Atrial natriuretic factor and salt wasting after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The causes of volume depletion and hyponatremia after subarachnoid hemorrhage are not fully understood but may be in part due to natriuresis or "cerebral salt wasting." Because previous studies using infrequent hormone sampling have given inconsistent results, we determined if elevations in atrial natriuretic factor concentrations preceded negative sodium and fluid balances. METHODS: We measured diurnal atrial natriuretic factor and vasopressin concentrations and sodium balance for 5 days in 14 consecutive patients after aneurysmal subarachnoid hemorrhage. RESULTS: Plasma concentrations of atrial natriuretic factor on admission were elevated in subarachnoid hemorrhage patients (mean +/- SD 106 +/- 59 pg/ml) compared with acutely ill controls (39 +/- 30 pg/ml). In eight patients, high peak concentrations of atrial natriuretic factor, greater than 300 pg/ml or a twofold increase above baseline, were followed by natriuresis and a negative sodium balance. Three patients, two of whom became hyponatremic, developed cerebral infarcts after natriuresis. Vasopressin concentrations were slightly elevated just after hemorrhage but subsequently declined to normal values. CONCLUSIONS: A markedly increased atrial natriuretic factor concentration precedes natriuresis in some patients and, with other abnormalities of water handling possibly including a relatively diminished vasopressin concentration, may cause volume depletion. Patients with natriuresis appear to be at increased risk for delayed cerebral infarction after subarachnoid hemorrhage.     

Suprasellar and intraventricular blood predict elevated plasma atrial natriuretic factor in subarachnoid hemorrhage.

Following subarachnoid hemorrhage, the plasma concentration of atrial natriuretic factor is elevated and appears to be independent of atrial stretch. While the hypothalamus and circumventricular organs contribute to sodium and intravascular volume regulation, their influence on atrial natriuretic factor is not known. We tested the hypothesis that, following subarachnoid hemorrhage, suprasellar cisternal blood, intraventricular blood, or ventricular enlargement would be associated with elevated plasma levels of atrial natriuretic factor. Computed tomograms of 26 patients performed less than or equal to 3 days after hemorrhage were analyzed to determine the presence of suprasellar or intraventricular blood and enlargement of the third or lateral ventricle. These results were correlated with the plasma atrial natriuretic factor and serum sodium concentrations. The initial atrial natriuretic factor concentration was elevated and was higher in patients with suprasellar or intraventricular blood than in those without (suprasellar: 131 +/- 20 and 54 +/- 10 pg/ml, respectively; intraventricular: 137 +/- 25 and 84 +/- 31 pg/ml, respectively). The atrial natriuretic factor concentration remained higher over the week following hemorrhage in patients with suprasellar blood than in those without (127 +/- 16 and 68 +/- 12 pg/ml, respectively). The atrial natriuretic factor concentration was not correlated with hyponatremia (125-134 meq/l) or age-corrected ventricular size. Hyponatremia did not correlate with the presence of intraventricular or suprasellar blood. Our data suggest that suprasellar and intraventricular blood disturb hypothalamic function, resulting in an elevated plasma atrial natriuretic factor concentration. The presence of a direct relation between atrial natriuretic factor and hyponatremia remains unclear.     

Serial measurement of bradykinin of the cerebrospinal fluid in patients with subarachnoid hemorrhage

The bradykinin (BK) concentration of the cerebrospinal fluid (CSF) in 21 patients with subarachnoid hemorrhage (SAH) was measured serially by radioimmunoassay (RIA). The values were 134.9 +/- 93.9 pg/ml (mean +/- standard deviation) on the day of onset, 38.3 +/- 31.8 pg/ml on the first day after onset, 23.4 +/- 22.8 pg/ml on the second day, 16.6 +/- 9.9 pg/ml on the third day, 15.5 +/- 6.0 pg/ml on the fourth day, and 14.8 +/- 5.9 pg/ml on the fifth day. In the controls the BK concentration in the CSF was 8.0 +/- 3.3 pg/ml (n = 10). On the other hand, none of 5 patients with intraventricular hematoma due to intracerebral hemorrhage had a high level of BK in the bloody CSF at the initial stage (15.2-26.0 pg/ml). This shows that BK is not produced only by the mixture of CSF and blood. BK is produced by the activation of Hageman factor that is considered to be activated by trabecula of collagen bundles in the subarachnoid space in the case of SAH.     

Cerebrospinal fluid vasopressin and increased intracranial pressure

Cerebrospinal fluid and plasma vasopressin were measured in patients with cerebral disorders associated with varying levels of elevated intracranial pressure. The mean cerebrospinal fluid vasopressin concentration was significantly increased in patients with pseudotumor cerebri (2.0 +/- 0.2 [SEM] pg/ml), intracranial tumor (2.3 +/- 0.4 pg/ml), and intracranial hemorrhage (1.9 +/- 0.3 pg/ml) compared with control patients (1.2 +/- 0.1 pg/ml). A significant relationship was found between intracranial pressure and the cerebrospinal fluid vasopressin concentration within all groups of patients and in the whole sample as well (r = 0.79; p less than 0.001). In the groups of patients with intracranial tumor, hydrocephalus, and intracranial hemorrhage, some individuals showed plasma vasopressin concentrations inappropriate to the corresponding plasma osmolality, but no relationship was found between intracranial pressure and plasma vasopressin concentration. It is suggested that increased intracranial pressure is a stimulus to centrally released vasopressin. The clinical importance of increased cerebrospinal fluid vasopressin concentrations is still not known.     

Hypervolemic therapy prevents volume contraction but not hyponatremia following subarachnoid hemorrhage.

Hyponatremia is common following subarachnoid hemorrhage and has alternatively been attributed to either the inappropriate secretion of antidiuretic hormone or natriuresis causing intravascular volume contraction. We prospectively studied body sodium and intravascular volume regulation in 19 patients, beginning within 3 days after acute aneurysmal subarachnoid hemorrhage occurred, in order to determine the impact of hypervolemic therapy on both hyponatremia and volume contraction and to ascertain whether humoral factors account for hyponatremia. Serial measurements of plasma arginine vasopressin, atrial natriuretic factor, renin activity, aldosterone, and catecholamines were correlated with body sodium and fluid balance, change in blood volume, serum sodium concentration, and osmolality. Six patients (32%) developed hyponatremia, but only 2 had a negative sodium balance. In most patients, levels of atrial natriuretic factor were elevated, while plasma renin activity and aldosterone concentrations were generally suppressed. Plasma arginine vasopressin levels were not suppressed during hypo-osmolality and did not correlate with serum osmolality in hyponatremic patients. Only 1 patient had a decrease in blood volume, which was associated with marked rises in aldosterone and plasma renin activity, but normal serum sodium and plasma atrial natriuretic factor levels. We conclude that following subarachnoid hemorrhage: (1) Hypervolemic therapy prevents volume contraction but not hyponatremia, (2) humoral factors may favor both sodium loss and water retention, and (3) arginine vasopressin regulation is disturbed and may contribute to hyponatremia.     

Studies of vasopressin in the human cerebrospinal fluid

The development of sensitive radioimmunoassays has permitted measurement of the low concentration of vasopressin in the human cerebrospinal fluid. There is accumulating evidence to suggest that vasopressin is involved in a variety of brain functions. As an effective blood-cerebrospinal fluid barrier to vasopressin has been demonstrated, the concentration of vasopressin in the cerebrospinal fluid probably reflects the release of vasopressin within the brain. In human subjects without intracranial disease, the concentration of vasopressin in the cerebrospinal fluid is in the range 0.5-2.0 pg/ml with only little diurnal variation. Intracranial disorders associated with increased intracranial pressure may cause increased cerebrospinal fluid vasopressin concentrations, whereas degenerative brain diseases are associated with low concentrations. Only little is known about the physiologic stimuli which alter the concentration of vasopressin in cerebrospinal fluid. The concentration in cerebrospinal fluid is not influenced by a number of stimuli that cause release of vasopressin into the blood, i.e. changes in plasma osmolality, postural changes, and nausea. Elevation of the intracranial pressure, changes in the composition of the cerebrospinal fluid, electrical stimulation of the hypothalamus, and severe hemorrhage provoke an increase in cerebrospinal fluid vasopressin level.     

The syndrome of psychosis, intermittent hyponatremia, and polydipsia: evidence for diurnal volume expansion

Seven patients (6 men and 1 woman, mean age 39.1 +/- SD 6.9 years) with psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome) underwent serial determinations of serum sodium (SOD), plasma atrial natriuretic peptide (ANP), and urinary osmolality (UOSM) at 7 AM and 4 PM. There was a diurnal increase in ANP (7 AM 17.9 +/- 5.1 pg/ml and 4 PM 27.7 +/- 9.0 pg/ml, p = 0.02), a diurnal decrease in serum sodium (7 AM 141.1 +/- 1.7 mEq/l, 4 PM 129.9 +/- 3.2 mEq/l, p less than 0.0001) and no diurnal change in UOSM. The diurnal increase in ANP in the the PIP syndrome contrasts to the diurnal decrease in ANP reported in normal subjects. Our data, while preliminary, suggest that patients with the PIP syndrome have increased intravascular volume leading to ANP secretion, natriuresis, and hyponatremia.     

Correlation between intracranial pressure (ICP) and changes in CT images of cerebral hemorrhage

Abstract

The relationship between intracranial pressure and CT images was investigated in 80 cases of cerebral hemorrhage that occurred between 1984 and 1990. In traumatic intracerebral hematoma, positive correlation was found between intracranial pressure and both shift of midline structures and volume of hematoma except in the occipital lobe or at the base of the frontal lobe. In nontraumatic intracerebral hematoma, increased intracranial pressure was found to correlate with changes in the configuration of the lateral ventricles, intraventricular hemorrhage, and compression of the basal cisterns and cortical sulci. No correlation between intracranial pressure and hematoma volume was observed, most likely due to the number of elderly patients in the subject population. In nontraumatic subarachnoid hemorrhage, positive correlation existed between increased intracranial pressure and intraventricular hemorrhage as well as Evans' ratio calculated using repeat CT images that were obtained due to disturbances in cerebrospinal fluid circulation. These results suggest that the degree by which intracranial pressure increases in patients with cerebral hemorrhage can be estimated by the changes in CT images. [Neural Res 1998; 20: 225-230]     

Increased neuropeptide Y concentrations in cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage

We investigated the possible relation between neuropeptides and cerebral vasoconstriction in samples of ventricular or cisternal cerebrospinal fluid from 14 patients with subarachnoid hemorrhage. Neuropeptide Y, calcitonin gene-related peptide, atrial natriuretic peptide, and pituitary polypeptide 7B2 were present in the cerebrospinal fluid of these patients. Concentrations of calcitonin gene-related peptide and 7B2 were not significantly different from those in control subjects, but that of atrial natriuretic peptide was significantly lower. Although the mean concentration of neuropeptide Y was not significantly higher than control, consecutive determinations showed an increase 6-11 days after the onset of subarachnoid hemorrhage. An initially high 7B2 concentration decreased gradually, although half the patients showed a second increase greater than 10 days after the onset. Considering the well-recognized vasoconstrictive effect of neuropeptide Y, it is possible that this increase in its concentration in the cerebrospinal fluid plays a role in the pathogenesis of the cerebral vasospasm that is often seen after subarachnoid hemorrhage.     

Levels of transforming growth factor alpha (TGF-alpha) in human cerebrospinal fluid.

In this study, we investigated cerebrospinal fluid of patients with various neurological symptoms for the presence of transforming growth factor alpha (TGF-alpha). 41 samples of cerebrospinal fluid were collected by lumbar puncture performed routinely due to the clinical suspicion of neurological disease from 22 females (age 15-80 years, median 42 years) and from 19 males (age 18-82 years, median 48 years). A highly sensitive and specific radioimmunoassay was used to determine the concentration of TGF-alpha in the samples. The detection limit of the assay was about 200 pg TGF-alpha. There was no cross-reactivity to human EGF. We showed CSF indeed does contain TGFalpha. As TGF-alpha was detected in all 41 samples investigated, this growth factor appears to be a constant component of CSF. The mean concentration was 5.5 ng TGF-alpha (S.D. +/- 2.7 pg/ml, range 1.1 to 13.9 pg/ml). There was no significant correlation between TGF-alpha concentration in CSF and age (r = -0.006) and there was no significant difference between females (mean 5.8+/-3.10 pg/ml) and males (mean 5.2+/-1.96 pg/ml). No diagnosis was over represented in patients with TGF-alpha concentrations above or below 1 S.D. off the mean. However, highest concentrations of TGF-alpha were found in the group of patients with peripheral neurological sensory dysfunctions and polyneuropathy. We conclude that TGF-alpha is not only a constant component of human cerebrospinal fluid in adults but could also be significantly involved in the pathophysiology of various neurological diseases. The earlier hypothesis that TGF-alpha could mainly have a role in brain development needs hence to be re-evaluated.     

Roles of arginine vasopressin and atrial natriuretic peptide in polydipsia-hyponatremia of schizophrenic patients

Respective contributions of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) to the urinary sodium concentration were evaluated in 23 naturalistic incidents of polydipsia-hyponatremia observed in 11 hospitalized schizophrenics (10 males and 1 female). The sodium concentration of the spontaneously excreted urine was examined before and after the forced water restriction. Before the water restriction, mean (+/-S.D.) plasma ANP was 52.8 +/- 33.9 pg/ml (range = 6.9-137). Plasma AVP levels were below 0.3 pg/ml in 15 episodes; relatively high levels (> or = 0.3) were noted in eight episodes. Means of urinary sodium concentration (mEq/l) were significantly higher in episodes with high AVP (> or = 0.3) alone (25.0 +/- 8.2, n=4), with high ANP (> 43) alone (21.3+/-7.4, n = 9), and with high AVP and ANP (26.8 +/- 6.4, n = 4) as compared to that of the low AVP (< 0.3) and ANP (< or = 43) group (13.5 +/- 3.7, n = 6). The data indicate that the elevated urinary sodium in polydipsic patients is possibly due to the AVP-induced antidiuresis and/or the ANP-induced natriuresis. In addition, we observed a close relationship between elevated plasma AVP and vomiting, suggesting that vomiting is one of the causal factors responsible for AVP elevations in this syndrome.     

Secretion and clinical significance of atrial natriuretic peptide in patients with muscular dystrophy

The plasma concentration of atrial natriuretic peptide was measured in patients with muscular dystrophies to study its relationship with congestive heart failure. In patients with Duchenne muscular dystrophy, the plasma atrial natriuretic peptide concentration was 35.5 +/- 3.3 pg/mL (mean +/- SE), which was higher than that in age-matched normal subjects (9.8 +/- 0.6 pg/mL). It increased with progression of disability and showed significant correlations with the cardiothoracic ratio and the ratio of the preejection period to the left ventricular ejection time. In patients with other types of muscular dystrophy, the plasma atrial natriuretic peptide concentration showed no significant change. Immunohistochemical examination demonstrated many atrial natriuretic peptide-positive cells in atrial muscle of an autopsied patient, indicating preservation of the peptide until the end stage. These findings suggest that measurement of the plasma atrial natriuretic peptide concentration is useful for evaluating heart failure in patients with Duchenne muscular dystrophy.     

Serum ANP and ADH after subarachnoid hemorrhage and hyponatremia]

We determined serum atrial natriuretic peptide (ANP) and anti-diuretic hormone (ADH) on a time course basis in cases of subarachnoid hemorrhage and studied their influence on the development of hyponatremia. Twenty six cases of subarachnoid hemorrhage were admitted to our hospital in the past 1 year, and by the site of ruptured aneurysms, there were Acom 6 cases, ICA 6 cases, MCA 5 cases and VA BA 4 cases. Serum ANP and ADH levels were determined in the acute phase on Day 1-4, in the hyponatremia phase on Day 5-14 and in the chronic phase on Day 15 downward. Levels of not more than 130 mEq/l were regarded as hyponatremia. Cases showing other evident causes such as heart failure and renal insufficiency were excluded. In the normal control group (n = 20) which was admitted to this hospital for a close check-up, serum ANP was 26.5 +/- 11.6 pg/ml (10-50); levels of more than 50 pg/ml were regarded as being abnormally high. 1) Hyponatremia was observed in 7 cases (26-9%); the day of onset was 11.9 hospital day. The duration was 5.0 days and the minimum serum Na level was 126.4 mEq/l. 2) The serum ADH level was high regardless of whether or not there was the development of hyponatremia in the acute phase but tended to decrease gradually and became normal in the hyponatremia phase. 3) The serum ANP level in the cases of hyponatremia was 40.7 +/- 9.1 pg/ml in the acute phase, 69.0 +/- 25.7 pg/ml in the hyponatremia phase and 40.2 +/- 21.5 pg/ml in the chronic phase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interleukin-1β and tumor necrosis factor-α in cerebrospinal fluid of children with bacterial meningitis

Certain cytokines may contribute to the sequence of events that lead to meningeal inflammation in bacterial meningitis. The purpose of this study was to determine the levels of cytokines in the cerebrospinal fluid (CSF) of children with bacterial meningitis and aseptic meningitis of different etiologies. We determined the concentrations of interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha) in the CSF of 171 specimens of 144 patients whose cases were classified as follow: bacterial meningitis (n=23), aseptic meningitis (n=26) and non-meningitis (n=95). The detectable IL-1beta concentration (> or =20 pg/ml) in the bacterial meningitis, aseptic meningitis and non-meningitis groups were observed with 78.3%, 3.8%, and 8.4%, respectively. Significantly higher serum IL-1beta concentrations were detected in those with bacterial meningitis than those with aseptic meningitis (538.93+/-605.32 pg/ml vs 2.52+/-11.57 pg/ml; P<0.001) or among non-meningitis subjects (2.90+/-11.91 pg/ml; P<0.001). The mean TNF-alpha concentration was 148.74+/-338.77 pg/ml. There was significantly more TNF-alpha than aseptic meningitis (6.85+/-17.93 pg/ml; P<0.001) or non-meningitis (7.67+/-16.07 pg/ml; P<0.001). With regard to diagnosis, measurement of IL-1beta and TNF-alpha levels showed sensitivities of 78% and 74%, respectively; specificities of 96% and 81%, respectively. It is suggested that the levels of these cytokines, especially IL-1beta and TNF-alpha, are useful markers for distinguishing bacterial meningitis from aseptic meningitis.     

Arginine vasopressin levels in cerebrospinal fluid in neurological disease

Levels of arginine vasopressin have been measured in the blood and cerebrospinal fluid of patients with benign intracranial hypertension and raised intracranial pressure, patients with other neurological diseases and in normal control subjects. There was no difference in blood levels in each of the 3 groups (mean ± SEM, 2.8 ± 0.5, 2.5 ± 0.25, 2.53 ± 0.4 pg/ml). However, levels of arginine vasopressin in the cerebrospinal fluid in patients with benign intracranial hypertension and other neurological diseases were higher (mean ± SEM, 0.64 ± 0.05, 0.61 ± 0.04 pg/ml), than in the control group (0.49 ± 0.06), but not different from each other. The origin of arginine vasopressin in cerebrospinal fluid is uncertain and a number of possibilities are discussed.     

Intracerebral hematoma following lumboperitoneal shunt insertion: a rare case report

Lumboperitoneal shunting is widely used for the surgical management of pseudotumor cerebri and other pathologies such as communicating hydrocephalus. Although it is a safe method, it could be associated with complications including subarachnoid hemorrhage, subdural and rarely intracerebral hematoma. A 44-year-old female applied to our clinic with complaints of severe headache, retroorbital pain and blurred vision. Lumbar puncture demonstrated cerebrospinal fluid opening pressure of cmH2O. A non-programmable lumboperitoneal shunt with two distal slit valves was inserted due to pseudotumor cerebri. She deteriorated shortly after surgery. Immediate cranial computed tomography scan revealed a right parietal intracerebral hematoma. Development of intracerebral hematoma following lumboperitoneal shunt is a rare complication. We discuss this rare event accompanied by the literature.     

Acute subdural hematoma without subarachnoid hemorrhage following rupture of a distal anterior cerebral artery aneurysm: a case report]

Acute subdural hematoma (ASDH) without subarachnoid or intracerebral hemorrhage following rupture of an intracranial aneurysm is rare. Only 34 cases of pure ASDH resulting from rupture of an intracranial aneurysm, and 5 cases of pure ASDH secondary to rupture of an anterior cerebral artery (ACA) aneurysm, have been reported in the literature. We report a case of a patient with a ruptured distal ACA aneurysm who presented pure ASDH on CT. A 63-year-old woman was admitted with the acute onset of severe headache, nausea, and dizziness. CT showed a right convexity and interhemispheric ASDH in the absence of subarachnoid or intracerebral hemorrhage. Cerebrospinal fluid was clear by lumbar puncture. However, we still suspected a ruptured intracranial aneurysm as the diagnosis. Angiography was performed and demonstrated a right distal ACA aneurysm with a daughter aneurysm. Evacuation of the subdural hematoma, with the clipping of the aneurysm was performed. Intraoperatively, adhesion between the dome of aneurysm and the falx cerebri was observed. The patient was discharged from the hospital without neurological deficits.     

Concentration of epidermal growth factor in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis

In 15 patients with SLA and 15 with discopathy regarded as a control group the level of epidermal growth factor (EGF) was determined by radioreceptor assay in the serum and cerebrospinal fluid. The EFG level in the serum could not be determined by this method. In the CSF of SLA patients this level was 587.6 +/- 257.7 pg/ml and was significantly lower in relation to the control group in which it was 990.9 +/- 297.5 pg/ml. The authors discuss in this connection the role of EGF in SLA pathogenesis.     

Cerebrospinal fluid neuropeptide Y in Alzheimer's disease

The cerebrospinal fluid neuropeptide Y level was measured by radioimmunoassay in 20 patients with probable Alzheimer's disease and in 19 controls. The mean level was lower in patients (69.5 +/- 36.7 pg/ml) than in controls (103 +/- 21.8 pg/ml; p less than 0.001). Patients with a disease duration of greater than 2 years had cerebrospinal fluid neuropeptide Y levels lower than those with shorter disease duration (p less than 0.02). These results suggest that neuropeptide Y containing cells may be involved in Alzheimer's disease. No correlation was found between neuropeptide Y levels and degree of cognitive impairment or age at disease onset.     

Beta-endorphin-like immunoreactivity increases in cerebrospinal fluid of acute head-injured patients

beta-endorphin-like immunoreactivity (beta-ELI) was measured in cerebrospinal fluid (CSF) of 36 acute head-injured patients and 12 patients without head injury as controls. The mean level of beta-ELI in CSF of controls, mild cerebral contusions, and severe cerebral contusion patients were 51.9 +/- 5.6 pg/ml, 110.5 +/- 14.5 pg/ml, and 173.8 +/- 20.1 pg/ml respectively, with significant difference between them. The results also showed that beta-ELI may reflect the prognosis of acute head-injured patients.