Martinez Aj

In vivo biological effects of stereotactic radiosurgery: a primate model.

Single-fraction, closed skull, small-volume irradiation (radiosurgery) of intact intracranial structures requires accurate knowledge of radiation tolerance. We have developed a baboon model to assess the in vivo destructive radiobiological effects of stereotactic radiosurgery. Three baboons received a single-fraction, 150-Gy lesion of the caudate nucleus, the thalamus, or the pons using the 8-mm diameter collimator of the gamma unit. Serial standard neurodiagnostic tests (neurological examination, computed tomographic scan, magnetic resonance imaging, stable xenon-enhanced computed tomographic scan of cerebral blood flow, somatosensory and brain stem evoked potentials, and myelin basic protein levels of cerebrospinal fluid) were compared with preoperative studies. Magnetic resonance imaging revealed the development of a lesion at the target site between 45 and 60 days after irradiation. Deterioration of the brain stem evoked potentials preceded imaging changes when the lesion encroached on auditory pathways. Myelin basic protein levels increased subsequent to imaging changes. Postmortem neuropathological examination confirmed a well-demarcated radionecrosis of the target volume. The baboon model appears to be an excellent method to study the in vivo biological effects of radiosurgery.

Acanthamoebiasis and immunosuppression. Case report.

Immunosuppression and debilitating illnesses are occasionally associated with multifocal brain lesions of Acanthamoebiasis, an encephalitis distinct from the acute, water-sport related meningoencephalitis caused by Naegleria fowleri. A 38-year-old man with a renal transplant two and one-half years before his final illness developed pneumonia due to Legionella micdadei. Candida albicans was isolated from sputum and cytomegalovirus was found in lung and liver biopsies. He had continuous corticosteroids, broad spectrum antibiotics, and immunosuppressive therapies. Coma developed and computerized tomography of the head revealed multifocal areas of decreased density, interpreted as cerebral abscesses. Brain biopsy demonstrated encephalitis and amocbae (Acanthamoeba castellanii). Four days after brain biopsy, he died and multifocal hemorrhagic lesions were found in the cerebral hemispheres, brainstem, and cerebellum. This case supports the hypothesis that Acanthamoebiasis is an opportunistic infection.

The neuropathology and epidemiology of AIDS. A Berlin experience. A review of 200 cases.

The brains of 200 patients who died with Acquired Immunodeficiency Syndrome (AIDS) from Berlin were examined retrospectively. This study was specifically intended to evaluate and document the prevalence of neuropathologic abnormalities, establishing the frequency of the various types of structural lesions, their combinations, their relative incidence, and the risk factors involved in different age groups. The data were compared and contrasted with the findings reported from other parts of the world and other German cities. It was found that the mean age of this group of patients was 41.4 years old, 75% were homosexual/bisexuals (H/B) and 18.5% were drug abusers (DA). Only 5.5% were women. Brain parenchymal changes, called in this report, HIV-related encephalopathy (HIVRE), characterized by vacuolization or spongy changes and astrocytosis in the subcortical white matter, and occasionally in gray matter, were found in 67 patients (33.5%). Drug abusers had a higher incidence of HIVRE (59.5%) compared with homosexual/bisexuals (28%). This is statistically significant (p < 0.0005). CMV encephalitis was found in 26 patients (13%) (8% of the drug abusers in contrast to 13% in the homosexual/bisexuals group). Primary central nervous system lymphoma (PCNSL) was seen in 28 patients (14%) regardless of the risk factor involved. 20 (13%) of the 150 H/B and 3 (8%) of the 37 DA had CMV encephalitis. Of the 150 H/B, 24 (16%) had PCNSL compared with only 4 of 37 (11%) of the DA. A significant incidence of opportunistic infections, both protozoal and viral was found in all groups. Cerebral toxoplasmosis occurred in 68 patients (34%). Microglial (phagocytic) nodules, probably related to CMV or cerebral Toxoplasmosis, were observed in 40 cases (20%). Diffuse microglial proliferation was noted in 104 patients (52%). Cerebral cryptococcosis was found in three patients. Progressive multifocal leukoencephalopathy was seen in 16 patients (8%). Various combinations of CNS pathological processes were found in 44 of the patients (22%). These include concomitant infections with Toxoplasma gondii and HIVRE in 13 patients; Toxoplasmosis and PCNSL in 8 patients; Toxoplasmosis with CMV and HIVRE in 4 patients; Toxoplasmosis with CMV in 2 patients; Toxoplasmosis with PCNSL and CMV in 2 patients; Toxoplasmosis with PCNSL and HIVRE in 2 patients and Toxoplasmosis with PML and HIVRE in 2 patients; Cerebral CMV with PCNSL and HIVRE in 4 patients; Cerebral CMV with HIVRE in 2 patients; PML with PCNSL in one patient; PML with HIVRE in 2 patients; and PML with PCNSL and HIVRE in one patient. Cerebrovascular lesions were found in 34 patients (17%).(ABSTRACT TRUNCATED AT 400 WORDS)

Radioprotective Effects of the 21-Aminosteroid U-74389G for Stereotactic Radiosurgery

OBJECTIVE Future improvements in the results of stereotactic radiosurgery will be related to better patient selection, dose planning, radiosensitization of the target, and, possibly, protection of the brain surrounding the target. 21-Aminosteroids may provide protection against brain radiation injury by inhibition of lipid peroxidation and a selective action on vascular endothelium. We hypothesized that the 21-aminosteroid U-74389G would reduce radiosurgery-related brain injury without attenuating the target volume response. METHODS One hundred and forty-five rats were divided into four experimental groups before undergoing radiosurgery: control (n = 47); low-dose U-74389G (5 mg/kg of body weight, n = 30); high-dose U-74389G (15 mg/kg, n = 20); and methylprednisolone (2 mg/kg, n = 48). The drug was administered 1 hour before radiosurgery (4-mm gamma knife collimator) of the normal rat frontal lobe (single-fraction maximum doses of 50, 100, or 150 Gy) was performed. All brains underwent histological examination at 90 or 150 days to evaluate the diameters of necrosis and the findings of radiation-induced vasculopathy, brain edema, and gliosis. RESULTS None of the animals that received 50-Gy radiation developed histological changes, whereas all of the animals that received 150-Gy radiation developed radiation necrosis without drug-induced protection from vascular changes or edema. In animals receiving 100-Gy radiation, high-dose aminosteroid reduced radiation-induced vasculopathy at 90 days (P = 0.06) and at 150 days (P = 0.02) and prevented regional edema at 90 days (P = 0.01) and at 150 days (P = 0.03). Low-dose aminosteroid and corticosteroid provided no protection. CONCLUSION The 21-aminosteroid U-74389G provided protection after a single intravenously administered dose of 15 mg/kg against radiation-induced vasculopathy and edema. High-dose 21-aminosteroids seem to have optimal properties for radiosurgery, surrounding brain protection without reducing the therapeutic effect desired within the target volume.

Metastatic tumor of the pituitary gland.

Although metastatic tumors of the pituitary gland and the sellar region are not common, they may radiographically mimic a pituitary tumor. Because the metastasis frequently involves the posterior lobe and because lateral extension to the cavernous sinus is common, patients may present with ptosis, diplopia, or diabetes insipidus. Decrease in anterior pituitary function is less common. Metastatic tumors contain abundant vascular networks, as evidenced by frequent blush on cerebral angiography and increased bleeding at operation. We report the case of a 57-year-old woman who presented with rapid onset of bilateral ptosis and ophthalmoplegia and was found to have a metastatic carcinoma within the pituitary gland.

Abscess formation within pituitary tumors.

Three consecutive cases where abscesses were found within pituitary tumors are presented. In all cases, the diagnosis was made preoperatively and the patients were begun on stress doses of hydrocortisone and antibiotics before surgical drainage of the abscess. All patients recovered with minimal neurological deficits. Review of the literature reveals that the diagnosis is seldom made preoperatively or before autopsy and is associated with high mortality and morbidity. Early suspicion of a pituitary abscess leading to early treatment with antibiotics and operative drainage seem to be important factors in decreasing this high mortality and morbidity.

Inhibition of peridural fibrosis after laminectomy using low-dose external beam radiation in a dog model.

OBJECTIVE Clinical studies have demonstrated a significant association between the presence of extensive postlumbar discectomy peridural scar formation and the recurrence of low back and radicular pain. Low-dose perioperative radiation therapy has previously been demonstrated to inhibit peridural fibrosis after laminectomy in a rat model. The current study was designed to measure the effect of low-dose radiation on postlaminectomy peridural fibrosis development in a larger animal model. METHODS Three dogs underwent a total of 12 lumbar hemilaminectomies. For each animal, two levels received 1) external beam radiation 24 hours before surgery, 2) surgery alone, or 3) radiation alone. Radiation was administered in a single fraction of 700 cGy using computed tomographic guidance for dosimetry planning. The isodose distribution was such that the dose conformed to the posterior epidural space with minimal exit dose to normal tissue. Port films were used to confirm the correct levels. Gadolinium-enhanced magnetic resonance imaging (MRI) of the lumbar spines was obtained before the animals were killed 12 weeks after surgery. The spines were harvested, and axial sections through the laminectomy defect were stained with hematoxylin and eosin and Massons trichrome. All specimens were evaluated for extent of fibrosis along the dura, density of fibrosis, nerve root entrapment, and sublaminar fibrosis. RESULTS There were no complications from the surgery, and no new neurological deficits were noted. There was a statistically significant difference between the irradiated and nonirradiated groups regarding the extent of fibrosis (P = 0.001) and the density of fibroblasts (P = 0.001). There was also a marked difference in nerve root entrapment (P = 0.182) and the presence of sublaminar fibrosis (P = 0.061) between the treatment and control groups. MRI revealed less gadolinium enhancement at the irradiated levels compared with the nonirradiated levels, confirming the usefulness of MRI in predicting the degree of epidural fibrosis. CONCLUSION Low-dose external beam radiation therapy administered 24 hours before laminectomy in a dog model significantly decreased the extent and density of peridural fibrosis as well as nerve root entrapment and sublaminar fibrosis. This treatment strategy may be efficacious in patients with recurrent radicular pain after lumbar discectomy that is thought to be secondary to peridural fibrosis on the basis of gadolinium-enhanced MRI studies, and who might benefit from reoperation for nerve root decompression.

Invasive pituitary adenoma with abscess formation: case report.

A case is presented and 10 cases are reviewed in which abscess formation developed in an intrasellar tumor. The diagnosis was made preoperatively or before autopsy in only 1 patient. The mortality rate was greater than 50%. The most common presentation was headache, fever, and visual disturbances with an abnormal sella and sterile cerebrospinal fluid (CSF). Nonconstant findings included meningeal signs and leukocytosis of the CSF. Trans-sphenoidal removal of the tumor and drainage of the abscess with appropriate antibiotic therapy is recommended. (Neurosurgery, 5: 718--722, 1979).

Chordomas: pathological features; ploidy and silver nucleolar organizing region analysis

Chordomas are slow growing malignant neoplasms with a prolonged clincial course which do not usually metastasize. They are histologically benign, locally invasive and often recur following resection. Survival has been shown to vary widely and prognostic indicators have been difficult to identify. Cellularity, mitotic activity and cellular pleomorphism have not been found to have prognostic significance. Thirty-six cases of clival, cervico-thoracic and sacral chordomas were evaluated utilizing four variables as possible predictors of survival: (1) silver nucleolar organizing region (AgNOR), (2) ploidy, (3) fibrosis, and (4) inflammatory response. AgNOR areas in approximately 200 cells per case were calculated and summed. DNA ploidy was obtained in 23 of the cases by analyzing deparaffinized Feulgen-stained tissue. Fibrosis and inflammation were evaluated by hematoxylin and eosin and by trichrome stains. Clinical follow-up was available in the 36 cases with survival ranging from 0.5 to 159 months. A statistical analysis employing the Cox-Proportional Hazards model disclosed no significant correlation between AgNOR area and clinical outcome (P>0.05). The variables, fibrosis, and inflammation, did not demonstrate prognostic significance (P>0.05). Ploidy demonstrated a statistical trend for prognostic significance (P=0.077). It is apparent that three of the four parameters studied do not independently affect survival. Although AgNOR has proved useful in the study of other neoplasms such as those of breast, prostate and bladder, it is not of significant importance in predicting the behaviour of chordomas. Ploidy, on the other hand, may be of value in predicting clinical outcome in chordomas and may be a useful marker in the evaluation of the aggressive biological behavior of these neoplasms.

Malignant fibrous histiocytoma of the clivus: case report.

A case of malignant fibrous histiocytoma of the clivus in a 2 1/2-year-old boy is reported. There are no prior reports of this tumor in this location. The child was treated with operation, radiation therapy, and chemotherapy. The tumor recurred locally 21 months later. The recurrence was palliated by operation and chemotherapy, permitting an additional 20-month survival.