Cerebrospinal Fluid Leukocytosis Research Articles

Clinical and imaging features of patients with late-onset myelin oligodendrocyte glycoprotein antibody-associated disease

BackgroundThere is an age-dependent change in the clinical phenotype of Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the clinical features of late-onset MOGAD have not been well described. MethodsClinical data of 110 MOGAD patients, including 21 late-onset patients with onset age greater than or equal to 50 years old were retrospectively analyzed. ResultsCompared to pediatric- and younger adult-onset ones, late-onset MOGAD patients experienced milder disease onset (p < 0.001), more monophasic course (p < 0.001), fewer relapses (p = 0.007), less cerebrospinal fluid leukocytosis (p = 0.021), less longitudinally extensive transverse myelitis (onset p = 0.026, whole course p = 0.028), fewer lesions in basal ganglia (whole course p = 0.012), thalamus (whole course p = 0.040) and cerebellum (whole course p = 0.028). However, they had more cerebral symptoms (p = 0.021 onset and whole course), more lesions in white matter (onset p = 0.005, whole course p < 0.001) and periventricular area (onset p = 0.026), along with longer and delayed therapeutic intervention (p < 0.001). The main differences in clinical characteristics between late-onset patients with and without these brain involvements might be comorbidities. ConclusionsLate-onset MOGAD are more likely to experience delayed diagnosis. Brain involvement may be modulated by comorbidities of the elderly, which alter the clinical manifestations of late-onset MOGAD.

A Little Neutrophil Predominance May Not Be a Harbinger of Death: Clinical and Laboratory Characteristics of Meningitis in Jordan.

Background This study aims to evaluate the clinical features, laboratory findings, and outcomes of children and adults diagnosed with meningitis in Jordan. Methodology This is a retrospective chart review study that targeted patients diagnosed with meningitis at King Abdullah University Hospital, a tertiary care center in Northern Jordan, from March 21, 2015, to March 31, 2019. Patients were included in this study if they were older than 28 days and had no risk factors for meningitis. Results A total of 169 patients met the inclusion criteria. Males were overrepresented (67%) and were significantly younger than females (6 vs. 17 years, p = 0.01). Positive meningeal signs were not predictive of greater cerebrospinal fluid leukocytosis (p = 0.348), and they did not provide sufficient sensitivity to be used as screening tools. The most common etiology was aseptic (49%), followed by enterovirus (43%), while bacterial meningitis was an uncommon diagnosis (3.5%). Nearly half of the patients took antibiotics prior to their hospital presentation. During in-hospital admission, six patients died, four of whom had bacterial and two had aseptic meningitis. Enteroviral meningitis showed neutrophil predominance in 44% of cases on lumbar puncture and had a higher neutrophil proportion compared to aseptic meningitis (p = 0.026). Streptococcus pneumoniae was the most common bacterial etiology identified. Conclusions Meningitis in Jordan is most commonly of aseptic and enteroviral origin, and these etiologies carry significantly more favorable outcomes compared to bacterial meningitis. Enteroviral meningitis displays a higher percentage of neutrophils in cerebrospinal fluid compared to aseptic meningitis. S. pneumoniae is the leading cause of bacterial meningitis.Slight neutrophil predominance above halfis a weak predictor of bacterial meningitis due to the small contribution of bacteria asa cause among enteroviruses and aseptic etiologies.

Human herpes virus type-6 is associated with central nervous system infections in children in Sudan.

BackgroundHuman herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan.ObjectiveWe investigated the involvement of HHV-6 in paediatric central nervous system (CNS) infections in Khartoum, Sudan.MethodsFebrile patients aged up to 15 years with suspected CNS infections at Omdurman Hospital for Children from 01 December 2009 to 01 August 2010 were included. Viral DNA was extracted from leftover cerebrospinal fluid (CSF) specimens and quantitatively amplified by real-time polymerase chain reaction (PCR) at Umeå University in Sweden.ResultsOf 503 CSF specimens, 13 (2.6%) were positive for HHV-6 (33.0% [13/40 of cases with proven infectious meningitis]). The median thermal cycle threshold for all HHV-6-positive specimens was 38 (range: 31.9–40.8). The median number of virus copies was 281.3/PCR run (1 × 105 copies/mL CSF; range: 30–44 × 103 copies/PCR run [12 × 103 – 18 × 106 copies/mL CSF]). All positive patients presented with fever and vomiting; 86.0% had seizures. The male-to-female ratio was 1:1; 50.0% were toddlers, 42.0% infants and 8.0% teenagers. Most (83.0%) were admitted in the dry season and 17.0% in the rainy season. Cerebrospinal fluid leukocytosis was seen in 33.0%, CSF glucose levels were normal in 86.0% and low in 14.0%, and CSF protein levels were low in 14.0% and high in 43.0%.ConclusionAmong children in Sudan with CNS infections, HHV-6 is common. Studies on the existence and spread of HHV-6 chromosomal integration in this population are needed.

Herpes Simplex Virus Encephalitis With Initial Negative Polymerase Chain Reaction in the Cerebrospinal Fluid: Prevalence, Associated Factors, and Clinical Impact.

To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis. Retrospective multicenter study from 2007 to 2017. Forty-seven French ICUs. Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV. None. We included 273 patients with a median Glasgow Coma Scale score of 9 (6-12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3-25 cells/mm3] vs 52 cells/mm3 [12-160 cells/mm3]; p < 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2-7 ] vs 0 d [0-0 d]; p < 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ≥ 4) (adjusted odds ratio, 9.89; 95% CI, 1.18-82.78). In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.

Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in 13 children

Objective: To analyze the clinical characteristics, treatment and prognosis of Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in children. Methods: A retrospective analysis was performed on the clinical features, laboratory tests, neuroelectrophysiological examination, imaging, treatment and outcomes of 13 patients with Hashimoto's encephalopathy presenting with isolated cerebellar ataxia, who were admitted to the Department of Pediatric Neurology of Guangzhou Women and Children's Medical Center from January 2016 to May 2021. Results: Among the 13 cases, 6 were males and 7 were females. The onset age was 2.6 (2.0,3.3) years, 9 children had precursor infection or vaccination before the first course of disease. All the 13 children had gait abnormalities or unsteady sitting, 10 had intentional tremor, 6 had dysarthria, 3 had body tremor, 2 had nystagmus, 3 had fatigue, 3 had hypotonia, 2 had vomiting and 1 had irritability. Thyroglobulin antibody (TgAb) was 500.0 (298.9,587.2) kU/L and thyroid peroxidase antibody (TPOAb) was 621.9 (449.6,869.4) kU/L in 13 cases. Autoantibodies were positive in 9 cases, and cerebrospinal fluid leukocytosis was seen in 4 cases. Regarding electroencephalography result, 4 cases had background slowing and 1 case had occasional sharp waves. Among the 3 patients who had relapses, 1 had cerebellar atrophy shown on cranial magnetic resonance imaging (MRI) during the recurrence. All the patients received intravenous immunoglobulin (IVIG) and intensive methylprednisolone therapy during the first onset, followed by the disappearance of the symptoms, 1 patient had repeated episodes which was decreased after immunosuppressive treatment with Rituximab.Followed up for 25.0 (22.5,33.3) months after the last episode, 12 achieved complete remission and 1 had a wide base gait. Conclusions: Trunk ataxia is the common symptom of Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in children.Children with cerebellar ataxia should be tested for TgAb and TPOAb to detect Hashimoto's encephalopathy, avoiding missed diagnosis and treatment delays; IVIG and intensive steroid therapy is effective, and immunosuppressive therapy for patients with multiple relapses could reduce the recurrence.

English

Meningitis is a public health concern. It is caused by several etiologic agents that vary by age group and geographical area. This study aims to highlight the etiological and predictive factors of acute meningitis in hospitalized febrile patients in Mansoura Fever Hospital, Egypt. This study includes cases admitted with suspected meningitis. The study is conducted in the period between April 2019 and March 2020. Lumbar puncture, CSF examination and blood culture and sensitivity were done. Brain Magnetic Resonance Imaging (MRI) was performed before lumbar puncture in some patients. Detailed analysis of epidemiologic characteristics, clinical data, laboratory findings, the causative organisms and predictors of patients with Bacterial Meningitis (BM) were studied. This study included 110 patients had BM with CSF leukocytosis &gt; 100 cells/mm3. Out of 110 CSF samples, 95 cases (86.4%) pathogens were detected by direct Gram-stained smear. Gram positive cocci were the commonest microorganism isolated. 66.4% of patients had blood culture growth of the same organism as the CSF culture. Reagent strip CSF examinations showed a positive correlation compared with laboratory tests. BM had 22.7% mortality rate. Predictive factors of poor outcomes include CSF/serum glucose ratio &gt;0.6, CSF protein &gt;80 mg/dl and Tonsillitis. Prognostic factors that are associated with poor outcome include old age, late presentation, delayed antibiotics treatment, neurologic complications and Glasgo Coma Scale (GCS). BM remains a leading cause of morbidity and mortality,so early diagnosis and treatment decrease both. Predictors of poor outcome of BM are CSF/serum glucose ratio &gt;0.6, CSF protein &gt;80 mg/dl and Tonsillitis. &nbsp; Key words: Bacterial meningitis, lumbar puncture, cerebrospinal fluid (CSF) analysis.

Central Nervous System Involvement in Extranodal Natural Killer/T-Cell Lymphoma: Case Series

▪Introduction：Extranodal NK/T-cell lymphoma, nasal type (NKTCL) is an aggressive subtype of non-Hodgkin lymphoma that is characterized by extranodal presentation. Central nervous system (CNS) involvement in NKTCL is very rare and carries dismal outcome, but lacks clear consensus on optimal treatment. This study summarized the clinicopathological features, treatment patterns and survival outcomes of NKTCL patients with CNS involvement, in order to improve the understanding of CNS involvement in NKTCL.Methods: 1019 patients diagnosed with extranodal NKTCL, from August 2010 to January 2021 were reviewed, and patients with CNS involvement were included in the analysis. The CNS involvement was diagnosed either pathologically or clinically. Due to the difficulties and potential hazards of brain biopsy, pathologic confirmation of CNS involvement was conducted by identifying malignant cells in the cerebrospinal fluid (CSF) by cytology and flow cytometry analysis. Clinically diagnosed CNS involvement was based upon the characteristic radiographic findings by magnetic resonance imaging (MRI), computed tomography (CT) or positron emission tomography (PET/CT), Circulating EBV-DNA was detected by quantitative polymerase chain reaction (PCR). Overall survival (OS) was defined as time from confirmation of CNS disease to death from any cause or last follow up.Results: Among 1019 patients diagnosed with NKTCL, 14 cases (1.3%) with CNS involvement were included. The general characteristics of these patients are listed in Table 1. Of these 14 patients, the median age was 40.5 years (range, 14-57 years) at the time of diagnosis of CNS involvement. Approximately 71.4%(10/14）of patients were men. The median time between initial diagnosis of NKTCL and diagnosis of CNS involvement was 3.0 months (range, 0-141.0 months). 5 patients suffered CNS involvement at initial diagnosis of NKTCL. The other 9 CNS involvement were identified as disease progression. All patients underwent radiological examination, which disclosed the lesion location in CNS of 9 patient. The other 5 patients were diagnosed with CNS involvement by the examination of CSF. The elevated protein concentration and leukocytosis in CSF were identified in 8 and 2 patients, respectively. Among these patients with CNS involvement, the median number of treatment lines after the diagnosis of CNS involvement was 1.5 (range, 1-4). The best response was complete response (CR) in 11 patients, partial response (PR) in 1 patient, stable disease in 1 patient and progressive disease in 1 patient. CR was achieved when patients were treated with pegaspargase- containing regimens(n=4), anti-PD-1 antibodies-containing regimens(n=3), chidamide-containing regimens(n=2) and HD-MTX-containing regimens(n=2). After achieving CR, 2 patients received anti-PD-1 antibodies as maintenance treatment, with the duration of response of 26 and 72 months, respectively. With the median follow-up of 24.5 months (range, 4-72 months), 5 patients died of NKTCL, and the median OS was not reached. 9 patients presented with high circulating EBV-DNA level at diagnosis of CNS involvement, and the post-treatment EBV-DNA descended to the normal level in 7 patients, among whom 6 patients achieved CR.Conclusions: The incidence of CNS involvement in NKTCL is low. Compared with previous studies, more patients received anti-PD-1 antibodies- and chidamide-containing regimens, which may contribute to the improved response rate and survival outcomes. Measurement of dynamic changes in EBV-DNA levels during the treatment process can be applied to monitor the treatment response. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle for Treatment of Glioblastoma Multiform: Safety and Feasibility Assessment.

Widespread investigation has revealed the promising ability of suicidal genes in the treatment of glioma tumors; nevertheless, promoting their effects relies on the ability to apply suitable vehicles and techniques. In this study, the safety and feasibility of using bone marrow-derived mesenchymal stem cells (MSCs) in combination with prodrug for treatment of patients with primary and secondary glioblastoma multiform (GBM) was assessed. Five GBM patients were recruited. Following gross total resection of the tumor and adjuvant radiotherapy and chemotherapy, intracerebral injection of autologous MSCs transduced with lentivirus containing herpes simplex virus thymidine kinase (HSV-TK) was performed followed by intravenous administration of ganciclovir for 2weeks. The treatment was well tolerated by all patients. Mild-to-moderate fever, headache, and cerebrospinal fluid leukocytosis were evident in three, two, and one patient, respectively. The progression-free survival (PFS) and overall survival (OS) of patients were 95.79 ± 51.40 and 128.85 ± 48.81weeks, respectively. The 1-year PFS and OS were 60% and 100%, respectively, among our patients, and two patients had more than 3years of OS and more than 2years of PFS. It seems that intracerebral administration of bone marrow MSC containing the HSV-TK gene in combination with intravenous ganciclovir would be safe and feasible in the treatment of patients with GBM.

Cerebrospinal fluid pleocytosis in immunocompromised patients: Can it be Cryptococcus.

Cryptococcal meningitis commonly affects immunocompromised cases and can have varied presentation. In some instances, the presence of a plethora of inflammatory cells on cerebrospinal fluid (CSF) in an immunosuppressed patient can lead to further investigations, which unravel the presence of cryptococcal meningitis. The aim of this retrospective study was to analyze the spectrum of CSF findings of immunosuppressed patients who were diagnosed to have cryptococcal meningitis. Retrospective analysis of CSF cytospin slides exhibiting pleocytosis and belonging to immunocompromised patients was performed, and these cases were found to have cryptococcal meningitis. Out of 932 cases of CSF (January 2016-July 2017), 10 had pleocytosis and 5 of these 10 cases demonstrated spores of Cryptococcus. Male-to-female ratio was 1:1.5. All the patients were immunocompromised and had CSF leukocytosis. Lymphocytes and monocytes were present in all samples while only one case showed plasma cells. Spores of Cryptococcus were also noted in all the cases and highlighted on India Ink Preparation and Gomori Methenamine Silver stain. All the cases were positive for agglutination-based cryptococcal antigen assay, except one where the test was not done. All immunosuppressed patients having pleocytosis in CSF were found to have cryptococcal infection. Therefore, pleocytosis in CSF in any immunosuppressed patient should raise the suspicion of cryptococcal meningitis. The pathologist and the clinician need to be vigilant in such scenarios to rule out any opportunistic infection and investigate the patient thoroughly for any underlying immunosuppression.

Varicella zoster virus infection of the central nervous system in a tertiary care center in Lebanon

ObjectiveTo describe the clinical manifestations and treatment outcomes of patients with VZV meningitis and encephalitis consulting at two medical centers in Lebanon. MethodsRetrospective study of patients with VZV meningitis and/or encephalitis confirmed by positive cerebrospinal fluid (CSF) VZV PCR. ResultsTwenty patients were identified (13 males). The average age was 49.7±22.2 years. The most common complaint was headache (n=17/20). Common comorbidities included hypertension (n=7/20) and diabetes mellitus (n=5/20). Immunosuppression was reported in two patients. Vesicles were only observed in eight patients. Altered mental status, focal neurological deficits, and fever were documented in six, two, and four patients respectively. All patients had CSF leukocytosis with lymphocytic predominance, normal CSF/serum glucose ratio, and high CSF protein. Eighteen patients had brain CT scans showing no relevant findings. Two of 12 patients with brain MRI had focal abnormalities. Unilateral temporal slow waves were observed in three of four patients who underwent electroencephalograms. Four patients had encephalitis and 16 had meningitis. Eighteen patients received an antiviral therapy. Treatment either included intravenous acyclovir or oral valacyclovir. The encephalitis and meningitis groups had comparable mean duration of treatment (13.5±6.6 vs. 12.2±5.4, respectively). All admitted patients showed clinical cure with no reported neurological sequelae. ConclusionVZV infection should be suspected in any patient with signs and symptoms of viral meningitis or encephalitis, irrespective of age, immune status, presence or absence of vesicles, fever, or neck stiffness.

Clinical features of syphilitic myelitis with longitudinally extensive myelopathy on spinal magnetic resonance imaging.

BACKGROUNDSyphilitic myelitis caused by Treponema pallidum is an extremely rare disease. However, symptomatic neurosyphilis, especially syphilitic myelitis, and its clinical features have been infrequently reported. Only a few cases of syphilitic myelitis have been documented. To the best of our knowledge, there are only 19 reported cases of syphilitic myelitis. However, the clinical features of syphilitic myelitis with longitudinally extensive myelopathy have been still not clear.AIMTo explore the clinical features of syphilitic myelitis with longitudinally extensive myelopathy on spinal magnetic resonance imaging (MRI).METHODSFirst, we report a patient who suffered from syphilitic myelitis with symptoms of sensory disturbance, with longitudinally extensive myelopathy with "flip-flop sign" on spinal MRI. Second, we performed a literature search to identify other reports (reviews, case reports, or case series) from January 1987 to December 2018, using the PubMed and Web of Science databases with the terms including "syphilis", "neurosyphilis", "syphilitic myelitis", "meningomyelitis", "central nervous system", and "spine". We also summarized the clinical features of syphilitic myelitis with longitudinally extensive myelopathy.RESULTSA total of 16 articles of 20 cases were identified. Sixteen patients presented with the onset of sensory disturbance (80%), 15 with paraparesis (75%), and 9 with urinary retention (45%). Eleven patients had a high risk behavior (55%). Five patients had concomitant human immunodeficiency virus infection (25%). Serological data showed that 15 patients had positive venereal disease research laboratory test (VDRL)/treponema pallidum particle agglutination (TPHA), and 17 had positive VDRL/TPHA in cerebrospinal fluid (CSF). Seventeen patients were found to have elevated leukocytosis and protein in CSF. On MRI, 16 patients showed abnormal hyperintensities involved the thoracic spine, 6 involved the cervical spine, and 3 involved both the cervical and thoracic spine. There were 3 patients with the "flip-flop sign". All the patients were treated with penicillin, and 15 patients had a good prognosis.CONCLUSIONOur case further raises awareness of syphilitic myelitis as an important complication of neurosyphilis due to homosexuality, especially in developing countries such as China.

Describing Symptom Burden and Functional Status at the Diagnosis of Leptomeningeal Metastasis.

To investigate the associations of primary cancer, tumor characteristics, and cancer treatment with symptom burden and functional status. 52 patients with leptomeningeal metastasis (LM) at the University of Texas MD Anderson Cancer Center in Houston. Records of 52 patients were reviewed, and presenting symptoms were recorded. Mean differences in number and specific symptoms and functional status were explored. Correlations between age and overall number of symptoms with specific symptoms were assessed with Pearson correlations. Pain was the most frequently reported symptom. Hormonal ablation therapy within six months of LM diagnosis was associated with a higher number of symptoms. Receiving biotherapy more than six months prior to an LM diagnosis was associated with pain, and cerebrospinal fluid leukocytosis was associated with a poor Karnofsky Performance Status score. Nurses caring for patients with advanced cancer can help ensure the highest possible quality of life by obtaining a careful history, assessing symptoms, and noting any changes since the last encounter.

Epidemiology of bacterial meningitis in children admitted to Gondar University Hospital in the post pneumococcal vaccine era.

IntroductionCommunity acquired bacterial meningitis (CABM) is responsible for high mortality and disabling sequelae. Introduction of pneumococcal conjugate vaccine (PCV-10) and haemophilus influenzeatype b (Hib) has changed the epidemiological and clinical features of patients presenting with CABM as it is shown in different literatures over the last decade. The aim of this study was to assess the clinical and epidemiologic features and outcomes of CABM after the introduction of PCV-10 in Gondar University Hospital (GUH).MethodsThis is a retrospective study among children between 2 months and 14 years of age discharged from Gondar University Hospital. All patient records discharged with a diagnosis of meningitis at GUH were reviewed from September 2011 - September 2013. The data was collected using a structured questionnaire from the patient record charts and analysis was done using SPSS-20.Results80 cases (1.6%) of CABM out of 4996 admissions were identified. There were 60 (75%) cases of CABM using WHO criteria of cerebrospinal fluid leukocytosis (CSF) > 100cells/mm3, or 10-100cells/mm3 with either hypoglycorrhea or increased protein; and 20 (25%) with culture confirmation. S. Pneumoniae was the most frequent pathogen identified in 14 (70%) children. The most common age group were infants 2-12 month old (n = 32, 40%). Children with adverse outcomes had shown a higher frequency of being older children (p = 0.045), loss of consciousness (p = 0.046), seizure at admission (p < 0.01), and a positive CSF culture (p = 0.03).ConclusionIntroduction of PCV-10 has shown a decreased admission rate, mortality, and neurologic sequelae due to CABM.

URGENT DIAGNOSTICS OF CEREBRAL VENOUS TROMBOSIS

Investigations were carried out in 24 patients in order to evaluate information value of the data of clinical, laboratory, neuroradiological methods of research and develop the diagnostic algorithm in case of cerebral venous thrombosis (CVT). The main group consisted of 11 patients (7 male, 4 female, average age 49,1±4,3) with CVT. The comparison group included 13 patients (6 male, 7 female; average age 68,1±9,5) with ischemic stroke (IS) of moderate severity. There were revealed changes in blood and cerebrospinal fluid (CSF) as form of leukocytosis of blood and moderately increased cell count with elevated protein in CSF and blood in case of CTV. The authors noted an elevated protein in CSF and blood and leukocytosis with predominant lymphopenia in blood and neurophilic predominance in CSF within the reference range of CSF in patient with ischemic stroke. The epileptic attacks, meningeal syndromes, headaches were more often among clinical syndromes at CTV than in case of ischemic stroke. The algorithm of neuroimaging research methods and modes of MRI were determined and allowed an effective diagnostics of damages of venous sinuses, superficial and deep cerebral veins in case of urgent hospitalization of patients. It was possible to suggest the venous pathology in 7 (63,6%) cases due to SKT (without contrast) and in case of application of MR venography (2D TOFmode), there were revealed 100% of cases.

Abstract WMP87: Inflammatory Response in Cerebrospinal Fluid is Triggered by Large Volume Intraventricular Hemorrhage

Introduction: Cerebrospinal fluid (CSF) pleocytosis has been consistently observed with intraventricular hemorrhage (IVH) in small case series. Its extent, time course, and relation to IVH volume and infection have never been studied in a large cohort with systematic data collection. Hypothesis: Inflammatory response in CSF follows a predictable pattern after IVH, and is more enhanced in cases with higher IVH volume and infection Method: We analyzed prospectively collected samples from 500 patients enrolled in the Clot Lysis Evaluation of Accelerated Resolution (CLEAR) phase III trial. Patients with obstructive IVH requiring external ventricular drainage (EVD) were randomized to receive thrombolytic or placebo injections via EVD. We analyzed 12,291 data points including daily peripheral WBC and RBC counts, CSF RBC, WBC and neutrophil count, protein and glucose. Corrected WBCs (coWBC) reflecting true inflammatory response in the CSF was calculated by controlling for RBC/WBC ratio in a contemporaneous blood sample of the patient. Consecutive values were adjusted to the date of ictus (day 0) and analyzed on days 1-9. Median daily values were chronologically plotted to define the temporal pattern for each parameter. Similar analyses were repeated after stratification based on IVH volume, time to EVD insertion, and presence of culture positive ventriculitis (14 cases, 3%) Result: CSF protein gradually declined with later clearance of RBCs after IVH. There was a surge in coWBC at days 3-5. All parameters of inflammatory response, and most notably the coWBC peak, were greater with larger volume of IVH. Subgroup analyses defined a threshold for significant inflammatory response with initial IVH volume 27mls (P=0.006). Bacterial ventriculitis resulted in significantly higher coWBCs (P&lt;0.001) and neutrophils (P=0.01), but only in cases with low volume IVH (&lt;27ml) Conclusion: Inflammation is an integral response to IVH and is more pronounced with large IVH volume. Bacterial ventriculitis is associated with CSF leukocytosis exceeding the aseptic inflammatory response, notably in lower volume bleeds. These results form a basis for future correlation with treatment rendered, rate of IVH clearance and clinical outcome, with upcoming unblinding of the trial.

Postoperative Central Nervous System Infection After Neurosurgery in a Modernized, Resource-Limited Tertiary Neurosurgical Center in South Asia

Postoperative central nervous system infections (PCNSIs) are rare but serious complications after neurosurgery. The purpose of this study was to examine the prevalence and causative pathogens of PCNSIs at a modernized, resource-limited neurosurgical center in South Asia. A retrospective analysis was conducted of the medical records of all 363 neurosurgical cases performed between June 1, 2012, and June 30, 2013, at a neurosurgical center in South Asia. Data from all operative neurosurgical cases during the 13-month period were included. Cerebrospinal fluid (CSF) analysis indicated that 71 of the 363 surgical cases had low CSF glucose or CSF leukocytosis. These 71 cases were categorized as PCNSIs. The PCNSIs with positive CSF cultures (9.86%) all had gram-negative bacteria with Pseudomonas aeruginosa (n = 5), Escherichia coli (n = 1), or Klebsiella pneumoniae (n = 1). The data suggest a higher rate of death (P = 0.031), a higher rate of CSF leak (P < 0.001), and a higher rate of cranial procedures (P < 0.001) among the infected patients and a higher rate of CSF leak among the patients with culture-positive infections (P = 0.038). This study summarizes the prevalence, causative organism of PCNSI, and antibiotic usage for all of the neurosurgical cases over a 13-month period in a modernized yet resource-limited neurosurgical center located in South Asia. The results from this study highlight the PCNSI landscape in an area of the world that is often underreported in the neurosurgical literature because of the paucity of clinical neurosurgical research undertaken there. This study shows an increasing prevalence of gram-negative organisms in CSF cultures from PCNSIs, which supports a trend in the recent literature of increasing gram-negative bacillary meningitis.

Redefining true leukocytosis in the traumatic lumbar puncture

Objective: To compare and contrast the observed versus predicted number of white blood cells (WBCs) in a traumatic cerebrospinal fluid (CSF) sample in children and adults. Background: Clinicians rely on a correction formula (Predicted_CSF_WBC=CSF_RBC×Blood_WBC/Blood_RBC) to determine if a true CSF leukocytosis exists. This formula may overestimate true CSF leukocytosis and lead to delayed treatment of meningitis. Methods: A retrospective review of CSF data of 105 patients who met the following criteria: 1) CSF from lumbar puncture (LP) contained≥1000 RBC/mm^3 and 2) CBC performed≤24 hours of LP; 3) negative CSF cultures. Regression analysis was performed to determine the relationship between actual and predicted CSF WBC values. Results: Regression modeling indicated a discrepancy in the predicted versus actual WBC values. Mean adult age was 48.9 years; CSF profile (mean WBC 146.3×10^6/L; RBC 17374×10^6/L; glucose 4.1 mmol/L; protein 1.4 g/L); mean peripheral WBC was 8.2×10^9/L; RBC 3.9×10^9/L. Mean pediatric age was 1.4 years; CSF profile (mean WBC 171.8x10^6/L; RBC 41763x10^6/L; glucose 2.7 mmol/L; protein 1.7 g/L); mean peripheral WBC was 12×10^9/L; RBC 7.2×10^9/L. Observed LP CSF WBC value was 47% of predicted (r^2=0.54 pediatric cohort; r^2=0.91 adults). Conclusion: True CSF leukocytosis could be missed in a traumatic CSF sample based on a currently applied correction formula. We propose the following modifcation: Observed_CSF_WBC=0.5x[CSF_RBC×Blood_WBC/Blood_RBC].

Brain parenchymal TNF-α and IL-1β induction in experimental pneumococcal meningitis

Triggers of brain inflammation in pneumococcal meningitis are unknown. TNF-α and IL-1β were upregulated (real time PCR and in situ hybridization) in neurons and astrocytes time-dependently and maximally in the hippocampus during murine pneumococcal meningitis. Upregulation of TNF-α and IL-1β mRNA in the brain parenchyma was independent of cerebrospinal fluid leukocytosis, pneumococcal pneumolysin and H2O2, but it was potently induced by pneumococcal cell wall (PCW) fragments. Brain TNF-α mRNA was downregulated by a matrix metalloproteinases inhibitor. PCW fragments were located in the brain parenchyma. In conclusion, PCW fragments and matrix metalloproteinases trigger cytokine induction in the brain parenchyma during pneumococcal meningitis.

Prevalence and Implications of Cerebrospinal Fluid Leukocytosis in Papua New Guinean Children Hospitalized with Severe Malaria

Cerebrospinal fluid (CSF) leukocytosis in severe malaria was assessed in 87 children in Papua New Guinea participating in a detailed longitudinal observational study who had undergone lumbar puncture for further investigation of altered consciousness and/or convulsions. After rigorous exclusion of non-malarial infection, 16 (20.5%) of 78 children with Plasmodium falciparum monoinfection but 0 of 9 with P. vivax/mixed-species malaria had a detectable CSF leukocytosis, which was unrelated to prior, including complex, seizures. There were eight children with a CSF leukocyte density > 10 cells/μL (9.2% of the total sample), half of whom had cerebral malaria (4 of 22, 18.1%). Cerebrospinal fluid leukocytosis is infrequent in severe pediatric malaria, especially in children with P. vivax infections, and it is generally mild. Its presence in a blood slide-positive child should prompt consideration of alternative diagnoses and empiric antibiotic therapy.

Immune response to intrathecal enzyme replacement therapy in mucopolysaccharidosis I patients

Intrathecal (IT) enzyme replacement therapy with recombinant human α-L-iduronidase (rhIDU) has been studied to treat glycosaminoglycan storage in the central nervous system of mucopolysaccharidosis (MPS) I dogs and is currently being studied in MPS I patients. We studied the immune response to IT rhIDU in MPS I subjects with spinal cord compression who had been previously treated with intravenous rhIDU. We measured the concentrations of specific antibodies and cytokines in serum and cerebrospinal fluid (CSF) collected before monthly IT rhIDU infusions and compared the serologic findings with clinical adverse event (AE) reports to establish temporal correlations with clinical symptoms. Five MPS I subjects participating in IT rhIDU trials were studied. One subject with symptomatic spinal cord compression had evidence of an inflammatory response with CSF leukocytosis, elevated interleukin-5, and elevated immunoglobulin G. This subject also complained of lower back pain and buttock paresthesias temporally correlated with serologic abnormalities. Clinical symptoms were managed with oral medication, and serologic abnormalities were resolved, although this subject withdrew from the trial to have spinal decompressive surgery. IT rhIDU was generally well tolerated in the subjects studied, although one subject had moderate to severe clinical symptoms and serologic abnormalities consistent with an immune response.