Content In Cerebrospinal Fluid Research Articles

Clinical features, cerebrospinal fluid changes, and prognosis in Chinese patients with autoimmune encephalitis.

Autoimmune encephalitis (AE) is a rare, treatable disease of the central nervous system (CNS) caused by an antibody-related immune response. This study is to investigate the correlation of clinical features, cerebrospinal fluid (CSF) characteristics, and prognosis in patients with AE. A total of 71 patients diagnosed with antibody-positive AE were retrospectively analyzed. The patients were divided into three groups: anti-NMDAR group, anti-LGI1 group, and other types. Clinical data were collected to analyze clinical features and CSF results, and prognosis was determined by modified Rankin Scale (mRS). There was statistical difference in the incidences of decreased consciousness level (P < 0.001), memory loss (P = 0.017), speech disorders (P = 0.035), and dyskinesia (P = 0.001) in different antibodies groups. Younger age (P = 0.018), elevated CSF chloride content (P = 0.006), and white blood cells > 50/mm3 (P = 0.026) were highly correlated with ICU admission. Anti-LGI1 encephalitis had a relatively small risk for ICU admission (P = 0.034), and a lower risk of poor functional recovery (P = 0.048) and recurrence (P = 0.041). Patients with first-line treatment failure (P = 0.021) had an increased risk of poor functional recovery. Delayed treatment (P = 0.011) would increase the risk of recurrence. There are differences in age, gender, clinical characteristics, and CSF results in different subtypes of AE. First-line therapy failure would have poor functional recovery, and delayed therapy would increase the risk of relapse. Chloride ion content and white blood cell count in cerebrospinal fluid are positively correlated with the patient's exacerbation and admission to ICU. These indicators have certain clinical value for the prognosis of AE patients.

Oral application of magnesium-L-threonate alleviates radicular pain by inhibiting neuro-inflammation dependent central sensitization of rats

BackgroundWe have reported neuro-inflammation is involved in radicular pain by enhancing the efficiency of pain synaptic transmission in spinal level. Recently, peers’ studies have confirmed that magnesium deficiency leads to neuro-inflammation, thus contributes to memory and emotional deficits and pain hypersensitivity in antineoplastic agents treated rats. In this study, we explore the effect of oral application of magnesium-L-threonate (L-TAMS) in radicular pain induced by lumbar disc herniation (LDH) of rats and the possible mechanisms. MethodsRat model of LDH was induced by autologous nucleus pulposus (NP) implantation. Mechanical and thermal pain thresholds were assessed by von Frey filaments and hotplate test respectively. L-TAMS was applied from drinking water at dosage of 604 mg/kg/day from 2 day before NP implantation and until the end of the experiment. Free Mg2+ content in serum and cerebrospinal fluid (CSF) was measured by calmagite chromometry. Synaptic transmission efficiency was determined by C-fiber evoked field potentials recorded by electrophysiologic recording in vivo. The activation of microglia in spinal dorsal horn was displayed by immunofluorescence staining and western blotting. The expressions of pro-inflammatory cytokines and glutamic N-methyl-D-aspartate receptor (NMDAR) subunits (NR2A, NR2B) were assessed by western blotting and enzyme-linked immunosorbent assay (ELISA) respectively. ResultsNP implantation induced mechanical allodynia and thermal hyperalgesia, accompanied by decreased Mg2+ concentration in serum and CSF which were both obscured by oral application of L-TAMS. L-TAMS inhibited spinal microglia activation and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) expression of rats with NP. L-TAMS decreased C-fiber evoked potentials and NR2B protein level in rats with NP, which were rescued by extra intrathecal delivery of TNF-α or IL-6 or IL-1β. ConclusionsOral application of L-TAMS alleviates radicular pain by inhibiting neuro-inflammation dependent central sensitization of rats.

Mycoplasma pneumoniae-Associated Encephalitis: Favorable Aggressive Immunosuppression in a Patient

AbstractMeningoencephalitis is the most important extrapulmonary manifestation of Mycoplasma pneumoniae infection. It is complicated by seizures in at least 40% of cases, and in half of them, status epilepticus can occur during the acute phase, often leading to severe neurological sequelae. Brain imaging ranges from normal to diffuse edema, focal changes, and abnormal signals in the white matter, basal ganglia, and hippocampi. Here, we describe a boy who presented with an acute onset of transient alteration of behavior, meningeal irritation, fever, vomiting, and leg pain. Meningoencephalitis due to M. pneumoniae infection was confirmed by focal pneumonia, positive immunological tests, and increased protein content in cerebrospinal fluid. Magnetic resonance imaging of the brain showed bilateral focal abnormalities in the temporoinsular cortex, and electroencephalographic recordings showed slow waves in the same regions. After early infusion of acyclovir on the first day, aggressive combination therapy with oral erythromycin, and intravenous methylprednisolone and immunoglobulin was promptly initiated once a complete diagnosis was obtained on the second day, and the boy recovered within a few days. Two weeks later, brain imaging findings had resolved completely. The rapid clinical and neuroradiological recovery after immunosuppressive therapy suggests an immune-mediated pathogenetic mechanism. He developed immune-mediated myositis 2 years later demonstrating the instability of his immunological status.

Liquid biopsy of circulating tumor DNA in cerebrospinal fluid for early diagnosis of brain malignancies: A review

Brain cancer is the most aggressive intracranial disease: once diagnosed, 70% of patients will not survive. Early and accurate diagnosis is essential to improving the survival rate of diagnosed patients. Currently, imaging scans and pathological biopsies are mainly relied on to confirm the diagnosis of brain tumors. However, imaging scans do not confirm the diagnosis or tumor grade, nor do assess response and monitor treatment effect. Similarly, pathological biopsies are highly invasive and difficult to repeat. To address these limitations, the field has proposed the use of cerebrospinal fluid (CSF) as a liquid biopsy method to detect circulating tumor DNA (ctDNA). This review focuses on how liquid biopsy of CSF ctDNA can facilitate and complement the clinical care of patients with brain tumors. Relevant reviews in the past five years show that ctDNA is highly expressed and its content in CSF is higher than that in plasma. By sequencing the ctDNA of CSF, the diagnosis and prognosis information of brain tumors can be obtained, the best treatment method can be selected, the treatment response can be monitored, and the tumor evolution can be tracked. Because ctDNA detection is still in the research stage and lacks standardized technology, its effectiveness and practicality require further investigation before they can be used in clinical practice.

Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults.

Strong evidence supports the benefits of exercise for healthy ageing, including reduced risk of neurodegenerative diseases. Recent studies suggested interorgan crosstalk as a key element of systemic adaptive response, however, the role of specific molecules in mediating exercise effects on the human brain are not fully understood. In the present study, we explored the exercise-related regulation of Growth Differentiation Factor 11 (GDF11) in cerebrospinal fluid (CSF) and blood. The samples of serum, plasma and CSF were obtained before and 60min after acute exercise (90min run) from twenty healthy young individuals. Additional serum and plasma samples were collected immediately after run. GDF11 protein content (immunoblotting), body composition (bioelectrical impedance), physical fitness (VO2max, cycle spiroergometry) and cognitive functions (standardized computerized tests, Cogstate) were evaluated. Running decreased GDF11 protein content in CSF (-20.6%. p=0.046), while GDF11 in plasma and serum were not regulated. Two GDF11-specific antibodies of different origin were used to corroborate this result. Individuals with higher physical fitness displayed greater exercise-induced decrease of GDF11 in CSF than those with lower physical fitness (p=0.025). VO2max correlated positively with GDF11 in serum (r=0.63, p=0.020) as well as with the exercise-induced change in GDF11 levels in CSF (r=0.59, p=0.042). Indirect measure of blood-brain barrier permeability (i.e. CSF/serum albumin ratio) tended to positively correlate with CSF/serum GDF11 ratio (p=0.060). CSF levels of GDF11 correlated positively with cognitive functions, including working memory, both before and after run (p<0.05). Running-induced down-regulation of the GDF11 protein in the cerebrospinal fluid of healthy young individuals indicates the potential role of GDF11 in the exercise-induced cross-talk between periphery and the brain.

Diagnosis Significance of the Levels of Cytokines IL-6, IL-10 and CXCL-13 in Cerebrospinal Fluid for Central Nervous System Infiltration of Lymphoma

To evaluate the diagnostic value of the expression levels of cytokines interleukin-6(IL-6), interleukin-10 (IL-10) and chemokine （C-X-C motif） ligand-13 (CXCL-13) in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma. Forty patients diagnosed as lymphoma or acute lymphoblastic leukemia in General Hospital of Northern Theater Command from July 2020 to July 2021 were collected and recorded their CSF indexes, including pressure, protein, Pandy test, nucleated cell count, glucose and chlorine content in CSF. The levels of cytokines IL-6, IL-10 and CXCL-13 were detected by Enzyme-linked immunosorbent assay. The patients were divided into CNSI (central nervous system infiltration) group and non-CNSI group, the average levels of IL-6, IL-10, CXCL-13 and IL-10/IL-6 ratio in CNSI group were higher than those in non-CNS group, but the difference of IL-10/IL-6 ratio between the two groups was statistically significant (P<0.05). Then the patients were divided into protein elevated(n=14) group and protein normal group(n=26), the levels of IL-6 ［ (5.78±2.69) pg/ ml］ and CXCL-13 ［(0.83±0.59) pg/ml］ in protein elevated group were significantly higher than those in the protein normal group ［IL-6: (2.41±1.16) pg/ml; CXCL-13: (0.38±0.18) pg/ml］ (P<0.05). Further analysis of the expression levels of the cytokines in non-CNSI group (n=32), IL-6, IL-10, CXCL-13 level and IL-10/IL-6 ratio in the protein elevated group (n=12) were higher than those in the protein normal group (n=20), but the difference was not statistically significant. The levels of IL-6, IL-10 and CXCL-13 in CSF of lymphoma patients with CNS infiltration were higher than those in non-CNS infiltration group, and those in patients with protein elevated group are higher than those in the protein normal group.

Risk Prediction of Central Nervous System Infection Secondary to Intraventricular Drainage in Patients with Intracerebral Hemorrhage: Development and Evaluation of a New Predictive Model Nomogram

BackgroundCurrently no reliable tools are available for predicting the risk of central nervous system (CNS) infections in patients with intracerebral hemorrhage after undergoing ventriculostomy drainage. The current study sought to develop and validate a nomogram to identify high-risk factors of CNS infection after ventriculomegaly drain placement for intracerebral hemorrhage.MethodsA total of 185 patients with intracerebral hemorrhage who underwent ventriculoperitoneal drainage were enrolled to the current study. Patients were divided into a CNS infection group (20 patients) and a non-CNS infection group (165 patients). The baseline data from both groups was used to develop and evaluate a model for predicting the likelihood of developing CNS infection after ventriculoperitoneal drain placement for intracerebral hemorrhage.ResultsThe finding showed that operative time, intraventricular drainage duration, postoperative temperature, white blood cell count in cerebrospinal fluid (CSF), neutrophils ratio in CSF, Red blood cell count in CSF, and glucose content in CSF were correlated with CNS infection. A nomogram for predicting the risk of CNS infection was constructed based on these variables. The c-index and the AUC of the ROC curve was 0.961, showing good discrimination. Clinical decision curve analysis indicated that the nomogram clinical application ranged between 1 and 100%. The clinical impact curve was generated to set with a threshold probability of 0.5.ConclusionThe nomogram reported in the current study can be used by clinicians to identify patients likely to have secondary CNS infections, so that clinicians can better treat these patients at earlier stages.

Extracellular vesicles derived from astrocyte-treated with haFGF14-154 attenuate Alzheimer phenotype in AD mice.

Background: aFGF content in serum and cerebrospinal fluid is increased in Alzheimer's disease (AD) patients and attenuates the activation of astrocytes. Extracellular vesicles (EVs) are a major mediator in astrocyte-neuron communications. Since excessive or persistent reactive astrocytes lead to chronic inflammation and neuronal dysfunction, and the activation of astrocytes can be inhibited by aFGF, we proposed that the cargoes of astrocyte-derived EVs (AEVs) might be modified by aFGF stimulation, playing an important role in AD progression. However, the mechanisms underlying the role of aFGF remain unclear.Methods: AEVs were isolated from damaged astrocytes, treated with or without aFGF in Aβ-loading condition, and were intranasally administered to AD mice. We determined the ability of AEVs to enter the brain, ameliorate cognitive behavior deficits, alleviate the Aβ burden in the brain, and improve synapse ultrastructure. Subsequently, the miRNAs enriched in AEVs were sequenced to identify the key molecules specifically modified by aFGF. Finally, we explored the protective effects of miR-206-3p inhibition on cognitive deficiency and its regulatory mechanism and determined its role as a specific biomarker for potential AD diagnosis.Results: AEVs stimulated by aFGF (defined as AEVs-Aβ+H) had favorable neuroprotection in AD pathology by enhancing neurite growth and reduction of Aβ loading on neurons in vitro. Following intranasal administration, AEVs-Aβ+H ameliorated cognitive behavior deficits, promoted synaptic plasticity, and alleviated brain Aβ burden in the APP/PS1 and Aβ brain-injected mice. AEVs-Aβ+H showed beneficial effects on AD similar to AEVs produced in normal situations (AEVs-Ctrl). aFGF stimulation modified the cargoes in EVs derived from Aβ damaged astrocytes, the most significant of which being the down-regulation of miR-206-3p. The miR-206-3p level was specifically high in the plasma of AD mice and patients, and miR-206-3p antagomir reversed the Alzheimer phenotype in AD mice. The brain-derived neurotrophic factor (BDNF) gene was negatively regulated by miR-206-3p and upregulated by AEVs-Aβ+H and miR-206-3p antagomir in AD mice. AEVs-Aβ+H inhibited δ-secretase (Asparagine endopeptidase, AEP) activation via the miR-206-3p/BDNF axis to alleviate Aβ burden in the AD brain.Conclusion: Our findings highlight the role of aFGF in the modification of AEVs cargoes, especially miR-206-3p that can potentially serve as a biomarker for AD diagnosis and therapeutic target.

Extracellular vesicle miRNA from cerebrospinal fluid as potential biomarkers for neurodegeneration

AbstractBackgroundExtracellular vesicles (EVs) are a diverse group of small membranous particles classified by protein and nucleic acid content, size, method of biogenesis, and cellular origin. The need for predictive biomarkers for neurodegenerative disease is critical for early detection and potential therapeutic intervention. We have previously identified multiple high ranking miRNAs in total cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD). To investigate whether these miRNAs are released from cells within EVs, we developed a pipeline to isolate and analyze EV miRNA.MethodEVs are isolated by size exclusion chromatography (SEC) from CSF collected from living donors. EV counts and sizes are determined by nanoparticle tracking analysis (NTA). Immunoblots are used to characterize EV composition and assess purity. Transmission electron microscopy (TEM) is used to assess size and EV structural characteristics. EV total RNA is isolated using commercial based methods. Quantitative PCR (qPCR) is performed using TaqMan Low Density Array (TLDA) miRNA cards.ResultThe CSF EV isolation protocol developed here is capable of isolating pure vesicles of the appropriate size and protein composition. Following miRNA qPCR, more than half of the high ranking miRNAs identified in total CSF from AD patients were observed in the isolated EV population.ConclusionThis pipeline is suitable for isolating EVs and assessing miRNA content in lumbar CSF. A large number of miRNAs isolated from EVs appear to correlate well with previously published data from total CSF, indicating a potential role for EV miRNA cargo as biomarkers for neurodegenerative diseases such as AD.

Herbal Medicine Must Be Treated with Care—A Case Report on Aconitine

Pathologists usually only request a screening for natural toxic substances if plant material has been observed during autopsy or if there exists a hint in the police investigation file. This situation is aggravated by the fact that most toxins are not covered by typical immunoassays and gas chromatography–mass spectrometry (GC–MS) profiling systems. In addition, only a few forensic toxicological libraries based on liquid chromatography coupled to high-resolution tandem mass spectrometry (LC–HRMS/MS) exist. In the following case, femoral blood and urine were applied to systematic toxicological analysis (STA). However, the concentrations determined in blood did not lead to death. Consequently, a liquid chromatography high-resolution tandem mass spectrometry (LC–HRMS/MS) screening approach was applied. Aconitine was quantitated in all specimens taken during autopsy and urine and bile fluid screened for aconitine metabolites. Aconitine, jesaconitine, hypaconitine, and mesaconitine were found in the root piece collected from the duodenum. Apart from aconitine, no other alkaloids were detected in the urine or in the femoral blood sample. The highest concentrations of aconitine were found in gastric content (55.2 μg/mL), bile fluid (11.7 μg/mL), and liver (9.14 μg/g), and least in femoral blood (0.15 μg/mL) and cerebrospinal fluid (0.07 μg/mL). The liver/peripheral blood ratio amounted to 61 L/kg and indicated that aconitine undergoes postmortem redistribution. During our metabolism investigation, we found 3-dehydrogen-aconitine in the urine and bile fluid sample and N-deethyl-aconitine only in the bile fluid sample. If the routine GC–MS screening approach does not come up with a toxin, then LC–HRMS/MS profiling could represent the method of choice. In this case aconitine was identified. The concentrations determined were compared to those reported in literature and clearly indicate that the deceased died due to an aconitine overdose.

Myelin basic protein and its diagnostic value in HIV-infected individuals with 4th clinical stage and neuroinfections

It was shown that in HIV-infected patients, pathomorphological changes in the white matter in the form of demyelinization are already observed in the early stages of the disease. The most studied marker of this process is myelin basic protein that can be detected in cerebrospinal fluid or serum immediately after acute myelin breakdown.&#x0D; The aim. To assess the diagnostic value of myelin basic protein content in serum and cerebrospinal fluid of HIV-infected individuals with 4th clinical stage and central nervous system opportunistic infections.&#x0D; Materials and methods. Using ELISA with diagnostic kit “MBP ELISA” (Ansh Labs, USA), we studied the myelin basic protein content in serum and cerebrospinal fluid of 53 HIV-infected patients with 4th clinical stage and central nervous system opportunistic infections depending on its etiology, the outcome of the diseases and according to Glasgow coma scale score. As well correlation analysis with some laboratory and clinical indicators was performed.&#x0D; Results. We found significantly increased myelin basic protein content in both cerebrospinal fluid and serum of HIV-infected patients 4th clinical stage with central nervous system opportunistic infections compared to control (p˂0.01), which indicate the presence of active demyelinization in central nervous system. The highest cerebrospinal fluid myelin basic protein was registered in patients with an unfavourable outcome of the disease, as death or residual neurologic deficit, and patients with cerebral toxoplasmosis. The cerebrospinal fluid myelin basic protein had an association with the size of white matter lesions on magnetic resonance imaging and serum myelin basic protein content.&#x0D; Conclusions. Myelin basic protein detection in cerebrospinal fluid as well as in serum can serve as an additional quantitative marker of myelin disruption, which can be used along with magnetic resonance imaging for the diagnosis improvement and prognosis of central nervous system opportunistic infections in HIV-infected individuals with 4th clinical stage

A Eu (III) metal–organic framework as sensitive fluorescent sensor for p-nitroaniline, treatment activity on the stigma and mental disorders in syphilis patients by regulating the dopamine content in the brain

In the present experiment, a new metal–organic framework (MOF) containing Eu(III) of {[Eu(CA)(OA)0.5(H2O)2]·H2O}n (1, in which H2OA = oxalic acid and H2CA = chelidonic acid) has been generated by using the solvothermal reaction approach. The as-prepared Eu-MOF was investigated for the high sensitive detection performance for the p-nitroaniline, a harmful chemical in food and water. As a kind of luminescent sensor, the Eu-MOF reflects an obvious fluorescent quenching toward the p-nitroaniline, while other similar nitroaromatic compounds only show weak quenching effects. To relieve the stigma and mental disorders in syphilis patients, the dopamine content in cerebrospinal fluid was detected by the enzyme-linked immunosorbent detection kit after the compound treatment. In addition to this, the real-time reverse transcription polymerase chain reaction was also implemented for the detection of the dopamine receptor relative expression levels in the striatum.

Correlation of Metabolic Profiles of Plasma and Cerebrospinal Fluid of High-Grade Glioma Patients.

This work compares the metabolic profiles of plasma and the cerebrospinal fluid (CSF) of the patients with high-grade (III and IV) gliomas and the conditionally healthy controls using the wide-range targeted screening of low molecular metabolites by HPLC-MS/MS. The obtained data were analyzed using robust linear regression with Huber’s M-estimates, and a number of metabolites with correlated content in plasma and CSF was identified. The statistical analysis shows a significant correlation of metabolite content in plasma and CSF samples for the majority of metabolites. Several metabolites were shown to have high correlation in the control samples, but not in the glioma patients. This can be due to the specific metabolic processes in the glioma patients or to the damaged integrity of blood-brain barrier. The results of our study may be useful for the understanding of molecular mechanisms underlying the development of gliomas, as well as for the search of potential biomarkers for the minimally invasive diagnostic procedures of gliomas.

High performance liquid chromatography determination of L-glutamate, L-glutamine and glycine content in brain, cerebrospinal fluid and blood serum of patients affected by Alzheimer's disease.

Altered glutamatergic neurotransmission is thought to play a crucial role in the progression of Alzheimer's disease (AD). Accordingly, the identification of peculiar biochemical patterns reflecting AD-related synaptopathy in blood and cerebrospinal fluid (CSF) could have relevant diagnostic and prognostic implications. In this study, we measured by High-Performance Liquid Chromatography the amount of glutamate, glutamine and glycine in post-mortem brain samples of AD patients, as well as in CSF and blood serum of drug-free subjects encompassing the whole AD clinical spectrum (pre-clinical AD, n = 18, mild cognitive impairment-AD, n = 29, dementia AD, n = 30). Interestingly, we found that glutamate and glycine levels, as well as total tau protein content, were significantly reduced in the superior frontal gyrus of patients with AD, compared with non-demented controls. No significant change was also found in glutamate, glutamine and glycine CSF concentrations between AD patients and neurological controls. Remarkably, serum glutamate levels were significantly higher in patients affected by early AD phases compared to controls, and were negatively correlated with CSF total tau levels. Conversely, serum glutamine concentration was significantly increased in AD patients, with a negative correlation with MMSE performances. Finally, we reported a significant correlation between serumL-glutamate concentrations and CDR score in female but not in male cohort of AD subjects. Overall, our results suggest that serum glutamate and glutamine levels in AD patients could vary across disease stages, potentially reflecting the progressive alteration of glutamatergic signaling during neurodegenerative processes.

Neurotoxic effects of nephrotoxic compound diethylene glycol

Context Diethylene glycol (DEG) is an organic compound found in household products but also as an adulterant in medicines by acting as a counterfeit solvent. DEG poisonings have been characterized predominately by acute kidney injury (AKI), but also by delayed neurological sequelae such as decreased reflexes or face and limb weakness. Objectives Characterizing the neurological symptoms of DEG poisoning in a subacute animal model would create a clearer picture of overall toxicity and possibly make mechanistic connections between kidney injury and neuropathy. Methods Male Wistar-Han rats were orally administered doses of 4 − 6 g/kg DEG every 12 or 24 h and monitored for 7 days. Urine was collected every 12 h and endpoint blood and cerebrospinal fluid (CSF) were collected for a renal plasma panel and total protein estimation, respectively. Motor function tests were conducted before and after treatment. Kidney and brain tissue was harvested for metabolic analysis. Results Of the 43 animals treated with DEG, 11 developed AKI as confirmed by increased BUN and creatinine levels. Renal and brain DGA accumulation was markedly increased in animals that developed AKI compared to animals without AKI. The total protein content in CSF in animals with kidney injury was markedly elevated compared to control and to treated animals without AKI. Significant decreases in forelimb grip strength and decreases in locomotor and rearing activity were observed in animals with AKI compared to control and to animals without AKI. Discussion Repeated dosing with DEG in an animal model produced nephrotoxic effects like those in studies with acute DEG administration. The decrease in motor function and increase in CSF protein were only present in animals that developed AKI. Conclusions These studies show development of neurotoxicity in this DEG animal model and suggest that neurological symptoms are observed only when DGA accumulation and kidney injury also occur.

Metabolic profiling in serum, cerebrospinal fluid, and brain of patients with cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is caused by autosomal recessive loss-of-function mutations in CYP27A1, a gene encoding cytochrome p450 oxidase essential for bile acid synthesis, resulting in altered bile acid and lipid metabolism. Here, we aimed to identify metabolic aberrations that drive ongoing neurodegeneration in some patients with CTX despite chenodeoxycholic acid (CDCA) supplementation, the standard treatment in CTX. Using chromatographic separation techniques coupled to mass spectrometry, we analyzed 26 sterol metabolites in serum and cerebrospinal fluid (CSF) of patients with CTX and in one CTX brain. Comparing samples of drug naive patients to patients treated with CDCA and healthy controls, we identified 7α,12α-dihydroxycholest-4-en-3-one as the most prominently elevated metabolite in serum and CSF of drug naive patients. CDCA treatment substantially reduced or even normalized levels of all metabolites increased in untreated patients with CTX. Independent of CDCA treatment, metabolites of the 27-hydroxylation pathway were nearly absent in all patients with CTX. 27-hydroxylated metabolites accounted for ∼45% of total free sterol content in CSF of healthy controls but <2% in patients with CTX. Metabolic changes in brain tissue corresponded well with findings in CSF. Interestingly, 7α,12α-dihydroxycholest-4-en-3-one and 5α-cholestanol did not exert toxicity in neuronal cell culture. In conclusion, we propose that increased 7α,12α-dihydroxycholest-4-en-3-one and lack of 27-hydroxycholesterol may be highly sensitive metabolic biomarkers of CTX. As CDCA cannot reliably prevent disease progression despite reduction of most accumulated metabolites, supplementation of 27-hydroxylated bile acid intermediates or replacement of CYP27A1 might be required to counter neurodegeneration in patients with progressive disease despite CDCA treatment.

Frequency of Autonomic Dysfunction in Patients of Guillain Barre Syndrome in a Tertiary Care Hospital.

IntroductionGuillain-Barré syndrome (GBS) is defined as a syndrome manifesting as an acute inflammatory demyelinating polyradiculoneuropathy (AIDP) with coexistent weakness and absent or diminished reflexes clinically.Autonomic dysfunction (AD) or dysautonomia is a common finding in GBS. Autonomic dysfunction usually occurs in the acute phase of the illness but can also be seen in the recovery phase. The rationale of our study is to determine the frequency of autonomic dysfunction in patients of GBS admitted to the Neurology department of Civil Hospital, Karachi.MethodsA total of 118 admitted patients at a tertiary care hospital in Pakistan who fulfilled the inclusion criteria were enrolled in the study after informed consent. The study was conducted for six months at the department of neurology, Civil Hospital, Karachi. Patients were assessed for autonomic dysfunction by recording blood pressures and pulse rate hourly (both lying and standing positions) by resident doctors. Urinary retention, diarrhea, and constipation were also recorded in a separate chart. All values entered in the pre-approved performa by researchers. The data was collected and analyzed on Statistical Package for Social Sciences (SPSS) version 18.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics included mean, standard deviation (SD) of continuous data, like age, duration of illness, motor weakness assessment by Medical Research Council (MRC) Scale, protein content in cerebrospinal fluid (CSF), pulse, and blood pressure at the time of presentation. Frequencies and percentages were calculated from the categorical data, like gender and patients with autonomic dysfunction (outcome variable). Effect modifiers were controlled by stratification of age, gender, duration of illness. Post-stratification chi-square test was applied with a p-value of ≤ 0.05 taken as significant.ResultsIn our study, the average age of the patients was 39.90±9.91 years. Frequency of autonomic dysfunction among patients with GBS was 41.53% (49/118). The most frequent autonomic manifestations were constipation and diarrhea; 22% and 21.2% respectively. Additional manifestations included urinary retention (15.3%) and fluctuation of blood pressure and heart rate at 13.6% each. ConclusionThis study showed that the frequency of autonomic dysfunction among patients of Guillain Barre Syndrome was significant, consistent with previous studies. Our study explored the adverse outcomes of autonomic dysfunction in patients with GBS. This will help physicians increase their understanding of dysautonomia so that effective management plans can be formulated for patients with GBS to prevent adverse outcomes and hence provide better patient care.

Case of secondary purulent meningitis in background of sepsis

The relevance of the work is associated with the identification of diagnostic capabilities of the automated analysis of biological fluids (blood and cerebrospinal fluid) in sepsis, complicated by bacterial meengitis. The purpose of the work is to analyze the results of dynamic monitoring of cerebrospinal fluid and venous blood samples from the perspective of searching foarkers of an unfavorable prognosis. Materials and methods . The work was carried out on the basis of Regional Clinical Hospital No. 2 (Krasnodar city, Russia). The patient’s medical history was retrospectively analyzed with the main clinical diagnosis of the econdary purulent meningitis against sepsis. Samples of biological fluids were repeatedly tested on a Sysmex XN-1000 analyzer (Sysmex, Japan). A number of traditional and new parameters of the general blood test were evaluated. In particular, the dynamics of the following indicators was analyzed: the content of leukocytes (WBC, 10 9 /l), the number of immature granulocytes (IG, %); the absolute number of reticulocytes (Ret, 10 12 /l); delta hemoglobin level (D-He, pg); relative number of high fluorescent lymphocytes (HFCL, %). As for the cerebrospinal fluid, all parameters of the automated analysis of biological fluids were analyzed: total cytosis index (TCN, 10 9 /l), leukocyte count (WBC-BF, 10 9 /l), number of mononuclear cells with high fluorescence (HF, % and HF, 10 9 /l), the absolute and relative number of leukocyte populations. According to the data obtained, the following can be distinguished as laboratory markers associated with an unfavorable prognosis: lack of positive dynamics regarding the absolute neutrophil content in cerebrospinal fluid; neutrophilic leukocytosis without a significant left shift in the general analysis of blood; an increase in the number of reticulocytes, not accompanied by an increase in reticulocytes of immature fractions.

Structural Diversity of Co(II) Coordination Polymers: Treatment Activity on Alzheimer’s Disease Via Reducing the Accumulation of Amyloid in Brain

Two novel coordination polymers (CPs) based on Co(II) ions as nodes with the chemical formula of {Co(DBTA)(phen)(H2O)}n (1) (phen = 1,10-Phenanthroline and H2DBTA = 2,5-Dibromo-terephthalic acid) and [Co(DBTA)(bimb)]n (2) (bimb = 1,4-bis(imidazole-1-ylmethyl)benzene) were prepared via Co(NO3)2·6H2O reacting with the H2DBTA in the existence of distinct nitrogen-donor co-ligands (phen for the complex 1 and bimb for the complex 2) under solvothermal conditions. Compounds 1 and 2 with novel structures were evaluated for Alzheimer’s disease (AD) treatment. Serious experiments were performed and the specific mechanism for compound also was investigated. Firstly, the AD animal model was constructed in the mice, then we injected the compound 1 or 2 into mice to perform the indicated treatment at 5 mg/kg concentration. After that, the brain volume and brain weight were measured. Then, the Amyloid (Aβ) content in cerebrospinal fluid was determined to assess the activity of compound. The inflammatory cytokines released into the cerebrospinal fluid was also determined with enzyme linked immunosorbent assay (ELISA) detection. Finally, the reactive oxygen species (ROS) accumulation in the cerebral cortex cells was detected.

The study of levels from redox-active elements in cerebrospinal fluid of amyotrophic lateral sclerosis patients carrying disease-related gene mutations shows potential copper dyshomeostasis.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by a loss of function of motor neurons. The etiology of this disorder is still largely unknown. Gene-environment interaction arises as a possible key factor in the development of amyotrophic lateral sclerosis. We assessed the levels of trace metals, copper (Cu), iron (Fe), and manganese (Mn), of 9 amyotrophic lateral sclerosis cases and 40 controls by measuring their content in cerebrospinal fluid. The following trace element species were quantified using ion chromatography-inductively coupled plasma mass spectrometry: univalent copper (Cu-I), divalent Cu (Cu-II), divalent Fe (Fe-II), trivalent Fe (Fe-III), divalent Mn (Mn-II), trivalent Mn (Mn-III), and also unidentified Mn species (Mn-unknown) were present in some samples. When computing the relative risks for amyotrophic lateral sclerosis through an unconditional logistic regression model, we observed a weak and imprecise positive association for iron (Fe III, adjusted odds ratio 1.48, 95% CI 0.46-4.76) and manganese (total-Mn and Mn-II; adjusted odds ratio 1.11, 95% CI 0.74-1.67, and 1.13, 95% CI 0.79-1.61, respectively). Increased risk for copper was found both in the crude analysis (odds ratio 1.14, 95% CI 0.99-1.31) and in multivariable analysis after adjusting for sex, age, and year of storage (1.09, 95% CI 0.90-1.32). Our results suggest a possible positive association between Cu and genetic amyotrophic lateral sclerosis, while they give little indication of involvement of Fe and Mn in disease, though some correlations found also for these elements deserve further investigation.