Malignant transformation of a spinal cord ganglioglioma--case report and review of the literature.

Gangliogliomas are tumors of mixed glial and neuronal phenotype that usually have a benign clinical course. Rare cases display anaplastic features at the time of first presentation or progress to anaplastic gliomas over extended times. We report on a ganglioglioma of the spinal cord that recurred as a malignant glioma one and a half years after resection. The initial neoplasm was composed of a mixture of well-differentiated ganglionic and astrocytic cells. The recurrent tumor was an anaplastic small-cell glioma. The sole unusual aspect in the initial neoplasm was an abundance of small vessels with calcified walls, which mimicked a vascular malformation.

"Tumor-mimicking" multiple sclerosis.

The spectrum of clinical manifestations of multiple sclerosis (MS) may include rare cases where cerebral lesions simulate brain tumors or abscesses on neuroimaging. We report here on a 43-year-old woman with numerous ring-enhancing cystic lesions in the white matter of cerebral hemispheres, brainstem and cerebellum. The radiological picture was overwhelmingly in favor of a metastatic or infectious etiology, but brain biopsy showed subacute demyelination with central necrosis.

A meningioma-mimicking tumor caused by Mycobacterium avium complex in an immunocompromised patient.

Intracranial tuberculomas manifesting radiologically as typical dural-based "meningiomas" have been reported, most frequently in immunosuppressed patients. Their incidence is high in developing countries; they are only sporadically observed in Western Europe and North America, usually in patients with acquired immunodeficiency syndrome (AIDS). According to published reports, intracranial tuberculomas are always due to infection by Mycobacterium tuberculosis. We report a case of a 50-year-old woman with systemic lupus erythematosus (SLE) who presented with a dural based, meningioma-like mass in the right frontal region, resulting from a localized infection by Mycobacterium avium complex. Histologically, the mass resembled a meningioma in being composed of spindly cells arranged in a fascicular pattern. Immunohistochemical stains showed this tumor to consist of a large aggregate of AFB-laden histiocytes without caseating necrosis or multinucleated giant cells.

Progression of clinical deterioration and pathological changes in patients with Alzheimer disease evaluated at biopsy and autopsy.

OBJECTIVES: To quantify the progression of senile plaques, neurofibrillary tangles, cerebral amyloid angiopathy, and microglial activation in the cortex and white matter of patients with Alzheimer disease evaluated at both biopsy and subsequent autopsy and correlate these changes with the progression of neurologic impairment. SETTING: Academic referral center for patient with Alzheimer disease. PATIENTS: Four patients meeting the clinical criteria for Alzheimer disease, enrolled in a pilot study for the evaluation of response to intracerebroventricular administration of bethanechol chloride. The patients were followed up until death occurred and autopsy was performed. RESULTS: All 4 patients had progressive deterioration from the time of biopsy to autopsy (9-11 years). Pathological investigations showed a striking increase in the density of senile plaques and neurofibrillary tangles in 2 of 4 patients from biopsy to autopsy, and a significant increase in microglial activation in 1 of 4 cases. Severity of cerebral amyloid angiopathy varied significantly among patients, 1 of whom displayed striking amyloid deposition with associated subcortical white matter atrophy. CONCLUSIONS: These unique data demonstrate that the progressive neurologic impairment in Alzheimer disease is accompanied by a significant increase in senile plaque and neurofibrillary tangle counts in the frontal cortex and, possibly in some patients, by increased microglial cell activation. Cerebral amyloid angiopathy was associated with significant white matter disease.

Chronic renal failure causing brown tumors and myelopathy. Case report and review of pathophysiology and treatment.

Brown tumors (osteoclastomas) are histologically benign lesions that are caused by primary or secondary hyperparathyroidism. Secondary hyperparathyroidism is a frequent complication of chronic renal failure. Skeletal brown tumors are relatively uncommon, and brown tumors that involve the spine are considered very rare. The authors present the case of a 37-year-old woman with systemic lupus erythematosus and hemodialysis-dependent anuric renal failure, in whom spinal cord compression developed due to a brown tumor and pathological fracture at T-9. The patient underwent transthoracic decompressive surgery and spinal reconstruction in which cadaveric femoral allograft and instrumentation were used. Brown tumors of the vertebral column require surgical treatment if medical therapy and parathyroidectomy fail to halt their progression or if acute neurological deterioration occurs. In patients with renal failure bone healing is delayed and there is an increased risk that healing will fail because the metabolic derangements can result in severe osteoporosis. Surgical reconstruction of the spine may require the use of augmentation with instrumentation and aggressive treatment of hyperparathyroidism to achieve successful outcomes.

Aspiration cytology of a case of tumoral calcinosis.

The fine-needle aspiration (FNA) cytologic findings in a case of non-familial tumoral calcinosis are described. These include abundant calcific amorphous deposits, mononuclear histiocytes, osteoclast-type multinucleated giant cells, and fragments of tissue consisting of osteoblast-type cells with atypical epithelial-like features mimicking an epithelial malignancy. This is the first reported case describing the cellular morphology of tumoral calcinosis in an FNA specimen. A previously reported case described the evacuation of acellular calcific fluid only. In the present case, vigorous aspiration of the solid portions of the lesion yielded cellular material representative of the histology of the lesion. Points of caution for a correct interpretation of the cytologic findings are discussed.

Differential visualization of cholinesterasic neuronal somata and fibers by use of modifications of acetylcholinesterase pharmacohistochemistry.

We modified existing acetylcholinesterase (AChE) histochemical techniques to visualize cholinergic neuronal somata and processes in the same rat brain. The AChE staining procedure of Karnovsky and Roots, combined with diisopropylfluorophosphate (DFP) pre-treatment, have previously allowed visualization of neuronal somata. Fibers have been visualized by nickel-diaminobenzidine (DAB)-hydrogen peroxide histochemical intensification. We combined novel modifications of these techniques to visualize cell bodies and fibers simultaneously. Maximal staining of neuronal somata occurs with a 1:1 dilution of both the Karnovsky-Roots medium and the nickel-DAB solution; diluting the Karnovsky-Roots medium 1:10 and increasing the concentration of the nickel-DAB solution twofold allows visualization of fibers previously unstainable with DFP pre-treatment and the classical AChE protocol. It is now possible to visualize both neuronal somata and fibers in adjacent sections of the same brain, in a quick and inexpensive manner.

Cytoskeletal alterations might account for the phylogenetic vulnerability of the human brain to Alzheimer's disease.

A theory is presented here in the attempt to explain why Alzheimer's disease (AD) primarily affects areas of the human brain that have been acquired recently in phylogenesis. Disturbances in cytoskeletal function are proposed to play a fundamental role in triggering the sequence of pathologic events leading to the occurrence of AD-related histopathological markers and to the degeneration and death of neurons. These deficits are supposed to occur more likely in neuronal populations that possess a high degree of plasticity, the substrate of memory functions, and that constitute, in fact, the phylogenetically new telencephalic regions of the human brain.

Cholinergic fiber perturbations and neuritic outgrowth produced by intrafimbrial infusion of the neurofilament-disrupting agent 2,5-hexanedione.

The compound 2,5-hexanedione (HD) produces axonopathies in peripheral nerves characterized by selective accumulation of neurofilaments. Its direct actions on neurotransmitter-specific neurons in the brain are unknown. In an attempt to address this latter issue, we infused HD into the fimbria and evaluated histochemically and immunohistochemically possible structural alterations in cholinergic neurons projecting from the basal nuclear complex to the hippocampus. Putative cholinergic fibers expressing nerve growth factor receptor and acetylcholinesterase showed increases in caliber and perturbations in trajectories 2-4 days following HD treatment. Similar morphologic changes were observed in neuronal elements processed for the 68 kDa neurofilament protein. At 7 days, short collateral ramifications appeared in many cholinergic axons that were suggestive of neurite outgrowth. Correlated with these fiber alterations was a transient reduction in the number of medial septal and diagonal band somata expressing choline acetyltransferase, which returned to control levels within 6 weeks following HD treatment. These data support the view that neurofilaments play an important, perhaps cytoarchitecturally stabilizing, role in regulating axonal morphology in certain populations of cholinergic neurons.

Intrafimbrial colchicine produces transient impairment of radial-arm maze performance correlated with morphologic abnormalities of septohippocampal neurons expressing cholinergic markers and nerve growth factor receptor.

The microtubule disrupting agent, colchicine, was infused both bilaterally and unilaterally into the fimbria of the rat brain. Such infusions produced a transient impairment in radial-arm maze performance during the first week following surgery but only in bilaterally injected animals. This behavioral finding was correlated with a reduction in the number of neurons expressing choline acetyltransferase and nerve growth factor receptor in the septum and vertical limb of the diagonal band but not in other regions of the basal nuclear complex. The altered expression of the two neurochemical markers was not due to cellular degeneration because numbers of neurons demonstrated by Nissl staining were unchanged. Putative cholinergic fibers in the fimbria demonstrating acetylcholinesterase and nerve growth factor receptor also showed aberrations in caliber, shape, and course.

Effects of nerve growth factor and GM1 ganglioside on the number and size of cholinergic neurons in rats with unilateral lesion of the nucleus basalis.

Four groups of rats with a unilateral ibotenic acid lesion of the nucleus basalis were treated with saline, nerve growth factor (NGF) 10 micrograms administered intracerebroventricularly twice per week, sialoganglioside GM1 30 m/kg daily i.p. and NGF twice per week plus GM1 10 mg/kg i.p. daily, respectively, beginning immediately after lesioning. Twenty-one days later the rats treated with saline showed a marked impairment in negotiating a 'step through' passive avoidance conditioned response, a 32% decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the lesioned nucleus basalis and a 12% decrease in their areas. The rats treated with NGF and NGF plus GM1 showed no difference from sham-operated rats. In the GM1-treated rats a 12% decrease only in the number of ChAT-positive neurons was detected while performance and neuronal areas were normal. These findings indicate that NGF and GM1 prevent the cholinergic deficit by protecting the cholinergic neurons of the nucleus basalis from ibotenic acid neurotoxicity.

GM1 ganglioside counteracts cholinergic and behavioral deficits induced in the rat by intracerebral injection of vincristine.

The intracerebroventricular injection of 0.5 mg of vincristine sulphate in adult male Wistar rats caused within 11 days the impairment of motor and reflexive behavior, evaluated by the elevated platform and hanging wire tests, a decrease in food consumption and loss of body weight, a 45% decrease in hippocampal choline acetyltransferase (ChAT) activity and a 35% decrease in the rate of high-affinity choline uptake (HACU) in the injected side. The latter effects are due to the death of neurons in the respective hemiseptum. Intrafimbrial injection of vincristine caused the same decrease in ChAT activity without behavioral alterations. Daily i.p. administration of GM1 ganglioside, beginning immediately after the vincristine injection, prevented dose dependently the decrease in ChAT activity and HACU rate. Prevention was complete with the 60 mg/kg dose. The same dose was equally active on ChAT activity when given s.c. but was inactive p.o. The ChAT decrease was also prevented when GM1 treatment began 5 days after vincristine. GM1 60 mg/kg i.p. also reduced the behavioral toxicity of vincristine. The possibility that GM1 might prevent vincristine toxicity by antagonizing its disruption of neurofilaments and axonal flow is discussed.

Interaction between nerve growth factor and GM1 monosialoganglioside in preventing cortical choline acetyltransferase and high affinity choline uptake decrease after lesion of the nucleus basalis.

Monosialoganglioside GM1 and nerve growth factor (NGF) were administered alone or concomitantly to adult male rats with a unilateral ibotenic acid lesion of the nucleus basalis magnocellularis (NBM). High-affinity choline uptake (HACU) rate and choline acetyltransferase (ChAT) activity were measured, 4 and 21 days after surgery, respectively, in the frontal and parietal cortices of both hemispheres. A 33-34% decrease in HACU rate and a 43-39% decrease in ChAT activity was found in the ipsilateral cortices 4 and 21 days, respectively, after the lesion. If the lesioned rats received NGF (10 micrograms i.c.v.) twice a week or daily administrations of GM1 (30 mg/kg, i.p.), beginning immediately after surgery the decrease in HACU rate and ChAT activity was smaller. If NGF and GM1 were given concomitantly no decrease in HACU rate and ChAT activity was detected in the lesioned hemisphere and a slight increase occurred in the contralateral hemisphere. However, after the concurrent administration of NGF (10 micrograms i.c.v.) and the inactive dose of GM1 10 mg/kg i.p. no decrease in HACU and ChAT activity was also found in the lesioned rats. The latter finding indicates a potentiation by GM1 of NGF effects on the cholinergic neurons of the NBM. The two drugs may either antagonize the neurotoxic effects of ibotenic acid or stimulate a compensatory activity in the remaining neurons.

Cholinergic and noradrenergic denervations decrease labelled purine release from electrically stimulated rat cortical slices.

The origin of cortical purine release was investigated by measuring [3H]purine release from electrically stimulated cortical slices of rats after neurotoxic lesions of cholinergic, noradrenergic and serotoninergic pathways innervating the cortex. Purines were labelled by incubating the cortical slices with [3H]adenine. The 3H efflux at rest and during stimulation, analysed by high performance liquid chromatography, consisted of adenosine, inosine, hypoxanthine and a small amount of nucleotides. Twenty days after unilateral or bilateral lesion of the nucleus basalis a marked decrease in choline acetyltransferase activity was associated with a decrease in [3H]purine release. A linear relationship was found between the decrease in choline acetyltransferase activity and [3H]purine release. A partial recovery in both choline acetyltransferase activity and [3H]purine release was observed eight months after the lesion. Twenty days after intra-cerebroventricular injection of 6-hydroxydopamine a 59% decrease in cortical noradrenaline content was associated with a 44% decrease in [3H]purine release. Conversely, no change in [3H]purine release was found in rats in which a 89% decrease in cortical serotonin content was induced by intra-cerebroventricular injection of 5,7-dihydroxytryptamine. The decrease in [3H]purine release after the lesion of the cholinergic and noradrenergic pathways may depend on metabolic changes, a loss of a stimulating influence of acetylcholine and noradrenaline or may indicate a release of [3H]purine from cholinergic and noradrenergic fibres.

Unilateral and bilateral nucleus basalis lesions: differences in neurochemical and behavioural recovery.

The neurochemical and behavioural recovery following unilateral and bilateral lesions of the nucleus basalis was investigated in adult male Wistar rats 20 days and 6 months after surgery. The lesions were made by stereotaxic injections of ibotenic acid. Twenty days after surgery there was a statistically significant choline acetyltransferase decrease in the frontal and parietal ipsilateral cortex of the unilaterally lesioned rats and in the cortex of both hemispheres after bilateral lesions. Cortical high affinity choline uptake rate was significantly decreased 4 days after lesions but showed a rapid recovery within 20 days post-lesion in unilaterally and bilaterally lesioned rats. However, at this time both groups of lesioned rats showed a marked impairment in the acquisition of passive and active (shuttle-box) avoidance conditioned responses. Six months after surgery the decrease in choline acetyltransferase activity was smaller and statistically significant in the ipsilateral frontal cortex only in the unilaterally lesioned rats and in the frontal and parietal cortex of both hemispheres in the bilaterally lesioned rats. High affinity choline uptake was increased in the contralateral hemispheres of the unilaterally lesioned rats and was significantly larger than in the bilaterally lesioned rats. There was no difference in the acquisition of both passive and active avoidance conditioned responses between the sham operated and unilaterally lesioned rats, while the bilaterally lesioned rats could only negotiate the active avoidance conditioned response. In conclusion, our experiments demonstrate a remarkable neurochemical and behavioural recovery within 6 months in rats with a unilateral lesion of the nucleus basalis and only a limited recovery in the bilateral lesioned rats.