On the importance of albumin binding for the flux of 7α-hydroxy-3-oxo-4-cholestenoic acid in the brain.

We confirmed previous findings by a Japanese group that there is an accumulation of 7α-hydroxy-3-oxo-4-cholestenoic acid (7-Hoca) in human subdural hematomas. The accumulation correlated with the time from the bleeding to the sample collection. We present evidence that these accumulations are likely to be caused by the strong affinity of 7-Hoca to albumin and the marked difference between plasma and brain with respect to levels of albumin. In the circulation, 80-90% of 7-Hoca is bound to albumin with a ratio between the steroid acid and albumin of ∼1.4 ng/mg. In cerebrospinal fluid (CSF), the ratio between 7-Hoca and albumin is ∼30 ng/mg. When albumin or hemolyzed blood in a dialysis bag was exposed to CSF, there was a flux of 7-Hoca from CSF to the albumin. We suggest that the major explanation for accumulation of 7-Hoca in subdural hematoma is a flux from the brain into the hematoma due to the high affinity to albumin and the high capacity of 7-Hoca to pass biomembranes. We discuss the possibility that the markedly different ratios between 7-Hoca and albumin in circulation and brain can explain the flux of 7-Hoca from the brain into circulation against a concentration gradient.

A series of patients with subpial hemorrhage: clinical manifestation, neuroradiological presentation and therapeutic implications.

Subpial hemorrhage is a rare finding in patients with a variable spectrum of neurological symptoms and signs. Here we present a series of 10 patients with subpial hemorrhage, 53 to 80 years old, diagnosed and treated within the last 4 years at a single center. Patients were identified based on imaging criteria with either magnetic resonance imaging (MRI) or computed tomography (CT) showing blood along the cortical surface. Presenting symptoms were diverse, with seizures being the most frequent followed by headaches and focal neurological signs such as sensory or motor deficits. Of 7 patients undergoing lumbar puncture, none showed fresh blood or cerebrospinal fluid (CSF) xanthochromia. Neither digital subtraction angiography (DSA) nor MR venography (MRV) confirmed cerebral vein thrombosis as a possible etiologic factor for subpial hemorrhage. Patients for whom follow-up was available (n=8), showed complete recovery indicating an excellent prognosis. Overall, the etiology of subpial hemorrhage remains obscure. Treatment should be symptomatic with particular attention to antiepileptic medication.

Subdural hematoma in spontaneous CSF hypovolemia.

Of 67 consecutive patients with spontaneous CSF hypovolemia (SCH), 11 (16.4%) had subdural hematoma (SDH). Patients with SDH were older (p = 0.005), more likely to be male (p = 0.035), and displayed longer time to diagnosis of SCH (p = 0.019) than those without SDH. All patients with SDH showed the findings of pseudo-subarachnoid hemorrhage on CT and responded favorably to epidural blood patches and neurosurgical drainage.

Implantation of a reservoir for refractory chronic subdural hematoma.

OBJECTIVE: Recurrence of chronic subdural hematoma is not rare. Among patients who experience recurrence, severe background disease may adversely influence the prognosis of chronic subdural hematoma. We treated patients with these refractory hematomas with an Ommaya cerebrospinal fluid (CSF) reservoir and analyzed the effectiveness of the treatment. METHODS: Sixteen patients with refractory chronic subdural hematoma were studied. These patients had severe diseases that adversely influenced the clinical course of chronic subdural hematoma, including cerebral infarction, liver cirrhosis, thrombocytopenia, severe Parkinsonism, severe heart disease, psychiatric disease, and spinocerebellar degeneration. All patients were treated initially in the standard fashion: evacuation of the hematoma followed by irrigation and drainage of the hematoma cavity. In each patient, an Ommaya CSF reservoir was implanted after the hematoma recurred. Whenever the volume of the hematoma either decreased very slowly or increased, the reservoir was punctured. RESULTS: The hematoma size decreased to less than 3 mm a median of 60 days after introduction of the reservoir. Postoperatively, 13 patients returned to their condition before the onset of hematoma. One patient died of myocardial infarction, and two patients with Parkinson's disease could not maintain their previous functional level; both remained in a partially dependent state. Complications consisted of minor bleeding in two patients and occlusion of the reservoir in two other patients. CONCLUSION: By use of this method, reoperation was avoided and the patients were mobile early in the postoperative period. This method was suitable for refractory chronic subdural hematoma accompanied by severe disease that adversely influenced the clinical course.

[Subdural effusions in children. Pathophysiology and treatment]. / Coleção subdural na criança. Fisiopatologia e tratamento.

Nine children harboring subdural effusions were treated by subduro peritoneal shunt. These patients were followed-up by CT scans. The area of the subdural effusions was measured by quantitative morphology with a planimeter. With the surgical treatment, the subdural effusion disappeared completely or near completely in 8 patients. The patient's functional state were excellent in 4, good in 3 and bad in 2 in the postoperative follow-up. We aldo reviewed the literature as far as the pathophysiology and the treatment of the subdural effusions are concerned.

Coleçäo subdural na criança: fisiopatologia e tratamento / Subdural effusions in children: pathophysiology and treatment

Nove crianças portadoras de coleçäo subdural (CSD) foram tratadas por meio de derivaçäo subduro-peritoneal. Todas foram submetidas a controle com tomografia computadorizada pelo encéfalo. O tamanho da coleçäo subdural foi avaliado por medida de sua área no corte tomográfico por meio de morfologia quantitativa com planímetro. Ocorreu regressäo completa ou quase completa da CSD em oito pacientes. Os resultados funcionais foram excelentes em quatro pacientes, bons em três e maus em dois. Foi feita uma revisäo da fisiopatologia e do tratamento da CSD na criança.

Concentration of enkephalins in cerebrospinal fluid of patients after severe head injury.

We studied head-injured patients treated at the Department of Neurosurgery, Silesian University School of Medicine, Katowice. The patients underwent lumbar puncture on days 1, 4 and 7 for diagnostic reasons. The levels of leu-enkephalin (LENK) and met-enkephalin (MENK) were examined in 4.5 ml of cerebrospinal fluid (CSF). The control group included patients with lumbar discopathy from whom CSF fluid was collected during myelography. Enkephalins were extracted by column chromatography and their levels were assayed radioimmunologically. The results indicate that enkephalins may play a certain role in the pathophysiological response of nervous tissue to traumatic injury. Constantly elevated MENK levels together with decreasing LENK levels in patients with a Glasgow coma scale score < or = 8 may be useful as a poor prognostic factor. It is also suggested that LENK and MENK play different pathophysiological roles.

Changes in the level of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fluid after subarachnoid hemorrhage.

A high concentration of a type of cholic acid, 7 alpha-hydroxy-3-oxo-4-cholestenoic acid, is observed in the content of chronic subdural hematoma. To investigate the possible causes, the level of this compound was measured in the cerebrospinal fluid of patients who underwent surgery for aneurysmal subarachnoid hemorrhage or non-hemorrhagic diseases. The maximum level was significantly higher in the aneurysmal subarachnoid hemorrhage patients, indicating that surgical intervention did not cause the postoperative increase in the level of this compound in the cerebrospinal fluid. Monitoring of plasma levels showed no postoperative increase. In vitro culture of a mixture of arterial blood and cerebrospinal fluid failed to show the de novo production of this compound. These results strongly suggest extrahepatic intracranial production of this cholic acid occurs in subarachnoid hemorrhage. The high concentration of this compound in both chronic subdural hematoma and subarachnoid hemorrhage suggests a possible role for 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in intracranial hemorrhagic disorders.

Reversed-phase high-performance liquid chromatography for the determination of haemorphin-like immunoreactivity in human cerebrospinal fluid.

The haemorphins are opioid peptides derived form the blood protein haemoglobin. This study was focused on the detection and determination of haemorphin-like immunoreactivity in human cerebrospinal fluid (CSF) by reversed-phase HPLC. For this purpose a SMART System, optimized for micropurification, was applied. Prior to application to HPLC, the peptide fraction of the CSF sample was extracted using a reversed-phase silica gel cartridge (Sep-Pak C18). In the HPLC separation, the peptide-like material associated with haemorphin-7 immunoreactivity was recovered and determined using a UV detector. The tryptophan residue present in the haemorphin sequence allowed UV detection at wavelengths (e.g., 276 nm) where interference with other co-eluting peptides lacking this residue is minimized. Recorded levels of haemorphin-like immunoreactivity were compared with those detected by radioimmunoassay.

[Dilated pericerebellar fluid space in patients with chronic subdural hematoma].

It is not uncommon to observe the dilation of the pericerebellar fluid space (PCFS) on CT in patients with chronic subdural hematoma (CSDH). CT scans of 92 patients with CSDH proven by surgery were reviewed with respect to the dilatation of PCFS and we evaluated the incidence of dilated PCFS and the relationship between PCFS and other factors. There were 68 males and 24 females. Patients ranged in age from 20 to 90 years (mean 65.2 years). Another 50 patients without CSDH were also reviewed as a control group. A new PCFS grading based on the CT findings was proposed, divided into 3 grades as follows. In grade 0, no PCFS could be seen on CT scans. In grade 1, PCFS could be detected along the posterior aspect of the petrous pyramid, and in grade 2, PCFS could be seen not only along the posterior aspect of the petrous pyramid but also under the tentorium cerebelli. The dilation of PCFS was seen in 78 patients (84.8%) out of the 92 cases. In 50 patients without CSDH (control group), the dilatation of PCFS was noted only in 6 (12%). The dilatation of PCFS was almost always seen on the same side as the CSDH. Among many factors, the significant factor was the degree of the midline shift, the bigger the midline shift caused by CSDH, the larger was the dilated PCFS. Although the mechanism of the dilated PCFS in patients with CSDH is not clear, it is postulated that the mechanism is caused by CSF flow disturbance, compression or adhesion of the subarachnoid space due to CSDH.(ABSTRACT TRUNCATED AT 250 WORDS)

Color Doppler flow imaging of CSF flow in infants with intracranial hemorrhage.

The color Doppler flow imaging (CDFI) technique was used to study the dynamics of cerebrospinal fluid (CSF) flow in 13 infants with intracranial hemorrhage. CDFI was performed 46 times in 6 intraventricular hemorrhage (IVH) patients and 7 subarachnoid hemorrhage (SAH) patients with or without subdural hemorrhage during different stages. CSF flow was observed in 8 infants with IVH (5) or SAH (3) on CDFI. CSF flow in the aqueduct, third ventricle and foramen of Monro was visualized in both the upward and downward directions, primarily reflecting respiration and/or cardiac pulsation in the acute stage. It is suggested that CDFI may allow evaluation of the CSF flow dynamics and an early diagnosis of intracranial hemorrhage in infants.

Isolation of a hemoglobin-derived opioid peptide from cerebrospinal fluid of patients with cerebrovascular bleedings.

The hemorphins are peptides with opioid activity, which are enzymatically released from hemoglobin. A decapeptide identical to the sequence 32-41 of the beta-, delta-, gamma- or epsilon-chains of hemoglobin has been isolated from human ventricular cerebrospinal fluid (CSF). The peptide, designated LVV-hemorphin-7, was recovered in relatively high amounts (115-300 pmol per ml) from samples of patients with cerebrovascular bleedings, but was not detectable in control CSF. Its identity with the hemoglobin fragment was confirmed by mass spectrometry and gas-phase sequencing.

[A case of primary low spinal fluid pressure syndrome complicated by bilateral subdural hematoma--study of the cerebrospinal fluid circulation].

A 43-year-old man with no history of trauma or neurosurgical procedure was admitted our hospital because of orthostatic headache made worse in upright position. Spinal fluid pressure was 0 mmH2O, and CT scan revealed wide cortical sulci and ventricles. In the 26th hospital day he had severe headache and CT scan revealed bilateral subdural hematoma, then neurosurgical procedure was done. About 2 months later, he was relieved of the headache and spinal fluid pressure returned to normal. We performed lumbar isotope cisternography and isotope choroid plexography in our case when low spinal fluid pressure and normalized pressure. Isotope cisternography revealed the radioactivity counts decreased rapidly in low pressure and normal in normal pressure. On the other hand isotope choroid plexography was almost no difference between low and normal pressure. Our data suggest that primary low spinal fluid pressure syndrome is not caused by hypoproduction, but by an undetectable leak from a minute tear in a spinal root sleeve or hyperabsorption at the spinal arachnoid membrane.

Endothelin immunoreactivity in cerebrospinal fluid of patients with subarachnoid haemorrhage.

A radioimmunoassay method for endothelin was developed. Antisera raised against endothelin 1 showed significant crossreaction with endothelin 2 and 3 (45 and 13%, respectively). Considerable endothelin immunoreactivity was shown to be present in the cerebrospinal fluid of patients with a subarachnoid hemorrhage, ranging from 0.3 pmol/l cerebrospinal fluid to 4.5 pmol/l cerebrospinal fluid, though no endothelin immunoreactivity was observed in the cerebrospinal fluid of controls and patients with cerebral infarction, subdural haematoma or brain tumours. Endothelin immunoreactivity was also observed in two out of five cerebrospinal fluid samples from patients with cerebral bleeding. Reverse phase high performance liquid chromatography showed that the main immunoreactive component in cerebrospinal fluid appeared to elute at the same position. There was, however, an immunoreactive component which eluted at the same position as endothelin 3. These results may support the idea that endothelin immunoreactivity in the cerebrospinal fluid originate mainly from endothelial and neural tissues and that endothelin may contribute to the generation of the vasospasm often observed in subarachnoid hemorrhage, a conclusion based on the exceptionally high endothelin immunoreactivity in cerebrospinal fluid observed in patients with subarachnoid haemorrhage.

Experimental intracerebral haematoma: the role of blood constituents in early ischaemia.

In patients with intracerebral haematoma, ischaemic damage and final outcome are often more serious than the size of the lesion would suggest. The aetiology of the ischaemia in relation to space-occupying effects or specific factors present in blood is unclear. In a rat model of an intracerebral space-occupying lesion, the pathophysiological effects of a haematoma were compared with those of an equal volume of inert fluid (mock cerebrospinal fluid [CSF] or silicone oil). Cerebral blood flow was measured at 1 min by 14C iodoantipyrine autoradiography, and ischaemic cell damage was assessed by light microscopy at 4 h. In all animals, cerebral blood flow was reduced immediately adjacent to the lesion. In the group with a haematoma, blood flow was reduced (p less than 0.001) over a greater radius and also in the ipsilateral frontal and parietal cortex. Ischaemic damage was seen in animals lesioned with blood or oil of blood viscosity, but not in animals with CSF lesions. These data suggest that both tissue pressure and vasoactive substances are components of the immediate reduction in blood flow following intracranial haemorrhage. Tissue pressure may be the more important factor in later ischaemic neuronal damage.

Haem derivatives in subdural haematomas.

The oxyhaemoglobin, methaemoglobin and bilirubin concentrations were determined in subdural haematomas and cerebrospinal fluid from 18 patients. The total haem derivative concentration ranged from 55 mumol/l to 13.9 mmol/l in the haematomas and from 0.1 mumol/l to 8.2 mumol/l in the cerebrospinal fluid. Bilirubin was the dominating fraction in haematomas with haem derivative concentrations lower than 1 mmol/l. For haematomas exceeding this value, the bilirubin transforming capacity seemed to have reached a maximum. More of the oxyhaemoglobin was oxidized to methaemoglobin in these cases, a reaction known to release superoxide radicals. The possible pathophysiological significance hereof, e.g. in cerebral vasospasm, is discussed.

[Observation of CSF pulsatile flow in MRI--the signal void phenomenon].

In a comparative study of MR images of 289 neurosurgical patients, loss of the signal intensity (signal void phenomenon) of CSF in the aqueduct was observed in 77 patients. This signal void phenomenon was seen most frequently in infants with chronic subdural hematoma (12 of 18) and patients of all age groups suffering from communicating hydrocephalus (10 of 14). It is known that CSF in the cranial cavity flows toward the spinal CSF space in to and fro manner responding to brain parenchyma pulsations. The velocity of this flow is to be faster in the narrower parts through the ventricular systems such as the aqueduct, Monro's foramen and the 4th ventricles. We think that in T2 weighted images signal void phenomenon reflects "high velocity signal loss" due to CSF flow. When the subarachnoid adhesions secondary to subarachnoid hemorrhage stagnate CSF flow in the subarachnoid space, the intraventricular CSF flow forms the main buffer for changes of the brain volume. This causes an increase in the amplitude of the pulsatile flow in the ventricular systems. Therefore the signal void phenomenon in the aqueductal CSF becomes more pronounced. It may be possible to differentiate normal circulation of CSF from abnormal with the bigger amplitude of CSF pulsatile flow, to understand the mechanisms of the normal pressure hydrocephalus or to diagnose a shunt malfunction. Therefore more insight in the CSF flow as imaged by MRI is needed, quantification of CSF flow will be the subjects of our further research.

Bloody cerebrospinal fluid: traumatic tap or child abuse?

A central nervous system dysfunction of nontraumatic etiology was initially suspected in three cases of shaken baby syndrome. Blood contaminating the cerebrospinal fluid was attributed to a traumatic lumbar puncture. Failure to detect retinal hemorrhages contributed to the misdiagnosis. Emergency physicians must consider the diagnosis of shaken baby syndrome in a critically ill infant with bloody cerebrospinal fluid. Ophthalmoscopy should be done routinely in these patients.