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Frontiers in Neurology 2019Autoimmune encephalitides (AIE) comprise a group of inflammatory diseases of the central nervous system (CNS), which can be further characterized by the presence of...
Autoimmune encephalitides (AIE) comprise a group of inflammatory diseases of the central nervous system (CNS), which can be further characterized by the presence of different antineuronal antibodies. Recently, a clinical approach for diagnostic criteria for the suspected diagnosis of AIE as well as definitive AIE were proposed. These are intended to guide physicians when to order the antineuronal antibody testing and/or facilitate early diagnosis even prior to the availability of the specific disease-confirming test results to facilitate prompt treatment. These diagnostic criteria also include the results of basic cerebrospinal fluid (CSF) analysis. However, the different antibody-defined AIE subtypes might be highly distinct with regard to their immune pathophysiology, e.g., the pre-dominance of specific IgG subclasses, IgG1, or IgG4, or frequency of paraneoplastic compared to idiopathic origin. Thus, it is conceivable that the results of basic CSF analysis might also be very different. However, this has not been explored systematically. Here, we systematically reviewed the literature about the 10 most important AIE subtypes, AIE with antibodies against NMDA, AMPA, glycine, GABA, and GABA receptors as well as DPPX, CASPR2, LGI1, IgLON5, or glutamate decarboxylase (GAD), with respect to the reported basic CSF findings comprising CSF leukocyte count, total protein, and the presence of oligoclonal bands (OCB) restricted to the CSF as a sensitive measure for intrathecal IgG synthesis. Our results indicate that these basic CSF findings are profoundly different among the 10 different AIE subtypes. Whereas, AIEs with antibodies against NMDA, GABA, and AMPA receptors as well as DPPX show rather frequent inflammatory CSF changes, in AIEs with either CASPR2, LGI1, GABA, or glycine receptor antibodies CSF findings were mostly normal. Two subtypes, AIEs defined by either GAD, or IgLON5 antibodies, did not fit into this general pattern. In AIE with GAD antibodies, positive OCBs in the absence of other changes were typical, while the CSF in IgLON5 antibody-positive AIE was characterized by elevated protein.
PubMed: 31404257
DOI: 10.3389/fneur.2019.00804 -
BMC Infectious Diseases Aug 2019Definitive diagnosis of meningitis is made by analysis of cerebrospinal fluid (CSF) culture or polymerase chain reaction (PCR) obtained from a lumbar puncture (LP),...
BACKGROUND
Definitive 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.
METHODS
Ovid/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.
RESULTS
A 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.
CONCLUSIONS
Meningitis 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.
Topics: Blood Culture; Cerebrospinal Fluid; Diagnostic Tests, Routine; Humans; Leukocyte Count; Leukocytosis; Meningitis; Polymerase Chain Reaction; Retrospective Studies; Spinal Puncture
PubMed: 31382892
DOI: 10.1186/s12879-019-4204-z -
The Journal of International Medical... Aug 2019This study was performed to investigate whether a definite correlation exists between alteration of blood biochemical parameters and immunosuppressive therapies in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study was performed to investigate whether a definite correlation exists between alteration of blood biochemical parameters and immunosuppressive therapies in patients with inflammatory bowel disease (IBD).
METHODS
A comprehensive search of PubMed, EMBASE, MEDLINE, and the Cochrane Library was conducted. Data on alterations in white blood cells, platelets, hemoglobin, serum creatinine, and liver enzymes in patients with IBD treated with immunomodulators were extracted.
RESULTS
Data from 1141 patients were included. The relative risk (RR) of leukopenia was significantly higher in the immunosuppressive therapies group than in the placebo group (RR, 12.91; 95% confidence interval [CI], 5.28–31.57). A statistically significant risk of leukocytosis during immunosuppressive therapies was observed (RR, 1.53; 95% CI, 1.05–2.23). Patients taking immunomodulators had increased risks of serum creatinine elevation (RR, 10.68; 95% CI, 2.07–55.12) and serum aminotransferase elevation (RR, 3.18; 95% CI, 1.24–8.17).
CONCLUSION
Immunosuppressive therapies might have an impact on variations in blood biochemical parameters in patients with IBD. Although the conclusion regarding leukopenia was reliable in this study, some confounding factors might reduce the reliability of the conclusions about leukocytosis, creatinine elevation, and aminotransferase elevation. Close monitoring is recommended during immunosuppressive therapies for IBD.
Topics: Creatinine; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Leukocytosis; Transaminases
PubMed: 31364448
DOI: 10.1177/0300060519864800 -
Neurology(R) Neuroimmunology &... Jul 2019We conducted a retrospective review of patients with a diagnosis of Guillain-Barré syndrome (GBS) to assess the diagnostic impact of applying age-adjusted upper limits...
OBJECTIVE
We conducted a retrospective review of patients with a diagnosis of Guillain-Barré syndrome (GBS) to assess the diagnostic impact of applying age-adjusted upper limits for CSF total protein (CSF-TP) supported by a systematic literature review.
METHODS
Cases coded as GBS or inflammatory neuropathy for the period 2001-2016 at The Ottawa Hospital were reviewed. Cases were included if they met the Brighton criteria for GBS with a diagnostic certainty level 1 or 2 and had contemporaneous CSF-TP data. We excluded cases with CSF pleocytosis >50 and cases with Miller-Fisher syndrome. Age-adjusted reference limits were compared with conventional 0.45 and 0.6 g/L upper limits.
RESULTS
One hundred thirty-eight cases met the study criteria, with a mean age of 47 years. The mean interval from symptom onset to lumbar puncture was 7.9 days, and mean CSF-TP was 1.23 g/L. There was a strong correlation between rising CSF-TP and time to lumbar puncture. Age-adjusted CSF-TP had a significantly lower sensitivity of only 45% in the first week (32% in the first 3 days) compared with 70% in the first week for the 0.45 g/L limit. All upper limits gained high sensitivity after the first week.
CONCLUSIONS
The low sensitivity of CSF-TP for the diagnosis of GBS is exacerbated by age-adjusted upper limits. The main role of lumbar puncture in GBS in the first week may be to help exclude other inflammatory or neoplastic etiologies of acute neuropathy. After the first week, the magnitude of the CSF-TP rise reduces the effect of different upper reference limits.
Topics: Adult; Age of Onset; Aged; Cerebrospinal Fluid; Diagnostic Tests, Routine; Female; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Proteins; Retrospective Studies; Spinal Puncture; Time Factors
PubMed: 31355312
DOI: 10.1212/NXI.0000000000000576 -
Medicine Jul 2019Intracerebral hemorrhage (ICH) is correlated with high rate of death and poor outcome. Leukocytes participate in secondary brain injury in ICH. It is still not clear... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intracerebral hemorrhage (ICH) is correlated with high rate of death and poor outcome. Leukocytes participate in secondary brain injury in ICH. It is still not clear that whether leukocytosis can predict outcome in ICH. This study was performed to summarize that current evidences about the association between baseline leukocytosis and outcome in ICH patients in a systematic review and meta-analysis.
METHODS
Published studies were searched in 5 databases. Original studies about association between baseline leukocytosis and outcome in ICH were included. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were achieved to evaluate the association between leukocytosis and prognosis.
RESULTS
A total of 19 eligible studies with 6417 patients were analyzed in this study. Meta-analysis showed baseline leukocyte count increase was significantly associated with worse overall (OR = 1.13, 95% CI 1.05-1.21, P = .001), short-term (OR = 1.20, 95% CI 1.05-1.38, P = .009), and long-term functional outcome (OR = 1.12, 95% CI 1.04-1.20, P = .004). Baseline leukocytosis defined by cut-off values had significant association with worse overall functional outcome (OR = 1.95, 95% CI 1.01-3.76, P = .046). Baseline leukocyte count increase was significantly associated with higher overall (OR = 1.10, 95% CI 1.02-1.18, P = .011) and long-term mortality (OR = 1.12, 95% CI 1.03-1.22, P = .007). Baseline leukocytosis defined by cut-off values was significantly associated with higher overall (OR = 1.67, 95% CI 1.23-2.27, P = .001) and short-term mortality (OR = 1.74, 95% CI 1.12-2.70, P = .014).
CONCLUSION
Baseline leukocytosis could be helpful in predicting prognosis in ICH patients. However, its prognostic value should be verified by further studies.
Topics: Cerebral Hemorrhage; Humans; Leukocytosis; Prognosis
PubMed: 31305410
DOI: 10.1097/MD.0000000000016281 -
Journal of Infection and Public Health 2019Leptospirosis is the most widely spread zoonosis and Leptospirosis Associated Acute Kidney Injury (LAKI) is common and fatal if not properly and swiftly treated. The aim...
Leptospirosis is the most widely spread zoonosis and Leptospirosis Associated Acute Kidney Injury (LAKI) is common and fatal if not properly and swiftly treated. The aim of this review is to evaluate the mortality of LAKI and to identify the risk factors for its development. An electronic search was performed to identify the studies included LAKI patients series. Only studies which investigated mortality or risk factors for LAKI development in adults were included. Twenty-three studies with 24 patients series were included in the final analysis and included 1698 patients. The median series mortality was 10.05% (range 0-33.3%) with a total of 223 death. Only four studies identified the independent risk factors for LAKI development which were oliguria, jaundice, arrhythmia, crackles, elevated direct bilirubin level, elevated activated prothrombin time, hyperbilirubinemia and leukocytosis. Although the mortality of LAKI is high, its predictors are not studied enough in literature.
Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Child; Female; Humans; Leptospirosis; Male; Middle Aged; Risk Factors; Survival Analysis; Young Adult
PubMed: 31281106
DOI: 10.1016/j.jiph.2019.06.014 -
Andrology Jan 2020The association of leukocytospermia with male fertility is still under debate. (Meta-Analysis)
Meta-Analysis
Relationship between leukocytospermia, reproductive potential after assisted reproductive technology, and sperm parameters: a systematic review and meta-analysis of case-control studies.
BACKGROUND
The association of leukocytospermia with male fertility is still under debate.
OBJECTIVE
To evaluate the impact of leukocytospermia (≥1 × 10 white blood cells/mL of semen, according to the World Health Organization) in men attending a fertility clinic for couple subfertility, on fertility outcomes after assisted reproductive technology (ART) and on semen quality.
MATERIALS AND METHODS
A systematic review with meta-analysis of case-control studies reporting mean ± standard deviation for values of different seminal parameters (sperm concentration, progressive motility, sperm morphology, sperm DNA fragmentation, semen volume, and Ph) and fertilization rate (FR), or the odds ratio (OR) for clinical pregnancy rate (PR) per cycle after ART in leukocytospermic and non-leukocytospermic patients was performed. A literature search was carried out in MEDLINE and SCOPUS for English-language studies published till June 2018.
RESULTS
Twenty-eight case-controlled retrospective studies met the inclusion criteria, comparing fertility outcomes after ART or semen parameters in men with or without leukocytospermia. FR and PR after ART were not significantly different in the two groups. Leukocytospermic samples showed a lower sperm concentration (pooled SMD = -0.14; 95% CI: -0.28, -0.01, I = 71%, p < 0.00001) and a lower progressive motility (pooled SMD = -0.18; 95% CI: -0.29, -0.06; I = 59%, p < 0.0001). However, the significant differences disappeared, along with the large inter-study heterogeneity, when analyses were restricted to studies clearly reporting the inclusion of men without clinical evidence of seminal tract infection.
DISCUSSION AND CONCLUSION
Leukocytospermia in men seeking consultation for couple subfertility is not associated with a reduced fertility after ART and with altered semen quality in populations asymptomatic for genital tract infection. Therefore, the current clinical criteria for definition of leukocytospermia should be re-assessed in subfertile couples attending a fertility clinic.
Topics: Case-Control Studies; Female; Humans; Infertility, Male; Leukocytosis; Male; Pregnancy; Pregnancy Rate; Semen; Sperm Injections, Intracytoplasmic
PubMed: 31250986
DOI: 10.1111/andr.12662 -
Blood Advances Jun 2019In the last years, a growing amount of evidence has been produced regarding the role of leukocytosis as a risk factor for thrombosis in patients with myeloproliferative... (Meta-Analysis)
Meta-Analysis
In the last years, a growing amount of evidence has been produced regarding the role of leukocytosis as a risk factor for thrombosis in patients with myeloproliferative neoplasms, predominantly in polycythemia vera (PV) and essential thrombocythemia (ET). Results from epidemiologic studies on this issue, however, are inconclusive. We conducted a systematic review and meta-analysis of articles published in the last 12 years addressing the issue, according to a predefined protocol. Forty-one articles analyzing >30 000 patients met our inclusion criteria and were deemed of acceptable methodologic quality. In addition to data on thrombosis, data were collected on bleeding, hematologic evolution, secondary cancer, and death. The relative risk (RR) of thrombosis in the presence of leukocytosis was 1.59 (95% CI, 1.40-1.80), mainly accounted for by ET (RR, 1.65; 95% CI, 1.43-1.91) and arterial thrombosis (RR, 1.45; 95% CI, 1.13-1.86) subgroups; the effect was not significant in venous thrombosis alone. Sensitivity analyses considering recurrent events as well as white blood cell estimates adjusted or unadjusted for confounding factors confirmed the primary results. In addition, the pooled RR of studies that tested white blood cell counts in time-dependent models suggested a causative effect of leukocytes in the mechanism that triggers thrombosis. The effect of leukocytosis on bleeding (RR, 1.87; 95% CI, 1.26-2.77) and death (RR, 1.89; 95% CI, 1.59-2.23) was confirmed, whereas conclusions on hematologic evolutions and solid tumors were uncertain. To confirm the accuracy of these results, an investigation on individual patient data in a large collective archive of homogeneous patients is warranted.
Topics: Female; Hemorrhage; Humans; Leukocytosis; Male; Polycythemia Vera; Risk Factors; Thrombocythemia, Essential; Thrombosis
PubMed: 31175128
DOI: 10.1182/bloodadvances.2019000211 -
Infectious Diseases and Therapy Jun 2019Pertussis is an under-recognized cause of neonatal morbidity and mortality. To review information on the epidemiology and disease burden of neonatal pertussis in South... (Review)
Review
Pertussis is an under-recognized cause of neonatal morbidity and mortality. To review information on the epidemiology and disease burden of neonatal pertussis in South and Southeast Asian countries, a systematic literature review of three bibliographic databases was undertaken. Peer-reviewed original studies on neonatal pertussis epidemiology and burden published since 2000, with a geographical scope limited to South and Southeast Asian countries, were included. Data were systematically extracted based on parameters defined a priori. Our findings show that the burden of neonatal pertussis and its complications is substantial. An increase in the number of pertussis cases has been noted since early 2000, ranging from 61 to 92.9% in infants 0-3 months old. The most common symptoms an infant is likely to present with are cough with or without paroxysms, cyanosis, apnea, tachypnea, difficulty in breathing and leukocytosis. In addition, it can lead to hospitalization (length of stay: 5-7 days), complications (e.g., pneumonia, seizures) and mortality ranging from 5.6 to 14.7%. Other observations indicate that diagnosis is challenging because of non-specific clinical symptoms. Specifically, for obstetricians and gynecologists, the information available for making informed decisions on the prevention of neonatal pertussis is unreliable. Maternal immunization against pertussis during late stages of pregnancy has proven to be efficacious and well tolerated. A high burden of neonatal pertussis, as well as its complications, is observed in South and Southeast Asian countries. There is a need to intensify efforts to protect this vulnerable population with maternal vaccination.Funding: GlaxoSmithKline Biologicals SAPlain Language Summary: Plain language summary available for this article. Please see Fig. 1 and the following link: https://doi.org/10.6084/m9.figshare.7951187 .
PubMed: 31054089
DOI: 10.1007/s40121-019-0245-2 -
PLoS Neglected Tropical Diseases Apr 2019Central nervous system (CNS) melioidosis is rare. However, delayed diagnosis and treatment could lead to fatality. To identify knowledge of CNS melioidosis, we...
BACKGROUND
Central nervous system (CNS) melioidosis is rare. However, delayed diagnosis and treatment could lead to fatality. To identify knowledge of CNS melioidosis, we systematically review case reports and case series.
METHODOLOGY/PRINCIPAL FINDINGS
We searched through PubMed, Web of Science and Thai-Journal Citation Index databases as well as Google Scholar with the last date on July 10, 2018. The diagnosis of CNS melioidosis had to be confirmed with culture, serology or polymerase chain reaction. We excluded the animal cases and the studies that the clinical data were not available. We identified 1170 relevant studies, while 70 studies with a total of 120 patients were analyzed. Ninety-three percent of patients were reported from the endemic area of melioidosis. Median age was 40 years (IQR 18-53), and 70% were men. A total of 60% had one or more risk factors for melioidosis. The median duration from clinical onset to diagnosis was ten days (IQR 5-25). Fever (82%), headache (54%), unilateral weakness (57%) and cranial nerve deficits (52%) are among the prominent presentation. Most patient (67%) had at least one extraneurological organ involvement. The CSF profile mostly showed mononuclear pleocytosis (64%), high protein (93%) and normal glucose (66%). The rim-enhancing pattern (78%) is the most frequent neuroimaging finding in encephalomyelitis and brain abscess patients. Both brainstem (34%) and frontal lobe (34%) are the most affected locations. Mortality rate was 20%.
CONCLUSIONS/SIGNIFICANCE
This study is the most extensive systematic review of case reports and case series of CNS melioidosis in all age groups. However, the results should be cautiously interpreted due to the missing data issue. The propensity of brainstem involvement which correlates with prominent cranial nerve deficits is the characteristic of CNS melioidosis especially encephalomyelitis type. The presenting features of fever and neurological deficits (especially cranial nerve palsies) along with the mononuclear CSF pleocytosis in a patient who lives in the endemic area and also has the risk factor for melioidosis should raise the CNS melioidosis as the differential diagnosis.
Topics: Brain; Burkholderia pseudomallei; Central Nervous System Bacterial Infections; Diagnosis, Differential; Humans; Melioidosis
PubMed: 31022232
DOI: 10.1371/journal.pntd.0007320