Vacuolation Of White Matter Research Articles

Distemper in wild carnivores: An epidemiological, histological and immunocytochemical study

Brain tissue from 236 wild carnivores, 146 mustelids and 90 foxes, originating from the same geographical area in southwest Germany was collected over a 2 year period between May 1989 and May 1991 and studied for the presence of canine distemper virus (CDV) antigen by immunohistochemistry. CDV antigen was found in the brains of 54 (37%) mustelids, predominantly in the cerebellar grey matter. Interestingly, no CDV infection was observed in foxes. An increasing number of CDV infections among mustelids was noted between November 1989 and November 1990, peaking in summer 1990. Histological brain lesions, demonstrated only in 45% of the CDV positive mustelids, were characterized by non-purulent encephalitis predominantly in the cerebrum and focal vacuolation of the cerebellar white matter, whereas demyelination was only rarely observed. Histological and immunocytochemical CNS findings indicate an early stage of distemper infection in these mustelids and the high percentage of CDV positive animals together with the seasonal prevalence are suggestive of a CDV epizootic among mustelids.

Non‐Wilson's Type Neurological Disorder Associated with Abnormal Copper Metabolism. The First Autopsy Case Report

This report concerns an autopsy case of a peculiar neurodegenerative disorder associated with abnormal copper metabolism. The patient was a 46‐year‐old woman, who presented with dementia and ataxia, and who died after a progressive clinical course of approximately 19 months. The patient had marked hypocupremia and hypoceruloplasminemia. The neuropathological examination revealed: (1) neuronal loss with remarkable rarefaction of the neuropil of the mammillary body; (2) severe thalamic degeneration; (3) degeneration and softening of the olivary nucleus, accompanied by remarkable capillary proliferation; (4) coarse spongy state or vacuolization of the cerebral white matter, and (5) degeneration of Clarke's column. The cerebral cortex, basal ganglia, and cerebellar cortex were preserved; brain deposition of iron and copper was not detected. The liver showed congestion, parenchymal atrophy and iron deposition, but neither copper deposition nor cirrhotic changes. Although the clinical features of patients with neurological disorders associated with abnormal copper metabolism, but distinct from both Wilson's disease and Menkes' kinky hair disease have been described, no autopsy case report has been published to date. It is of particular interest that the subnuclear distribution pattern of the thalamic lesion and the isolated degeneration of Clarke's column and the posterior spinocerebellar tract of the spinal cord of the present patient closely resembled the lesions in Menkes' kinky hair disease.

Bilateral Optic Nerve Cryptococcosis in Sudden Blindness in Patients with Acquired Immune Deficiency Syndrome

Purpose: A neuroanatomic study was undertaken to search for the cause of sudden, simultaneously bilateral blindness in a patient with acquired immune deficiency syndrome who had cryptococcal meningitis. Methods: Careful gross examination was performed, and microscopic sections were cut at 50- to 100-µm intervals of the entire visual pathway. Results: Focal cryptococcosis destroyed segments of the right intracanalicular optic nerve and the left intraorbital optic nerve adjacent to the optic canal. The meninges were heavily infiltrated by Cryptococcus organisms around the optic tracts, optic nerves, and optic chiasm; however, only a few scattered cryptococcal organisms were found in the periphery of the chiasm contiguous with heavy meningeal infection. Blood vessels supplying the chiasm appeared normal. Generalized cerebral edema and focal vacuolization of periventricular white matter were evident. Conclusion: The authors believe that sudden, simultaneously bilateral visual loss in this patient was caused by focal but fulminant necrosis of both optic nerves. However, the presence of cryptococcal organisms throughout the basal meninges and in the sheaths of both optic nerves suggests that cryptococcosis may produce visual loss by damaging multiple areas of the anterior visual pathway.

GUINEA-PIG SPINAL-CORD AS A MODEL FOR THE STUDY OF LATE RADIATION-INJURY AND REPAIR

The risk of normal tissue damage imposes severe limitations on the radiotherapy of malignant tumours. The aim of this study was to examine the morphology of late radiation injury with special reference to microvasculature in the irradiated guinea pig spinal cord. Gamma radiation from a cobalt-60 source was used to irradiate the lumbar region of guinea pigs. A total dose of up to 94.5 Gy was given using 4.5 Gy fractions. Twenty such guinea pigs which survived more than 2 years post-irradiation were deeply anaesthetized and Mercox resin was perfused through the thoracic aorta. Ten minutes following perfusion, irradiated segments of the spinal cords were removed and either fixed in formalin for histology and morphometry or corroded in KOH for microvascular cast preparation. The latter were observed under the scanning electron microscope. All irradiated specimens showed multifocal white matter vacuolation. None of these spaces communicated with blood vessels. No such vacuolation was observed in grey matter. Glial cell counts in the irradiated white matter were reduced. Microvascular morphometry revealed 3.30% of the area was occupied by vasculature in the non-irradiated white matter. The corresponding value for irradiated white matter was 2.38% (p=0.003). No difference in the vascular area was noted in the non-irradiated grey matter (9.75%) and irradiated grey matter (10.36%; p=0.36) Microvascular casts did not reveal telangiectasia. However, irradiated specimens showed focal avascular regions. This was consistent with the light microscopic observation of focal degeneration and necrosis of irradiated white matter. These results suggest that late radiation injury in guinea pigs results primarily from damage to glial elements and the microvasculature is secondarily affected.

Bilateral Optic Nerve Cryptococcosis in Sudden Blindness in Patients with Acquired Immune Deficiency Syndrome

A neuroanatomic study was undertaken to search for the cause of sudden, simultaneously bilateral blindness in a patient with acquired immune deficiency syndrome who had cryptococcal meningitis. Careful gross examination was performed, and microscopic sections were cut at 50- to 100-microns intervals of the entire visual pathway. Focal cryptococcosis destroyed segments of the right intracanalicular optic nerve and the left intraorbital optic nerve adjacent to the optic canal. The meninges were heavily infiltrated by Cryptococcus organisms around the optic tracts, optic nerves, and optic chiasm; however, only a few scattered cryptococcal organisms were found in the periphery of the chiasm contiguous with heavy meningeal infection. Blood vessels supplying the chiasm appeared normal. Generalized cerebral edema and focal vacuolization of periventricular white matter were evident. The authors believe that sudden, simultaneously bilateral visual loss in this patient was caused by focal but fulminant necrosis of both optic nerves. However, the presence of cryptococcal organisms throughout the basal meninges and in the sheaths of both optic nerves suggests that cryptococcosis may produce visual loss by damaging multiple areas of the anterior visual pathway.

Diversity in the neuropathology of scrapie-like diseases in animals

The main diagnostic histology in the spongiform encephalopathies consists of a degenerative and usually symmetrical vacuolation of neurons and a spongiform lesion in the neuropil. Sometimes there can be asymmetry. This pathology is usually confined to grey matter, but an additional white matter vacuolation is sometimes typical. The degeneration can progress to neuronal necrosis, with reactive glial changes. Photoreceptor loss in the retina occurs in some experimental models. Cerebral amyloidosis is conspicuous in many types of scrapie-like pathology in animals, but is sometimes not recognised or may be absent. Abnormal immunolabelling with anti-PrP is always associated with both the degenerative and amyloid lesion and precedes the occurrence of the degeneration in experimental scrapie models. All aspects of the pathology are closely controlled by host genetic factors and by the strain of the infecting, causal agent.

Neuropathological findings in cattle with clinically suspect but histologically unconfirmed bovine spongiform encephalopathy (BSE)

Neuropathological observations were made in 200 clinically suspected cases of bovine spongiform encephalopathy (BSE) in which pathognomonic vacuolar changes were absent. Routine histological and immunocytochemical techniques were applied to formalin-fixed, paraffin-embedded sections of the central nervous system. Significant neuropathological findings were detected in 85 (42.5 per cent) cases. The most frequent lesion, detected in 46 (23 per cent) cases, was a focal white matter vacuolation principally affecting the substantia nigra, but its clinical significance was unclear. Listeriosis was diagnosed in 17 (8.5 per cent) cases. In three of seven cases of non-suppurative encephalitis, lesions suggested sporadic bovine encephalomyelitis, a disease not previously reported in the UK. Suppurative thromboembolic or granulomatous lesions accounted for other inflammatory changes. Neuroectodermal tumours were present in five cases (2.5 per cent); three were identical in form and considered to be atypical ependymoma. Cerebrocortical necrosis, oedema or both were detected in four cases. The remaining cases (4.5 per cent), comprised those in which the changes were minor and of doubtful significance. Incidental pathological findings included occasional degenerating or vacuolated neurones, which occurred in the red nucleus in 105 brains, in the habenular nucleus in 71 brains, and singly at other sites in 17 brains. In sections of 37 brains immunostained with antiserum to prion protein (PrP), no evidence of PrP accumulation was found, providing some evidence that the series did not contain bovine prion disease cases which, based on the histological diagnosis, had given a false negative result. It is suggested that, of 115 cases (57.5 per cent) which lacked significant histological lesions, some were suffering from metabolic disorders. The study identified diseases and lesions which feature in the differential diagnosis of BSE. Their more accurate diagnosis may become particularly important if, as predicted, the BSE epidemic declines.

Vigabatrin (gamma-vinyl-GABA): neuropathologic evaluation in five patients.

We performed neuropathologic examination of cerebral cortex specimens from 4 patients who underwent epilepsy surgery and the brain of 1 patient who died suddenly. All had severe epilepsy and had received gamma-vinyl-GABA (GVG, vigabatrin) for 3-5.5 years. Neither the surgically resected temporal lobe specimens nor the frontal and temporal lobes autopsy specimens showed abnormal white matter vacuolation.

Neuropathology of the Acquired Immune Deficiency Syndrome (AIDS): Report of 39 Autopsies from Vancouver, British Columbia

Neuropathological findings from 39 acquired immune deficiency syndrome (AIDS) autopsies of primarily neurologically symptomatic patients and 7 brain biopsies from AIDS patients performed at St. Paul's Hospital, Vancouver, British Columbia are reported. Autopsy findings included human immunodeficiency virus-1 (HIV)-type multinucleated giant cell (MNGC)-associated encephalitis seen in 17 patients, toxoplasmosis in 7 patients, and cytomegalovirus encephalitis and/or microglial nodule-associated nuclear inclusions in brain parenchyma in 9 patients. Central nervous system lymphoma was identified in 11 autopsy patients and in 4 of 7 brain biopsies. Infectious processes including HIV encephalitis were seen in 10 of 11 autopsied patients with lymphoproliferative lesions in the brain parenchyma, while 40% of patients without lymphoma had HIV-type MNGC or opportunistic infections. CNS lymphoma was not significantly increased in incidence in patients with a clinical history of zidovudine treatment, but increased duration of survival after the diagnosis of AIDS was associated with increased incidence of lymphoma in both untreated and zidovudine-treated patients. Patients displaying HIV MNGC within microglial nodules had a shorter mean duration of survival after diagnosis of AIDS than those patients with HIV encephalitis with dispersed MNGC, white matter vacuolation, and gliosis.

Brain lesions of naturally occurring pregnancy toxemia of sheep.

The neuropathology and biochemical features of 17 sheep with clinical signs and gross necropsy features of naturally occurring pregnancy toxemia were retrospectively evaluated. The sheep ranged in age from 3 to 6 years and were of seven different breeds and three breed crosses. Thirteen sheep (case Nos. 1-4, 6-9, 11-14, 16) showed astrocytic nuclear swelling, hypertrophy and proliferation, and cerebrocortical neuronal necrosis. Seven of these sheep had Purkinje cell necrosis (case Nos. 2, 3, 6, 11, 12, 14, 16), and seven had vacuolation of cerebral and cerebellar sub-cortical white matter (case Nos. 1-4, 9, 12, 13). The neuropathologic features were similar to those of naturally occurring hypoglycemia of human beings and experimentally induced hypoglycemia of primates and the rat. The lesions seen in the sheep studied may have been caused by cerebral hypoglycemia, but data for blood or cerebral glucose concentrations were not available.

Cerebral vasculopathy in divers.

Brains from 12 amateur and 13 professional divers, all but one of whom died accidentally, were examined neuropathologically. Grossly distended, empty vessels (presumably caused by gas bubbles) were found in the brains of 15 out of 22 divers who died from diving accidents. Perivascular lacuna formation was found in cerebral and/or cerebellar white matter in three amateurs and in five professionals. In addition to lacuna formation, hyalinization of vessel walls was present in the brains of three amateurs and five professionals. Necrotic foci in grey matter occurred in seven cases and perivascular vacuolation of white matter occurred in seven cases. The vascular changes probably arose from intravascular gas bubble formation. In one professional diver, there was also unilateral necrosis of the head of the caudate nucleus.

Neurotoxic effects of the anti-varicella zoster virus agent 2′-valeryl-6-methoxypurine arabinoside in monkeys and rats dosed orally for 90 days

The 2′-valerate ester of 6-methoxypurine arabinoside (170U88), a nucleoside analog with anti-varicella zoster virus (VZV) activity, was given to monkeys and rats. In subchronic preclinical toxicity studies, dosing was by gavage to monkeys (distilled water vehicle) and rats (0.5% methylcellulose vehicle) for 90 days. Groups of 5 male and 5 female monkeys ( Macaca fascicularis) were given 170U88 at 0, 25, 50, or 100 mg/kg/day. The daily dose was given in two equal portions with 6 hr between doses. Monkeys in the high-dose group lost weight. Food consumption was decreased for mid- and high-dose monkeys and for low-dose female monkeys. Slightly decreased values for erythrocyte and leukocyte counts at the mid- and high dose were fully reversed during an 8-week recovery period. Two high-dose male monkeys and a middose female monkey developed signs of central nervous system toxicity and were necropsied before dosing was complete. These signs were first observed in the fifth week of dosing and included body tremors, incoordination, reduced activity, sleepiness, stupor, and lack of eye tracking. Axonal lesions were observed in histologic sections of sciatic nerve in monkeys at all dose levels. Neither the signs of central nervous system toxicity nor the axonal lesions reversed during the 8-week recovery period. Groups of 14 male and 14 female CD rats (Sprague-Dawley derived) were given single daily doses of 170U88 at 0, 150, 300, or 600 mg/kg. Body weights were decreased at all dose levels and food consumption was decreased for mid- and high-dose rats. Small increases in values for erythrocyte count, hemoglobin, and packed cell volume and small decreases in values for glucose, serum protein, and serum albumin were limited to high-dose rats and reversed during a 4-week recovery period. High-dose rats also had reversible liver lesions consisting of necrosis of individual hepatocytes, megalocytosis, occasional mitotic figures, and biliary stasis. Clinical and morphologic indications of central nervous system toxicity in the rats consisted of altered exploratory behavior at the high dose and groups of small vacuoles in cerebellar white matter at all dose levels. Cerebellar vacuolation was observed in rats examined at the end of the exposure period and also in rats examined after the 4-week postdose recovery period. Signs interpreted as peripheral nervous system toxicity were limited to rats in the high-dose group and consisted of hindquarter weakness, slow righting and placing reflexes, and ataxia. Again, these findings did not reverse during the recovery period. Thus, signs of both central and peripheral nervous system toxicity were observed in both monkeys and rats. These neurotoxic effects resulted in the decision to stop further development of 170U88.

Distal motor axonopathy and central nervous system myelin vacuolation caused by cycloleucine, an inhibitor of methionine adenosyltransferase.

Cycloleucine (CL), an inhibitor of methionine adenosyltransferase, has previously been used to produce an experimental model of subacute combined degeneration of the spinal cord. A re-investigation of its effects on the morphology of the nervous system and on brain concentrations of methionine and S-adenosylmethionine (SAM) was undertaken. Cycloleucine was administered as a single dose intraperitoneally (2 mg/g body weight) to young mice aged 21 d and adults aged 6 or 10 wks. The 21-day-old mice showed clinical evidence of toxicity within 24 h and thereafter developed progressive muscle weakness and ataxia. Animals did not survive longer than 1 wk. Light and electron microscopic examination of the central and peripheral nervous systems showed that intramyelinic vacuolation developed in the white matter of brain and cord within 12 h. The intramyelinic vacuolation in the white matter of brain and cord became more severe with longer survival, vacuoles coalescing and secondary axonal degeneration becoming evident. There was no myelin vacuolation in peripheral nerves. Axonal lesions occurred in the distal parts of motor nerves within 12-24 h resulting in degeneration of intramuscular nerve fibres and terminals. Later there was evidence of axonal degeneration in tibial and sciatic nerves. Many dorsal root ganglion cells became vacuolated or necrotic and numerous degenerated fibres were noted in the white matter of the spinal cord, particularly in the gracile funiculus. The optic nerves were not affected at any stage. In adult mice the pathology consisted of distal motor axonal degeneration which developed at 1-2 d. Little or no intramyelinic vacuolation in white matter was noted. Brain concentrations of SAM were reduced and levels of methionine became greatly elevated. The morphological effects of CL are considered to be the result of SAM deficiency impairing transmethylation processes known to be important in the formation and stabilization of myelin through the methylation of myelin basic protein. The immature developing central nervous system is much more vulnerable than the fully myelinated adult brain and spinal cord. The distal, predominantly motor axonopathy is a new observation and may be a reflection of the importance of transmethylation processes in the maintenance of axonal terminal membranes and the mechanisms of release of acetylcholine at the neuromuscular junction.

Neurotoxic Effects of the Anti-Varicella Zoster Virus Agent 2′-Valeryl-6-methoxypurine Arabinoside in Monkeys and Rats Dosed Orally for 90 Days

The 2′-valerate ester of 6-methoxypurine arabinoside (170U88), a nucleoside analog with anti-varicella zoster virus (VZV) activity, was given to monkeys and rats. In subchronic preclinical toxicity studies, dosing was by gavage to monkeys (distilled water vehicle) and rats (0.5% methylcellulose vehicle) for 90 days. Groups of 5 male and 5 female monkeys (Macaca fascicularis) were given 170U88 at 0, 25, 50, or 100 mg/kg/day. The daily dose was given in two equal portions with 6 hr between doses. Monkeys in the high-dose group lost weight. Food consumption was decreased for mid- and high-dose monkeys and for low-dose female monkeys. Slightly decreased values for erythrocyte and leukocyte counts at the mid- and high dose were fully reversed during an 8-week recovery period. Two high-dose male monkeys and a middose female monkey developed signs of central nervous system toxicity and were necropsied before dosing was complete. These signs were first observed in the fifth week of dosing and included body tremors, incoordination, reduced activity, sleepiness, stupor, and lack of eye tracking. Axonal lesions were observed in histologic sections of sciatic nerve in monkeys at all dose levels. Neither the signs of central nervous system toxicity nor the axonal lesions reversed during the 8- week recovery period. Groups of 14 male and 14 female CD rats (Sprague-Dawley derived) were given single daily doses of 170U88 at 0, 150, 300, or 600 mg/kg. Body weights were decreased at all dose levels and food consumption was decreased for mid- and high-dose rats. Small increases in values for erythrocyte count, hemoglobin, and packed cell volume and small decreases in values for glucose, serum protein, and serum albumin were limited to high-dose rats and reversed during a 4- week recovery period. High-dose rats also had reversible liver lesions consisting of necrosis of individual hepatocytes, megalocytosis, occasional mitotic figures, and biliary stasis. Clinical and morphologic indications of central nervous system toxicity in the rats consisted of altered exploratory behavior at the high dose and groups of small vacuoles in cerebellar white matter at all dose levels. Cerebellar vacuolation was observed in rats examined at the end of the exposure period and also in rats examined after the 4-week postdose recovery period. Signs interpreted as peripheral nervous system toxicity were limited to rats in the high-dose group and consisted of hindquarter weakness, slow righting and placing reflexes, and ataxia. Again, these findings did not reverse during the recovery period. Thus, signs of both central and peripheral nervous system toxicity were observed in both monkeys and rats. These neurotoxic effects resulted in the decision to stop further development of 170U88.

Pathology of radiation injury to the canine spinal cord

The histopathologic response of the canine spinal cord to fractionated doses of radiation was investigated. Forty-two dogs received 0, 44, 52, 60, or 68 Gy in 4 Gy fractions to the thoracic spinal cord. Dogs were evaluated for neurologic signs and were observed for 1 or 2 years after irradiation. Six major lesion types were observed; five in the irradiated spinal cord and one in irradiated dorsal root ganglia. The three most severe spinal cord lesions were white matter necrosis, massive hemorrhage, and segmental parenchymal atrophy which had an ED 50 of 56.9 Gy (51.3–63.3 Gy 95% CI) in 4 Gy fractions. These lesions were consistently associated with abnormal neurologic signs. Radiation damage to the vasculature was the most likely cause of these three lesions. The two less severe spinal cord lesions were focal fiber loss, which had an ED 50 of 49.5 Gy (44.8–53.6 Gy 95% CI) in 4 Gy fractions and scattered white matter vacuolation that occurred at all doses. These less severe lesions were not consistently associated with neurologic signs and indicated the presence of residual damage that may occur after lower doses of radiation. Radiation damage to glial cells, axons, and/or vasculature were possible causes of these lesions. In the irradiated dorsal root ganglia, affected sensory neurons contained large intracytoplasmic vacuoles, and there was loss of neurons and satellite cells. Such alterations could affect sensory function. The dog is a good model for spinal cord irradiation studies as tolerance doses for lesions causing clinical signs are close to the estimated tolerance doses for humans, and studies involving volume and long-term observation can be done.

Idiopathic myelopathies with white matter vacuolation in non-acquired immunodeficiency syndrome patients

Postmortem examination of 21 patients showed a vacuolar myelopathy resembling that associated with the acquired immunodeficiency syndrome. Underlying diseases included six cases of leukemia or lymphoma, five of carcinoma, three of systemic lupus erythematosus, two of chronic lung disease, and one each of cadaveric renal transplant, cirrhosis, diabetes, hemophagocytic syndrome, and viral encephalitis. Fourteen patients were on long-term steroid therapy and 10 of these also had immunosuppressive chemotherapy. No patient had the acquired immunodeficiency syndrome, although one received blood transfusions in 1978. Signs and symptoms consistent with myelopathy included paraparesis in seven patients, ataxia in one, and bilateral extensor plantar reflexes in one. Microscopic examination showed vacuolation in spinal cord white matter primarily located in posterior and lateral columns. Lipid-laden macrophages and axonal changes were proportional to the severity of the vacuolation, which was severe in five patients, moderate in 10, and mild in six. Eight patients had coexistent viral diseases elsewhere in the central nervous system, but viral-associated antigens or genomic material was not found in regions of vacuolated spinal cord white matter. Although the etiology of these myelopathies is unknown, their association with immune suppression and coexistent viral infection of the central nervous system suggests that an opportunistic viral infection may be important.

Cortical Dysgenesis in a Variant of Phenylketonuria (Dihydropteridine Reductase Deficiency)

The neuropathology of a 2 1/2-year-old patient with dihydropteridine reductase deficiency showed diffuse demyelination throughout white matter and spongy vacuolation in the long tracts of the brain stem. These changes are characteristic neuropathologic observations in untreated phenylketonuria. In addition, extensive neuronal loss, calcification and abnormal vascular proliferation were noted in the cerebral cortex, white matter, basal ganglia, and thalamus. Golgi studies demonstrated an abnormal orientation of neurons together with abnormalities of dendrites and dendritic spines. The pathogenesis of the vascular abnormalities in this condition is unknown, although folate deficiency may be involved. The secondary deficiency of serotonin and dopamine occurring during neuronal growth and differentiation may also affect the terminal stages of neuronal maturation.

A rodent model of infusion brain edema: Methodology and pathophysiological effects of saline and protein infusions

To evaluate the potency of putative secondary mediators of brain edema and their possible contribution to edema related brain dysfunction an infusion model of brain edema was developed in rats. 100 ul of fluid (saline, 20% nonautologous protein) was infused over one hour into the left forebrain white matter through a stereotaxically placed (+1.2 mm ant to bregma, 3 mm lateral and 2.9 mm depth) 25 G needle. Brain tissue hydraulic resistance (Rt), regional cerebral blood flow (rCBF), cortical somatosensory evoked potentials (SEPs) and intracranial pressure (ICP) (intraventricular needle) were monitored during the infusion and rCBF CO2 reactivity (hydrogen clearance), local brain water content (microgravimetry), BBB integrity (Evans Blue 2%) and brain histology (H & E. Solochrome-cyanin) were evaluated after the infusion. Saline infusates caused no physiological dysfunction despite ipsilateral expansion and vacuolation of the subcortical white matter, separation of axonal bundles and a significant decrease (p = 3.8 x 10(-5] in local subcortical tissue specific gravity. Cortical histology and specific gravity adjacent to the infusion locus were normal. Rt significantly decreased (p = 6.5 x 10(-4] during the infusion but there were only minor increases in ICP. Findings with 20% protein infusates were similar despite a focal 65% decrement in the rCBF CO2 reactivity adjacent to the infusion site. This study has shown that a simple and inexpensive model of infusion brain edema can be created in the rat and that it provides a useful model for assessing the physiological effects of mediator compounds in the infusate. Potential applications and methodological improvements for this model are discussed.

Marek's disease virus-induced transient paralysis in chickens: Demonstration of vasogenic brain oedema by an immunohistochemical method

The presence of vasogenic brain oedema and its distribution in Marek's disease virus (MDV)-induced transient paralysis (TP) were determined in genetically resistant and susceptible inbred White Leghorn chickens. MDV-inoculated TP-susceptible chickens with nervous signs (9 days post-inoculation) had severe vacuolation of cerebellar white matter and associated diffuse leakage of albumin and IgG. The serum protein leakage was associated morphologically with a vasculitis and intramural pseudocyst formation in the walls of blood vessels cuffed by mononuclear cells. This transient vasculitis and resulting vasogenic oedema coincided with the temporary neurological signs seen in TP-susceptible chickens. The vasculitis and vasogenic oedema were not present in brain tissue from recovered MDV-inoculated TP-susceptible chickens, MDV-inoculated TP-resistant chickens, or uninoculated control chickens from either line.

Pathogen studies of bovine progressive degenerative myeloencephalopathy (weaver) of Brown Swiss cattle

Results are given from further studies on the clinical signs and pathology of cattle affected with this disease. Clinical signs of bovine degenerative myeloencephalopathy ("weaver") in Brown Swiss cattle, appear when calves are 6 to 8 months old and progress during the next 12 to 18 months to recumbency. Four basic criteria for diagnosis are: 1. onset of bilateral hind leg weakness and ataxia between 5 and 8 months of age; 2. deficient proprioceptive reflexes, normal motor and sensory reflexes, and no other clinically detectable neurological abnormality; 3. absence of clinically significant skeletal or muscular abnormaltiy; and 4. adherence to familial relationship. There are no gross lesions typical for weavers, and primary microscopic lesions are confined to the central nervous system. Spinal cord lesions consisted of axonal degeneration including spheroid formation, loss of axons and myelin, and vacuolation of white matter due to large, empty intercellular spaces. Lesions were quantitatively similar at all spinal cord levels in the same funiculi. Cerebellar lesions were limited to selective degeneration and loss of Purkinje cells and occasional swelling of Purkinje cell axons in the granular layer of the cerebellar cortex. Progressive degenerative myeloencephalopathy is the single most important genetic disease of purebred Brown Swiss cattle and may be an inherited congenital metabolic defect of axon transport.