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International Journal of Infectious... Mar 2021Limited literature exists on Cerebrospinal fluid (CSF) findings in COVID-19 patients with neurological symptoms. In this review, we conducted a descriptive analysis of...
BACKGROUND
Limited literature exists on Cerebrospinal fluid (CSF) findings in COVID-19 patients with neurological symptoms. In this review, we conducted a descriptive analysis of CSF findings in patients with COVID-19 to understand prognosis and explore therapeutic options.
METHODS
We searched PubMed, Google Scholar, and Scopus databases using the keywords "SARS-CoV-2 in cerebrospinal fluid" and "SARS-CoV-2 and CNS Complications"" for reports of CSF findings in COVID-19 related neurological manifestations. Descriptive analyses were conducted to observe the CSF protein and cell counts based on age, gender, severity, fatality of COVID-19, and whether central (CNS) or peripheral nervous system (PNS) was associated.
RESULTS
A total of 113 patients were identified from 67 studies. Of these, 7 patients (6.2%) were fatal COVID-19 cases and 35 patients (31%) were considered severe COVID-19 cases. CSF protein was elevated in 100% (7/7) of the fatal cases with an average of 61.28 mg/dl and in 65.0% (52/80) in non-fatal cases with an average 56.73 mg/dl. CSF protein levels were elevated in 74.5% (38/51) patients with non-severe COVID-19 and 68.6% (24/35) in those with a severe COVID-19 infection. CSF cell count was increased in 43% of fatal cases, 25.7% severe cases, and 29.4% of non-severe cases.
CONCLUSION
Our analysis showed that the most common CSF findings situation in COVID-19 infection is elevated protein with, very occasionally, mild lymphocyte predominant pleocytosis. Further studies to elucidate the pathophysiology of neurological complications in COVID-19 are recommended.
Topics: COVID-19; Humans; Leukocytosis; Nervous System Diseases; SARS-CoV-2
PubMed: 33434662
DOI: 10.1016/j.ijid.2021.01.002 -
Transfusion Oct 2020Up to 20% of patients with acute myeloid leukemia (AML) present with hyperleukocytosis, usually defined as a white blood cell (WBC) count greater than 100 × 10 /L.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Up to 20% of patients with acute myeloid leukemia (AML) present with hyperleukocytosis, usually defined as a white blood cell (WBC) count greater than 100 × 10 /L. Given the high early mortality rate, emergent cytoreduction with either leukapheresis, hydroxyurea, or chemotherapy is indicated, but the optimal strategy is unknown.
STUDY DESIGN AND METHODS
For this systematic review and meta-analysis we searched MEDLINE and EMBASE via Ovid, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception through March 2020 for multiarm studies comparing early mortality rates of patients with AML treated with leukapheresis and those who were not. The risk ratio (RR) of early death for patients who received leukapheresis vs patients who did not was estimated using a sum of the log-ratio of individual study estimates weighted by sample size.
RESULTS
Among 13 two-arm, retrospective studies with 1743 patients (486 leukapheresis and 1257 nonleukapheresis patients), leukapheresis did not improve the primary outcome of early mortality compared to treatment strategies in which leukapheresis was not used (RR, 0.88; 95% confidence interval [CI], 0.69-1.13; P = .321) without statistically significant heterogeneity between studies (Cochran's Q, 18; P = .115; I , 33.4%). Patients presenting with clinical leukostasis tended to be more likely to undergo leukapheresis (odds ratio, 2.01; 95% CI, 0.99-4.08; P = .052).
CONCLUSION
As we did not find evidence of a short-term mortality benefit and considering the associated complications and logistic burden, our results argue against the routine use of leukapheresis for hyperleukocytosis among patients with AML.
Topics: Disease-Free Survival; Humans; Hydroxyurea; Leukapheresis; Leukemia, Myeloid, Acute; Leukocytosis; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 32776542
DOI: 10.1111/trf.15994 -
BMC Cancer Jun 2022Anal cancer is primarily treated using concurrent chemoradiotherapy (CRT), with conformal techniques such as intensity modulated radiotherapy (IMRT) and volumetric arc...
AIMS
Anal cancer is primarily treated using concurrent chemoradiotherapy (CRT), with conformal techniques such as intensity modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT) now being the standard techniques utilised across the world. Despite this, there is still very limited consensus on prognostic factors for outcome following conformal CRT. This systematic review aims to evaluate the existing literature to identify prognostic factors for a variety of oncological outcomes in anal cancer, focusing on patients treated with curative intent using contemporary conformal radiotherapy techniques.
MATERIALS AND METHODS
A literature search was conducted using Medline and Embase to identify studies reporting on prognostic factors for survival and cancer-related outcomes after conformal CRT for anal cancer. The prognostic factors which were identified as significant in univariable and multivariable analysis, along with their respective factor effects (where available) were extracted. Only factors reported as prognostic in more than one study were included in the final results.
RESULTS
The results from 19 studies were analysed. In both univariable and multivariable analysis, N stage, T stage, and sex were found to be the most prevalent and reliable clinical prognostic factors for the majority of outcomes explored. Only a few biomarkers have been identified as prognostic by more than one study - pre-treatment biopsy HPV load, as well as the presence of leukocytosis, neutrophilia and anaemia at baseline measurement. The results also highlight the lack of studies with large cohorts exploring the prognostic significance of imaging factors.
CONCLUSION
Establishing a set of prognostic and potentially predictive factors for anal cancer outcomes can guide the risk stratification of patients, aiding the design of future clinical trials. Such trials will in turn provide us with greater insight into how to effectively treat this disease using a more personalised approach.
Topics: Anus Neoplasms; Chemoradiotherapy; Humans; Prognosis; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Retrospective Studies
PubMed: 35659632
DOI: 10.1186/s12885-022-09729-4 -
Journal of Neurology, Neurosurgery, and... Oct 2020A systematic review from 1 January to 30 June 2020 revealed 42 patients with Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection. Single cases and small...
A systematic review from 1 January to 30 June 2020 revealed 42 patients with Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection. Single cases and small series were reported from 13 countries, the majority from Europe (79.4%) and especially from Italy (30.9%). SARS-CoV-2 infection was demonstrated by nasopharyngeal swab (85.7%) and serology (14.3%). Median time between COVID-19 and GBS onset in 36 patients was 11.5 days (IQR: 7.7-16). The most common clinical features were: limb weakness (76.2%), hypoareflexia (80.9 %), sensory disturbances (66.7 %) and facial palsy (38.1%). Dysautonomia occurred in 19%, respiratory failure in 33.3% and 40.5% of patients were admitted in intensive care unit. Most patients (71.4%) had the classical clinical presentation but virtually all GBS variants and subtypes were reported. Cerebrospinal fluid (CSF) albumin-cytological dissociation was found in 28/36 (77.8%) and PCR for SARS-CoV-2 was negative in 25/25 patients. Electrodiagnosis was demyelinating in 80.5% and levels 1 and 2 of Brighton criteria of diagnostic certainty, when applicable, were fulfilled in 94.5% patients. Antiganglioside antibodies were positive in only 1/22 patients. Treatments were intravenous immunoglobulin and/or plasma exchange (92.8%) with, at short-time follow-up, definite improvement or recovery in 62.1% of patients. One patient died. In conclusion, the most frequent phenotype of GBS in SARS-CoV-2 infection is the classical sensorimotor demyelinating GBS responding to the usual treatments. The time interval between infectious and neuropathic symptoms, absence of CSF pleocytosis and negative PCR support a postinfectious mechanism. The abundance of reports suggests a pathogenic link between SARS-CoV-2 infection and GBS but a case-control study is greatly needed.
Topics: Adult; Aged; Betacoronavirus; COVID-19; Coronavirus Infections; Female; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Young Adult
PubMed: 32855289
DOI: 10.1136/jnnp-2020-324491 -
Neurology Jul 2021To determine the clinical and laboratory features of immune checkpoint inhibitor (ICPI)-associated autoimmune encephalitis (ICPI-AIE), an increasingly recognized adverse...
OBJECTIVE
To determine the clinical and laboratory features of immune checkpoint inhibitor (ICPI)-associated autoimmune encephalitis (ICPI-AIE), an increasingly recognized adverse event with ICPI treatment.
METHODS
We searched PubMed, The Cochrane Library, and Embase for ICPI-AIE cases from the first description in 2015 until January 2020 using standard bibliographic measures including PRISMA guidelines and preregistration with PROSPERO.
RESULTS
Thirty-nine studies met inclusion criteria, resulting in 54 patients with ICPI-AIE (mean age 58.6 years; 43% female). Common cancers included melanoma (30%) and non-small cell lung cancer (30%). Brain metastases were found in 16 patients (30%). The most frequent ICPI was nivolumab (61%). Onset of ICPI-AIE occurred after a median of 3.0 treatment cycles, but very early and late presentations were common. Nonlimbic AIE was roughly twice as frequent as limbic AIE ( < 0.05). The most common laboratory abnormalities included bitemporal fluid-attenuated inversion recovery lesions on MRI, continuous slow waves and diffuse slowing on EEG, and monocytic pleocytosis on CSF analysis. Intraneuronal antibodies were more frequent than neuronal surface antibodies and a significant predictor for lack of improvement after first-line immunotherapy ( < 0.05).
CONCLUSIONS
ICPI-AIE consists of a heterogenous group of conditions. Neurologists will likely encounter ICPI-AIE more often in the future, but important unresolved questions include the pathophysiologic mechanisms, the epidemiology, and the best treatment approaches associated with ICPI-AIE.
Topics: Antineoplastic Agents; Encephalitis; Female; Hashimoto Disease; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Neoplasms; Treatment Outcome
PubMed: 33952651
DOI: 10.1212/WNL.0000000000012122 -
Frontiers in Pediatrics 2021This study aimed to identify potential risk factors for severe hand-foot-mouth disease (HFMD). The PubMed, Embase, the Cochrane Library, Sinomed, WanFang, CNKI, and...
This study aimed to identify potential risk factors for severe hand-foot-mouth disease (HFMD). The PubMed, Embase, the Cochrane Library, Sinomed, WanFang, CNKI, and VIP databases were searched (up to August 2021). Twenty-nine studies (9,241 and 927,355 patients with severe HFMD and controls, respectively; all from China) were included. EV71 was associated with higher odds of severe HFMD compared with other agents (OR = 4.44, 95%CI: 3.12-6.33, < 0.001). Being home-raised (OR = 1.99, 95%CI: 1.59-2.50, < 0.001), higher number of children in the family (OR = 2.09, 95%CI: 1.93-2.27, < 0.001), poor hand hygiene (OR = 2.74, 95%CI: 1.78-4.23, < 0.001), and no breastfeeding (OR = 2.01, 95%CI: 1.45-2.79, < 0.001) were risk factors for severe HFMD. First consulting to a district-level or above hospital (OR = 0.34, 95%CI: 0.25-0.45, < 0.001) and diagnosis of HFMD at baseline (OR = 0.17, 95%CI: 0.13-0.24, < 0.001) were protective factors against severe HFMD. Fever, long fever duration, vomiting, lethargy, leukocytosis, tic, and convulsions were each associated with severe HFMD (all < 0.05), while rash was not. EV71, lifestyle habits, frequent hospital visits, and symptoms are risk factors for severe HFMD in children in China, while early diagnosis and admission to higher-level hospitals are protective factors.
PubMed: 34858899
DOI: 10.3389/fped.2021.716039 -
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 Cochrane Database of Systematic... Jun 2020Meningitis is inflammation of the meninges, the layers that protect the brain and spinal cord. Acute meningitis is an emergent disease that develops over the course of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Meningitis is inflammation of the meninges, the layers that protect the brain and spinal cord. Acute meningitis is an emergent disease that develops over the course of hours to several days. Delay in treatment can lead to serious outcomes. Inflammation of the meninges is assessed by analysing cerebrospinal fluid. Identifying the pathogen in cerebrospinal fluid is another way to diagnose meningitis. Cerebrospinal fluid is collected by doing a lumbar puncture, which is an invasive test, and can be avoided if a physical examination excludes the diagnosis of meningitis. However, most physical examinations, such as nuchal rigidity, Kernig's test, and Brudzinski's test, are not sufficiently sensitive to exclude meningitis completely. Jolt accentuation of headache is a new and less well-recognised physical examination, which assesses meningeal irritation. It is judged as positive if the headache is exacerbated by rotating the head horizontally two or three times per second. A 1991 observational study initially reported high sensitivity of this examination to predict pleocytosis. Pleocytosis, an abnormally high cerebrospinal fluid sample white cell count, is an accepted indicator of nervous system infection or inflammation. Jolt accentuation of headache may therefore accurately rule out meningitis without the use of lumbar puncture. However, more recent cross-sectional studies have reported variable diagnostic accuracy.
OBJECTIVES
To estimate the diagnostic accuracy of jolt accentuation of headache for detecting acute meningitis in emergency settings. Secondary objectives: to investigate the sources of heterogeneity, including study population, patient condition, and types of meningitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), and Embase (Elsevier) to 27 April 2020. We searched ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Ichushi-Web Version 5.0 to 28 April 2020.
SELECTION CRITERIA
We included cross-sectional studies that assessed the diagnostic accuracy of jolt accentuation of headache for people with suspected meningitis in emergency settings. We included participants of any age and any severity of illness. Meningitis should be diagnosed with any reference standard, such as cerebrospinal fluid pleocytosis, proof of causative agents, or autopsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently collated study data. We assessed methodological quality of studies using QUADAS-2 criteria. We used a bivariate random-effects model to determine summary estimates of sensitivity and specificity where meta-analysis was possible. We performed sensitivity analyses to validate the robustness of outcomes. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included nine studies (1161 participants). Five studies included only adults. Four studies included both adults and children; however, the proportion was not reported in three of these studies. The youngest child reported in the studies was aged 13 years. There was no study including only children. The reference standard was pleocytosis in eight studies, and the combination of pleocytosis and increased protein in the cerebrospinal fluid in one study. Two studies also used smear or positive culture of cerebrospinal fluid. Risk of bias and concern about applicability was high in the participant selection domain for all included studies and the consciousness subgroup. Overall, pooled sensitivity was 65.3% (95% confidence interval (CI) 37.3 to 85.6), and pooled specificity was 70.4% (95% CI 47.7 to 86.1) (very low-certainty evidence). We established the possibility of heterogeneity from visual inspection of forest plots. However, we were unable to conduct further analysis for study population, types of meningitis, and participants' condition, other than disturbance of consciousness (a secondary outcome). Amongst participants whose consciousness was undisturbed (8 studies, 921 participants), pooled sensitivity and specificity were 75.2% (95% CI 54.3 to 88.6) and 60.8% (95% CI 43.4 to 75.9), respectively (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Jolt accentuation for headache may exclude diagnoses of meningitis in emergency settings, but high-quality evidence to support use of this test is lacking. Even where jolt accentuation of headache is negative, there is still the possibility of acute meningitis. This review identified the possibility of heterogeneity. However, factors that contribute to heterogeneity are incompletely understood, and should be considered in future research.
Topics: Acute Disease; Adolescent; Adult; Bias; Confidence Intervals; Critical Pathways; Disease Progression; Emergencies; False Negative Reactions; False Positive Reactions; Head Movements; Headache; Humans; Leukocytosis; Meningitis; Physical Examination; Rotation; Sensitivity and Specificity
PubMed: 32524581
DOI: 10.1002/14651858.CD012824.pub2 -
Frontiers in Neurology 2023Relapsing polychondritis (RP) is a rare rheumatologic disorder that may affect the neurological system with various presentations. In this study, we present a case and...
BACKGROUND AND PURPOSE
Relapsing polychondritis (RP) is a rare rheumatologic disorder that may affect the neurological system with various presentations. In this study, we present a case and summarize the clinical characteristics of RP-associated meningoencephalitis.
CASE PRESENTATION
A 48-year-old man presented with first-ever seizures that were well controlled by valproate. Physical examination results were unremarkable, except for binaural deformation. The initial brain magnetic resonance imaging (MRI) without contrast and electroencephalogram (EEG) findings were normal. However, the patient subsequently developed recurrent fever, scleritis, headache, lethargy, and left arm paresis. Repeated brain MRI with contrast demonstrated increased enhancement of the pia mater and abnormal diffusion-weighted imaging (DWI) signals in the bilateral auricles. The cerebrospinal fluid (CSF) analysis showed 2 leukocytes/μL, 736.5 mg/L of protein, and no evidence of infectious disease or autoimmune encephalitis. Meningoencephalitis secondary to RP was considered. The patient's condition improved significantly and quickly with the administration of dexamethasone (10 mg per day). Oral methylprednisolone was continued, and the patient remained well without relapse during the 9-month follow-up period.
CONCLUSION
RP-associated meningoencephalitis is rare but fatal. Although symptoms vary, red or deformed ears remain the most common and suggestive features. Non-specific parenchymal changes and/or meningeal enhancement can be observed on brain MRI scans. CSF lymphocytic pleocytosis with mild protein elevation was observed in most patients.
PubMed: 38033767
DOI: 10.3389/fneur.2023.1265345 -
Multiple Sclerosis and Related Disorders Aug 2023tumefactive multiple sclerosis (TmMS) is a rare subtype of a demyelinating disease that develops over time. Cases of hyperacute presentations mimicking cerebrovascular...
BACKGROUND
tumefactive multiple sclerosis (TmMS) is a rare subtype of a demyelinating disease that develops over time. Cases of hyperacute presentations mimicking cerebrovascular disorders have been reported; however, detailed clinical and demographic data are lacking.
METHODS
this study aimed to systematically review the literature on tumefactive demyelinating disorders presenting as strokes. After screening the PubMed, PubMed Central, and Web of Science databases, 39 articles describing 41 patients were identified, including 2 historical patients from our center.
RESULTS
23 (53.4%) patients were diagnosed with multiple sclerosis variants (vMS), 17 (39.5%) with inflammatory demyelinating variants (vInf), and 3 with tumors; however, only 43.5% of cases were verified histologically. In subgroup analysis, vMS differed from vInf in several aspects. Inflammatory cerebral spinal fluid parameters, including pleocytosis, proteinorachia was more commonly observed in vInf [11 (64.7%) vs. 1 (5.2%), P = 0.001 and 13/17 (76.4%) vs. 6/23 (31.5%), P = 0.02] than that in vMS. Neurological deterioration and fatal outcomes were more commonly observed in vInf [13/17 (76.4%) vs. 7/23 (30.4%), P = 0.003, and 11/17 (64.7%) vs. 0/23 (0%), P = 0.0001] than that in vMS.
CONCLUSIONS
Clinicodemographic data might aid in recognizing different subtypes of TmMS and warrant consideration of unconventional therapies because outcomes may be poor in the vInf of TmMS.
Topics: Humans; Demyelinating Diseases; Multiple Sclerosis; Stroke; Magnetic Resonance Imaging
PubMed: 37295321
DOI: 10.1016/j.msard.2023.104792