Human arachnoid villi response to subarachnoid hemorrhage: possible relationship to chronic hydrocephalus.

OBJECT: The origin of chronic communicating hydrocephalus following subarachnoid hemorrhage (SAH) is not well understood. Fibrosis of the arachnoid villi has been suggested as the cause for obstruction of cerebrospinal fluid (CSF) flow, but this is not well supported in the literature. The goal of this study was to determine the relationship between blood, inflammation, and cellular proliferation in arachnoid villi after SAH. METHODS: Arachnoid villi from 50 adult patients were sampled at autopsy. All specimens were subjected to a variety of histochemical and immunohistochemical stains. The 23 cases of SAH consisted of patients in whom an autopsy was performed 12 hours to 34 years post-SAH. Fifteen cases were identified as moderate-to-severe SAH, with varying degrees of hydrocephalus. In comparison with 27 age-matched non-SAH controls, the authors observed blood and inflammation within the arachnoid villi during the 1st week after SAH. Greater mitotic activity was also noted among arachnoid cap cells. The patient with chronic SAH presented with ventriculomegaly 2 months post-SAH and exhibited remarkable arachnoid cap cell accumulation. CONCLUSIONS: The authors postulate that proliferation of arachnoidal cells, triggered by the inflammatory reaction or blood clotting products, could result in obstruction of CSF flow through arachnoid villi into the venous sinuses. This does not exclude the possibility that SAH causes generalized fibrosis in the subarachnoid space.     

Disturbance of CSF absorption after experimental subarachnoid hemorrhage; correlation with subarachnoid fibrosis

Correlation between subarachnoid fibrosis and absorption resistance of cerebrospinal fluid (CSF) after experimental subarachnoid hemorrhage (SAH) was studied in dogs. Scanning electron microscope (SEM) was used along with steady-state infusion method. Experimental SAHs were produced by injecting 0.6-1.0 ml/kg of blood into the cisterna magna singly, twice and three times for 11, 7 and 8 dogs respectively. All dogs were sacrificed by perfusing their brain with 10% formaldehyde solution immediately after completion of the measurement of CSF absorption resistance. This was conducted at various periods ranging from 3 to 7 weeks after the first blood injection. Measurement of absorption resistance was performed by infusion of physiological saline solution into the spinal subarachnoid space at speeds of 0.1, 0.2 and 0.3 ml/min for 30, 15 and 10 minutes respectively. The measurement was also conducted in 9 dogs without producing SAH as a control study. Specimens collected from basal cistern, lateral cerebral fissures and parasagittal sulci were observed in their subarachnoid spaces under SEM, and the degree of subarachnoid fibrosis was expressed by one of 5 grades for comparison with the absorption resistance in each dog. The grade of subarachnoid fibrosis significantly correlated with the absorption resistance. The absorption disturbances tended to improve after about a month along with disappearance of subarachnoid fibrosis. The results in this study suggest that subarachnoid fibrosis might be involved in inducing CSF absorption disturbances by affecting both the major and the lesser pathways of CSF.     

Changes in the subarachnoid space after experimental subarachnoid haemorrhage in the dog: Scanning electron microscopic observation

Summary The possible changes in the subarachnoid space after subarachnoid haemorrhage were studied in animals by using a scanning electron microscope (SEM).About 1 ml/kg of autogenous blood was injected intracisternally in 36 adult mongrel dogs to investigate changes in the subarachnoid space, over periods ranging from immediately after the injection to as long as 6 months.We have come to the conclusion that the injected blood disappears in about one to two weeks; the fibrosis or thickening of the arachnoid membrane appears in one to three weeks, and then returns to normal in a month in instances of rapid recovery, but there are some cases in which fibrosis persists for a long period and becomes chronic. The fact that an increase of fibrous tissue was found in the parietal region, where the injected blood had hardly reached, appears to indicate that the fibrosis is not always limited to the site of the haemorrhage but can occur in remote regions.We also discuss the usefulness of the SEM in the observation of the subarachnoid space, and the finding that vascular specimen preparations can be made by perfusing the brain with 2–10% phosphate-buffered formaldehyde solution.     

Subarachnoid haemorrhage induced proliferation of leptomeningeal cells and deposition of extracellular matrices in the arachnoid granulations and subarachnoid space

Summary Subarachnoid haemorrhage (SAH) often leads to subarachnoid fibrosis and resultant normal pressure hydrocephalus; however, how subarachnoid fibrosis occurs is unknown. We examined the changes within arachnoid granulations (AGs) and the subarachnoid space (SAS) chronologically at the parasagittal region obtained from patients with SAH at autopsy and made comparison with controls by immunostaining for cytokeratin, specific marker for leptomeningeal cells and by the elastica Masson-Goldner methods. Within a week some AGs were torn, and many inflammatory cells filled the AGs and SAS. Cytokeratin positive cells were scarce. During the next two weeks cytokeratin positive cells increased. After three weeks, AGs and SAS were filled by dense deposits of extracellular matrices surrounded by multiple layers of leptomeningeal cells.     

Liliequist membranotomy for patients with ruptured intracranial aneurysms (author's transl)

In order to reconstruct the blocked CSF pathway, we attempted to excise the Liliequist membrane in 22 patients with subarachnoid hemorrhage resulted from ruptured intracranial aneurysms. After clipping the aneurysmal neck, the Liliequist membrane was reached through the space between the optic nerve and the internal carotid artery within the same operative field. As a result, the incidence of postoperative ventricular dilatation was remarkably reduced in comparison with control cases without Liliequist membranotomy. The necessity for the shunt operation for post-SAH hydrocephalus was also reduced. On the other hand, the incidence of postoperative subdural effusion increased in the group with Liliequist membranotomy. This suggests that the blockage of the arachnoid villi is probably the cause of disturbances in CSF absorption in some cases following subarachnoid hemorrhage. In such cases, the Liliequist membranotomy may be ineffective in restoring CSF circulation following subarachnoid hemorrhage.     

Effect of antifibrinolytic therapy on subarachnoid fibrosis in dogs after experimental subarachnoid haemorrhage

Summary The effect of antifibrinolytic therapy on posthaemorrhagic subarachnoid fibrosis was observed experimentally in dogs with the scanning electron microscope (SEM). The subchronic subjects, given intravenous injections of tranexamic acid (1 mg/day) for 12 days and sacrificed 3 weeks after cisternal blood injection, showed residual clot with thick fibrosis, especially around the haemorrhage. The chronic subjects, to which the same procedure was applied and which were sacrificed three months after cisternal blood injection, showed significant increases in the subarachnoid fibrosis, most remarkably in the parasagittal region.Tranexamic acid is widely used for preventing the recurrence of subarachnoid haemorrhage. However, it was revealed in this study that antifibrinolytic therapy might increase chronic posthaemorrhagic subarachnoid fibrosis, which is considered to be responsible for communicating hydrocephalus by disturbing epicortical CSF flow⁴.     

Post-haemorrhagic subarachnoid fibrosis in dogs. Scanning electron microscopic observation and dye perfusion study

Summary Scanning electron microscopic observations of the subarachnoid space were made in dogs focussing upon the fibre components in both the normal subarachnoid space and in areas of post-haemorrhagic fibrosis. It was concluded that the fibrous tissue originates from the arachnoid membrane itself, while organized haematoma is considered to form a component of the fibrosis.Perfusion of the subarachnoid space of dogs with a solution of 0.1% Toluidine Blue was also done. This showed that cerebrospinal fluid (CSF) is carried from the subarachnoid space directly to the dural sinuses through a fine string-like structure, which is conceivably one of the collateral CSF absorptive pathways.     

Access to cerebrospinal fluid absorption sites by infusion into vascular channels of the skull diplö

OBJECT: The purpose of this human cadaver study was to determine whether or not an intraosseous skull infusion would access the superior sagittal sinus (SSS) via intradural venous channels. The diploic space of the skull bone contains a sinusoidal vascular network that communicates with the underlying dura mater. Diploic veins in the parasagittal area connect with endothelium-lined intradural channels in the subjacent dura and ultimately with the dural venous sinuses. A significant proportion of cerebrospinal fluid (CSF) absorption is thought to occur via arachnoid granulations in the region of the SSS and especially along the parasagittal dura where arachnoid granulations are surrounded by intradural venous channels (lateral lacunae). The CSF is likely to be conducted from the subarachnoid space into the venous system via the fine intradural channels making up the lateral lacunae. METHODS: Infusion of vinyl acetate casting material into the diploic space of the human cadaveric skull resulted in complete filling of the lateral lacunae and SSS. Corrosion casting techniques and examination under magnification were used to characterize the anatomical connections between diploic spaces and dural venous sinuses. RESULTS: Corrosion casting, performed on five formalin-fixed cadavers, clearly showed the anatomical connections between the diploic infusion site and the venous sinuses in the underlying parasagittal dura where some of the CSF is thought to be absorbed. CONCLUSIONS: The diploic vascular channels of the human skull may represent an indirect pathway into the dural venous sinuses. Intraosseous skull infusion may represent another possible strategy for diversion of CSF into the vascular system in the treatment of hydrocephalus.     

Subarachnoid haemorrhage and communicating hydrocephalus scanning electron microscopic observations

Summary Scanning electron microscopic changes in the subarachnoid space after subarachnoid haemorrhage are described. The obstructive changes were classified into five grades ranging from patency to total obstruction. We report a correlation between communicating hydrocephalus and obstruction above grade 3 in the parasagittal region (p < 0.01) and the lateral cerebral fissure (p < 0.05).     

Shunting Effects in Patients with Idiopathic Normal Pressure Hydrocephalus; Correlation with Cerebral and Leptomeningeal Biopsy Findings

Summary  Normal Pressure Hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space have been suggested as one of the patho-anatomical substrates. However, other types of adult onset dementia, predominantly Alzheimer's disease and Vascular Dementia, may mimic the clinical NPH characteristics.  The purpose of the present study was to correlate cerebral parenchymal and leptomeningeal biopsy findings to the clinical outcome after CSF shunting in a prospective group of idiopathic NPH (INPH) patients. The study comprises 27 patients with INPH, diagnosed and shunted according to generally accepted clinical, imaging and hydrodynamic criteria. In all patients a frontal leptomeningeal and brain biopsy was obtained prior to the shunt insertion.  Degenerative cerebral changes, most often Alzheimer (6 cases) or vascular changes (7 cases) were described in 14 out of 27 biopsies. Arachnoid fibrosis was found in 9 of the 18 biopsies containing arachnoid tissue. Overall, nine patients (33%) improved, of whom 6 presented Alzheimer or vascular changes in their biopsies. No correlation was found between clinical outcome and the presence or absence of degenerative cerebral changes and/or arachnoid fibrosis. However, a tendency towards higher improvement rates was noted in the subgroups presenting degenerative cerebral changes or arachnoid fibrosis. The results suggest that no constant morphological element exists in the syndrome of INPH. Various aetiologies may be involved in the pathogenesis and possibly in some cases co-existing: Patients may also improve by shunting despite the presence of degenerative cerebral parenchymal changes.     

Clearance of macromolecular and particulate substances from the cerebrospinal fluid system of the rat.

Arachnoid villi in the intracranial dural sinuses constitute the principal sites for absorption of proteins and particulates from the cerebrospinal fluid (CSF) system. Although arachnoid villi in the rat are morphologically less complex than those found in other mammals, their resistance to CSF outflow, as assessed by a graded series of contstant flow manometric infusions, is similar to that found in other species. Moreover, inulin and polystyrene beads, when infused into the spinal subarachnoid space of rats, are rapidly cleared from the CSF system into intracranial dural sinuses. Inulin appeared in sinus blood 3 minutes after onset of infusion and reached concentrations 26 times greater than those found in the systemic circulation; particulate matter in the form of 0.5 micrometer polystyrene beads showed similar efflux characteristics. Hence, the CSF system of the rat is functionally similar to that found in other mammalian species, with arachnoid villi constituting a major efflux route for clearance of macromolecular and particulate substances.     

Arachnoid cyst of the quadrigeminal cistern

Arachnoid cyst located near the quadrigeminal cistern has been reported as paracollicular arachnoid cyst, arachnoid cyst of the quadrigeminal cistern, paramesencephalic arachnoid cyst, arachnoid cyst posterior to the third ventricle, cyst of the cisterna ambiens. The purpose of this paper is to present the clinical pictures, diagnostic studies and treatment of 5 cases of the arachnoid cyst of the quadrigeminal cistern. (1) The clinical symptoms and signs result from increased intracranial pressure without lateralizing signs (mid-line syndrome) due to hydrocephalus, precocious puberty and supra-collicular sign due to direct compression of the adjacent structures. (2) Endocrinological study of the pituitary gland shows no abnormal findings, but the patients with precocious puberty shows adult type response in LH and FSH. (3) Metrizamide CT cisternography could be considered as a safe and reliable neurological procedures in evaluating the communication between the cyst and the subarachnoid space as well as CSF dynamics, and subarachnoid space. (4) Patients were treated with ventriculoperitoneal shunt, followed by craniotomy and resection of the cyst wall with good results.     

Disturbances of cerebrospinal fluid circulation during the acute stage of subarachnoid hemorrhage

Radioisotope cisternography was performed and the erythrocyte and hemoglobin contents of the cerebrospinal fluid (CSF) were determined within the first 4 days after subarachnoid hemorrhage in 42 patients. The clinical condition of the patients was related to the severity of the CSF circulation disturbances. Thirty-five patients had some degree of disturbance of CSF flow, and only 2 of the 42 patients had normal flow. In 5 cases the cisternograms were inconclusive. The severity of CSF circulation disturbances correlated well with clinical condition. No relationship was found between the number of erythrocytes in the CSF and the development of CSF circulation disturbances. The CSF erythrocyte content did not correlate with the clinical condition. It is suggested that flow disturbances of the CSF during the acute stage of subarachnoid hemorrhage might play an important role in the pathomechanism of the disease.     

Disturbed spatial learning of rats after intraventricular administration of transforming growth factor-beta 1

Patients with subarachnoid hemorrhage (SAH) who later suffer hydrocephalus show persistently high levels of transforming growth factor-beta 1 (TGF-beta 1) in the cerebrospinal fluid after the onset of SAH. Recombinant TGF-beta 1 induces hydrocephalus in mice. This study examined the spatial learning ability of rats after intraventricular administration of TGF-beta 1. Thirteen-week-old Wistar rats were treated with 0.8 or 8.0 micrograms of human recombinant TGF-beta 1 by direct injection or via osmotic pump. Three months later, their spatial learning ability was evaluated with a Morris water maze. Ventricular size, ultrastructural features, and sodium-potassium-adenosine triphosphatase (Na+, K(+)-ATPase) activity of the subarachnoid space were examined. All three TGF-beta 1-treated groups clearly exhibited impaired spatial learning ability, but they did not exhibit ventricular dilation. Histological examination revealed subarachnoid fibrosis and deactivation of Na+, K(+)-ATPase in the arachnoid cells. These findings are similar to those of our previous experiments involving injection of TGF-beta 1 in mice. The present and previous studies suggest that subarachnoid fibrosis is an important factor in the disturbance of the spatial learning ability of rats, whereas ventricular size is less important.     

Cerebral arterial responses to induced hypertension following subarachnoid hemorrhage in the monkey.

Regional cerebral blood flow (rCBF), angiographic cerebral arterial caliber, and cerebrospinal fluid (CSF) pressure were measured in rhesus monkeys to determine the effect of experimentally induced subarachnoid hemorrhage (SAH) on cerebral arterial responses to graded increases in blood pressure. These measurements were also performed in a control group of monkeys subjected to a mock SAH by injection of artificial CSF into the cerebral space. Before subarachnoid injection of blood or artificial CSF, graded increases in mean arterial blood pressure (MABP) to a level 40% to 50% above baseline values had no effect on rCBF. The major cerebral arteries constricted and CSF pressure remained unchanged. Similar responses were observed after injections of artificial CSF. When MABP was increased in animals that had been subjected to subarachnoid injection of blood, rCBF increased and was associated with dilatation of the major cerebral arteries and moderate increases in CSF pressure. These results demonstrate that cerebral arterial responses to increases in blood pressure may be abnormal in the presence of subarachnoid blood. The manner in which abnormal cerebral arterial reactivity, changes in blood pressure, and vasospasm combine to determine the level of cerebral perfusion following SAH is postulated.     

Delayed Postoperative CSF Rhinorrhea of Intrasellar Arachnoid Cyst

Summary  CSF rhinorrhea due to a transsphenoidal approach usually follows accidental or intentional arachnoid opening. We report a patient with an intrasellar arachnoid cyst, who developed delayed onset of CSF rhinorrhea. A sixty-two-year-old man presented with bitemporal type visual field defect for the last 3 years. With the diagnosis of arachnoid cyst or Rathke's cleft cyst, based on MRI findings of intra-and supra-sellar cyst with CSF intensity, he successfully underwent transsphenoidal surgery without evidence of intra-operative CSF leakage. He developed CSF rhinorrhea one week later. This needed another operation for sellar floor repair. The pathomechanism of this delayed onset is explained as follows. Incomplete or one-way communication of subarachnoid space to cyst cavity, unrecognized during surgery, might cause delayed onset of CSF rhinorrhea. By using MRI, identification of the residual gland, which was compressed posteriorly, is useful for differentiating an arachnoid cyst from other cystic lesions. In highly suspect cases, even without evidence of intra-operative CSF leakage, peri-operative measures to prevent occurrence of postoperative CSF rhinorrhea are required.     

Remote cerebellar hemorrhage after foramen magnum decompression surgery for Chiari I malformation--case report

A 47-year-old woman underwent decompressive suboccipital craniectomy and C1 laminectomy with duroplasty in the prone position for Chiari malformation type I and syringomyelia. The arachnoid membrane was not injured. Intraoperative echography showed good enlargement of the subarachnoid space. No closed subcutaneous drain was used. The patient complained of repeated nausea and vomiting 3 hours after the operation, and computed tomography revealed remote cerebellar hemorrhage on postoperative day 1. The cerebellar hemorrhage was treated conservatively, and the symptoms continued only for 3 days after surgery. Dural opening with rapid loss of cerebrospinal fluid (CSF) has occurred in every reported case of remote cerebellar hemorrhage complicating intracranial and spinal procedures. Loss of CSF is the main pathogenesis of this condition. In our case, the most probable pathomechanism seems to involve stretching of the infratentorial cerebellar bridging veins due to cerebellar sagging because of dural opening in the prone position and drop in CSF pressure. Such a complication is rare but should be considered after foramen magnum decompression surgery if the patient shows unusual symptoms of repeated vomiting.     

Non-hindbrain-related syringomyelia. Obstruction of the subarachnoid space and the central canal in rats. An experimental study

BACKGROUND: The aim is to determine the mechanism of non-hindbrain-related syringomyelia in experimental models. The effects of obstruction of central canal and subarachnoid space on occurrence of cavities were discussed. METHODS: 31 Sprague-Dawley rats were used with eight (Group D) as a control. In 10 rats (Group A) 1.5 microl kaolin was microinjected into the dorsal columns and central gray matter of the spinal cord at the level of Th6-10. In 10 rats (Group B) 0.1 cc kaolin was injected into the subarachnoid space at the same level. In 3 rats (Group C), 1.5 microl kaolin was administered into both dorsal midline of the spinal cord and the subarachnoid space. RESULTS: In Group A, histological examination revealed cystic cavity and dilatation of the central canal in five rats; denuded ependymal line and multicystic formations in ependymal and periependymal areas in seven rats. In Group B, denuded ependymal line in three rats and microcystic formations in ependymal and periependymal areas in four rats were revealed. In Group C, there were microcystic formations in two rats and syrinx cavity in one rat. CONCLUSIONS: Developments leading to occurrence of cavities are focused on the central canal in all groups. These models indicate that the CSF-flow is from the subarachnoid space to the central canal leading to changes of cavities. In cases of obstruction of the subarachnoid space or the central canal, the occurrence of syrinx cavity initially is due to increased CSF (cerebrospinal fluid) pressure in the central canal. Flow changes in spinal cord is indicated by this study.     

Non-ionic water soluble contrast medium 3-Deoxy-3-Iodo-D-Glucose (DIG) for use in the CSF space. An experimental study with mongrel and beagle dogs

Summary A non-ionic water soluble contrast medium, 3-Deoxy-3-Iodo-d-Glucose (DIG), was experimentally evaluated for use in the cerebrospinal fluid (CSF) space, and compared with other contrast media.Two ml (180 mgI/ml) of DIG were injected either intraventricularly or intracisternally in 15 adult mongrel dogs (average weight: 6.4 kg), and X-ray photographic, CSF, EEG, and histological studies were then performed. Additional tests were made on four beagle dogs (average weight: 9.8 kg), focussing particularly on changes in cell count and protein in the CSF following alternate intracisternal injections of 2 ml (170 mgI/ml) of DIG and metrizamide (Amipaque^®), and on epileptogenicity following intracisternal injection of 3 ml (300 mgI/ml)of DIG.That DIG provides adequate definition was demonstrated both by the ventriculograms and cisternograms, and by comparison with metrizamide. Neither epileptic discharges in the EEG nor epileptic symptoms were seen in any of the dogs used in the studies. In the CSF drawn 24 hours after the injection, protein tended to increase moderately with DIG, but pleocytosis was mild with both media. Histological studies of the central nervous system structures around the cisterna magna revealed no definite abnormal findings. Neither fibrosis nor arachnoid adhesions were seen in scanning electron microscopic observations of the basal subarachnoid spaces.     

改良血管穿刺法大鼠蛛网膜下腔出血模型的制作及评价

目的 探讨改良血管内穿刺法制作大鼠蛛网膜下腔出血(SAH)模型的制作方法,以及此模型蛛网膜下腔积血分布、吸收与神经元损伤病理特征的动态变化规律.方法 SD大鼠随机分为正常、假手术和手术组,采用改良血管内穿刺法制作SAH模型,观察各组脑组织的大体形态,以及手术组各个时间点蛛网膜下腔内血液分布情况;通过苏木素-伊红(HE)染色,观察神经组织的病理学变化.结果 3～24 h蛛网膜下腔的积血由穿刺的局部脑底面逐渐向大脑凸面蛛网膜下腔弥散;48 h第四脑室可见明显积血;大脑皮层神经元水肿随时间的增加逐渐加重,24 h达到水肿高峰,并持续到48 h;7 d时神经元水肿基本恢复.结论 改良血管穿刺是制作SAH模型较为理想的方法,蛛网膜下腔内血液的吸收再分布规律及神经元的动态损伤过程为SAH模型构建的评价提供了更完备的实验数据.