Cerebrospinal Fluid Ion Analysis in Neonatal Seizures.

BACKGROUND: There is a gap of knowledge regarding cerebrospinal fluid (CSF) ion concentrations in normal and pathological states, particularly during the neonatal period. We aim to compare CSF ion concentrations in newborns with different causes of neonatal-onset epilepsy (NOE) and acute symptomatic seizures (ASS) and controls, to examine their usefulness for diagnostic purposes. METHODS: A descriptive retrospective study was conducted from January 2019 to June 2020 in a tertiary hospital. We analyzed CSF K+, Na+, Cl-, and Ca2+ concentrations in frozen samples from patients with neonatal seizures (NS) secondary to NOE and ASS (neonatal arterial ischemic stroke [NAIS] and hypoxic-ischemic encephalopathy). As the control group, we selected CSF samples from newborns who had undergone CSF analysis as part of the diagnostic workup and in whom central nervous system infections had been ruled out, without signs of dehydration, gastroenteritis, or history of seizures. RESULTS: Sixty-eight newborns were included, 16 with NOE, 13 with ASS, and 39 without NS (control group). In comparison with the control group, [K+]CSF was lower in patients with KCNQ2-related epilepsy (P = 0.007), other causes of NOE (P = 0.010), and NAIS (P = 0.002). Changes in [Na+]CSF, [Cl-]CSF, and [Ca2+]CSF were less consistent among subgroups. CONCLUSIONS: Here we report for the first time ionic imbalances in the CSF of neonates with NOE and NAIS. No differences were observed between newborns with different causes of NS. Further studies should be undertaken to investigate the physiopathology behind these changes and their impact on biological function.

Ion concentrations in cerebrospinal fluid in wakefulness, sleep and sleep deprivation in healthy humans.

Sleep is controlled by a circadian rhythmicity, via a reduction of arousal-promoting neuromodulatory activity, and by accumulation of somnogenic factors in the interstitial fluid of the brain. Recent experiments in mice suggest that a reduced neuronal excitability caused by a reduced concentration of potassium in the brain, concomitant with an increased concentration of calcium and magnesium, constitutes an important mediator of sleep. In the present study, we examined whether such changes in ion concentrations could be detected in the cerebrospinal fluid of healthy humans. Each subject underwent cerebrospinal fluid collection at three occasions in a randomized order: at 15:00 hours-17:00 hours during waking, at 06:00 hours-07:00 hours immediately following 1 night of sleep, and at 06:00 hours-07:00 hours following 1 night of sleep deprivation. When compared with wakefulness, both sleep and sleep deprivation produced the same effect of a small (0.1 mm, about 3%), but robust and highly significant, reduction in potassium concentration. Calcium and magnesium concentrations were unchanged. Our results support a circadian modulation of neuronal excitability in the brain mediated via changes of the interstitial potassium concentration.

Sample Fractionation Techniques for CSF Peptide Spectral Library Generation.

Data-independent acquisition (DIA) is becoming more prominent as a method for comprehensive proteomic analysis of clinical samples due to its ability to acquire essentially all fragment ion spectra in a single LC-ESI-MS/MS experiment. Since the direct correlation between a precursor and its fragment ions is lost when acquiring all ions in a defined m/z range, one data analysis strategy is using so-called peptide spectral libraries. These are usually generated by measuring similar biological samples in data-dependent (DDA) mode. The peptide spectral library content is a major limitation for the successful identification from DIA data. This is because a fragment ion spectrum from the sample can only be matched, and thus identified, when it is present in the peptide spectral library. In order to enhance peptide spectral library size, the sample for generating the peptide spectral library can be subjected to extended separation strategies prior to DDA. These strategies are of special relevance for biological samples containing a few very high-abundant proteins, such as CSF, as they enlarge the identification of low-abundant proteins. In instances of CSF separation, suitable methods include the 1D SDS-PAGE of proteins and high-pH reversed-phase peptide fractionation. Both methods are based on different protein/peptide characteristics, are complementary with one another, and are inexpensive and easy to establish. Ideally, DDA spectra from samples generated with both methods combine to achieve a comprehensive spectral library.

Capillary electrophoresis of small ions and molecules in less conventional human body fluid samples: A review.

In recent years, advances in sensitive analytical techniques have encouraged the analysis of various compounds in biological fluids. While blood serum, blood plasma and urine still remain the golden standards in clinical, toxicological and forensic science, analyses of other body fluids, such as breast milk, exhaled breath condensate, sweat, saliva, amniotic fluid, cerebrospinal fluid, or capillary blood in form of dried blood spots are becoming more popular. This review article focuses on capillary electrophoresis and microchip electrophoresis of small ions and molecules (e.g. inorganic cations/anions, basic/acidic drugs, small acids/bases, amino acids, peptides and other low molecular weight analytes) in various less conventional human body fluids and hopes to stimulate further interest in the field.

Time-dependent changes in cerebrospinal fluid metal ions following aneurysm subarachnoid hemorrhage and their association with cerebral vasospasm.

Aneurysm subarachnoid hemorrhage affects 10 in 100,000 people annually, 40 % of whom will develop neurological deficits from ischemic stroke caused by cerebral vasospasm. Currently, the underlying mechanisms are uncertain. Metal ions are important modulators of neuronal electrophysiological conduction and smooth muscle cell activity, thereby potentially contributing to vasospasm. We hypothesized that metal ion concentrations in the cerebrospinal fluid (CSF) after aneurysm rupture would change over time and be associated with vasospasm. To test this hypothesis, for 21 days, we collected CSF from patients with aneurysmal rupture and subjected it to spectrometry to detect metals. A repeated measures analysis was performed to analyze concentration changes over time. Six of the seven patients with aneurysmal rupture experienced vasospasm, all resolving by day 14. Changes in Fe²âº and Zn²âº concentrations in the CSF paralleled the incidence of vasospasm in this study population. Na²âº, Ca²âº, Mg²âº, and Cu²âº concentrations exhibited no statistically significant changes over time. In conclusion, Fe²âº concentration in the CSF was significantly elevated during days 7-10, whereas Zn²âº concentrations spiked shortly thereafter, during days 11-14. This suggests that Fe²âº may be related to the induction of vasospasm and Zn²âº may be a marker of early brain injury secondary to ischemic injury and inflammation.

Cerebral blood flow, glucose use, and CSF ionic regulation in potassium-depleted rats.

Rats were kept on a low-K+ diet for 25 or 70 days. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured in 31 different structures of the brain by means of the [14C]iodoantipyrine and [14C]2-deoxy-D-glucose method. After 25 and 70 days of K+ depletion LCBF was decreased significantly in 27 and 30 structures, respectively, the average decrease being 19 and 25%. In contrast, average LCGU was not changed. Cisternal cerebrospinal fluid (CSF) K+ concentration decreased significantly from 2.65 +/- 0.02 mM in controls to 2.55 +/- 0.02 mM and 2.47 +/- 0.02 mM in the two treated groups (P less than 0.01). CSF [HCO3-], pH, and PCO2 were increased in K+-depleted animals. These data show that K+ depletion induces an increase in CSF pH and a decrease in CSF K+ concentration, both of which cause a reduction in cerebral blood flow. The increased CSF PCO2 is secondary to the reduction of blood flow, since brain metabolism and arterial PCO2 remained constant.

Ionic mechanisms of cerebrospinal fluid acid-base regulation.

This review emphasizes the importance of strong ions in the regulation of cerebrospinal fluid (CSF) acid-base balance. In a solution like CSF that is devoid of nonbicarbonate buffers. [H+] and [HCO-3] are dependent variables, the independent variables being the CO2 partial pressure (PCO2) and the strong ion difference. Any measureable changes in CSF [HCO-3] and any change in [H+] that occur independent of changes in PCO2 must be accompanied by, if not caused by, changes in strong ions. The role of H+ and HCO-3 vs. strong ions in the ionic mechanisms of CSF acid-base regulation is unknown. For example, these mechanisms could depend only on changes in strong ions that accompany acid-base disorders, or they could be triggered by changes in [H+] or PCO2. These ideas are presented within the context of current concepts concerning the relationship of CSF to brain interstitial fluid (ISF) and the importance of choroid plexus and blood-brain barrier mechanisms in determining CSF and ISF ionic composition. Studies concerning CSF strong ions in normal and abnormal acid-base states are reviewed.

[Ion concentration in the cerebrospinal fluid in multiple sclerosis]. / Zur Ionenkonzentration im Liquor cerebrospinalis bei Multipler Sklerose.

The concentrations of electrolytes Na, K, Ca, Mg, and Cl and trace elements Cu and Zn were determined in the lumbar cerebrospinal fluids of forty patients with multiple sclerosis. Metal ion concentrations were measured using atomic absorption spectroscopy and flame photometry, respectively. Compared with corresponding values obtained from a control group, statistically significant increases in concentration of Na, Cl, Ca, and Zn have been found. Also reported are the results of determinations of ion concentrations in cerebrospinal fluids obtained from patients suffering from diseases other than multiple sclerosis. Possible causes of deviations from the norm are discussed.