[Angiogenic growth factors in the ceresbropinal liquid of pregnant women during planned cesarean section under combined spinal - epidural anaesthesia].

The content of soluble angiogenic growth factors in cerebrospinal liquid and blood serum in 33 pregnant women aged from 21 to 37 years (30.9 +/- 6.2 years) before spinal - epidural anaesthesia during Cesarean section was studied in observative, prospective, stratificative research. All patients without somatic pathology were divided into 2 groups -control and main. 12 pregnant women with high degree myopia as a main indication for Cesarean section were included in the 1st control group. 21 pregnant women were included in the 2nd main group. This group was divided into 2 subgroups: group 2a--with eukinetic haemodynamics type (12 patients), group 2b--with hyperkinetic haemodynamics type and moderate hypoxemia (9 patients). The indications for planned Cesarean section in patients of the 2nd group were uterine scar and/or pelvis bones pathology. The analysis of angiogenic growth factors content in cerebrospinal liquid revealed differences between group 2b and group 2a. Results of angiogenic growth factors content in cerebrospinal liquid testify hidden intracerebral hypoxemia and can be used for its assessment before anaesthesia and for the testifying of the haemodynamics status and system hypoxemia relationship.

Validation of the ICSD-2 criteria for CSF hypocretin-1 measurements in the diagnosis of narcolepsy in the Danish population.

STUDY OBJECTIVES: The International Classification of Sleep Disorders (ICSD-2) criteria for low CSF hypocretin-1 levels (CSF hcrt-1) still need validation as a diagnostic tool for narcolepsy in different populations because inter-assay variability and different definitions of hypocretin deficiency complicate direct comparisons of study results. DESIGN AND PARTICIPANTS: Interviews, polysomnography, multiple sleep latency test, HLA-typing, and CSF hcrt-1 measurements in Danish patients with narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (NwC), CSF hcrt-1 measurements in other hypersomnias, neurological and normal controls. Comparisons of hypocretin deficiency and frequency of HLA-DQB1*0602-positivity in the Danish and eligible NC and NwC populations (included via MEDLINE search), by (re)calculation of study results using the ICSD-2 criterion for low CSF hcrt-1 (< 30% of normal mean). MEASUREMENTS AND RESULTS: In Danes, low CSF hcrt-1 was present in 40/46 NC, 3/14 NwC and 0/106 controls (P < 0.0001). Thirty-nine of 41 NC and 4/13 NwC patients were HLA-DQB1*0602-positive (P < 0.01). Hypocretin-deficient NC patients had higher frequency of cataplexy, shorter mean sleep latency, more sleep onset REM periods (P < 0.05) and more awakenings (NS) than did NC patients with normal CSF hcrt-1. Across populations, low CSF hcrt-1 and HLA-DQB1*0602-positivity characterized the majority of NC (80% to 100%, P = 0.53; 80% to 100%, P = 0.11) but a minority of NwC patients (11% to 29%, P = 0.75; 29% to 89%, P = 0.043). CONCLUSION: The study provides evidence that hypocretin deficiency causes a more severe NC phenotype. The ICSD-2 criterion for low CSF hcrt-1 (< 30% of normal mean) is valid for diagnosing NC, but not NwC. HLA-typing should precede CSF hcrt-1 measurements because hypocretin deficiency is rare in HLA-DQB1*0602-negative patients.

Vasodilatory prostaglandins in perinatal hypoxic brain damage.

Prostaglandin (PGE2 and PGI2) synthesis was determined in the cerebrospinal fluid (CSF) and serum of 19 hypoxic neonates at the age of 5-96 hours by using Enzyme Linked Immunosorbent Assay (ELISA) method. Control group consisted of 8 children of the same age whose samples were taken due to initial suspicion of neonatal meningitis. The prostaglandin concentrations in CSF were correlated with initial hypoxic-ischemic encephalopathy (HIE) stage and neurological findings of patients at the age of 12 months. The values of PGE2 and PGI2 in the CSF of children with perinatal hypoxia (PNH) were significantly higher than in the children from the control group. The values of PGI2 in serum were significantly higher than in "CSF" of patients with PNH. Although average values of PGE2 and PGI2 in the liquor were higher in children with advanced stage of HIE, the differences between different stages were not statistically significant. We did not find any significant correlation between average concentrations ofprostaglandins and neurological findings of the 12-month-old children.

A comparison of blood and cerebrospinal fluid cytokines (IL-1ß, IL-6, IL-18, TNF-α) in neonates with perinatal hypoxia.

Perinatal hypoxia-ischemia is a specific and important pathological event in neonatal care practice. The data on relationship between the concentrations of cytokines in blood and cerebrospinal fluid (CSF) and perinatal brain injury are scarce. The aim of this study is to evaluate changes in interleukin (IL-1ß, IL-6, and IL-18) and tumor necrosis factor alpha (TNF-α) levels in newborns with perinatal hypoxia (PNH). CSF and serum samples of 35 term and near-term (35-40 weeks) newborns with PNH, at the age of 3-96 hours, were analyzed using enzyme-linked immunosorbent assay. Control group consisted of 25 non-asphyxic/non-hypoxic infants of the same age sampled for clinically suspected perinatal meningitis, but proven negative and healthy otherwise. The cytokine values in CSF and serum samples were determined in relation to initial hypoxic-ischemic encephalopathy (HIE) staged according the Sarnat/Sarnat method, and compared with neurological outcome at 12 months of age estimated using Amiel-Tison procedure. The concentrations of IL-6 and TNF-α in serum of PNH patients were significantly higher compared to control group (p = 0.0407 and p = 0.023, respectively). No significant difference between average values of cytokines in relation to the stage of HIE was observed. Significantly higher levels of IL-6 and IL-18 corresponded to a mildly abnormal neurological outcome, while higher levels of IL-6 and TNF-α corresponded to a severely abnormal neurological outcome, at 12 months of age. Elevated serum levels of IL-6 and TNF-α better corresponded with hypoxia/ischemia compared to CSF values, within 96 hours of birth. Also, higher serum levels of IL-6, TNF-α, and IL-18 corresponded better with abnormal neurological outcome at 12 months of age, compared to CSF values.

Excitatory amino acids and magnesium sulfate in neonatal asphyxia.

OBJECTIVE: The excitatory amino acids (EAA); glutamate and aspartate are released into the cerebrospinal fluids (CSF) of asphyxiated newborns. The objectives of this study were: (a) to examine the relation of the concentration of EAA in the CSF with the degree of brain injury, (b) To determine the time of the release of these EAA into the CSF, and (c) to detect the effect of magnesium sulfate (MgSO(4)) on their levels. DESIGNS AND METHODS. A randomized controlled trial was conducted on 47 full term asphyxiated newborns. Twenty three infants received an intravenous 10% solution of MgSO(4) at a dose of 250 mg/kg within the first 24h of life while the other 24 newborns received isotonic saline (0.9%) of an equal volume. Levels of glutamate and aspartate were measured before and 72 h after giving the trial solution. Results. In the study population (n=47) both glutamate and aspartate were significantly elevated in infants with higher grades of HIE compared to those with lower grades (P=0.013 and 0.031, respectively). Compared to baseline level, glutamate decreased significantly over time in placebo group (-8.28+/-14.26, P=0.025) and in MgSO(4) group (-14.39+/-18.72, P=0.005). Glutamate concentration did not differ between groups when measured at baseline (29.26+/-16.31 vs. 31.27+/-22.62, P=0.82) and at 72 h (19.28+/-15.63 vs. 19.6+/-16.54, P=0.87). The change in aspartate concentration over time was not significant in placebo group (-0.45+/-1.96, P=0.34) or in MgSO(4) group (-0.7+/-3.19, P=0.37). Aspartate did not differ between groups when measured at baseline (3.52+/-2.4 vs. 3.92+/-2.59, P=0.49) or at 72 h (2.79+/-1.24 vs. 3.05+/-2.48, P=0.92). Conclusions. The EAA; glutamate and aspartate are released in the CSF of asphyxiated newborns immediately after birth and declined by 72 h. Their initial concentrations correlated with the severity of HIE. Postnatal administration of MgSO(4) did not alter the levels of these 2 EAA.

Pseudo-subarachnoid hemorrhage in a patient with hypoxic encephalopathy.

The authors report an unusual case of diffuse subarachnoid hemorrhage on brain computed tomography (CT) scan in a patient with post-resuscitation anoxic encephalopathy. A 42-year-old woman suffered both respiratory and cardiac arrest, associated with hypoxic encephalopathy, which occurred during a visit to our gynecology clinic. CT examination was performed the next day, which revealed a hyperdensity in the basal cisterns with a diffuse cerebral edema. Lumbar puncture was applied for diagnosis. No yellow coloration or red cells were observed in the cerebrospinal fluid. Nineteen days after treatment, the CT examination revealed features of a subarachnoid hemorrhage with a significantly increased cerebral edema. The patient died two months later. This clinical case illustrates that hypoxic encephalopathy can mimic diffuse subarachnoid hemorrhage on CT scan.

Delayed postanoxic encephalopathy after strangulation. Serial neuroradiological and neurochemical studies.

A 13-year-old boy was the victim of attempted strangulation. His condition had returned to normal by the sixth day after the assault; however, from the seventh day, choreoathetosis, dystonia, and marked pseudobulbar paralysis developed in the boy. The computed tomographic scans and T2-weighted magnetic resonance images that were obtained at this time revealed low-density and high-signal intensities in the region of the bilateral putamen and caudate nucleus. These symptoms and the changes in his computed tomographic scans and magnetic resonance images subsided gradually during a 2-month period. Sequential analysis of the cerebrospinal fluid for gamma-aminobutyric acid and dopamine concentrations during his illness revealed reciprocal changes with normal recovery. Because of the delayed onset of neurological changes and the cerebrospinal fluid showing reversible symptoms, the delayed encephalopathy after strangulation had been related to the biochemical alterations that followed anoxia in the vulnerable basal ganglia.

Intravenous glycerol and mannitol therapy in children with intracranial hypertension.

Acute intracranial hypertension may respond to intravenous mannitol, but frequent administration can cause cerebral edema or renal problems. We evaluated the use of 20% glycerol administered intravenously as an alternative to mannitol. Intravenous glycerol and mannitol were equally effective in lowering acute elevations of intracranial pressure. The duration of effect was similar for both agents. Side effects of intravenous glycerol were related to concentration, rate, and frequency of administration. In severe encephalopathies, such as Reye syndrome, we recommend infusions of 20% glycerol or 20% mannitol at a dose of 0.5-1.0 gm per kilogram. Glycerol should be administered in 0.45% or 0.9% saline, no faster than 1.5 ml (3.3 mOsm) per minute.

Neuron-specific enolase and myelin basic protein: relationship of cerebrospinal fluid concentrations to the neurologic condition of asphyxiated full-term infants.

OBJECTIVE: We questioned whether neuron-specific enolase (NSE) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) in the first 72 hours of life are correlated with the neurologic condition of asphyxiated full-term infants in the neonatal period and at 1 year of age. PATIENTS AND METHODS: Sixty-nine asphyxiated infants were studied with serial neurologic examination, cranial ultrasonography, and neurologic follow-up. CSF samples were obtained by lumbar puncture at 12 and 72 hours of life. NSE was measured by enzyme immunoassay, and MBP was measured by radioimmunoassay. RESULTS: Twenty infants had no neonatal encephalopathy and 49 exhibited different stages of encephalopathy. NSE and MBP concentrations in CSF at 12 and 72 hours of life were related to the degree of neonatal encephalopathy. Neither NSE nor MBP levels were correlated with any perinatal factors. Infants with documented brain injury had the highest concentrations of both NSE and MBP. The concentrations of these two biochemical markers at both 12 and 72 hours correlated with adverse outcome (death or cerebral palsy at 1 year). Based on a receiver operating characteristics curve analysis for any given specificity, NSE at 12 hours was a more accurate marker than MBP at either 12 or 72 hours for distinguishing infants with motor impairment at age 1 year from infants with normal outcome at the same age. CONCLUSIONS: Our findings suggest that NSE and MBP are reliable biochemical markers for early estimates of hypoxic-ischemic brain damage in asphyctic full-term newborns, NSE being superior to MBP.

CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man.

Creatine kinase (CK) and its brain-specific isoenzyme (CK-BB), neuron-specific enolase (NSE), neural cell adhesion molecule (NCAM) and the ions sodium, potassium, chloride and calcium were measured both in CSF and serum and inorganic phosphate in CSF in order to assess their prognostic value in total brain ischemia due to cardiac arrest. The samples were collected at 4, 28 and 76 h after resuscitation. Twenty consecutive patients resuscitated from ventricular fibrillation or asystole were included in the study. Nine of the patients recovered consciousness (recovered) but eleven remained comatose (disabled). The follow-up period was 2 years after which only one patient was still alive. The earliest statistically significant differences between neurologically recovered and disabled patient groups were seen in CSF inorganic phosphate (P = 0.030) already at 4 h and CK-BB (P = 0.046) and NSE (P = 0.020) activity at 28 h. Later, at 76 h after the resuscitation CSF NSE differentiated the groups most clearly (P = 0.014). The values were higher in the disabled patients. A negative correlation between CSF parameters and Glasgow Coma scores was also seen at these timepoints. Statistically significant differences between the groups were seen in both CSF and blood pCO2, pO2, base excess (BE) and actual bicarbonate (HCO3-). CSF or serum NCAM has no prognostic value in anoxic-ischemic coma. The results suggest that in CSF CK-BB and NSE are useful prognostic indicators of hypoxic brain injury when measured 28-76 h after cardiac arrest whereas blood samples have no prognostic value.

Predictive value of plasma and cerebrospinal fluid tumour necrosis factor-alpha and interleukin-1 beta concentrations on outcome of full term infants with hypoxic-ischaemic encephalopathy.

AIM: To determine the predictive value of plasma and cerebrospinal fluid (CSF) tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) concentrations on the outcome of hypoxic-ischaemic encephalopathy (HIE) in full term infants. METHODS: Thirty term infants with HIE were included in the study. HIE was classified according to the criteria of Sarnat and Sarnat. Blood and CSF were obtained within the first 24 hours of life and stored until assay. Five infants died soon after hypoxic insult. Neurological examinations and Denver Developmental Screening Test (DDST) were performed at 12 months in the survivors. RESULTS: At the age of 12 months neurological examination and DDST showed that 11 infants were normal; 14 had abnormal neurological findings and/or an abnormal DDST result. Eleven normal infants were classified as group 1 and 19 infants (14 with abnormal neurological findings and/or an abnormal DDST and five who died) as group 2. CSF IL-1 beta and TNF-alpha concentrations in group 2 were significantly higher than those in group 1. Plasma IL-1 beta and TNF-alpha concentrations were not significantly different between the two groups. IL-1 beta, but not TNF-alpha concentrations, in group 2 were even higher than those in group 1, although non-survivors were excluded from group 2. When the patients were evaluated according to the stages of Sarnat, the difference in the three groups was again significant. Patients whose CSF samples were taken within 6 hours of the hypoxic insult had higher IL-1 beta and TNF-alpha concentrations than the patients whose samples were taken after 6 hours. CONCLUSIONS: Both cytokines probably contribute to the damage sustained by the central nervous system after hypoxic insult. IL-1 beta seems to be a better predictor of HIE than TNF-alpha.

Neuron specific enolase in asphyxiated newborns: association with encephalopathy and cerebral function monitor trace.

Neuron specific enolase (NSE) in serum and cerebrospinal fluid (CSF) and glutamate in CSF were investigated in the immediate postasphyctic period in 22 term newborn infants. The cerebral function monitor (CFM) pattern was also assessed and hypoxic-ischaemic encephalopathy (HIE) was graded. NSE was significantly increased in the CSF of infants with HIE (median value 25.4 micrograms/l) compared with control infants (10.0 micrograms/l). Infants with the highest concentrations died. NSE in CSF correlated with the degree of asphyxial damage. Glutamate and NSE in CSF did not correlate, presumably due to the different time factors of the release after the insult. NSE in CSF corresponded well with the type of CFM pattern, which was also highly predictive of outcome.

The effect of perinatal anoxia on amino acid metabolism in the developing brain. Part II: The effect of perinatal anoxia on the free amino acid patterns in CSF of infants and children.

To clarify the effects of perinatal anoxia on the subsequent amino acid metabolism in the brain of children, free amino acid levels in the cerebrospinal fluid (CSF) were determined in 15 children diagnosed as having cerebral palsy and/or mental retardation with perinatal anoxia, and 58 control children without anoxia, aged from 4 days to 12 yrs. There was no significant difference in total amino acid levels between anoxic children and the controls. In the controls, the Gln level in CSF was high, Arg, Asp and Glu levels in CSF were almost the same during infancy and childhood, and the levels of Orn, Lys, His, Tau, Thr, Ser, Asn, Gly, Ala, Val, Met, Ile, Leu, Tyr and Phe in CSF decreased with age until pre-school age. In the newborns and infants among the anoxic children, the levels of most free amino acids in CSF were relatively high compared with those of the controls and, except Glu and Gln, decreased with age during infancy. The Orn, His, Gly, Tyr and Phe levels in CSF of anoxic children were lower than those of the controls in older infants. These results suggest that perinatal anoxia affected free amino acid patterns in CSF of newborns and infants and that the subsequent disturbance of amino acid metabolism in their brains remained after birth.

Cerebrospinal fluid lactate levels in term infants with perinatal hypoxia.

The prognostic value of cerebrospinal fluid (CSF) lactate concentration after an hypoxic-ischemic brain insult was evaluated. Three groups of neonates were studied and followed. Group 1A included 19 asphyxiated neonates who subsequently developed normally, Group 1B included 6 asphyxiated neonates who died or developed neurologic sequelae, and Group 2 consisted of 20 control (comparison) infants. A CSF sample was obtained within the first day of life for cytochemical analysis, culture, and lactate determination with simultaneous determination of serum lactate. The mean CSF lactate level in Group 1B (4.5 mmol/L) was significantly higher than in Group 1A (2.5 mmol/L) (p less than .001). In comparison to the highest CSF lactate concentrations in the normal range in Group 2 (2.7 mmol/L), all Group 1B neonates had elevated CSF lactate levels, and eight neonates (34%) of Group 1A had increased levels. A correlation was found between blood and CSF lactate levels in asphyxiated infants (r = .42, p less than .05), but its meaning is uncertain. We conclude that CSF lactate determinations may be helpful in the evaluation of perinatal hypoxic-ischemic encephalopathy.

[Study on the concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the lumbar cerebrospinal fluid (CSF) in neurological diseases].

Experimental evidence has shown that the amount of 5-HIAA in the CSF reflects the metabolism of serotonin in the brain if this metabolite is eliminated from the brain and flows into the CSF at a constant rate. We studied the concentration of 5-HIAA in the lumbar CSF in several neurological diseases to elucidate the alteration in abnormalities of serotonin metabolism. The concentration of 5-HIAA in the CSF was measured in 94 patients with cerebral infarction, 30 with vascular dementia, 25 with dementia of the Alzheimer type, 28 with Parkinson's disease and 6 with hypoxic encephalopathy. Patients with cerebral infarction were classified into 24 with a solitary cerebral infarct and 70 with multiple cerebral infarcts. Patients with Parkinson's disease were subdivided into 12 with various psychiatric symptoms including depressive state, hallucination and/or intellectual impairment and 16 without psychiatric symptoms. Patients with hypoxic encephalopathy consisted of 5 with apallic syndrome and one patient with Lance-Adams syndrome. The concentration of 5-HIAA in solitary cerebral infarct, multiple cerebral infarcts and vascular dementia did not exhibit a significant difference from that in control cases (54.6 +/- 23.1 ng/ml). But patients with dementia of the Alzheimer type (34.5 +/- 10.9, p less than 0.001) showed a significantly lower concentration. This fact seems to reflect the pathological finding that the number of large neurons is decreased and neurofibrillary tangles are increased in the nucleus raphe dorsalis of patients with Alzheimer type dementia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Delayed postanoxic encephalopathy after strangulation--the serial neuroradiological and neurochemical studies].

A 13-year-old boy was the victim of a strangulation attempt. His behavior was normal by the 6th day after the assault. However, from the 7th day, he developed choreoathetosis, dystonia and marked pseudobulbar palsy. CT and T2-weighted MRI at this time revealed a low density and high signal intensity in the region of the bilateral putamen and caudate respectively for the first time. Thereafter, these symptoms and changes in CTs and MRIs subsided gradually over two months. Sequential analysis of CSF for GABA and dopamine during illness revealed reciprocal changes each other with normal recovery. Because of delayed onset of neurological changes, and findings of CSF with reversible symptoms the delayed encephalopathy after strangulation is probably related to biochemical alteration secondary to anoxia in vulnerable basal ganglia.

[Monoamines, monoamine metabolites, neuron specific enolase and myelin basic protein concentrations in cerebrospinal fluid of resuscitated patients].

Changes of monoamines, monoamine metabolites, neuron specific enolase (NSE) and myelin basic protein (MBP) levels in cerebrospinal fluid were measured in 8 patients for up to 7 days after cardiopulmonary resuscitation. The outcomes were assessed by the Glasgow Outcome Scale. One showed good recovery 3 developed a persistent vegetate state (PVS) and 4 became brain dead (BD). The concentration of NSE increased to a peak about 3 days after resuscitation, then gradually decreased. MBP also showed an increase with time up to 7 days. The time course suggests that neuronal and/or axonal damage progresses for several days after hypoxic or anoxic brain insult. NSE and MBP in the BD group were higher than those in the PVS group, thus CSF levels may be prognostic with regard to hypoxic brain injury. Tyrosine, dopamine, 3-methoxytyramine (3-MT), 3-dihydroxy-4-phenylacetic acid (DOPAC), homovanillic acid (HVA), vanillylmanderic acid (VMA), normetanephrine (NMN), metanephrine (MN), 3-methoxy-4-hydroxyphenylglycol (MHPG), vanillic acid (VA), tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were analyzed by HPLC with an electrochemical detector. Concentrations changed within 2 or 3 days after resuscitation, so concentrations at that period may indicate neuronal damage. However, there are some cases with abnormal NSE and MBP levels without abnormal monoamine levels, suggesting that differences in concentrations are not the consequence of the amount of affected neurons, but of the sites of regions.

[Lactate dehydrogenase in the cerebrospinal fluid in 57 hypoxic neonates]. / Laktikodehydrogenáza v mozkomísním moku u 57 hypoxických novorozencu.

The authors used assessment of lactic dehydrogenase activity in cerebrospinal fluid to evaluate the severity of hypoxic damage of the CNS of neonates. The highest activity was recorded in infants who died in conjunction with the hypoxic lesion of the CNS. The lowest activity was found in neonates with a permanently normal neurological finding during infancy. From the results ensues the prognostic importance of the above examination for subsequent psychomotor development of children.

Pitfalls in measuring cerebrospinal fluid glycine levels in infants with encephalopathy.

In encephalopathic infants, cerebrospinal fluid hyperglycinemia and elevated cerebrospinal fluid to plasma glycine ratio are considered pathognomonic of nonketotic hyperglycinemia. To evaluate the significance of cerebrospinal fluid hyperglycinemia and elevated cerebrospinal fluid to plasma glycine ratio in acutely encephalopathic infants, a retrospective chart review of all cases of isolated elevation of cerebrospinal fluid glycine levels at Arkansas Children's Hospital from January 1995 to December 2000 was performed. Twenty-two patients (14 males) were included. The most common diagnosis was hypoxic ischemic encephalopathy (n = 8). Nine patients had elevated cerebrospinal fluid to plasma glycine ratio, which was transient in 7 patients. This study shows that elevated cerebrospinal fluid to plasma glycine ratio can be encountered in a variety of clinical conditions. The significance of this observation in light of the poor prognosis of nonketotic hyperglycinemia and the possible role of glycine in the mechanism of ischemic neuronal injury is addressed.