John C. E. Kaufmann

The histotoxicity of cyanoacrylates

SummaryCyanoacrylates, 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.

Long-Term Pathological Follow-up of Cerebral Arteriovenous Malformations Treated by Embolization with Bucrylate

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).

Role of Free Radical Scavenger in Protection of Spinal Cord during Ischemia

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.

Neuropathology of heart transplantation

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.

Fibrosarcoma complicating irradiated pituitary adenoma

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.

Encephalopathy in liver transplantation: neuropathology and CMV infection.

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.

Severe cerebellar degeneration in a patient with T-cell lymphoma.

SummaryA 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.

Gerstmann-Sträussler-Scheinker disease with coincidental familial onset

A family with Gerstmann-Straussler-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.

Prolonged progressive multifocal leukoencephalopathy without immunosuppression

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.

Pathological and molecular biological features of a myelopathy associated with HTLV-1 infection

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.