Initial Cerebrospinal Fluid Research Articles

Ventriculitis: A Severe Complication of Central Nervous System Infections.

BackgroundVentriculitis, a dreaded complication of brain abscess, meningitis, and various neurosurgical procedures, has attracted limited attention in the medical literature.MethodsThis is a retrospective, single-center study. We screened the medical files of all patients who had a brain imaging report that included the word “ventriculitis” during years 2005–2019. Only patients with clinical, microbiological, and imaging features of ventriculitis were included. Data were collected through a standardized questionnaire.ResultsNinety-eight patients fulfilled inclusion criteria: 42 women and 56 men, and the median age was 60 years (interquartile range, 48–68). The primary mechanism for ventriculitis was classified as follows: brain abscess (n = 29, 29.6%), meningitis (n = 27, 27.6%), intraventricular catheter-related (n = 17, 17.3%), post-neurosurgery (n = 13, 13.3%), and hematogenous (n = 12, 12.2%). The main neuroimaging features were intraventricular pus (n = 81, 82.7%), ependymal enhancement (n = 70, 71.4%), and intraventricular loculations (n = 15, 15.3%). The main pathogens were streptococci (n = 44, 44.9%), Gram-negative bacilli (n = 27, 27.6%), and staphylococci (n = 15, 15.3%). In-hospital and 1-year mortality rates were 30.6% (n = 30) and 38.8% (n = 38), respectively. Neurological sequelae were reported in 34 of 55 (61.8%) survivors, including cognitive impairment (n = 11), gait disturbances (n = 9), paresis (n = 7), behavior disorder (n = 6), and epilepsy (n = 5). On multivariate analysis, age >65 years, Glasgow Coma Scale score <13 at initial presentation, status epilepticus, hydrocephalus, and positive cerebrospinal fluid culture were associated with 1-year mortality. We built a scoring system to stratify patients with ventriculitis into low risk (12.5%), intermediate risk (36.5%), and high risk (71.4%) of death.ConclusionsVentriculitis is a severe complication of brain abscess, meningitis, or neurosurgery, with an in-hospital mortality rate of 30% and neurological sequelae in 60% of survivors.

Longitudinal CSF Findings in Autoimmune Encephalitis-A Monocentric Cohort Study.

Autoimmune encephalitis (AIE) poses a diagnostic challenge due to its heterogeneous clinical presentation, which overlaps with various neurological and psychiatric diseases. During the diagnostic work-up, cerebrospinal fluid (CSF) is routinely obtained, allowing for differential diagnostics as well as for the determination of antibody subclasses and specificities. In this monocentric cohort study, we describe initial and serial CSF findings of 33 patients diagnosed with antibody-associated AIE (LGI1 (n=8), NMDA (n=7), CASPR2 (n=3), IgLON5 (n=3), AMPAR (n=1), GAD65/67 (n=4), Yo (n=3), Ma-1/2 (n=2), CV2 (n=2)). Routine CSF parameters of 12.1% of AIE patients were in normal ranges, while 60.6% showed elevated protein levels and 45.4% had intrathecal oligoclonal bands (OCBs). Repeated CSF analyses showed a trend towards normalization of initial pathological CSF findings, while relapses were more likely to be associated with increased cell counts and total protein levels. OCB status conversion in anti-NMDARE patients coincided with clinical improvement. In summary, we show that in routine CSF analysis at diagnosis, a considerable number of patients with AIE did not exhibit alteration in the CSF and therefore, diagnosis may be delayed if antibody testing is not performed. Moreover, OCB status in anti-NMDAR AIE patients could represent a potential prognostic biomarker, however further studies are necessary to validate these exploratory findings.

The chemotactic cytokines in the cerebrospinal fluid of patients with neuroborreliosis

BackgroundThe outcome of neuroborreliosis (NB) is variable and may partially depend on host-related immune factors. In NB, the cerebrospinal fluid (CSF) contains a large population of T lymphocytes, but the mechanisms and consequences of their recruitment have not been fully elucidated. We have studied expression of T lymphocyte chemoattractant cytokines in association with CSF cytometric parameters and clinical data in NB patients. MethodsThe blood and CSF of 17 patients with NB and blood of 12 patients with erythema migrans (EM) were obtained before the antibiotic administration, and in fraction of NB patients during and/or after antibiotic treatment. The control samples came from blood donors (blood) and patients in whom neuroinfection was excluded by a lumbar puncture (CSF). Concentrations of IL-16, CXCL9, CXCL10, CXCL11, CCL2 and CCL5 in serum and CSF were measured with commercial ELISA. Data were analyzed with non-parametric tests, p < 0.05 considered significant. ResultsThe serum concentrations of IL-16, CXCL9, CXCL10 and CCL5 were increased, higher in NB than in EM. In CSF all the cytokines were upregulated, CXCL10, CXCL9 and IL-16 over ten-fold. The CSF concentration index favored the intrathecal synthesis of all the cytokines except CCL5, for which it could not be reliably estimated. CCL2, CXCL10 and CXCL9 created concentration gradients towards CSF. The intrathecal expression of IL-16, CCL5 and CXCL9 correlated with CSF lymphocyte counts, of IL-16, CXCL9 and CXCL10 - with a blood-brain barrier disruption, and of CXCL9 and CXCL10 with intrathecal specific IgG synthesis. The expression of CCL2, CXCL10 and CXCL11 peaked early after NB onset and decreased naturally afterwards. High initial CSF CXCL9, CXCL10 and CXCL11 levels associated with a persistent CSF pleocytosis and BBB disruption after treatment, but no cytokine was predictive of clinical outcome. In follow up (post-treatment) examinations, CSF CXCL10 and CCL5 associated positively and CCL2 negatively with a protracted lymphocytic pleocytosis. ConclusionsSeveral cytokines chemotactic for T lymphocytes are upregulated intrathecally in NB, with different dynamics and relation to other inflammatory parameters, suggesting their distinct pathogenetic roles. CXCL10 and CXCL9 are vividly upregulated and seem deeply involved in the pathogenesis of the intrathecal inflammation. IL-16 and CCL5 may directly drive T lymphocyte migration from periphery, but their ability to create an adequate chemotactic gradient remains to be confirmed. A delayed normalization of pleocytosis is accompanied by higher intrathecal expression of Th1-related and lower of Th2-related chemokines, in agreement with the protective role of Th1 to Th2 transition in the course of NB.

Decreased Superoxide Dismutase Concentrations (SOD) in Plasma and CSF and Increased Circulating Total Antioxidant Capacity (TAC) Are Associated with Unfavorable Neurological Outcome after Aneurysmal Subarachnoid Hemorrhage.

Background: Subarachnoid hemorrhage (SAH) is a devastating disease with high morbidity and mortality. Hypoxia-induced changes and hemoglobin accumulation within the subarachnoid space are thought to lead to oxidative stress, early brain injury, and delayed vasospasm. This study aimed to evaluate the antioxidant status and its impact on neurological outcome in patients with aneurysmal SAH. Methods: In this prospective observational study, 29 patients with aneurysmal SAH were included (mean age 54.7 ± 12.4). Blood and cerebrospinal fluid (CSF) samples were collected on days (d) 1, 3, and 7. In addition, 29 patients without intracranial hemorrhage served as controls. The antioxidant system was analyzed by glutathione peroxidase (GSH-Px; U/L) and total and free glutathione-sulfhydryl (GSH; mg/L) in the plasma. Superoxide dismutase (SOD, U/mL) and total antioxidant capacity (TAC, µmol/L) were measured in the serum and CSF. Clinical data were compiled on admission (Hunt and Hess grade, Fisher grade, and GCS). Neurological and cognitive outcome (modified Rankin scale (mRS), Glasgow Outcome Scale Extended (GOSE) and Montreal Cognitive Assessment (MoCA)) was assessed after 6 weeks (6 w) and 6 months (6 m). Results: Plasma levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.36 U/L; d3: 1.25 ± 0.33 U/L, p = 0.99; d7: 1.52 ± 0.4 U/L, p = 0.019) and were significantly higher compared to controls (1.11 ± 0.27 U/L) at day 7 (p < 0.001). Concordantly, CSF levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.41 U/L; d3: 1.77 ± 0.73 U/L, p = 0.10; d7: 2.37 ± 1.29 U/L, p < 0.0001) without becoming significantly different compared to controls (1.74 ± 0.8 U/L, p = 0.09). Mean plasma TAC at day 1 (d1: 77.87 ± 49.72 µmol/L) was not statistically different compared to controls (46.74 ± 32.42 µmol/L, p = 0.25). TAC remained unchanged from day 1 to 7 (d3: 92.64 ± 68.58 µmol/L, p = 0.86; d7: 74.07 ± 54.95 µmol/L, p = 0.8) in plasma. TAC in CSF steeply declined from day 1 to 7 in patients with SAH becoming significantly different from controls at days 3 and 7 (d3: 177.3 ± 108.7 µmol/L, p = 0.0046; d7: 85.35 ± 103.9 µmol/L, p < 0.0001). Decreased SOD levels in plasma and CSF are associated with a worse neurological outcome 6 weeks (mRS: CSF p = 0.0001; plasma p = 0.027/GOSE: CSF p = 0.001; plasma p = 0.001) and 6 months (mRS: CSF p = 0.001; plasma p = 0.09/GOSE: CSF p = 0.001; plasma p = 0.001) after SAH. Increased plasma TAC correlated with a worse neurological outcome 6 weeks (mRS: p = 0.001/GOSE p = 0.001) and 6 months (mRS p = 0.001/GOSE p = 0.001) after SAH. Conclusion: In our study, a reduction in the antioxidative enzyme SOD and elevated TAC were associated with a poorer neurological outcome reflected by mRS and GOSE at 6 weeks and 6 months after SAH. A lower initial SOD CSF concentration was associated with the late deterioration of cognitive ability. These findings support the mounting evidence of the role of oxidative stress in early brain injury formation and unfavorable outcome after SAH.

Bacterial Meningitis in the Absence of Pleocytosis in Children: A Systematic Review.

One of the main features of bacterial meningitis is pleocytosis. However, when children with meningitis present within hours of onset of symptoms, there is the possibility that the meninges are not yet sufficiently inflamed to lead to a raised cerebrospinal fluid (CSF) white blood cell count. A systematic search was done to identify published studies reporting children with culture- or polymerase chain reaction-proven bacterial meningitis in the absence of pleocytosis. We identified 26 studies describing 62 children (18 neonates). In those in whom fever duration was specified, 32 (80%) of 40 had a fever for less than or equal to 24 hours before lumbar puncture (LP). In those in whom the glucose level was reported, it was normal in 14 (82%) of 17 neonates and 33 (80%) of 41 older infants and children. The protein level was normal in 8 (44%) of 17 neonates and 32 (80%) of 40 older infants and children. Twelve of the 62 children had a Gram stain of their CSF and this was positive in 2 (17%). Simultaneous blood cultures were positive in 5 (28%) of 18 neonates and 21 (68%) of 31 older infants and children. There was no association between the absence of pleocytosis and particular bacteria. All of the 10 children who had a second LP had an abnormal CSF including pleocytosis. These findings indicate that the absence of pleocytosis does not exclude bacterial meningitis reliably and should be interpreted in the context of the duration of illness. CSF samples, particularly those from cases with relatively short symptom duration, should be cultured even when the cell count and biochemistry are normal. A second LP can be helpful when bacterial meningitis is suspected despite a normal initial CSF.

49. Clinical Characteristics of the 2019 Eastern Equine Encephalitis Virus Outbreak in Michigan

BackgroundEastern Equine Encephalitis Virus (EEEV) is a mosquito-borne alphavirus responsible for unpredictable outbreaks of severe neurologic disease in humans. While the vast majority of human EEEV infections are either asymptomatic or clinically nonspecific, a minority of patients develops neuroinvasive disease (EEE), which is a devastating illness with a mortality of at least 30%. No treatments are known to be effective. EEEV infection is relatively rare in the United States, with an annual average nationwide incidence of 7 cases between 2009 and 2018. However, 2019 was an exceptionally active year for human EEEV disease, yielding 38 nationwide confirmed cases, including 10 in Michigan, comprising the state’s largest outbreak to date.MethodsEEE cases were identified by a regional network of physicians. Cases were defined by presentation with clinical symptoms of encephalitis, and by identification of EEEV IgM antibodies or RNA in cerebrospinal fluid (CSF), or EEEV-specific IgM in serum as confirmed by plaque reduction neutralization test. Radiographic images were evaluated and clinical data abstracted through chart review and clinical follow-up where possible.ResultsRecords from 7 patients were identified and reviewed. The median age was 64, with a male predominance, and all presented in August. Notably, commercial arboviral CSF serology was uniformly negative on the initial CSF sample, and diagnosis was not made until a mean of 23 days (range: 12–38 days) after presentation. Testing in public health laboratories yielded the diagnosis in 5 out of 7 cases. Imaging findings were heterogeneous, but most patients exhibited abnormal findings in the thalamus and/or basal ganglia, and one patient displayed prominent pons and midbrain abnormalities. 4 patients died, while 2 patients survived with severe neurologic sequelae, and 1 patient recovered without sequelae. One patient underwent a limited postmortem examination, which revealed diffuse meningoencephalitis and focal vascular necrosis.ConclusionEEE is a frequently fatal condition whose diagnosis is often delayed, and for which no effective treatments are known. Improved diagnostics are needed to facilitate further clinical studies of EEE and encourage the development of potential therapies.Disclosures All Authors: No reported disclosures

GCT-75. ISOLATED PITUITARY STALK THICKENING

OBJECTIVESOnly few studies have examined the predictive factors and outcome of isolated pituitary stalk thickening (PST) in children. We aim to describe our institutional cohort to determine predictors of future malignancy.METHODSA search of the radiology, endocrinology and neuro-oncology databases was performed to identify patients with isolated PST diagnosed between January 2000 and June 2019. Clinical data was collected. A detailed radiology review of baseline and follow up magnetic resonance imaging (MRI) was undertaken in a blinded fashion by two examiners.RESULTSForty-four patients were identified, with 37 meeting criteria for isolated PST and adequate imaging. Median age of baseline MRI was 9.9 years (range 0.9–17.5). Twenty-three were female (62%). Median follow up time was 5 (0.31–18.6) years. Indication for MRI was symptoms of diabetes insipidus (DI) in 28 patients with the remainder having other concerns for endocrine disturbance (7), headache (1) or visual impairment (1). Thirty-five subjects had pituitary dysfunction (95%), including 30 with diabetes insipidus (81%). Nine patients developed a malignancy (24%), with germinoma (5), Langerhans cell histiocytosis (3) and lymphoma (1) at a median of 0.36 years, 0.63 years and 1.1 years respectively. Elevated white blood cell count (>5 x 106/L) in initial cerebrospinal fluid analysis was predictive of future diagnosis of germinoma or lymphoma (p=0.027).CONCLUSIONIn this cohort 24% of children with PST were eventually diagnosed with a neoplasia after a median of 0.63 years. Pleocytosis in initial CSF samples was predictive for future development of germinoma or lymphoma.

CTNI-06. SINGLE-CENTER REAL-WORLD ANALYSIS ON CEREBROSPINAL FLUID IN PATIENTS WITH LEPTOMENINGEAL METASTASES OF NON-SMALL CELL LUNG CANCER

Abstract OBJECTIVE To investigate the clinical values of real-world cerebrospinal fluid (CSF) examination in the diagnosis and prognosis of leptomeningeal metastases (LM) in the patients with non-small cell lung cancer (NSCLC). METHODS The clinical manifestations of patients diagnosed with NSCLC-LM in Guangdong Sanjiu Brain Hospital from 2010 until 2019 and the results from the routine, biochemical and cytologic examinations of their CSF were analyzed retrospectively. Moreover, the effects of different indicators on the prognosis of patients were determined by survival analysis. RESULTS Fifty-eight of the 80 patients underwent CSF examination, and the median values of the initial CSF pressure measured by lumbar puncture was 255mmH2O (60-350mmH2O). Tumor cells were found by the cytologic examination of CSF in 56 of the 58 cases (96.6%). The median levels of protein, glucose, chloride, lactate dehydrogenase (LDH) and carcinoembryonic antigen (CEA) in CSF were 0.4g/L (0–8.3g/L), 2.7mmol/L (0–11.9mmol/L), 120.7mmol/L (0–140.5mmol/L), 21.3U/L (0–221.5U/L) and 31.4ng/ml (0–784.2ng/ml), respectively. Sixteen patients underwent gene detection, and the results showed that there were 4 cases of wild type and 12 cases of mutation type. The survival analysis revealed that the median overall survival (mOS) after being diagnosed with LM, patients in LDH≤37U/L group and those in LDH &amp;gt;37U/L group were 8.0 months, 23.7 months and 4.6 months (P=0.039), respectively, which indicated that the LDH level in CSF was the independent prognostic factor for the survival. CONCLUSION Using the cytologic examination of CSF in patients with LM to detect tumor cells is conducive to the early diagnosis of LM. The high CSF pressure in patients with LM is one of the reasons for the neurologic signs and symptoms. The gene mutations found in the CSF in some patients can be used to guide the further systematic treatment. The LDH level in CSF is the independent prognostic factor affecting the survival.

Mononeuritis multiplex secondary to Lyme neuroborreliosis

Lyme neuroborreliosis (LNB) typically presents as a painful radiculitis or a cranial mononeuropathy with lymphocytic meningitis (Bannwarth’s syndrome). Isolated peripheral mononeuropathy or multiple mononeuropathy is less frequently recognised. A 58-year-old female with a background of IgA nephropathy and chronic kidney disease presented with a painful left ulnar neuropathy followed within 3 months by superficial radial neuropathy. Initial serum and cerebrospinal fluid (CSF) analysis were unremarkable; nerve conduction study was in keeping with a mononeuritis multiplex. A superficial radial nerve biopsy demonstrated inflammation with axonal injury consistent with a pathologically possible vasculitis. Borrelia antibodies were identified using enzyme-linked immunosorbent assay and immunoblot in serum consistent with active recent Lyme borreliosis. A 6-week course of doxycycline was initiated with gradual resolution of pain and improved power. A repeat nerve conduction study demonstrated improvement in sensory and motor responses. This case report identifies a peripheral nerve syndrome of a mononeuritis multiplex secondary to LNB in the absence of CSF pleocytosis with excellent outcome following antibiotic treatment. Peripheral nervous system manifestations of Lyme borreliosis can mimic a vasculitic neuropathy and therefore should be considered in individuals presenting with a painful mononeuritis multiplex.

Paediatric onset of multiple sclerosis: Analysis of chemokine and cytokine levels in the context of the early clinical course

BackgroundInflammatory activity in children with paediatric onset multiple sclerosis (POMS) is higher than that in adults with MS. Chemokine/cytokine profiling in children may provide new insights into the disease pathogenesis and clinical course. The levels of chemokines/cytokines and their roles in POMS remain largely unknown. ObjectiveTo identify the possible utility of chemokines/cytokines in children with POMS, we analysed their levels at the time of disease diagnosis and in the context of subsequent clinical relapse. MethodsCC and CXC motif ligand chemokines (CCL2, CXCL8, CXCL10, and CXCL13), interleukin (IL)-4, IL-17A, interferon gamma and B cell-activating factor in the blood and cerebrospinal fluid (CSF) of 34 POMS patients and 20 age-related controls were measured using Luminex multiplex bead and enzyme-linked immunosorbent assay techniques. Nonparametric tests were used for statistical analyses. ResultsThe CSF levels of CXCL8 (p = 0.002), CXCL10 (p = 0.001), and CXCL13 (p<0.0001) were higher in POMS than in controls; CXCL10 and CXCL13 correlated with pleocytosis and oligoclonal bands. A subsequent clinical relapse occurred in 17/34 of the children; the median time from the diagnosis of POMS was 6 months (range, 2–64 months). The follow-up period of patients who did not experience a clinical relapse was significantly longer than the time to first relapse (p = 0.003). The initial CCL2 level was lower in relapsing than in non-relapsing patients (p = 0.063) and correlated negatively with the CSF/serum albumin ratio and positively with the time to relapse (p<0.04). ConclusionsElevated CSF levels of CXL10 and CXCL13 in children with POMS at the time of disease diagnosis reflect inflammatory activity and suggest the involvement of adaptive immunity; elevated CXCL8 levels further indicate the involvement of innate immunity. An initial low CSF level of CCL2 may be associated with an unfavourable early MS course.

Laparoscopic sleeve gastrectomy for the treatment of idiopathic intracranial hypertension in patients with severe obesity.

Severe obesity is a major risk factor for idiopathic intracranial hypertension (IIH). Data on the role of bariatric surgery for the treatment of this condition are scarce. To evaluate the effectiveness of laparoscopic sleeve gastrectomy (LSG) on treating IIH in severely obese patients. Two university bariatric surgery centers. Prospectively collected data from consecutive patients undergoing LSG were retrospectively analyzed. Patients with IIH and referred by neuroophthalmologists for bariatric surgery were included in the analysis. Fifteen female patients with IIH underwent LSG (median age: 31 yr). Median preoperative body mass index was 42.1 kg/m2. Preoperatively, 14 patients (93.3%) had chronic headaches, 8 (53.3%) pulsatile tinnitus, and 1 (6.6%) epistaxis episodes. Ophthalmologic assessment showed bilateral papilledema in all patients, of whom 13 had visual symptoms. Median initial cerebrospinal fluid opening pressure was 31 cmH2 O (range: 25-50 cmH2 O); 4 patients required repeated decompressing lumbar punctures (1 ventriculoperitoneal shunt). LSG was successfully performed in all patients. No patients were lost to follow-up. Mean excess weight loss was and 87.4% and 88.1% 1 and 2 years after LSG, respectively. Headaches totally resolved in 13 patients (93.3%) and improved in 1 (P < .001). Pulsatile tinnitus (P = .013), epistaxis, visual symptoms (P < .001), and papilledema (P < .001) significantly resolved. Medication was stopped in 14 patients (93.3%). Two years after LSG, IIH outcomes for 7 patients reaching this time point remained unchanged. This study suggests that LSG is effective for severely obese patients with IIH, resulting in complete remission or significant improvement of their symptoms as well as medication discontinuation.

Usefulness of Yeast Cell Counting and Lack of Clinical Correlation of the Antifungal Susceptibility Testing Results in Management of Aids-associated Cryptococcal Meningitis

Cryptococcal meningitis is one of the most seriously opportunistic infections in people living with HIV. We evaluated clinical and laboratorial features (minimum inhibitory concentrations for fluconazole, initial fungal burden in cerebrospinal fluid) and risk factors associated with in-hospital mortality. There is no good evidence for the use of minimum inhibitory concentrations for fluconazole in routine practice for the management of cryptococcosis patients. Counting yeast cells at cerebrospinal fluid can predict positive culture by not death. Data from 46 cryptococcal meningitis patients were reviewed, retrospectively. Patients who presented yeast cell count greater than 400 yeast cells/μ in their initial cerebrospinal fluid sample were associated with higher mortality (p = 0.014); moreover, the yeast cell count is an easy and cheap assay, with high values possibly associated to poor prognosis. Additionally, we verified no significant differences between fluconazole susceptibility profile, molecular type, clinical presentation, cytological analyses, time to sterilize the cerebrospinal fluid, agent recovering out of central nervous system, previous diagnosis of cryptococcal meningitis or usage of fluconazole, and overall mortality.

Initial cerebrospinal fluid-restricted oligoclonal bands associate with anti-N-methyl-D-aspartate receptor encephalitis severity: a pilot study.

Intrathecal antibody production is thought to underly the pathogenesis and symptomatology of N-methyl-D-aspartate receptor encephalitis (NMDARE). In the present study, the clinical correlation of cerebrospinal fluid (CSF) restricted oligoclonal bands (OCBs), as a measure of intrathecal antibody synthesis, was examined in confirmed NMDARE cases. The present study included patients with a confirmed diagnosis of NMDARE who underwent initial CSF evaluation and were followed up for a minimum of 12 months. Disease severity was assessed at baseline and 1, 3, 6, 9, and 12 months. Data regarding duration of hospitalization and intensive care unit (ICU) stay, the presence of uncontrolled seizures, and antiepileptic drug requirement were obtained for each patient. Among the 14 confirmed NMDARE patients, seven had CSF-OCBs. The presence of CSF-OCBs was associated with a more severe disease at baseline (p = 0.004), worse final outcome (p = 0.005), and longer hospitalization (median, 19 vs. 173 days; p < 0.001) and ICU stay (median, 0 vs. 29 days; p = 0.006). CSF-OCB positivity was closely associated with treatment refractoriness within 4 weeks (p = 0.029). The presence of CSF-OCBs at the onset of disease in NMDARE patients was associated with initial treatment refractoriness and a more severe disease course leading to longer hospitalization, ICU admission, intractable seizures, and a poorer outcome. The results indicate that CSF-OCBs may be useful for prognostication. Furthermore, severe disease in NMDARE may be accompanied by oligoclonal expansion antibody-producing B cells.

Determinants of Disability in Progressive Onset Multiple Sclerosis.

To describe the clinical and socio-demographic profiles of the patients with the progressive onset Multiple Sclerosis (MS) and to explore the determinants of disability. This is a retrospective study, which was conducted in a university hospital. Patients with a progressive clinical course at onset were included in the study. In the first analysis, the clinical and demographic properties of the cohort were defined. In the second analysis the effects of age, sex, clinical activity during course, initial clinical symptoms and cerebrospinal fluid analyses on the course were evaluated. Clinical activity during the course, older age, male gender, medulla spinalis involvement at onset and detection of paraparesis at initial neurological examination was found as a poor prognostic factor. This research confirms previous findings of the studies conducted in populations of Europe and America. Further studies are needed to confirm and validate these findings and to provide greater insight into the effects of ethnic or geographical differences on the course.

Feasibility and diagnostic benefit of increased cerebrospinal fluid volume and frequency in the diagnosis of tuberculous meningitis

Background: Definite diagnosis of tuberculous meningitis (TBM) requires demonstration of TB bacilli in the cerebrospinal fluid (CSF) on smear, culture, or nucleic acid amplification. However, the sensitivity of these tests is low. This study was done to see if smear and culture done on a larger volume and repeated samples of CSF increases the diagnostic yield of these tests. Methods: Adult patients with clinical features of meningitis for >5 days were prospectively and consecutively recruited. At admission, the usual 1 ml of CSF was taken for mycobacterial testing; another 4–8 ml was also taken for the same as the comparison. On the 3rd hospital day, 4–8 ml of CSF was taken for mycobacterial testing. Mycobacterial smear and culture were done by Auramine O stains and on modified Lowenstein–Jensen medium, respectively. The composite reference standard for TBM was considered the gold standard for the diagnosis of TBM. Definite and probable diagnosis was taken as positive, while a possible diagnosis and no TB were considered negative for TBM. In a subset, Xpert MTB/Rif assay was also performed on the CSF samples as per the routine diagnostic protocol. Results: 66/80 (82.5%) had the initial CSF examination in the emergency department, 80 (100%) had large-volume CSF on day 1, while 22/80 (27.5%) consented for the second large-volume CSF examination on day 3. There was a marginal increase in sensitivity from 22% to 26% with increasing CSF volume from 1 ml to 4–8 ml and 36% if another large-volume CSF was collected at 72 h. The specificity was 100% at all times. The negative likelihood ratios were 0.78, 0.74, and 0.64, respectively. The sensitivity of Xpert MTB/RI compared to the composite reference standard of TBM was 30.4%. Conclusions: Increasing the volume and frequency of CSF testing for Mycobacterium tuberculosis, marginally improves the sensitivity and negative likelihood ratios, but may not be adequate to rule out TBM with the certainty required to withhold antitubercular therapy. The feasibility of repeat CSF examinations needs to be considered while making guidelines.

Protein Oxidation Biomarkers and Myeloperoxidase Activation in Cerebrospinal Fluid in Childhood Bacterial Meningitis.

The immunological response in bacterial meningitis (BM) causes the formation of reactive oxygen and nitrogen species (ROS, RNS) and activates myeloperoxidase (MPO), an inflammatory enzyme. Thus, structural oxidative and nitrosative damage to proteins and DNA occurs. We aimed to asses these events in the cerebrospinal fluid (CSF) of pediatric BM patients. Phenylalanine (Phe), para-tyrosine (p-Tyr), nucleoside 2′-deoxiguanosine (2dG), and biomarkers of ROS/RNS-induced protein and DNA oxidation: ortho-tyrosine (o-Tyr), 3-chlorotyrosine (3Cl-Tyr), 3-nitrotyrosine (3NO₂-Tyr) and 8-oxo-2′-deoxyguanosine (8OHdG), concentrations were measured by liquid chromatography coupled to tandem mass spectrometry in the initial CSF of 79 children with BM and 10 without BM. All biomarkers, normalized with their corresponding precursors, showed higher median concentrations (p < 0.0001) in BM compared with controls, except 8OHdG/2dG. The ratios o-Tyr/Phe, 3Cl-Tyr/p-Tyr and 3NO₂-Tyr/p-Tyr were 570, 20 and 4.5 times as high, respectively. A significantly higher 3Cl-Tyr/p-Tyr ratio was found in BM caused by Streptococcus pneumoniae, than by Haemophilus influenzae type b, or Neisseria meningitidis (p = 0.002 for both). In conclusion, biomarkers indicating oxidative damage to proteins distinguished BM patients from non-BM, most clearly the o-Tyr/Phe ratio. The high 3Cl-Tyr/p-Tyr ratio in pneumococcal meningitis suggests robust inflammation because 3Cl-Tyr is a marker of MPO activation and, indirectly, of inflammation.

P14.87 Leptomeningeal dissemination in high grade glioma: Correlation of MRI, cytology and standard CSF indices

Abstract BACKGROUND Only few studies report the incidence of leptomeningeal dissemination (LMD) in patients with high grade glioma (HGG), although LMD is not a rare condition of recurrence. We aimed to describe the diagnostic features and treatment modalities in a series of patients treated for HGG in our institution. METHODS Review of clinical presentation, radiological features and CSF analysis in a case series. RESULTS 17 patients from our institution were diagnosed with LMD. The diagnosis of LMD was based on magnetic resonance image and/or cerebrospinal fluid (CSF) analysis. The spectrum of clinical presentation was broad, mainly intracranial hypertension, impaired general condition, pain, worsening of pre-existing symptoms, and epileptic seizures. Median time from onset of clinical deterioration to diagnosis of LMD was 3 weeks (0–16). Leptomeningial involvement was reported in 6/17 at initial MRI reading, whereas reassessment with careful comparison to previous MRI showed signs of LMD in all patients. CSF analysis revealed pleocytosis (11/17), high proteinorrachia (13/17), elevated lactate levels (15/16), low glucose levels (5/17), and increased CSF pressure (5/9). Nevertheless, diagnostic accuracy of initial CSF cytological analysis was low (2/17). A reassessment of the specimen by an experienced neuropathologist disclosed 1 additional positive and 1 additional suspect cytology. After diagnosis of LMD, salvage treatments comprised Bevacizumab, Lomustine, Fotemustine, liposomal cytarabine and best supportive care. The median overall survival after the diagnosis was 3 months. DISCUSSION AND CONCLUSIONS LMD in HGG is not a rare condition of recurrence, and its outcome is poor. It remains a diagnostic challenge, as it may be overlooked on MRI follow-up at its early stage. In case of clinical progression with no overt cause reported on MRI, we recommend careful second MRI reading. In case of doubt lumbar puncture should be performed in order to prove LMD and eliminate infection (i.e. HSV). Upon standard CSF indices, elevated lactate levels should give rise to the suspicion of LMD. Cytological CSF analysis seems to be of low diagnostic yield: This may be improved by faster processing after sampling and by standardized workup including staining with IDH, GFAP and Olig2.

Rapid diagnosis of bacterial meningitis by nanopore 16S amplicon sequencing: A pilot study

Early administration of antibiotics is crucial in the management of bacterial meningitis. Rapid pathogen identification helps to make a definite diagnosis of bacterial meningitis and enables tailored antibiotic treatment. We investigated if the 16S amplicon sequencing performed by MinION, a nanopore sequencer, was capable of rapid pathogen identification in bacterial meningitis. Six retrospective cases of confirmed bacterial meningitis and two prospective cases were included. The initial cerebrospinal fluid (CSF) samples of these patients were used for the experiments. DNA was extracted from the CSF, and PCR was performed on the 16S ribosomal DNA (16S rDNA). Sequencing libraries were prepared using the PCR products, and MinION sequencing was performed for up to 3 h. The reads were aligned to the bacterial database, and the results were compared to the conventional culture studies. Pathogenic bacteria were successfully detected from the CSF by 16S sequencing in all retrospective cases. 16S amplicon sequencing was more sensitive than conventional diagnostic tests and worked properly even in antibiotics-treated samples. MinION sequencing significantly reduced the turnaround time, and even 10 min of sequencing was sufficient for pathogen detection in certain cases. Protocol adjustment could further increase the sensitivity and reduce the turnaround time for MinION sequencing. Finally, the prospective application of MinION 16S sequencing was successful. Nanopore 16S amplicon sequencing is capable of rapid bacterial identification from the CSF of the bacterial meningitis patients. It may have many advantages over conventional diagnostic tests and should therefore be applied in a larger number of patients in the future.

A systematic review of cases of meningitis in the absence of cerebrospinal fluid pleocytosis on lumbar puncture

BackgroundDefinitive diagnosis of meningitis is made by analysis of cerebrospinal fluid (CSF) culture or polymerase chain reaction (PCR) obtained from a lumbar puncture (LP), which may take days. A timelier diagnostic clue of meningitis is pleocytosis on CSF analysis. However, meningitis may occur in the absence of pleocytosis on CSF.Areas of Uncertainty: A diagnosis of meningitis seems less likely without pleocytosis on CSF, leading clinicians to prematurely exclude this. Further, there is little available literature on the subject.MethodsOvid/Medline and Google Scholar search was conducted for cases of CSF culture-confirmed meningitis with lack of pleocytosis. Inclusion criterion was reported cases of CSF culture-positive or PCR positive meningitis in the absence of pleocytosis on LP. Exclusion criteria were pleocytosis on CSF, cases in which CSF cultures/PCR were not performed, and articles that did not include CSF laboratory values.ResultsA total of 124 cases from 51 articles were included. Causative organisms were primarily bacterial (99 cases). Outcome was reported in 86 cases, 27 of which died and 59 survived. Mortality in viral, fungal and bacterial organisms was 0, 56 and 31%, respectively. The overall percentage of positive initial CSF PCR/culture for viral, fungal and bacterial organisms was 100, 89 and 82%, respectively. Blood cultures were performed in 79 of the 124 cases, 56 (71%) of which ultimately cultured the causative organism. In addition to bacteremia, concomitant sources of infection occurred in 17 cases.ConclusionsMeningitis in the absence of pleocytosis on CSF is rare. If this occurs, causative organism is likely bacterial. We recommend ordering blood cultures as an adjunct, and, if clinically relevant, concomitant sources of infection should be sought. If meningitis is suspected, empiric antibiotics/antifungals should be administered regardless of initial WBC count on lumbar puncture.

64-Year-Old Man With Subacute Altered Mental Status and Headache

64-Year-Old Man With Subacute Altered Mental Status and Headache