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Background: Primary of the brain and meninges are uncommon tumors. Information regarding optimum treatment is limited due to their rarity, and the best form of therapy is not yet known., Methods: Nine patients between the ages of 22 and 61 years with primary fibrosarcomas confined to the brain and meninges were studied clinicopathologically. Tumors were superficially located in five patients and intracerebrally or deep in four patients. Treatment consisted of maximum feasible surgical resection (seven patients, gross total; one, subtotal; one, no surgery before death) and radiation therapy (45-60 Gy conventional fractionation) in eight of nine patients., Results: Fibrosarcomas were moderate or high grade in seven of nine patients (78%). Immunohistochemical reactions with antisera to glial fibrillary acid protein (GFAP), cytokeratin, vimentin, desmin, and S-100 demonstrated vimentin positivity in five of nine patients and cytokeratin positivity in two of nine patients. Individual GFAP-positive cells were seen in two cases, thought to represent trapped reactive astrocytes. None were S-100-positive or desmin-positive. Eight patients have died, with a median survival time of 7.5 months (range, 1 day-96 months). Local recurrence developed in eight patients and distant recurrence in six patients. Systemic metastases developed in four patients (50%) and meningeal seeding in four patients (50%). Longer survival was observed in superficially located tumors (range, 7.5 months-96 months) compared with intracerebral tumors (range, 1 day-9 months)., Conclusions: Primary fibrosarcomas of the brain are uncommon tumors, usually of high histologic grade, with a high rate of local recurrence. Their propensity for meningeal and distant relapse distinguishes them from tumors of glial origin. Immunohistochemistry is of limited diagnostic value, although it may facilitate exclusion of other diagnoses. Because the prognosis after conventional surgery with 50-60 Gy external beam radiation therapy is relatively poor, the authors recommend more aggressive therapy with maximal feasible resection followed by external beam radiation therapy to doses of 64-66 Gy. When effective chemotherapy is established for soft tissue sarcomas of the extremities, this should be evaluated in view of the high incidence of distant metastases.

We report the pathological and molecular biological findings of human T-cell lymphotropic virus type 1 (HTLV-1) infection of the spinal cord in a patient with a chronic progressive myelopathy. Light microscopy disclosed loss of myelin and axons, thickening of blood vessels and a lymphocytic cell infiltrate in the spinal cord especially at the cervical and thoracic levels. Electron microscopy confirmed the vascular appearance seen with light microscopy but virus particles were not observed. The HTLV-1 gag gene could be amplified (by polymerase chain reaction) from cervical spinal cord tissue while not from elsewhere in the neuroaxis. The presence of HTLV-1 genomic material in spinal cord tissue has not been previously reported.

The clinical histories and pathological findings of 27 autopsied cases of orthotopic liver transplantation (OLT) were reviewed. Fatal OLT was complicated in 93% of cases by neurological dysfunction, usually manifested by encephalopathy, with or without seizures. The etiology of the encephalopathy was largely multifactorial (44%) or undetermined (20%). Subarachnoid hemorrhage, central pontine myelinolysis, meningitis, brain infarction, polyclonal B cell lymphoma and spinal cord necrosis were common neuropathological findings. These diagnoses were often masked by other systemic illnesses. The role of cytomegalovirus (CMV) in neurologic dysfunction was explored with in situ hybridization and immunohistochemical techniques. OLT cases showed a significantly higher (89%) frequency of CMV genomic material in brain tissue compared to age-matched non immunocompromised (NIC) patients (23%). All OLT cases with encephalopathy of undetermined cause demonstrated usually prominent hybridization to the CMV probe. CMV may be an important cause of encephalopathy in such patients.

An immunohistochemical study was performed on the paraffin sections of 25 tumors in the central nervous system (CNS) with prominent papillary configurations. These tumors included seven metastatic papillary carcinomas, six choroid plexus tumors, four papillary ependymomas, two myxopapillary ependymomas, two papillary pituitary adenomas, two astroblastomas, one papillary meningioma, and one anaplastic astrocytoma with significant papillary changes. The panel of antibodies applied included anti-glial fibrillary acidic protein (GFAP), anti-carcinoembryonic antigen (CEA), anti-vimentin (VM), anti-S-100 protein (S-100 P), anti-cytokeratin, and anti-prealbumin antisera. All ependymomas and astroblastomas examined expressed both VM and GFAP, which were either absent or focally expressed in choroid plexus tumors. In contrast, all choroid plexus tumors showed anti-cytokeratin immunoreactivity that was absent in the ependymomas and astroblastomas. Five choroid plexus tumors also expressed S-100 P, thus differentiating them from metastatic carcinoma that showed negative immunostaining. Anti-CEA antisera immunoreactivity was seen in six metastatic tumors, whereas none of the primary CNS tumors expressed CEA. Prealbumin was expressed in four choroid plexus tumors and two metastatic tumors. Immunohistochemical typing using a panel of antibodies has allowed the differentiation of most of the papillary tumors in the CNS examined in this study.

The clinical and pathological features, including electron microscopy of a sporadic case of neuroaxonal dystrophy with findings of both Hallervorden-Spatz syndrome (HS) and Seitelberger's disease (SD) are presented. The patient presented with a slowly progressive illness with seizures, extrapyramidal symptoms, cerebellar ataxia, dementia, spasticity, myoclonic movements and a severe demyelinating peripheral neuropathy with secondary muscular atrophy. Neuropathological examination disclosed cerebral and cerebellar atrophy and excessive pigmentation of the globus pallidus and substantia nigra. Spheroids were widely distributed within the central and peripheral nervous system. Numerous neurofibrillary tangles (NFTs) were found within the hippocampal cortex, neocortex and brain stem. Extensive granulovacuolar degeneration (GVD), Hirano bodies and Lewy bodies were also demonstrated. Severe loss of myelin from the peripheral nerves and muscular denervation were striking features. We wish to report this case which shares findings of both entities, HSS and SD.

We have investigated alterations in the structure and function of nuclei isolated from normal and pathological brains in a number of neurodegenerative diseases including scrapie and Alzheimer's disease. Here we summarize both general and specific changes in chromatin structure, gene expression, and neuropathological features for each encephalopathy and compare them in terms of their molecular biological similarities and differences. While both scrapie and Alzheimer's disease share a number of common alterations in genomic organization and gene activity during the pathogenic process, each neurological disease appears to operate on fundamentally different mechanisms.

Seven fusiform aneurysms were found at autopsy in five patients (two males and three females) over a 13-year period. The subjects were between 56 and 65 years of age. The basilar trunk was the most frequent site. Four aneurysms were of giant proportions and contained laminated thrombi. Subarachnoid hemorrhage occurred in four patients. Microscopic examination of the aneurysm walls revealed atheromatous degeneration, focal wall attenuation, mural hemorrhage, rupture, and acute and chronic inflammatory cell infiltration. These findings suggest that rupture is not rare and that atherosclerosis is but one mechanism in the pathogenesis of these lesions.

A case of motor neuron disease with clinical and pathological resemblance to amyotrophic lateral sclerosis (ALS) in a woman who was severely bitten on the ankle by a cat is described. Weakness first appeared at the ankles and relentlessly advanced proximally, terminating in death from pulmonary failure in a year. A number of unusual features that are uncharacteristic of ALS were found that included a markedly elevated antinuclear antibody titre in the serum and the presence of prominent oligoclonal bands in the cerebrospinal fluid. The spinal cord showed loss of anterior horn cells and pyramidal degeneration that are characteristic of ALS, but an extraordinary finding was the presence of transmural granulomatous inflammation of numerous small and medium sized vessels, especially veins, in the subarachnoid space around the cord. There were also inflammatory changes in the brainstem and spinal cord consisting of microglial and astrocytic nodules and perivenous cuffing by mononuclear cells. Ill-defined hyaline eosinophilic cytoplasmic inclusions were seen in some remaining anterior horn cells. No viral particles were found by electron microscopy despite an extensive search. Virological studies were inconclusive but there is reason to believe that this patient's illness was caused by an as yet unidentified virus.

In ongoing research into potential embolic agents, three substances were evaluated for their effectiveness in occluding the pig rete. Selective injection of these agents produced varying degrees of occlusion, with the most effective a microfibrillar collagen hemostat in a 33% ethanol solution. Angiostat, a collagen particulate, did not produce rete occlusion, and all pigs injected with it developed adverse effects, including coma and apnea. Tisseel, a tissue sealant, produced partial rete occlusion, but was uniformly difficult to manage through long catheters, and its use was discontinued. Microfibrillar collagen hemostat with ethanol appears to have the greatest potential as an embolic agent in low-flow structures.

The clinical pathological features of fatal arterial dissection confined to the intracranial vessels are described. Three patients with anterior circulation dissections presented with focal ischaemic neurological deficits and pathological examination of involved vessels revealed a dissection plane between internal elastic lamina and media accompanied by intravascular thrombosis. Three of four patients with posterior circulation dissections had clinical pathological features of subarachnoid haemorrhage and at necropsy had transmural dissections. In contrast to previous reports, primary vasculopathies either degenerative or inflammatory were not identified in affected vessels. The pathogenesis of intracranial arterial dissection is discussed and the clinical features are correlated with the pathological abnormalities.

The neuropathology of 18 cardiac transplant recipients was reviewed with the clinical findings. Pathological changes were noted in the central nervous system (CNS) in 94% of the patients, the most frequent being cerebral vascular in origin (72%). Eight patients (44%) had multiple cerebral infarcts and morphologically, a large number of these antedated the transplantation. In addition 4 patients had acute focal ischemic changes which occurred after transplantation. Intracranial hemorrhage was noted in 5 patients (28%), including one case of fatal intracerebral hemorrhage following an acute hypertensive episode after the transplantation. While systemic infection was common (10 patients), there were only 5 cases of intracranial infection; including 3 cases of cytomegalovirus infection, one of candidiasis and one of aspergillosis. Post-transplant seizures, occurring in a third of the patients, were related to a variety of causative factors such as sepsis, intracranial hemorrhage, cerebral ischemia, metabolic encephalopathy and cyclosporin neurotoxicity. Of note in this series was the absence of CNS lymphoma or other systemic lymphoproliferative disorder.

Eight years after radiation therapy (5000 rads of 60Co) for a pituitary adenoma, a patient developed a sellar fibrosarcoma. The tumor had an aggressive growth pattern: it infiltrated the optic nerve, sphenoidal air sinus, hypothalamus, and both cavernous sinuses, where compression of the left internal carotid artery resulted in a massive hemispheric infarction. Surgery was ineffective in arresting rapid growth of the lesion; death occurring 5 months after onset of symptoms.

A comparison of clinical, EEG, and pathologic features was carried out on all cases of autopsy-proven Creutzfeldt-Jakob disease (CJD) studied over the last 10 years. Periodic sharp wave complexes (PSWCs) were present in three but absent in seven patients. Myoclonus was documented in two of the three with and in only one of the seven without PSWCs. The three with PSWCs had severe neocortical and at least mild thalamic involvement; those without PSWCs had more variable disease topography. The diagnosis of CJD should not be rejected if PSWCs are absent.

Previous work in our laboratory established an experimental model for the production of paraplegia in the anesthetized normothermic adult mongrel dog. The current study involves 24 animals divided into two equal groups: Group 1 served as control, and Group 2 received treatment with scavenger agent. Vascular occlusive clamps were placed on the thoracic aorta proximal to the left subclavian artery, on the left subclavian artery at its origin, and on the distal thoracic aorta at the diaphragm for 30 minutes. In Group 1,200 ml of normal saline solution (37 degrees C) was perfused into the occluded aortic segment at the rate of 0.33 ml per kilogram of body weight per minute. In Group 2, 90% dimethyl sulfoxide (DMSO) in a dose of 0.1 gm/kg in normal saline solution (37 degrees C) for a total volume of 200 ml, was likewise injected into the occluded aortic segment at the same infusion rate. Animals were observed for evidence of paresis in the postoperative period. Microscopic analysis revealed evidence of ischemic myelopathy in the control group but none in the treated group. Under the conditions of this experiment, we conclude that the scavenger agent DMSO has a highly protective effect on the spinal cord during ischemic insult.

A patient developed paraparesis and signs of meningeal irritation spontaneously while on anticoagulant therapy. At autopsy, a subdural hematoma of the thoracic cord and evidence of widespread subarachnoid hemorrhage were found. The possible mechanism for these combined hemorrhages is discussed.

Postmortem neuropathological findings in a patient with biopsy-proved familial Gerstmann-Sträussler-Scheinker disease of eight years' duration included severe spongy change in the neocortex, extensive and often large amyloid deposits throughout the cerebral hemispheres and cerebellum, and severe astrocytic gliosis throughout all areas of gray and white matter within the brain. The degree of cortical spongy change was much greater than that in relatives who died with a similar clinical history, indicating the phenotypic heterogeneity in this familial disorder.

The operation of selective spinal cordectomy is rarely performed. The cases of 10 paraplegic patients who underwent this procedure are presented. Their clinical indications were varied, including posttraumatic syringomyelia, uncontrollable leg spasticity, posttraumatic spontaneous neurogenic leg pain, and repair of a myelomeningocele gibbus. The cordectomy specimen was available for pathological examination in nine cases. Specimens removed from or near the site of spinal cord trauma showed extensive gliosis, leptomeningeal fibrosis, and schwannosis. This latter feature possibly represents an attempt at spinal cord repair by the dorsal root ganglion cells. Four specimens contained a syrinx with features including a thick gliotic wall and enlarged Virchow-Robin spaces, features that have been implicated in the pathogenesis of posttraumatic syringomyelia. Clinical results in the patients with syringomyelia and uncontrollable leg spasticity have been excellent. Cordectomy did not provide permanent relief in the patients with neurogenic leg pain. The authors conclude that selective spinal cordectomy is a valuable procedure for specific indications.

A 53-year-old man with an aggressive T-cell lymphoma was found at autopsy to have severe cerebellar degeneration, presumably as a 'remote' effect of malignancy. The degree of cerebellar atrophy was unusually pronounced and widespread, involving both Purkinje cell and granule cell layers, although patches of preserved and essentially normal cerebellar cortex were identified. This case is of particular interest in view of data which indicate that cerebellar Purkinje cells and T-lymphocytes share antigenic surface markers.

A 58-year-old man presented with a 4-month history of personality changes and transient episodes of right lower extremity weakness, as well as transient episodes of aphasia. Computerized tomography revealed a large basal frontotemporal mass with extensive surrounding edema which was confirmed on angiography to be a partially thrombosed giant aneurysm. Pathologically, the lesion was extraordinary, demonstrating extensive organization, with the entire cavity of the aneurysm occupied by vascular channels of different sizes, some of which were thrombosed. These findings were substantiated by scanning electron microscopy which also illustrated areas of active platelet-fibrin interaction on the remaining luminal surface.

Isobutyl-2-cyanoacrylate (bucrylate) is commonly used as a material for therapeutic embolization. Histologic sections of embolized tissue routinely stained with hematoxylin-eosin show the bucrylate as a translucent material. We outline a staining procedure that demonstrates bucrylate in tissue sections. It is useful in routinely prepared paraffin-embedded tissue, and it is also effective after embolized tissues have been processed with petroleum ether rather than xylene. This stain may be effectively utilized to assess harmful tissue reactions to bucrylate.

Sixteen of 35 patients (46%) 21 years old or less who underwent surgical resection of a longstanding epileptic focus harbored tumors. The median duration of the seizure disorder prior to operation was 6.0 years for patients with and 7.6 years for those without tumor. Among the 35 patients, tumor was more common when intelligence and results of neurological examination were each normal, a plausible cause for uncontrolled seizures was lacking, and persistent focal delta activity occurred in a majority of electroencephalograms (EEGs). The type of seizures and the distribution of EEG spikes failed to distinguish patients with tumor from those without. Multifocal EEG spikes appeared in a majority of each group.

This paper reports an experimental study of iris wound-healing and the response of iris tissue in baboons to different suture materials following a planned surgical incision. The wound was sutured with 8-0 virgin silk, 22 mum Ethilon or 7-0 chromacised catgut, or left unsutured. The iris produces a minimal inflammatory response to aseptic trauma characterised by round cell infiltration, clump cell proliferation, pigment cell proliferation from the posterior epithelial surface and proliferation of non-pigmented ciliary epithelium (knots). This response is associated with microscopic hemorrhages in the iris. There does not appear to be any fibrous union of wound edges, instead the wound surfaces become lined with a layer of pigmented cells, probably from the posterior epithelium. Sutures play the dual role of accurately apposing the wound edges and, because there is no fibrous union of iris tissue, of keeping them in apposition. Therefore, they must remain in situ permanently. Catgut is poorly tolerated by the iris and is eventually absorbed. For these two reasons it is unsuitable. Ethilon is the least reactive and virgin silk only slightly more reactive. Both of these are suitable for iris suture. The suture material at present available is not entirely satisfactory. Finer suture material is required to reduce even more the iris response to sutures. Needles, even those supplied with Ethilon or virgin silk, are too large and clumsy. The answer to this problem probably lies in strengthening and sharpening the suture material ends so that they can act as needles.

A 33-year-old man, an immunosuppressed renal allograft recipient, developed fever of unknown etiology, multiple pulmonary densities, space-occupying lesions in the liver, confusion, disorientation, and seizures with cerebral infarcts. At autopsy, changes classical of active lymphomatoid granulomatosis (LYG) were found in the brain but those studied in the lungs and liver were in the healing phase. In addition, one cerebral focus in the right temporo-occipital lobe showed a lymphomatous transformation. Immunofluorescence studies done on this focus showed monoclonal IgG-lambda cytoplasmic staining in the perivascular infiltrate. Immunoperoxidase studies confirmed the monoclonal nature of this focus but showed a polyclonal pattern in the other foci. This finding is discussed along with the relationship between LYG and lymphoma.

Atypical forms of progressive multifocal leukoencephalopathy (PML) may simulate other disorders. A previously healthy 70-year-old female developed unsteadiness of gait, dysarthria, dementia and weakness leading to inanition and death from bronchopneumonia over a 43 month period. The diagnosis of PML was not suspected prior to death. Neuropathologic examination of the brain disclosed characteristic findings of PML-deep bilateral cerebral demyelinative foci with enlarged gemistocytic astrocytes and swollen oligodendrocytes containing intranuclear inclusions. Electron microscopy identified papova virus particles within these inclusions. An underlying source of immunosuppression was not identified either premortem nor at the time of autopsy. The prolonged clinical course, simulating that of a primary degenerative disease, and the lack of apparent immunocompromise are unusual features of PML and lend credence to the suggestions that variations in its expression and course are to be expected.

Among 84 surgically resected arteriovenous malformations (AVMs), four were found to have refractile foreign particles lined by endothelium in the vessel walls. In three cases, this was associated with granuloma formation. The particles were probably introduced during cerebral angiography. They represent a not unusual pathologic finding, are relatively more common in AVMs than in other neurosurgically excised lesions, and may have clinical significance, especially if abundant.

A series of 9 patients have experienced hemisphere and retinal ischemia at an interval after occlusion of appropriate internal carotid arteries. All had radiological evidence of a persisting proximal stump to the occluded artery and, in most, pathological evidence of thrombotic material attached to atheromatous lesions within the stump. Thromboembolism from the stump via the anastomotic supply through ipsilateral common and external carotid arteries is thought to be responsible for the ischemic events to the brain or retina despite absence of flow through the internal carotid artery. Seven of the 9 were treated by surgical excision or obliteration of the stump and, when indicated, common and external carotid endarterectomy. Turbulence in the stump contributed to progressive atherosclerotic changes and probably aggravated thrombogenesis in this location with subsequent embolization into the anastomotic arteries.

Although oligoclonal banding is a characteristic feature of MS spinal fluid, some patients do not show this abnormality. Four of 18 consecutive patients with autopsy-proven MS had no oligoclonal bands (OB) in CSF during life or at postmortem. Patients with OB had numerous plasma cells in meninges and plaques (confirmed in sections stained for cytoplasmic immunoglobulin). The four patients without bands had few or no identifiable plasma cells. Therefore, lack of OB correlates with both inactivity of plaques and absence of plasma cells in plaques or meninges. This is another form of heterogeneity in MS.

Seventy-eight carotid endarterectomy specimens were reviewed microscopically for the presence of mural capillary atheromatous emboli. Twelve specimens (15%) were found to contain these emboli. An attempt to correlate this finding with clinical and radiologic data yielded no evidence of an increased predisposition to recurrent transient ischemic attacks or stroke in the affected patients even in the absence of ulceration. Nevertheless, further attention must be given to defining the drainage patterns of such embolized mural capillaries and elucidating their role, if any, in the pathophysiology of stroke.

Forty patients who had intractable temporal lobe epilepsy had surgery for treatment of their seizures following study by computed tomography (CT). Fifteen of 19 patients with tumors had good correlation between CT and pathological findings. Another group of patients had macroscopic changes that were demonstrated on CT and verified at surgery. Sixteen patients had microscopic pathological diagnoses including cytoarchitectural abnormalities, Chaslin gliosis, and ectopic neurons. Six of these had enlarged temporal horns on the ipsilateral and five on the contralateral side to the electroencephalographic-pathological abnormality. In the investigation of temporal lobe epilepsy we believe that CT, especially with the newer generation scanners, records tumors and other larger macroscopic changes but that temporal horn size is unreliable in predicting the abnormal side if only microscopic changes are present.

We report two cases of thrombotic thrombocytopenic purpura (TTP). The first case illustrates the clinical findings and fluorescein angiographic features of this disease, notably the serous macular detachments and focal areas of choriocapillaris occlusion. The second case demonstrates a more severe case of TTP, with neurologic complications that led to death; histopathological examination of the eyes showed serous retinal detachments and choriocapillaris occlusion, with electron microscopic evidence of intravascular fibrin-platelet thrombi.

A 24 year old woman with a 15 year history of intractable seizures underwent resection of a small low grade astrocytoma of the right mesial frontal lobe. The tumor arose beneath a benign scalp nevus that had been treated in infancy with radium patches and focal x-irradiation. Neuropathological changes within the tumor were compatible with radiation injury. Meningiomas and sarcomas complicate cranial irradiation but the evidence that gliomas do so is less convincing. Our observations support an association between radiation exposure and the subsequent development of glial tumors.

When two disposable serological pipettes with an external diameter of 1 cm are placed on the cutting surface on either side of the brain and the knife rides across them, it will cut even slices precisely 1 cm thick. Both coronal and horizontal slices can be cut as well as oblique slices for comparison with computerized tomographic scan roentgenograms although for the latter the initial cut will have to be made freehand. For practical purposes, brain slices obtained by this simple technique are as good as those made with a mechanical jig or electric machine and are superior to those made freehand.

A recent publication described autopsy samples from five brains in which positive staining for iron was observed as surrounding demyelinated plaques. Because this has not been previously reported, autopsy material from 13 patients who were being followed up at the Multiple Sclerosis (MS) Clinic, University Hospital, The University of Western Ontario, London, Ontario, was reviewed. A total of 32 paraffin-embedded blocks containing demyelinated plaques of varying age were sectioned and stained using a standard acid ferrocyanide technique (Peris' test) for iron. Microscopic examination failed to detect the presence of significant positive staining either within or surrounding the areas of demyelination. Positive histochemical staining for iron identifies hemosiderin, the presence of which suggests either iron overload or remote hemorrhage. Support for these two processes in the pathogenesis of MS could not be provided from our material.

There is controversy as to the possible toxic effects of isobutyl-2-cyanoacrylate (bucrylate) when this substance is used for purposes of therapeutic embolization. Two cases are presented in which cerebral arteriovenous malformations were resected, one 42 days and the other a year after bucrylate embolization. In both, pathological examination revealed a brisk intimal foreign-body giant-cell reaction wherever bucrylate was present in a vessel, along with chronic inflammation in the vessel walls and adjacent brain parenchyma. The findings are discussed in the light of other observations on the histotoxicity of bucrylate.

A patient with sudden apoplexy and coma was found to have hydrocephalus on computed tomographic scan, and metrizamide was instilled into the ventricles. Subsequent autopsy disclosed a brainstem infarct secondary to a primary dissecting aneurysm of the basilar artery, and a histologic picture of encephalitis in the walls of the lateral and third ventricles. Metrizamide may cause pathologic changes that must be recognized for the correct interpretation by the pathologist of tissue sections previously exposed to metrizamide. In the present case, the changes were seen 11 days after exposure of the tissue to metrizamide, consonant with the time course of similar changes observed in animals. The localization of the cellular infiltrates to the Virchow-Robin spaces corroborates evidence from the literature that metrizamide enters brain parenchyma via these spaces.

Cervical myelopathy has become commonly recognized as a complication of rheumatoid atlantoaxial subluxation. A small group of patients with atlantoaxial subluxation may have intermittent symptoms associated with change of head position and which are due to vertebral artery compression. Two such cases are reported, one with necropsy findings of infarction in the area supplied by the vertebrobasilar system. The pathogenesis of the symptomatology and infarction is discussed.

The unique ultrastructure of brain endothelial cells restricts nonspecific leakage of blood-borne molecules across the blood-brain barrier (bbb). Human barrier ultrastructure has not been studied extensively because of the rapid ultrastructural degeneration that takes place after death. We have obtained living, structurally normal neocortex and underlying white matter at biopsy from patients of various ages, and have quantitated ultrastructural features that are associated with the bbb so that we could characterize human barrier ultrastructure and determine whether it changes with age. We found that gray matter capillaries have thinner walls than white matter capillaries, and that during aging white matter capillary walls became thinner until they approached the dimensions of those in gray matter. Thinning is due to loss of pericytes and thinning of the endothelial cytoplasm. The mitochondrial density was found to be higher in gray matter than in white matter, but this is a consequence of there being a smaller cytoplasmic volume and not more (or larger) mitochondria. The mitochondrial population did not change with age. Presumptive nonspecific permeability routes (endothelial vesicles, junctional gaps) did not change with age; therefore we found no morphological substrate for increased nonspecific bbb permeability in the aging human. The loss of pericytes, however, suggests that the bbb in the elderly may be less able to compensate for transient leaks.

This patient presented as a subacute progressive cervical myelopathy and the differential diagnosis included cervical spondylotic myelopathy and intramedullary mass. Microscopically, vascular lesions plus a patchy myelomalacia indicated a vasculitis. However, there was no suggestion of a generalized vasculitis at autopsy and the only supporting laboratory study was a raised erythrocyte sedimentation rate. It would seem that a vasculitis similar to polyarteritis nodosa or other collagen disease may be confined to the spinal cord.

A family with Gerstmann-Sträussler-Scheinker disease had coincidental clinical onset in three members of two generations, a phenomenon suggesting a common source of a transmissible agent. A regular dietary supplement in this family was home-bred rabbit. The clinical picture, although generally similar to that in previous accounts, included the unusual findings of visual loss (one patient) and sensory loss (one patient), and dementia was not apparent until late in the illness in two patients. Pathological examination of a cerebellar cortical biopsy specimen from one patient and postmortem tissue from two patients revealed multicentric amyloid plaques located in cerebral and cerebellar cortex, basal ganglia, and white matter with degeneration of corticospinal, dorsal spinocerebellar, dentatorubral, and geniculocalcarine tracts and dorsal columns. Spongiform change was focal and confined to the superficial cerebral cortical layers.

We examined 17 intracranial arteriovenous malformations that were resected after treatment by embolization using bucrylate (isobutyl-2-cyanoacrylate). In nine specimens removed 5 days to 16 months after embolization therapy, a series of pathologic changes was seen, including patchy mural angionecrosis (adjacent to bucrylate fragments) up to six weeks after embolization, the presence of bucrylate in vessel walls and fibromuscular intimal cushions, and the occurrence (after several months) of entirely extravascular bucrylate. Occasional parts of recanalized vascular malformations were identified. Bucrylate was present within arteriovenous malformations as late as 16 months after embolization, although the amount appeared to be diminished. These findings suggest a specific sequence of events in the interaction between bucrylate and mural components within the malformations and may explain some important complications of embolization therapy (e.g., delayed hemorrhage after embolization).

Cyanoacrylates, a group of rapidly polymerizing adhesives, have found widespread uses in oral and general surgery as well as surgical subspecialties, for example as hemostatic and anastomotic agents. They have been utilized most recently as materials for embolotherapy of complex cerebral and extra-cerebral vascular anomalies. The histopathology that results from their deposition in human tissues is thus an important consideration, and the subject of this review. Particular attention is given to the fate of cyanoacrylates in cerebral lesions after iatrogenic embolization procedures. The apparent toxicity of these plastics on blood vessel walls is discussed in relation to experimental observations. It is imperative that clinicians who use this group of substances evaluate their potential functions in the light of the pathologic findings.

Wernicke disease (WD) is a complication of alcoholism and malnutrition and usually presents acutely and is characterized by disturbances of consciousness, paralysis of the external ocular muscles, and ataxia. The disease results from deficiency of vitamin B 1, or thiamine, an essential coenzyme in intermediate carbohydrate metabolism. On the other hand, Jakob-Creutzfeldt disease (J-C) results from infection with an unconventional agent with a long incubation period and is characterized by a rapidly progressive dementia and histologically by a spongiform encephalopathy associated with neuronal destruction and pronounced astrogliosis. Combination of both diseases has not been reported in the literature previously and their relationship is uncertain. We present 3 cases with this interesting association and consider their relationship.

Despite the development of new alternative embolic agents, the endovascular treatment of brain arteriovenous malformations continues to frequently require the use of cyanoacrylic glue, especially in situations where particulate or sclerosing agents are ineffective, such as when flow is very rapid or fistulous. Because isobutyl 2-cyanoacrylate (IBCA), the most commonly used embolic glue, is no longer available or manufactured, a real need exists for an alternative fast polymerizing agent. In vivo and in vitro studies were performed to compare IBCA with n-butyl 2-cyanoacrylate (NBCA, supplied as Histoacryl Blue), a tissue adhesive approved for surgical use in some countries. Polymerization times in static plasma were compared, and the effect of the addition of iophendylate oil or glacial acetic acid on polymerization was assessed. Polymerization times in vivo were compared after intraarterial injection into the internal carotid artery in pigs using a standardized technique. The histopathologic reactions to each glue in the embolized pig rete were assessed and compared over a period of 0-60 days after embolization. Our results show that while NBCA polymerization is demonstrably faster than IBCA in vitro, intraarterial injections of each glue show no significant difference in polymerization times. Like IBCA, NBCA polymerization can be predictably prolonged by the addition of oil or glacial acetic acid, though the effect is less for NBCA. Histopathologic reactions were similar, with acute vasculitis observed, becoming chronic and granulomatous after about 1 month. Both glues showed frequent foci of extravascular extrusion through the embolized rete and recanalization of previously occluded embolized vessels. We conclude that NBCA has clinical and biologic behaviors similar to IBCA, and therefore should be an acceptable alternative to IBCA for intravascular use.