scholarly journals Biochemical profile of human infant cerebrospinal fluid in intraventricular hemorrhage and post-hemorrhagic hydrocephalus of prematurity

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ayodamola Otun ◽  
Diego M. Morales ◽  
Maria Garcia-Bonilla ◽  
Seth Goldberg ◽  
Leandro Castaneyra-Ruiz ◽  
...  

Abstract Background Intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) have a complex pathophysiology involving inflammatory response, ventricular zone and cell–cell junction disruption, and choroid-plexus (ChP) hypersecretion. Increased cerebrospinal fluid (CSF) cytokines, extracellular matrix proteins, and blood metabolites have been noted in IVH/PHH, but osmolality and electrolyte disturbances have not been evaluated in human infants with these conditions. We hypothesized that CSF total protein, osmolality, electrolytes, and immune cells increase in PHH. Methods CSF samples were obtained from lumbar punctures of control infants and infants with IVH prior to the development of PHH and any neurosurgical intervention. Osmolality, total protein, and electrolytes were measured in 52 infants (18 controls, 10 low grade (LG) IVH, 13 high grade (HG) IVH, and 11 PHH). Serum electrolyte concentrations, and CSF and serum cell counts within 1-day of clinical sampling were obtained from clinical charts. Frontal occipital horn ratio (FOR) was measured for estimating the degree of ventriculomegaly. Dunn or Tukey’s post-test ANOVA analysis were used for pair-wise comparisons. Results CSF osmolality, sodium, potassium, and chloride were elevated in PHH compared to control (p = 0.012 − < 0.0001), LGIVH (p = 0.023 − < 0.0001), and HGIVH (p = 0.015 − 0.0003), while magnesium and calcium levels were higher compared to control (p = 0.031) and LGIVH (p = 0.041). CSF total protein was higher in both HGIVH and PHH compared to control (p = 0.0009 and 0.0006 respectively) and LGIVH (p = 0.034 and 0.028 respectively). These differences were not reflected in serum electrolyte concentrations nor calculated osmolality across the groups. However, quantitatively, CSF sodium and chloride contributed 86% of CSF osmolality change between control and PHH; and CSF osmolality positively correlated with CSF sodium (r, p = 0.55,0.0015), potassium (r, p = 0.51,0.0041), chloride (r, p = 0.60,0.0004), but not total protein across the entire patient cohort. CSF total cells (p = 0.012), total nucleated cells (p = 0.0005), and percent monocyte (p = 0.016) were elevated in PHH compared to control. Serum white blood cell count increased in PHH compared to control (p = 0.042) but there were no differences in serum cell differential across groups. CSF total nucleated cells also positively correlated with CSF osmolality, sodium, potassium, and total protein (p = 0.025 − 0.0008) in the whole cohort. Conclusions CSF osmolality increased in PHH, largely driven by electrolyte changes rather than protein levels. However, serum electrolytes levels were unchanged across groups. CSF osmolality and electrolyte changes were correlated with CSF total nucleated cells which were also increased in PHH, further suggesting PHH is a neuro-inflammatory condition.

2021 ◽  
Author(s):  
Ayodamola Otun ◽  
Diego Morales ◽  
Maria Garcia-Bonilla ◽  
Seth Goldberg ◽  
Leandro Castaneyra-Ruiz ◽  
...  

Abstract BACKGROUND Intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) have complex pathophysiology involving inflammatory response, ventricular zone and cell-cell junction disruption, and choroid-plexus (ChP) hypersecretion. Increased cerebrospinal fluid (CSF) cytokines, extracellular matrix proteins, and blood metabolites have been noted in IVH/PHH, but osmolality and electrolyte disturbances have not been evaluated in human infants with these conditions. We hypothesized that CSF total protein, osmolality, electrolytes, and immune cells increase in PHH. METHODS CSF samples were obtained from lumbar punctures in control infants and infants with IVH prior to development of PHH and any neurosurgical intervention. Osmolality, total protein, and electrolytes were measured in 52 infants (18 controls, 10 low grade (LG) IVH, 13 high grade (HG) IVH, and 11 PHH). Serum electrolyte concentrations, and CSF and serum cell counts within 1-day of clinical sampling were obtained from clinical charts. Dunn or Tukey’s post-test ANOVA analysis were used for pair-wise comparisons. RESULTS CSF osmolality, sodium, potassium, and chloride were elevated in PHH compared to control (p=0.012 - <0.0001), LGIVH (p=0.023 - <0.0001), and HGIVH (p=0.015 - 0.0003), while magnesium and calcium levels were higher compared to control (p=0.031) and LGIVH (p=0.041). CSF total protein was higher in both HGIVH and PHH compared to control (p=0.0009 and 0.0006 respectively) and LGIVH (p=0.034 and 0.028 respectively). These differences were not reflected in serum electrolyte concentrations nor calculated osmolality across the groups. However, quantitatively, CSF sodium and chloride contributed 86% of CSF osmolality change between control and PHH; and CSF osmolality positively correlated with CSF sodium (r,p=0.55,0.0015), potassium (r,p=0.51,0.0041), chloride (r,p=0.60,0.0004), but not total protein across the entire patient cohort. CSF total cells (p=0.012), total nucleated cells (p=0.0005), and percent monocyte (p=0.016) were elevated in PHH compared to control. Serum white blood cell count increased in PHH compared to control (p=0.042) but there were no differences in serum cell differential across groups. CSF total nucleated cells also positively correlated with CSF osmolality, sodium, potassium, and total protein (p=0.025-0.0008) in the whole cohort. CONCLUSIONS CSF osmolality increased in PHH, largely driven by electrolyte changes rather than protein levels. However, serum electrolytes levels were unchanged across groups. CSF osmolality and electrolyte changes were correlated with CSF total nucleated cells which were also increased in PHH, further suggesting PHH is a neuro-inflammatory condition.


Stroke ◽  
2020 ◽  
Vol 51 (6) ◽  
pp. 1712-1719 ◽  
Author(s):  
Kelly B. Mahaney ◽  
Chandana Buddhala ◽  
Mounica Paturu ◽  
Diego Morales ◽  
David D. Limbrick ◽  
...  

Background and Purpose— Preterm neonates with intraventricular hemorrhage (IVH) are at risk for posthemorrhagic hydrocephalus and poor neurological outcomes. Iron has been implicated in ventriculomegaly, hippocampal injury, and poor outcomes following IVH. We hypothesized that levels of cerebrospinal fluid blood breakdown products and endogenous iron clearance proteins in neonates with IVH differ from those of neonates with IVH who subsequently develop posthemorrhagic hydrocephalus. Methods— Premature neonates with an estimated gestational age at birth <30 weeks who underwent lumbar puncture for clinical evaluation an average of 2 weeks after birth were evaluated. Groups consisted of controls (n=16), low-grade IVH (grades I–II; n=4), high-grade IVH (grades III–IV; n=6), and posthemorrhagic hydrocephalus (n=9). Control subjects were preterm neonates born at <30 weeks’ gestation without brain abnormality or hemorrhage on cranial ultrasound, who underwent lumbar puncture for clinical purposes. Cerebrospinal fluid hemoglobin, total bilirubin, total iron, ferritin, ceruloplasmin, transferrin, haptoglobin, and hemopexin were quantified. Results— Cerebrospinal fluid hemoglobin levels were increased in posthemorrhagic hydrocephalus compared with high-grade IVH (9.45 versus 6.06 µg/mL, P <0.05) and cerebrospinal fluid ferritin levels were increased in posthemorrhagic hydrocephalus compared with controls (511.33 versus 67.08, P <0.01). No significant group differences existed for the other cerebrospinal fluid blood breakdown and iron-handling proteins tested. We observed positive correlations between ventricular enlargement (frontal occipital horn ratio) and ferritin (Pearson r =0.67), hemoglobin (Pearson r =0.68), and total bilirubin (Pearson r =0.69). Conclusions— Neonates with posthemorrhagic hydrocephalus had significantly higher levels of hemoglobin than those with high-grade IVH. Levels of blood breakdown products, hemoglobin, ferritin, and bilirubin correlated with ventricular size. There was no elevation of several iron-scavenging proteins in cerebrospinal fluid in neonates with posthemorrhagic hydrocpehalus, indicative of posthemorrhagic hydrocephalus as a disease state occurring when endogenous iron clearance mechanisms are overwhelmed.


2006 ◽  
Vol 34 (4) ◽  
pp. 393-395 ◽  
Author(s):  
Alok K. Sharma ◽  
Albert E. Schultze ◽  
Dale M. Cooper ◽  
Rachel Y. Reams ◽  
William H. Jordan ◽  
...  

1995 ◽  
Vol 35 (4) ◽  
pp. 427 ◽  
Author(s):  
MJ Auldist ◽  
S Coats ◽  
GL Rogers ◽  
GH McDowell

Variations in milk composition during lactation were studied in normal and mastitic dairy cows from 2 seasonally calving herds in northern Victoria. Milk yields, somatic cell counts (SCC), and concentrations of lactose, fat, total protein (TP), casein protein (CP), non-casein protein (NCP), sodium, potassium, and calcium varied considerably as lactation progressed. The basic patterns of change over lactation were similar whether cows were healthy or mastitic (SCC >3 x 105 cells/mL milk). Milk from mastitic cows had higher concentrations of TP, NCP, and sodium, but lower concentrations of fat, lactose, CP, and potassium, than milk from healthy cows, although differences were not consistently significant. The activity of the milk protease, plasmin, was positively correlated with log10SCC in both herds.


Neurosurgery ◽  
1984 ◽  
Vol 14 (5) ◽  
pp. 574-577 ◽  
Author(s):  
Muhammed Yacob Memon ◽  
A. Neal ◽  
R. Imami ◽  
N. Villareal

Abstract During the last 2 years, we treated three cases of brain tumor that presented with intracranial hemorrhage. Two of the three tumors were metastatic. They presented with hemorrhage into the tumor, but no blood in the cerebrospinal fluid. One tumor was a low grade astrocytoma that presented as subarachnoid and intraventricular hemorrhage in a 15-year-old child. It was removed with no neurological sequelae.


Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 317
Author(s):  
Ling-Sai Chang ◽  
Ken-Pen Weng ◽  
Jia-Huei Yan ◽  
Wan-Shan Lo ◽  
Mindy Ming-Huey Guo ◽  
...  

(1) Background: Desquamation is a common characteristic of Kawasaki disease (KD). In this study, we analyzed patients’ varying desquamation levels in their hands or feet, in correlation with clinical presentation, to assess the relationship. (2) Methods: We retrospectively reviewed children with KD. We analyzed their age, laboratory data before intravenous immunoglobulin (IVIG) treatment and coronary artery abnormalities (CAA) based on the desquamation level of their hands and feet. We classified the desquamation level from 0 to 3 and defined high-grade desquamation as grade 2 and 3. (3) Results: We enrolled a total 112 patients in the study. We found the hands’ high-grade desquamation was positively associated with age and segmented neutrophil percentage (p = 0.047 and 0.029, respectively) but negatively associated with lymphocyte and monocyte percentage (p = 0.03 and 0.006, respectively). Meanwhile, the feet’s high-grade desquamation was positively associated with total white blood cell counts (p = 0.033). Furthermore, we found that high-grade hand desquamation had less probability of CAA formation compared with that of a low grade (7.1% vs. 40.8%, p = 0.016). (4) Conclusions: This report is the first to demonstrate that the desquamation level of hands or feet in KD is associated with different coronary artery abnormalities and laboratory findings.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1123
Author(s):  
Wendy C. Ziai ◽  
Adrian R. Parry-Jones ◽  
Carol B. Thompson ◽  
Lauren H. Sansing ◽  
Michael T. Mullen ◽  
...  

We investigated cerebrospinal fluid (CSF) expression of inflammatory cytokines and their relationship with spontaneous intracerebral and intraventricular hemorrhage (ICH, IVH) and perihematomal edema (PHE) volumes in patients with acute IVH. Twenty-eight adults with IVH requiring external ventricular drainage for obstructive hydrocephalus had cerebrospinal fluid (CSF) collected for up to 10 days and had levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), and C-C motif chemokine ligand CCL2 measured using enzyme-linked immunosorbent assay. Median [IQR] ICH and IVH volumes at baseline (T0) were 19.8 [5.8–48.8] and 14.3 [5.3–38] mL respectively. Mean levels of IL-1β, IL-6, IL-10, TNF-α, and CCL2 peaked early compared to day 9–10 (p < 0.05) and decreased across subsequent time periods. Levels of IL-1β, IL-6, IL-8, IL-10, and CCL2 had positive correlations with IVH volume at days 3–8 whereas positive correlations with ICH volume occurred earlier at day 1–2. Significant correlations were found with PHE volume for IL-6, IL-10 and CCL2 at day 1–2 and with relative PHE at days 7–8 or 9–10 for IL-1β, IL-6, IL-8, and IL-10. Time trends of CSF cytokines support experimental data suggesting association of cerebral inflammatory responses with ICH/IVH severity. Pro-inflammatory markers are potential targets for injury reduction.


2021 ◽  
Vol 11 (3) ◽  
pp. 296
Author(s):  
Lars Hendrik Müschen ◽  
Alma Osmanovic ◽  
Camilla Binz ◽  
Konstantin F. Jendretzky ◽  
Gresa Ranxha ◽  
...  

Approval of nusinersen, an intrathecally administered antisense oligonucleotide, for the treatment of 5q-spinal muscular atrophy (SMA) marked the beginning of a new therapeutic era in neurological diseases. Changes in routine cerebrospinal fluid (CSF) parameters under nusinersen have only recently been described in adult SMA patients. We aimed to explore these findings in a real-world setting and to identify clinical and procedure-associated features that might impact CSF parameters. Routinely collected CSF parameters (leukocyte count, lactate, total protein, CSF/serum albumin quotient (QAlbumin), oligoclonal bands) of 28 adult SMA patients were examined for up to 22 months of nusinersen treatment. Total protein and QAlbumin values significantly increased in the first 10 months, independent of the administration procedure. By month 14, no further increases were detected. Two patients developed transient pleocytosis. In two cases, positive oligoclonal bands were found in the beginning and in four patients throughout the whole observation period. No clinical signs of inflammatory central nervous system disease were apparent. Our data confirm elevated CSF total protein and QAlbumin during nusinersen treatment. These alterations may be caused by both repeated lumbar punctures and the interval between procedures rather than by the medication itself. Generally, there were no severe alterations of CSF routine parameters. These results further underline the safety of nusinersen therapy.


Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 268
Author(s):  
Kosuke Saito ◽  
Kotaro Hattori ◽  
Shinsuke Hidese ◽  
Daimei Sasayama ◽  
Tomoko Miyakawa ◽  
...  

Lipidomics provides an overview of lipid profiles in biological systems. Although blood is commonly used for lipid profiling, cerebrospinal fluid (CSF) is more suitable for exploring lipid homeostasis in brain diseases. However, whether an individual’s background affects the CSF lipid profile remains unclear, and the association between CSF and plasma lipid profiles in heathy individuals has not yet been defined. Herein, lipidomics approaches were employed to analyze CSF and plasma samples obtained from 114 healthy Japanese subjects. Results showed that the global lipid profiles differed significantly between CSF and plasma, with only 13 of 114 lipids found to be significantly correlated between the two matrices. Additionally, the CSF total protein content was the primary factor associated with CSF lipids. In the CSF, the levels of major lipids, namely, phosphatidylcholines, sphingomyelins, and cholesterolesters, correlated with CSF total protein levels. These findings indicate that CSF lipidomics can be applied to explore changes in lipid homeostasis in patients with brain diseases.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
F. Schleich ◽  
S. Graff ◽  
F. Guissard ◽  
M. Henket ◽  
V. Paulus ◽  
...  

Abstract Background Elderly asthmatics represent an important group that is often excluded from clinical studies. In this study we wanted to present characteristics of asthmatics older than 70 years old as compared to younger patients. Methods We conducted a retrospective analysis on a series of 758 asthmatics subdivided in three groups: lower than 40, between 40 and 70 and older than 70. All the patients who had a successful sputum induction were included in the study. Results Older patients had a higher Body Mass Index, had less active smokers and were more often treated with Long Acting anti-Muscarinic Agents. We found a significant increase in sputum neutrophil counts with ageing. There was no significant difference in blood inflammatory cell counts whatever the age group. Forced expiratory volume in one second (FEV1) and FEV1/FVC values were significantly lower in elderly who had lower bronchial hyperresponsiveness and signs of air trapping. We found a lower occurrence of the allergic component in advanced ages. Asthmatics older than 70 years old had later onset of the disease and a significant longer disease duration. Conclusion Our study highlights that asthmatics older than 70 years old have higher bronchial neutrophilic inflammation, a poorer lung function, signs of air trapping and lower airway variability. The role of immunosenescence inducing chronic low-grade inflammation in this asthma subtype remains to be elucidated.


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