of Tocilizumab may have a role in the management of NBrIHwCVT. Based on our literature review, patients were more likely to be young, female, display a non-inflammatory CSF picture, be treated with steroids and harbour a possibility of recurrence.

Persistent headaches one year after bacterial meningitis: prevalence, determinants and impact on quality of life.

Little is known on headaches long-term persistence after bacterial meningitis and on their impact on patients' quality of life. In an ancillary study of the French national prospective cohort of community-acquired bacterial meningitis in adults (COMBAT) conducted between February 2013 and July 2015, we collected self-reported headaches before, at onset, and 12months (M12) after meningitis. Determinants of persistent headache (PH) at M12, their association with M12 quality of life (SF 12), depression (Center for Epidemiologic Studies Depression Scale) and neuro-functional disability were analysed. Among the 277 alive patients at M12 87/274 (31.8%), 213/271 (78.6%) and 86/277 (31.0%) reported headaches before, at the onset, and at M12, respectively. In multivariate analysis, female sex (OR: 2.75 [1.54-4.90]; p < 0.001), pre-existing headaches before meningitis (OR: 2.38 [1.32-4.30]; p < 0.01), higher neutrophilic polynuclei percentage in the CSF of the initial lumbar puncture (OR: 1.02 [1.00-1.04]; p < 0.05), and brain abscess during the initial hospitalisation (OR: 8.32 [1.97-35.16]; p < 0.01) were associated with M12 persistent headaches. Neither the responsible microorganism, nor the corticoids use were associated with M12 persistent headaches. M12 neuro-functional disability (altered Glasgow Outcome Scale; p < 0.01), M12 physical handicap (altered modified Rankin score; p < 0.001), M12 depressive symptoms (p < 0.0001), and M12 altered physical (p < 0.05) and mental (p < 0.0001) qualities of life were associated with M12 headaches. Persistent headaches are frequent one year after meningitis and are associated with quality of life alteration. NCT01730690.

Cohort profile: a longitudinal study of HIV infection in the central nervous system with focus on cerebrospinal fluid – the Gothenburg HIV CSF Study Cohort

PurposeIn order to enable long-term follow-up of the natural course of HIV infection in the central nervous system, a longitudinal cohort study with repeated cerebrospinal fluid (CSF) analyses at intervals...

Wernicke’s Encephalopathy Preceded by COVID-19 Infection: A Case Report (P2-7.006)

<h3>Objective:</h3> To describe a case of post-infectious encephalopathy following COVID-19 with MRI brain changes suggestive of Wernicke’s encephalopathy and a transient presence of anti-GAD65 autoantibodies in the cerebrospinal fluid (CSF). <h3>Background:</h3> Chronic malnutrition and alcoholism are known risk factors for developing Wernicke’s encephalopathy. However, it is not typically associated with thiamine deficiency resulting from acute starvation as in this case of severe respiratory syndrome due to coronavirus-2 (SARS-CoV-2). <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 59 year-old female presented to the neurointensive care unit with subacute disorientation, decreased verbal fluency, memory deficits, gait dysfunction, confusion, and rapid weight loss that progressed to coma over two months following COVID-19 infection. Initial lumbar puncture (LP) one month following infection was notable for positive anti-GAD65 autoantibodies and elevated protein which was suggestive of post-infectious encephalitis. MRI brain at the time of initial evaluation was unremarkable for abnormalities and the patient’s symptoms continued to progress to include depressed mentation. Subsequent MRIs of the brain with and without contrast showed T2 FLAIR abnormalities in the periaqueductal grey, lateral walls of the third ventricle, splenium, and mammillary bodies. Repeat LP showed similar CSF profile and absence of anti-GAD65 autoantibodies. Electroencephalogram showed slowing with frequent generalized periodic discharges. Patient’s treatment course included high dose thiamine, methylprednisolone, intravenous immunoglobulin, and plasmapheresis without clinical improvement. The patient did not show meaningful cognitive recovery and was transitioned to comfort care. <h3>Conclusions:</h3> The patient’s progression to coma was suspected to be due to development of COVID-19 encephalopathy precipitating Wernicke’s encephalopathy in the setting of severely diminished oral intake. Because Wernicke’s encephalopathy is potentially reversible with thiamine administration, we propose that early empiric treatment should be considered in all patients suffering from persistent encephalopathy following COVID-19 infection. <b>Disclosure:</b> Dr. Volski has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Chakrabarti Pulakanti has nothing to disclose. Dr. Dolla has nothing to disclose.

Lumbar puncture for treating acute hydrocephalus after aneurysmal subarachnoid haemorrhage

BackgroundExternal ventricular drainage (EVD) for acute hydrocephalus after aneurysmal subarachnoid haemorrhage (aSAH) carries a risk of complications. We studied the proportion of patients in whom EVD can be avoided by treating acute hydrocephalus with ≥1 lumbar punctures (LP). MethodsFrom a prospectively collected database, we retrieved data on all aSAH patients admitted between 2007 and 2017 who developed acute hydrocephalus (i.e. neurological deterioration and ventricular enlargement <72 h after aSAH). Our regime is to consider LP as initial treatment. We calculated the proportions of patients (with corresponding 95% confidence interval (CI)) who improved after the initial LP and the extent of clinical improvement, the proportions of patients who were treated with only ≥1 LP(s), and those of patients needing continuous external ventricular or external lumbar drainage, or permanent ventriculoperitoneal or lumboperitoneal drainage. ResultsOf 1391 consecutive aSAH patients, 473 (34%) had acute hydrocephalus, of whom 388 (82%) were treated. Of the 86 patients with LP as initial treatment, 70 (81% [95% CI 72–88]) showed initial improvement (with increase in median Glasgow Coma Score from 10 (IQR 7–12) to 12 (IQR 9–14) after initial LP), 39 (45% [95% CI 35–56]) improved with LP only, 41 (48% [95% CI 37–58]) needed continuous drainage and six (7% [95% CI 3–14]) needed permanent drainage. ConclusionAround half the patients treated with LP for deterioration from acute hydrocephalus after aSAH does not require continuous extraventicular or extralumbar drainage.

Is Lateral Decubitus or Upright Positioning Optimal for Lumbar Puncture Success in a Teaching Hospital?

BackgroundLumbar puncture is a common procedure performed by emergency physicians and trainees. The optimal patient positioning for lumbar puncture procedures has not been studied adequately. ObjectivesWe performed a prospective randomized study in an urban, level I academic trauma center. Patients of all ages were included. Patients were randomized to either lateral decubitus or upright positioning. Patient demographic characteristics, level of physician training and experience, number of needle insertions and redirections, need for repositioning, alternative operator use, and laboratory results of the cerebrospinal fluid were recorded. We compared the success rate of each position as our primary outcome measure. We also evaluated number of needle insertions and re-directions and success rates based on experience and patient age. ResultsA total of 116 patients were enrolled, with 55 patients assigned to lateral decubitus and 61 to upright position for initial lumbar puncture attempt. Spinal fluid was obtained successfully in 47 of the lateral decubitus group (85.5%; 95% CI 73.8–92.4%) vs. 49 (80.3%; 95% CI 68.7–88.4%) in the upright assignment group. Comparable results were also obtained for first-pass success, number of failures, and number of bloody taps. Postgraduate year 2 residents or those with 31–50 previous lumbar punctures had the highest success rates at 94.3% (95% CI 81.2–98.4%) and 90.3% (95% CI 75.1–96.7%), respectively. ConclusionsLateral decubitus and upright positioning for emergency lumbar puncture yielded equal success rates in emergency physicians and trainees.

NCMP-17. BEWARE: ALL POSTERIOR FOSSA MASSES IN CHILDREN ARE NOT BRAIN TUMORS

Abstract INTRODUCTION Isolated Myeloid sarcoma (MS) of the central nervous system (CNS-MS) is a very rare presentation of Acute Myeloid Leukemia (AML). A 10-year-old boy with a two-week history of intermittent headaches was referred to the emergency department (ED) by an optometrist for evaluation of bilateral papilledema. Physical examination in the ED confirmed the presence of papilledema with no other abnormal neurologic findings. Emergent MRI of the brain showed an avidly homogeneously enhancing extra-axial dural based mass in the right posterior fossa measuring 4.8 cm (AP) x 3.2 cm (CC) x 4.6cm (T), with significant mass effect and peri-tumoral vasogenic edema. Neuro-surgery consultation was obtained and complete blood count (CBC) was normal except for the presence of 13% blasts with occasional Auer rods seen on the peripheral blood smear. Bone marrow aspirate demonstrated 56% myeloblasts; A diagnosis of AML with CNS-MS (CNS-3c) was made and the initial lumbar puncture (LP) was deferred due to the risk of CNS herniation. Induction chemotherapy was initiated as per protocol. A CT scan done two weeks later showed complete resolution of the intracranial mass. DISCUSSION The incidental finding of papilledema, with imaging to investigate the intracranial pathology revealed a large posterior fossa mass in our patient. However, the atypical features of the mass (dural based extra-axial location; extensive infiltration into adjacent structures) and the finding of blasts with Auer rods in peripheral blood helped us to diagnose CNS-MS, and avoided an extensive neurosurgical procedure and a delay in definitive therapy. Our patient had a normal CBC and the review of the peripheral blood film by an experienced Hematologist was very crucial in making a clinical diagnosis of MS. CONCLUSION Myeloid sarcomas should be considered in the differential diagnosis of an intracranial mass, particularly when accompanied by abnormal findings in the CBC.

GET THE MUNKII OFF YOUR BACK! A RARE BLACK MOLD CAPRONIA MUNKII CAUSING INVASIVE FUNGAL INFECTION IN AN IMMUNOCOMPROMISED INDIVIDUAL

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Individuals receiving chemotherapy or undergoing transplantation are increasingly susceptible to invasive fungal infections. They are commonly caused by opportunistic pathogens like Aspergillus and Candida and are associated with high morbidity and mortality. Such individuals are also susceptible to invasive mold infections. We present a rare case of a black mold Capronia munkii causing cavitary lung lesions in a patient with NHL. CASE PRESENTATION: A 65-year-old female with non-Hodgkin's Lymphoma, CNS lymphoma treated with chemotherapy and autologous stem cell transplant five years ago, had progression of disease last year. She began Ibrutinib therapy for her lymphoma. She was admitted to the hospital for altered mental status due to progression of CNS disease. She developed worsening respiratory failure during hospitalization requiring intubation and mechanical ventilation. She was empirically treated with intravenous vancomycin and piperacillin-tazobactam. Her initial infectious workup and lumbar puncture was negative. Computed tomography (CT) of her chest showed new diffuse ground glass opacities.Bronchial wash was notable for black mold Capronia munkii. She was started on Voriconazole and Amphotericin B. Repeat CT chest showed improving opacities with increasing apical cystic lesions. Respiratory failure can be attributed to mold infection in the lung, immunotherapy-induced pneumonitis and organizing pneumonia. After multiple failed spontaneous breathing trials and septic shock necessitating vasopressors, she was transitioned to comfort care and subsequently expired. DISCUSSION: Capronia munkii is a saprotrophic yeast commonly found on decaying plant matter. There is a lack of clinical information on this mold in literature. It is closely related phylogenetically to Exophiala dermatides which is a neurotrophic black mold. It typically causes a non-specific granulomatous inflammatory response. The host responses are highly variable, and include pulmonary cyst formation and tissue necrosis. The patient's immunosuppression and cystic lesions on CT scan make invasive black mold infection likely. Biopsy of the cavitary lesions to determine the presence of mold would have been confirmatory. The lack of response to anti-fungal treatment reiterates the high mortality associated with this rare infection. CONCLUSIONS: Invasive fungal infections have become more prevalent due to increasing number of individuals undergoing transplantation or receiving aggressive immunosuppression and chemotherapy. Early diagnosis and prompt treatment of uncommon pathogens like black mold with appropriate azole and caspofungin antibiotics is essential to prevent poor outcomes. Newer molecular techniques such as 18S ribosomal RNA PCR and genome sequencing have led to improved diagnosis.Treatment algorithms should be adapted to accommodate changing epidemiologies and anti-fungal drug resistance patterns. REFERENCE #1: Bassetti M, Bouza E. Invasive mould infections in the ICU setting: complexities and solutions. J Antimicrob Chemother. 2017 Mar 1;72(suppl_1):i39-i47. doi: 10.1093/jac/dkx032. PMID: 28355466. REFERENCE #2: Enoch DA, Yang H, Aliyu SH, Micallef C. The Changing Epidemiology of Invasive Fungal Infections. Methods Mol Biol. 2017;1508:17-65. doi: 10.1007/978-1-4939-6515-1_2. PMID: 27837497. REFERENCE #3: Badiee P, Hashemizadeh Z. Opportunistic invasive fungal infections: diagnosis & clinical management. Indian J Med Res. 2014 Feb;139(2):195-204. PMID: 24718393; PMCID: PMC4001330. DISCLOSURES: No relevant relationships by Padmastuti Akella, source=Web Response No relevant relationships by Saira Imran, source=Web Response No relevant relationships by Shashank Nuguru, source=Web Response

Decreasing Dose and Duration of Dexamethasone Therapy for Low-Risk Childhood Acute Lymphoblastic Leukemia Aiming to Avoid Serious Viral Infections Results in Significant Increase in Isolated CNS Relapse: A Prospective Study

Background: In the era of treating childhood acute lymphoblastic leukemia (ALL) without cranial irradiation, optimization of central nervous system (CNS) active therapeutic agents is needed to prevent CNS relapse. Dexamethasone is an essential part of maintenance therapy in most current protocols for its excellent CNS penetration and anti-leukemic effect. The dose and duration of dexamethasone treatment for low-risk patients vary across trials. In our institution, we adopted the St Jude Total XV protocol with minor modifications since 2002. This treatment has resulted in 5-year OS and EFS rates of 96.4% and 94% respectively for low-risk patients. However, around 11% of patients developed serious viral infections, mainly disseminated varicella (6%), CMV retinitis (3.6%) and progressive multifocal encephalopathy (1.1%). The aim of this trial was to decrease the incidence of serious viral infections by decreasing the dose and the duration of dexamethasone treatment during maintenance therapy.Patients and Methods: This is a prospective, non-randomized trial of all consecutive low-risk ALL patients aged 1-18 years treated at the Children's Cancer Center of Lebanon that included patients diagnosed after June 2013 as well as patients diagnosed earlier who had not reached week 100 of maintenance therapy by June 2013. Low-risk patients were defined elsewhere [Muwakkit et al, Am J Hematol. 2012 Jul;87(7):678-83].For patients diagnosed after June 2013; dexamethasone dose was decreased by 25% (from 8 to 6 mg/m2/day for 5 days/week every 4 weeks) and dexamethasone pulses were stopped at week 69 instead of week 100 from start of maintenance therapy. For patients on therapy who had not reached week 69 of maintenance; dexamethasone pulses were stopped at week 69, and dexamethasone dose was decreased by 25% (from 8 to 6 mg/m2/day for 5 days/week every 4 weeks) starting June 2013. For patients who had completed 69 weeks but did not reach week 100 of maintenance by June 2013, dexamethasone pulses were stopped. The interval between dexamethasone pulses was 4 weeks for all patients, before and after the change.The number of intrathecal chemotherapy injections was not changed.For analysis, historical control patients who completed therapy before June 2013 and patients on therapy who completed more than half of their planned dexamethasone pulses (week 50) by June 2013 were assigned to group 1. Patients who were diagnosed after June 2013 and those who had received less than half of their planned dexamethasone pulses (week 50) by June 2013 were assigned to group 2.The trial was stopped in May 2017 due to the observed increased incidence of isolated CNS relapse in group 2.Results: The total number of patients was 84 in group 1 and 33 in group 2. There was no significant difference in patient characteristics between the two groups. After a median follow-up of 88 months (range: 24-177), the 4-year cumulative incidence of isolated CNS relapse increased from 0% in group 1 to 9.5% (n=3) (95% CI: 0-19.2%) in group 2 (P : 0.005). The mean cumulative dose of dexamethasone was 1129 mg/m2 (SD 49 mg/m2) for group 1 and 838 mg/m2 (SD 31 mg/m2) for group 2 (P : <0.001). The mean total duration of dexamethasone pulses from start of maintenance treatment was 97 weeks (SD 8 weeks) for group 1 and 69 weeks (SD 0 weeks) for group 2 (P <0.001). The cumulative dose of dexamethasone received by patients with isolated CNS relapse was 824, 876 and 930 mg/m2. The isolated CNS relapses occurred at weeks 74, 95 and 116 of maintenance therapy. None of the patients with isolated CNS relapse had an initial traumatic lumbar puncture. None of group 2 patients developed disseminated varicella, CMV retinitis, or progressive multifocal encephalopathy. None of the patients in both groups developed bone marrow relapse within 4 years of diagnosis. The 4-year cumulative incidence of infection-related mortality was 3.5% (95% CI: 0-7.4%) for group 1 and 0% for group 2 (P : 0.27). The 4-year OS rate was 96.4% (95% CI: 89.3-98.8%) for group 1 and 100% for group 2 (P : 0.27). The 4-year EFS rate was 96.4% (95% CI: 89.3-98.8%) for group 1 and 90.5% (95% CI: 73.2-96.8%) for group 2 (P : 0.24).Conclusions: Decreasing dose and duration of dexamethasone therapy for low-risk childhood ALL patients aiming to avoid serious viral infections led to significant increase in isolated CNS relapse. Further studies are needed to identify the optimal dose and duration of dexamethasone therapy for these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Outcomes Based on CNS Disease Status in Pediatric Acute Myeloid Leukemia and the Role of Peripheral Blood Contamination in Diagnostic Lumbar Punctures; A Report from the Children's Oncology Group Studies AAML0531 and AAML1031

The diagnosis and treatment of CNS leukemia in AML differs between pediatric and adult oncology. Adult AML patients generally receive no prophylactic intrathecal (IT) treatment. Here we evaluate an approach utilized on 2 recent Children's Oncology Group (COG) clinical trials for pediatric AML which included CNS prophylaxis and a low threshold to initiate CNS leukemia directed therapy.A total of 2119 patients with de novo AML were evaluable from COG trials AAML0531 and AAML1031. Patients with FLT3/ITD on AAML1031 are excluded as that cohort remains eligible for ongoing accrual. The median (range) follow-up time was 7.1 (0 - 10.5) years for AAML0531 and 2.5 (0 - 5.7) years for AAML1031. All patients received IT cytarabine once with each induction and intensification cycle (except for one of the intensification cycles with high dose cytarabine). An LP to determine CNS status was performed at start of induction therapy. CNS positive (CNSpos) leukemia was treated with twice weekly IT cytarabine until 2 negative CSF samples were obtained (minimum 4 and maximum 6 ITs). CNSpos was defined similarly on both trials (Table 1). In order to understand the role of traumatic LP in CNS status and outcomes, CNS status in this analysis was further classified according to criteria used for ALL (Table 1). Comparing the ALL criteria to the AML CNS definition, CNS1 patients are CNS negative (CNSneg) and CNS3 patients are CNSpos, however among patients with CNS2 by ALL criteria, the AML CNS definition does not take into account the number of CSF WBCs in an atraumatic LP and also uses a higher CSF RBC number (100 versus 10) to require use of the Steinherz/Bleyer algorithm.The rate of CNS relapse (isolated CNS and combined CNS and bone marrow) was evaluated separately on each trial since the protocols differed in number of chemotherapy courses and SCT allocation. On AAML0531, the 5 year CNS relapse rate was lower for CNS1 (4.5 ± 1.7%) compared to CNS2 (9.1 ± 4.5%) or CNS3 (17.7 ±9.4%), P<0.001. This finding was replicated in the AAML1031 outcomes; CNS relapse rates were 4.9 ± 1.8% (CNS1), 11.7 ± 5.0% (CNS2) and 19.3 ±8.8% (CNS3), P<0.001. Patients who were CNSpos had a higher 5 year CNS relapse rate on both studies (CNSpos 13.2 ± 5.1% vs. CNSneg 4.9 ± 1.7% on AAML0531, P<0.001; CNSpos 12.9 ± 4.3 % vs. CNSneg 5.6 ± 1.8% on AAML1031, P<0.001). Event free survival (combined AAML0531 and AAML1031) differed by CNS category (CNS1 51.2%, CNS2 43.5%, CNS3 37.7%, P<0.001) and AML CNS group (CNSneg 41.2%, CNSpos 49.9%, P<0.001), but overall survival did not differ significantly.We evaluated the role of peripheral blood contamination. For patients with CSF RBC ≥100, the majority of patients were classified by ALL criteria as CNS2 or CNS3, and the rate of CNS3 disease increased approximately two fold compared to those with CSF RBC <100 (Fig 1a). When considering the COG AML definition, CNSpos rate was substantially higher among those with CSF RBC 10-99 (41%) compared to those with CSF RBC <10 (24%) or RBC ≥100 (27%; Fig 1b). This difference is likely due to the presence of peripheral blood blasts without “correction” for this blood contamination because the Steinherz/Bleyer algorithm was not used to determine CNSpos when CSF RBC <100.The median blood WBC count was significantly lower in patients with CNS1 (14,650; 95% CI 13,200-15,900) compared to CNS2 (46,200; 95% CI 40,500-53,700) or CNS3 (32,400; 95% CI 21,900-43,500). Further, when this analysis was restricted to patients with an atraumatic tap (CSF RBC <10), those with CNS1 still had significantly lower WBC compared to those with CNS2 or CNS3 (median WBC [95% CI]: CNS1 15,100 [13,400-16,800]; CNS2 53,700 [45,800-62,000]; CNS3 35,500 [21,000-50,100]). This suggests that the biologic drivers resulting in leukocytosis may also increase the risk of CNS leukemia.This analysis demonstrates that CNS disease in AML is associated with a higher CNS relapse risk but caution must be used in interpreting disease status at diagnosis. Due to the worse prognosis associated with CNS disease, we advocate continued use of diagnostic lumbar punctures and intensified treatment for pediatric patients with CNS disease. However, we also speculate that deferring the initial diagnostic lumbar puncture until clearance of peripheral blasts (which usually occurs by day 5-8 of induction) may minimize the risk of false positive diagnosis of CNS disease resulting from high peripheral WBC and blast contamination of CSF samples. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The value of repeated lumbar puncture to test for xanthochromia, in patients with clinical suspicion of subarachnoid haemorrhage, with CT-negative and initial traumatic tap

Objectives For the diagnosis of subarachnoid haemorrhage (SAH), the presence of cerebrospinal fluid (CSF) xanthochromia is still considered the gold standard for patients with a thunderclap headache, in the absence of blood on brain CT scan. However, a traumatic lumbar puncture (LP) typically results in high concentrations of oxyhaemoglobin in CSF, impairing the detection of xanthochromia and preventing the reliable exclusion of SAH. In this context, the value of a repeat lumbar puncture has not yet been described. Materials and methods A retrospective case series of suspected SAH patients, with a negative CT scan and initial traumatic LP, managed with a repeat LP to assess for CSF xanthochromia. Clinical notes, laboratory and imaging results were reviewed. Results Between August 2011 and January 2020, 31 patients with suspected SAH were referred to our neurosurgical unit following negative CT and traumatic LP. A repeat LP was performed in 7 of the 31 patients, 2.4 days (±0.79 SD) after the first traumatic LP. CSF spectrophotometry analysis from repeated LP in all 7 patients was negative for xanthochromia. No adverse clinical events were recorded on average 18 months following discharge. Conclusion A repeat LP performed following a traumatic tap can still yield xanthochromia-negative CSF, thereby, excluding SAH, avoiding unnecessary invasive angiography and overall promoting the safer management of these patients.

Delays in lumbar puncture are independently associated with mortality in cryptococcal meningitis: a nationwide study

Background Cryptococcal meningitis (CM) is the most serious presentation of invasive cryptococcosis. Seen in patients with and without HIV infection, CM is associated with significant morbidity and mortality. Early lumbar puncture is a cornerstone of treatment in cryptococcal meningitis. We present findings from a nationwide analysis of patients admitted with CM in the United States between 2007 and 2016, with the aim of determining the impact of delays in lumbar puncture on inpatient outcomes. Methods The national inpatient sample (NIS) database was queried for all inpatient visits for cryptococcal meningitis between January 2007 and December 2016. Logistic regression models were used to determine risk factors for inpatient mortality, prolonged admissions, and delays in obtaining an initial lumbar puncture. Results The annual number of admissions for CM decreased during the study interval, from 3590 in 2007 to 2830 in 2016. Mortality did not change over this period (9.9%); however, length of stay and inpatient cost significantly increased. The proportion of patients with HIV declined from 70.7% to 54.0%. Delay in lumbar puncture beyond the first 24 h was independently associated with mortality (OR = 1.55, CI = 1.31–1.82, p-value <.001). Patients admitted on a weekend, those of African–American ethnicity, and those without a known history of HIV were more likely to have delays in obtaining an early LP. HIV patients had a lower risk of mortality (OR = 0.77, CI = 0.68–0.86, p-value <.001). Conclusion We found an independent association of delay in early lumbar puncture with worsened patient outcomes. Inpatient mortality for patients with CM continues to remain high, with an increasing proportion of patients without underlying HIV infection. There were significant deviations in management of CM from Infectious Diseases Society of America (IDSA) guidelines.

The Contribution of Lumbar Puncture in Neonatal Infections - About 206 cases

Background: Neonatal meningitis is a serious infection, no clinico-biological score has been established to accurately identify neonates at high risk of developing neonatal meningitis.Objective: The aim of this work is to clarify the place of lumbar puncture in neonatal infections and to identify the predictive factors of meningeal localization in case of neonatal infection.Materials and methods: This is a prospective study of 861 observations of newborns hospitalized in the pediatric department of Mohammed V Hospital, CHU of Tangier, during a 14-month period from 1January 2019 to 29 February 2020. Among these patients the diagnosis of neonatal infection (NNI) was retained in 473 cases. Initial lumbar puncture was performed in 206 cases (43%). We included neonates aged 0 to 28 days, suspected of NNI, who had a lumbar puncture. Neonates treated as carriers of neonatal infection without sufficient anamnestic and clinical evidence and with an inconclusive or unperformed biological workup were excluded from the study.Results: During the study period, 861 newborns were hospitalized and the diagnosis of neonatal infection was retained in 473 cases, a rate of 55%, and the initial lumbar puncture was performed in 206 cases (43%). 61 newborns were diagnosed with neonatal meningitis, with fever in 76% of cases, 85% with convulsions, hypotonia and/or refusal to suckle in 63% of cases, and CRP &gt;25mg/l in 67% of newborns.Conclusion: Lumbar puncture is the only diagnostic means of meningitis. Indeed, the indication of this procedure should not be systematic, but it should be dictated by the careful and simultaneous analysis of the anamnestic, clinical and biological criteria evocative of the infection and its meningeal localization in order to diagnose meningitis early and treat it correctly. The need to establish scores combining these different parameters, in order to accurately identify newborns at high risk of developing neonatal meningitis

52. A Nationwide Analysis of the Trends and Outcomes of Cryptococcal Meningitis in the United States

BackgroundCryptococcal Meningitis (CM) is the most common presentation of invasive cryptococcosis. Seen in patients with and without HIV, CM is associated with significant morbidity and mortality. We present findings from a nationwide analysis of patients admitted with CM in the United States between 2007 and 2016.MethodsThe national inpatient sample (NIS) database was queried for all inpatient visits for Cryptococcal Meningitis between January 2007 and December 2016. Logistic regression models were used to determine risk factors for mortality, prolonged admissions, and delays in obtaining an initial lumbar puncture.ResultsThe number of admissions for CM decreased during the study interval, from 3590 in 2007 to 2830 in 2016. Mortality did not change over this period (9.9%), however length of stay and inpatient cost significantly increased (P = 0.003 and P < 0.001 respectively). The proportion of patients with HIV declined from 70.7% to 54.0% (P < 0.001). HIV patients had a lower risk of mortality (OR = 0.77, CI 0.68–0.86, P < 0.001), whereas Africa-American, Hispanic and Native American ethnicities had a significantly increased association with mortality. Delay in lumbar puncture beyond the first 24 hours was independently associated with mortality, with an OR of 1.55 (CI 1.31–1.82, P < 0.001). . Patients admitted on a weekend, those of African-American ethnicity, and those without a known history of HIV were more likely to have delays in obtaining an early LP.ConclusionInpatient mortality for patients with CM continues to remain high, with an increasing proportion of patients without underlying HIV infection. We found significant deviations in management of CM from IDSA guidelines, and an independent association of delay in early lumbar puncture with worsened patient outcomes.Disclosures All Authors: No reported disclosures

RARE-40. CASE REPORT: LONG-TERM SURVIVOR OF A RARE, PEDIATRIC PRIMARY HISTIOCYTIC SARCOMA (HS) OF THE CENTRAL NERVOUS SYSTEM (CNS) FOLLOWING COMPLETE RESECTION, CHEMOTHERAPY AND ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (ALLO-HCT)

We report an unusual case of a patient with primary CNS-HS a very rare neoplasm of histiocytic lineage with usually poor prognosis. An 8 year old boy presented with a one month history of headaches, nausea and vomiting. Physical examination revealed nystagmus and dysmetria. Brain MRI revealed a localized 2.4 cm posterior fossa (cerebellar) mass with restricted diffusion. The patient underwent a gross total resection of the mass. Initial post-operative lumbar puncture was positive for rare malignant cells. Pathology showed a focally necrotic neoplasm, composed of nests and cords of large relatively uniform cells with abundant eosinophilic cytoplasm, moderately pleomorphic nuclei and numerous mitotic figures, consistent with CNS-HS with juvenile xanthogranuloma phenotype, as supported by positive IHC expression of CD163, CD68, CD14, fascin, and Factor XIIIa, while negative for CD1a, Lymphoid and Myeloid markers, and BRAFv600e mutation. He was treated with two cycles of clofarabine and cytarabine and triple intrathecal (IT) chemotherapy. He developed generalized seizures and MRI showed demyelination consistent with IT methotrexate toxicity; MTX was then discontinued. He was then given two additional cycles of cladribine and weekly intrathecal therapy prior to consolidation with an Allo-HCT using a 10/10 HLA allelic-matched unrelated donor. His conditioning regimen included total body irradiation and cyclophosphamide. He did well post-transplant with peripheral blood chimerism at 1 year showing > 95% donor cells. He remains disease-free with an excellent quality of life since August 2016. We report one of the few known survivors of this unusual and highly malignant entity.

Variability of Consecutive Lumbar Puncture Opening Pressures.

Lumbar puncture (LP) opening pressures (OPs) are known to fluctuate based on diurnal, environmental, and pathologic conditions. Despite their dynamic nature, single OPs are often deemed sufficient for diagnosis of elevated intracranial pressures (ICPs) in nonspecialists' hands. The purpose of this study was to determine the variability of consecutive LP OPs at a large referral center to determine the potential range of variability for a given LP OP. In this retrospective cohort study, medical records of all patients seen at Mayo Clinic, Rochester, MN, from January 1, 2001, through June 1, 2016, were screened for ≥2 LP OPs within 30 days of each other. Patients with pathologic conditions known to influence ICP were excluded. There were 148 eligible patients (39.2% female) with mean age of 63.5 ± 15.5 years and mean body mass index (BMI) 28.0 ± 6.0. The LPs were a mean of 10 ± 9 days apart. Mean OP for the first and second LP was 149 ± 51 mm H2O and 148 ± 48 mm H2O (P = 0.78), respectively, with a mean difference of 1 mm H2O, providing an overall coefficient of repeatability (CR) of 86.4 between consecutive LPs. There was a significant correlation between initial OP and BMI (r = 0.39, P < 0.001). OP >200 mm H2O had a significantly higher CR of 111.4, compared to OP <200 mm H2O, with CR 74.6 (P = 0.006). CRs were also higher for patients with diagnoses of headache (P = 0.002) or anxiety (P = 0.03). Higher initial LP OP, headache, and anxiety were associated with greater variability on subsequent LPs. OPs that are not consistent with the patients' clinical signs and symptoms should therefore be interpreted with caution.

16 Variability in lumbar punctures and neuroimaging in infants less than 90 days with acute bacterial meningitis at a provincial children’s hospital in Canada

Abstract Background Bacterial meningitis remains a significant cause of morbidity and mortality in infants, necessitating appropriate and timely investigations and treatment. Despite this, there are no current Canadian practice guidelines outlining the recommended management of infants with bacterial meningitis beyond empiric antimicrobial choice. As bacterial meningitis remains one of the most severe infectious diseases managed by general pediatricians, it warrants an attempt at practice standardization. Objectives The purpose of this study is to review and identify variation in the timing and frequency of lumbar punctures (LPs) and the use of neuroimaging for the management of bacterial meningitis for infants less than 90 days of age at BC Children’s &amp; Women’s Hospital (BCCWH). Design/Methods A retrospective chart review at BCCWH identified confirmed, presumed or possible bacterial meningitis in infants less than 90 days of age over a five-year period (2013-2018). Anonymized data was collected from medical charts, de-identified and stored in REDCap. Results Eighty-one patients were included. Fifty-three percent of all patients had a delay in receiving an initial LP. The most common reasons for delays were that the patient was too unstable (42%) or that the first LP attempt was unsuccessful (26%). Forty-six percent of all patients had only one LP while 36% had at least one repeat LP. Most repeat LPs were done within 7 days of diagnosis. Twenty-nine percent of patients had an end of treatment LPs. Of all patients, 80% had neuroimaging. Head ultrasound (US) was the most commonly used imaging modality for both first image (68%) and subsequent images (64%). Seventeen percent of patients received a CT scan and 15% an MRI as their first image. In most cases, there was no clear clinical indication for imaging noted other than a diagnosis of meningitis (44%). Conclusion This retrospective study confirms that there is variability in the management of bacterial meningitis with respect to lumbar punctures and neuroimaging in young infants. The findings demonstrate LPs are commonly delayed, and suggest a need to develop clearly defined criteria for evaluating instability before an initial LP. Furthermore, the findings raise concern regarding the common practice of ordering head ultrasound for meningitis, given lower sensitivity in detecting disease complications and therefore disputed clinical utility.

Post-influenza meningitis in an immunosuppressed man

Background: We report a case of post-influenza invasive aspergillosis causing ventriculitis in a patient immunosuppressed on methotrexate for rheumatoid arthritis. Summary: A 63-year-old male with a positive H1N1 throat swab presented with increasing dyspnoea and pyrexia that failed to improve despite broad-spectrum antibiotics and zanamivir. Imaging of his chest showed cavitating lung disease and a possible post influenza fungal infection. He was initiated on antifungal treatment that was stopped after 10 days following a negative bronchoalveolar lavage and serum galactomann test. Respiratory symptoms and inflammatory markers improved but he developed confusion and falls. Computed tomography of the head showed hydrocephalus but there was no papilloedema. Examination of the cerebrospinal fluid (CSF) showed lymphocytosis with elevated proteins but negative initial investigations. Subsequent magnetic resonance imaging of the head with contrast showed obstructing hydrocephalus with ventriculitis. He underwent an urgent ventriculostomy by the neurosurgeons which demonstrated purulent CSF. CSF testing was strongly positive for beta-D glucan, a positive PCR result for aspergillus in CSF was received from the initial lumbar puncture and histology from operative samples showed fungal hyphae. Dual antifungal treatment was recommenced but the patient’s conditioned worsened, and he died on ITU. Conclusion: Whilst invasive pulmonary aspergillosis is a recognised complication of influenza, extrapulmonary infection is less well documented. This is the first case in the literature in which ventriculitis due to aspergillus is described as a sequel to infection with influenza. Clinicians should remain vigilant for fungal infection in patients with influenza who are immunosuppressed.