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.     

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.     

Scanning electron microscopy of the subarachnoid macrophages after subarachnoid haemorrhage,and their possible role in the formation of subarachnoid fibrosis

Summary Sixty dogs with experimental subarachnoid haemorrhage (SAH), repeated SAH, and subarachnoid fibrosis (examined three weeks and three months after SAH, and treated with urokinase or dexamethasone) were examined by scanning electron microscope (SEM). The authors observed the resting and activated macrophages, the erythrophagocytosis, and giant cells in the subarachnoid space after SAH. They consider that the macrophages play an important role in the formation of subarachnoid fibrosis, similar to the role of macrophages in fibrosis in other sites.This work was supported by the Japan Society for the Promotion of Science.     

Subarachnoid hemorrhage and circulatory disturbance of cerebrospinal fluid--scanning electron microscopid study in clinical and autopsy cases (author's transl)]

The scanning electron microscopy (SEM) gives intersting information about the changes of the subarachnoid space. In this study, specimens from 16 patients (one during surgery and others at autopsy) were examined by SEM: 11 cases of subarachnoid hemorrhage, 2 of posterior fossa brain tumor operated and 3 of control cases without CNS diseases. In cases of subarachnoid hemorrhage, there seemed to be three stages of the obstruction in the subarachnoid space: a) obstruction by blood clots mainly consisted of red blood cells, b) obstruction by subarachnoid fibrosis with thickening of arachnoid, c) obstruction by arachnoid adhesion obliterating subarachnoid space. Specimens from parietal parasagittal area, lateral cerebral fissure and temporal base on both sides were systematically examined by SEM, and the degree of the obstructive changes of the subarachnoid space were classified into five grades: 0) no changes 1) minimal changes--slight thickening of arachnoid and perivascular fibrosis in subarachnoid space 2) moderate changes--thickening of arachnoid and fibrosis in subarachnoid space with patent meshwork 3) severe obstruction of subarachnoid meshwork 4) complete obstruction of subarachnoid space--no space for CSF circulation. We found high incidence of communicating hydrocephalus after SAH in those cases in which epicortical CSF circulation was obstructed more than grade 3 in the parasagittal area bilaterally.     

Arachnoid cysts of the sylvian fissure. Evidence of fluid secretion

Morphological and enzyme ultracytochemical evidence is presented to support the contention that the walls of arachnoid cysts secrete fluid. Clinical evidence has already suggested this phenomenon, including intracranial pressure elevation and expansion in some cases, and the observation that arachnoid cysts constitute closed compartments with a fluid content that cannot be derived from other cerebrospinal fluid-containing spaces. Ultrastructurally, the cyst lining showed a similarity to subdural neurothelium and the neurothelial lining of arachnoid granulations in such morphological features as intercellular clefts with sinusoid dilatations, desmosomal intercellular junctions (upon which tonofilaments may be abutting), pinocytotic vesicles, multivesicular bodies, lysosomal structures, and the presence of a basal lamina. Some of these features, together with the presence of microvilli on the luminal surface, are consistent with fluid secretion. Moreover, enzyme cytochemistry demonstrated (Na+ + K+)-ATPase in the plasma membranes lining the cavity, either directly (the apical membranes), or via the intercellular clefts (the basolateral membranes), and, with alkaline phosphatase occupying the opposite plasma membranes, this structural organization indicates fluid transport toward the lumen. It may be surmised that arachnoid cysts derive from subdural neurothelium differentiating towards arachnoid villus mesothelium.     

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.     

Dural and Arachnoid Membraneous Protection of the Abducens Nerve at the Petroclival Region

The goal of this study was to determine the membranous protection of the abducens nerve in the petroclival region. The petroclival portion of the abducens nerve was studied in ten dissections from five cadaveric head specimens. One of the heads was used for histological sections. Four heads were injected with colored latex for microsurgical dissections. The histological sections were prepared from petroclival dura mater, embedded in paraffin blocks, stained, sectioned in the axial, coronal, and sagittal planes, and evaluated by light microscopy. The abducens nerve was covered by a dural sleeve and arachnoidal membrane during its course within the petroclival area. Following the petrous apex, the abducens nerve was fixed by a sympathetic plexus and connective tissue extensions to the lateral wall of the cavernous segment of the internal carotid artery and to the medial wall of Meckel's cave. Fibrous trabeculations inside the venous space were attached to the dural sleeve. The lateral clival artery accompanied the dural sleeve of the abducens nerve and supplied the petroclival dura mater. The arterioles accompanying the abducens nerve through the subarachnoid space supplied the nerve within the dural sleeve. The arachnoid membrane covered the abducens nerve within the dural sleeve to the petrous apex, and arachnoid granulations found on the dural sleeve protruded into the venous space. The extension of the arachnoid membrane to the petrous apex and the presence of arachnoid granulations on the dural sleeve suggest that the subarachnoid space continues in the dural sleeve.     

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.     

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.     

Protruding arachnoid granulations mimicking dermoid cysts

This is the report of two children who had prominent arachnoid granulations that were mistaken clinically for dermoid cysts. These lesions appeared in the midline, primarily posteriorly. During surgery, the lesions extended through the dura connected by a stalk. A pathologic examination confirmed the lesions to be arachnoid granulations.     

Fluid secretion in arachnoid cysts as a clue to cerebrospinal fluid absorption at the arachnoid granulation

The morphological similarity of the lining of arachnoid cysts to subdural neurothelium and the mesothelium of arachnoid granulations suggested that the latter tissues might be the origin of arachnoid cysts. Transport Na+-K+-adenosine triphosphatase was shown by enzyme ultracytochemistry to be an indication of secretory activity in the lining of arachnoid cysts and in the endothelial lining of arachnoid granulations. This secretory activity suggests the existence of a biochemical mechanism for cerebrospinal fluid absorption at these granulations separate from the mechanisms already demonstrated.     

Arachnoid cyst and arachnoiditis following idiopathic spinal subarachnoid haemorrhage

We describe 8 years follow-up of a case of arachnoid cyst developing after spinal subarachnoid haemorrhage. The cyst was removed by hemilaminectomy; an arachnoid cyst of the same size was again observed by MRI 2 weeks later. We suggest that conservative approach could be the best choice.     

Prevention of subarachnoid fibrosis after subarachnoid haemorrhage with urokinase. Scanning electron microscopic study in the dog.

The author used the scanning electron microscope (SEM) to study the influence of urokinase on subarachnoid fibrosis after experimental subarachnoid haemorrhage (SAH). In the subchronic group of dogs, which were sacrificed three weeks after SAH, an average of 45--50 IU/kg of intrathecal urokinase diminished the fibrosis. In the chronic group, which was sacrificed three months after SAH, an average of 250 IU/kg of intrathecal urokinase also had considerable reducing effect. The author supposes that fibrinolytic therapy, with lysis of blood clot, contributes to clearance of the blood. We contrast this mechanism with the mechanism and effect of antifibrinolytic therapy. This experiment is the first successful attempt to influence subarachnoid fibrosis, and also the first experiment in which subarachnoid fibrosis could to some extent be prevented.     

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.     

Less invasive cistemal approach and removal of subarachnoid hematoma for the treatment of ruptured cerebral aneurysms

The risk of pial or brain injury while dissecting the cerebral cistern to treat acute subarachnoid hemorrhage might be higher than that of unruptured aneurysms, because visualizing the arachnoid trabeculae between the pia mater and the vessels can be complicated by thick subarachnoid clots filling the cerebral cistern. The author describes technical points of dissecting the cerebral cistern and the removal of subarachnoid hematomas during acute surgical treatment for subarachnoid hemorrhage. Tough arachnoid trabeculae form a "perivascular cistern" around the relatively major vessels in both the sylvian and interhemispheric fissures. The cistern can be separated without pial injury by identifying the microstructure surrounding the major vessels in the cistern and then cutting the arachnoid trabeculae. After bloodless dissection of the cistern, the subarachnoid hematoma can easily be irrigated and removed. The subarachnoid clot must be repeatedly irrigated by flushing the micro-space between arachnoid trabeculae with jets of water to ensure efficient removal. When the arachnoid trabeculae become transparent, small vessels and the arachnoid trabeculae can be differentiated as well as whether or not they can be cut. To treat sylvian hematoma, subpial hematomas extending from the insular cistern and intra-cisternal clots must be removed. Furthermore, inducing complete hemostasis by coagulating the subpial vessels is indispensable to prevent postoperative rebleeding.     

Meningioma Manifesting Intracerebral Haemorrhage: A Possible Mechanism of Haemorrhage

We present a possible mechanism of intracerebral peritumoural haemorrhage in meningioma based on the clinical data of three of our cases. A meningioma manifesting intracerebral haemorrhage is uncommon and some sporadic case reports have been presented, but without any proven mechanisms. We are presenting three cases of convexity meningioma manifesting spontaneous intracerebral haemorrhage with apoplectiform onset. All three patients had no evidence of bleeding tendency or other predisposing factors for haemorrhage. Preoperative radiological studies showed a solid mass attached to the dura with intracerebral peritumoural haematoma. Total removal of the tumour and haematoma could be achieved in every case. Histological investigation revealed extensive tumour infarction in two cases and fibrosis related to pre-existing ischaemia in the other case. The diagnoses were atypical meningioma in two cases and transitional type in one case. We suggest that extensive tumour infarction might be a cause of spontaneous intracerebral peritumoural haemorrhage in our series of patients.     

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.     

Evaluation of the Production and Absorption of Cerebrospinal Fluid

The traditional hypothesis of cerebrospinal fluid (CSF) hydrodynamics presumes that CSF is primarily produced in the choroid plexus (CP), then flows from the ventricles into the subarachnoid spaces, and mainly reabsorbed in the arachnoid granulations. This hypothesis is necessary to reconsider in view of recent research and clinical observations. This literature review presents numerous evidence for a new hypothesis of CSF hydrodynamics—(1) A significantly strong relationship exists between the CSF and interstitial fluid (IF), (2) CSF and IF are mainly produced and absorbed in the parenchymal capillaries of the brain and spinal cord. A considerable amount of CSF and IF are also absorbed by the lymphatic system, and (3) CSF movement is not unidirectional flow. It is only local mixing and diffusion.     

Arachnoid villi affected by subarachnoid pressure and haemorrhage

The arachnoid villi of 18 dogs were studied. The authors confirmed the pressure gradient changes of the morphology of arachnoid villi of dogs with the scanning electron microscope (SEM). A subarachnoid infusion with 5--10 times higher pressure gradient than the physiological one, tore the superficial endothelial layer from the villi, and the inner part could also be observed stereoscopically. On the surface of the arachnoid villi, the authors observed microvilli, openings of vacuoles and intercellular gaps, but did not find openings of performed channels. After subarachnoid haemorrhage (SAH) generally the villi were blocked but the authors have observed a red blood cell escaping from a villus intercellularly.