A model of coccidioidal meningoencephalitis and cerebrospinal vasculitis in the rabbit.

Coccidiodal meningitis is a devastating complication of disseminated coccidioidomycosis. An animal model of this infection could enhance understanding of the pathogenesis of the disease and lead to improvements in therapy. A rabbit model of central nervous system infection simulating human disease was established using a blind cisternal tap technique to inoculate 4 x 10(3)-1 x 10(6) arthroconidia of Coccidioides immitis into the cisterna magna. Systemic, neurologic, and histopathologic findings of meningitis were observed in all rabbits, but an inoculum of 2 x 10(4) arthroconidia produced a chronic illness in which meningeal endarteritis obliterans was consistently observed. Serial sampling of cerebrospinal fluid demonstrated an inflammatory response. Growth of C. immitis was demonstrated by quantitative fungal culture from brains and proximal spinal cords.

Noninvasive measurement of pulsatile intracranial pressure using ultrasound.

The present study was designed to validate our noninvasive ultrasonic technique (pulse phase locked loop: PPLL) for measuring intracranial pressure (ICP) waveforms. The technique is based upon detecting skull movements which are known to occur in conjunction with altered intracranial pressure. In bench model studies, PPLL output was highly correlated with changes in the distance between a transducer and a reflecting target (R2 = 0.977). In cadaver studies, transcranial distance was measured while pulsations of ICP (amplitudes of zero to 10 mmHg) were generated by rhythmic injections of saline. Frequency analyses (fast Fourier transformation) clearly demonstrate the correspondence between the PPLL output and ICP pulse cycles. Although theoretically there is a slight possibility that changes in the PPLL output are caused by changes in the ultrasonic velocity of brain tissue, the decreased amplitudes of the PPLL output as the external compression of the head was increased indicates that the PPLL output represents substantial skull movement associated with altered ICP. In conclusion, the ultrasound device has sufficient sensitivity to detect transcranial pulsations which occur in association with the cardiac cycle. Our technique makes it possible to analyze ICP waveforms noninvasively and will be helpful for understanding intracranial compliance and cerebrovascular circulation.

Intracranial pressure dynamics during simulated microgravity using a new noninvasive ultrasonic technique.

It is believed that intracranial pressure (ICP) may be elevated in microgravity because a fluid shift toward the head occurs due to loss of gravitational blood pressures. Elevated ICP may contribute to space adaptation syndrome, because as widely observed in clinical settings, elevated ICP causes headache, nausea, and projectile vomiting, which are similar to symptoms of space adaptation syndrome. However, the hypothesis that ICP is altered in microgravity is difficult to test because of the invasiveness of currently-available techniques. We have developed a new ultrasonic technique, which allows us to record ICP waveforms noninvasively. The present study was designed to understand postural effects on ICP and assess the feasibility of our new device in future flight experiments.

Development of a noninvasive technique for the measurement of intracranial pressure.

Intracranial pressure (ICP) dynamics are important for understanding adjustments to altered gravity. Previous flight observations document significant facial edema during exposure to microgravity, which suggests that ICP is elevated during microgravity. However, there are no experimental results obtained during space flight, primarily due to the invasiveness of currently available techniques. We have developed and refined a noninvasive technique to measure intracranial pressure noninvasively. The technique is based upon detecting skull movements of a few micrometers in association with altered intracranial pressure. We reported that the PPLL technique has enough sensitivity to detect changes in cranial distance associated with the pulsation of ICP in cadavera. In normal operations, however, we place a transducer on the scalp. Thus, we cannot rule out the possibility that the PPLL technique picks up cutaneous pulsation. The purpose of the present study was therefore to show that the PPLL technique has enough sensitivity to detect changes in cranial distance associated with cardiac cycles in vivo.

Central neurocytoma: one associated with a fourth ventricular PNET/medulloblastoma and the second mixed with adipose tissue.

We report two cases of central neurocytoma; one located in the right lateral ventricle and associated with a distinctly separate primitive neuroectodermal tumor (PNET)/medulloblastoma of the fourth ventricle, and the other admixed with fat cells and arising from the left lateral and third ventricles with extension into the corpus callosum. We discuss that concurrent occurrences of PNET and adipose tissue are not fortuitous events, but an evidence that neurocytomas and PNETs originate in the residual germinal pool from common progenitor cell rests recapitulating features of developing neurons and with a potential for mesenchymal differentiation.

Pleomorphic granular cell astrocytoma of the pineal gland.

BACKGROUND: Primary neoplasms of the pineal gland are uncommon. Two patients with unusual primary pineal tumors that had similar distinctive histologic features are reported. METHODS: The surgically resected neoplastic pineal tissue from these patients were examined by light microscopy, immunohistochemistry, and electron microscopy and correlated with the patients' clinical course. RESULTS: These pineal tumors consisted of a mixture of spindle-shaped cells with fibrillated cell processes and many large lipidized and/or granular pleomorphic cells, some of which were multinucleated. These two tumors superficially resembled pleomorphic xanthoastrocytoma and granular cell tumors of the central nervous system. The pleomorphic tumor cells expressed glial fibrillary acidic protein and some also produced retinal S-antigen, a marker for retinal photoreceptor cells. Long-term follow-up (8 years) on one of these patients suggested a relatively "benign" clinical course. CONCLUSIONS: It is possible that this newly described tumor may be a distinct subset of pineal gland neoplasias with a favorable biologic behavior despite the histologic features that would suggest otherwise.

Stereotactic helium ion Bragg peak radiosurgery for intracranial arteriovenous malformations. Detailed clinical and neuroradiologic outcome.

89 patients with angiographically documented arteriovenous malformations were treated with helium ion Bragg peak radiation. The rate of complete angiographic obliteration 2 years after radiation was 94% in those lesions smaller than 4 cm3 (2.0 cm in diameter), 75% for those 4-25 cm3 and 39% for those larger than 25 cm3 (3.7 cm in diameter); at 3 years after radiation, the corresponding obliteration rates were 100, 95 and 70%. Major clinical complications occurred in 10 patients (8 permanent, 2 transient) between 3 and 21 months after treatment; all were in the initial stage of the protocol (higher radiation doses). 10 patients bled from residual malformation between 4 and 34 months after treatment. Seizures were improved in 63% and headaches in 68% of patients. Excellent or good clinical outcome was achieved in 94% of patients. Compared to the natural history and risks of surgery for these difficult malformations, we consider these results encouraging. Heavy-charged-particle radiation is a valuable therapy for surgically inaccessible symptomatic cerebral arteriovenous malformations. The current procedure has two disadvantages: the prolonged latent period before complete obliteration and the small risk of serious neurological complications.

Maternally administered esmolol decreases fetal as well as maternal heart rate.

Fetal heart rate was monitored during the administration of esmolol 100 micrograms/kg/min to a 36-year-old, 29-week pregnant woman who was undergoing craniotomy for surgical treatment of six cerebral aneurysms. During stable general anesthesia, sodium nitroprusside was administered to induce moderate hypotension; at the same time, esmolol was infused to control maternal tachycardia. Within minutes after starting the esmolol infusion, maternal heart rate decreased from 100 beats/minute to 65 beats/minute, and fetal heart rate decreased from 160 beats/minute to 130 beats/minute. Upon termination of the infusion 3 hours later, both maternal and fetal heart rate returned to preinfusion values. No adverse effects of esmolol infusion were noted in the mother or fetus.

Occult vascular malformations of the optic chiasm: magnetic resonance imaging diagnosis and surgical laser resection.

Angiographically occult vascular malformations of the optic nerve and chiasm are extremely rare. Before the advent of magnetic resonance imaging (MRI), it was difficult to diagnose these lesions preoperatively. We report MRI scan findings of optic chiasm cavernous angiomas in two patients with chiasmal syndrome. MRI was useful in localizing the vascular malformation and delineating its characteristics, especially chronic hemorrhage. One patient underwent biopsy of the lesion. The other patient underwent complete microsurgical resection of the malformation with the carbon dioxide laser with preservation of vision. Occult vascular malformations of the optic nerve and chiasm may be a more common cause of visual deterioration than previously recognized. The MRI scan is the imaging modality of choice for diagnosing and following these lesions. In certain patients, these vascular malformations may be amenable to complete surgical removal with stabilization or improvement of visual function.

Stereotactic heavy-charged-particle Bragg-peak radiation for intracranial arteriovenous malformations.

BACKGROUND: Heavy-charged-particle radiation has several advantages over protons and photons for the treatment of intracranial lesions; it has an improved physical distribution of the dose deep in tissue, a small angle of lateral scattering, and a sharp distal falloff of the dose. METHODS: We present detailed clinical and radiologic follow-up in 86 patients with symptomatic but surgically inaccessible cerebral arteriovenous malformations that were treated with stereotactic helium-ion Bragg-peak radiation. The doses ranged from 8.8 to 34.6 Gy delivered to volumes of tissue of 0.3 to 70 cm3. RESULTS: Two years after radiation treatment, the rate of complete obliteration of the lesions, as detected angiographically, was 94 percent for lesions smaller than 4 cm3, 75 percent for those of 4 to 25 cm3, and 39 percent for those larger than 25 cm3. After three years, the rates of obliteration were 100, 95, and 70 percent, respectively. Major neurologic complications occurred in 10 patients (12 percent), of whom 8 had permanent deficits. All these complications occurred in the initial stage of the protocol, before the maximal dose of radiation was reduced to 19.2 Gy. In addition, hemorrhage occurred in 10 patients from residual malformations between 4 and 34 months after treatment. Seizures and headaches were less severe in 63 percent of the 35 and 68 percent of the 40 patients, respectively, who had them initially. CONCLUSIONS: Given the natural history of these inaccessible lesions and the high risks of surgery, we conclude that heavy-charged-particle radiation is an effective therapy for symptomatic, surgically inaccessible intracranial arteriovenous malformations. The current procedure has two disadvantages: a prolonged latency period before complete obliteration of the vascular lesion and a small risk of serious neurologic complications.

Effect of hyperglycemia on neuronal changes in a rabbit model of focal cerebral ischemia.

In clinical medicine, cerebral ischemia is frequently due to a focal, rather than global, insult. The effect of hyperglycemia in focal cerebral ischemia is not well defined. We studied the effect of hyperglycemia on neuropathologic changes in a rabbit model of focal cerebral ischemia. Rabbits were randomized to receive saline (n = 12) or glucose (n = 12) infusions. The left anterior cerebral and left internal carotid arteries were clipped after the infusion began. After 6 hours of occlusion, the area of severe ischemic neuronal damage in the left neocortex and striatum on two standard sections of brain was calculated and expressed as a percentage of the total area of the left cortex or striatum. The mean +/- SEM cortical area of severe ischemic neuronal damage was 22.1 +/- 2.8% in the glucose-treated rabbits and 34.0 +/- 4.6% in the saline-treated rabbits (p less than 0.05). The cortical area of severe ischemic neuronal damage was inversely correlated with plasma glucose concentration at the time of arterial clipping (p less than 0.05). We conclude that hyperglycemia is associated with decreased histologic neuronal injury in this model of focal cerebral ischemia and may be protective when cerebral ischemia occurs from a focal insult.

Hyperglycemia decreases acute neuronal ischemic changes after middle cerebral artery occlusion in cats.

Hyperglycemia has been reported to worsen the tolerance of the brain to ischemia, and it has therefore been recommended that patients undergoing neurosurgical procedures not receive glucose-containing solutions. However, whereas most animal studies have used global ischemia models, most neurosurgical procedures are associated with risks of focal rather than global ischemia. We therefore studied the effects of glucose administration in an animal model of focal cerebral ischemia. We anesthetized 20 cats with halothane (0.85% end tidal in oxygen), and a focal cerebral ischemic lesion was produced by clip ligation of the left middle cerebral artery using a transorbital approach. Hyperglycemia (10 cats, mean +/- SEM plasma glucose concentration 561 +/- 36 mg/dl) was established before ligation by infusion of 50% glucose in 0.45% saline; the control group (10 cats, mean +/- SEM plasma glucose concentration 209 +/- 28 mg/dl) received 0.45% saline only. Total fluid administered, mean arterial blood pressure, body temperature, and arterial blood gas values did not differ between the two groups 0, 2, and 6 hours after ligation. The cats were killed 6 hours after ligation, and the area of severe ischemic neuronal damage was determined by microscopic examination of a coronal section at the level of the optic chiasm. The mean +/- SEM area of left cortical severe ischemic neuronal damage was 12 +/- 2% of the left cortex in the hyperglycemic group compared with 28 +/- 5% in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Evolution and outcome in malignant astroglial neoplasms of the cerebellum.

Malignant astroglial neoplasms of the cerebellum are rare and the clinical behavior of these tumors is unpredictable. The authors describe the histological characteristics and clinical outcome in 10 patients; eight had malignant cerebellar astrocytomas, and one each had an astroblastoma and a true polar spongioblastoma. Malignant glial tumors involving the cerebellum usually behave very aggressively. Cerebellar astroblastomas and polar spongioblastomas are too rare to predict their natural history. Some hypotheses are proposed concerning the evolution and interrelationship of malignant glial tumors of the cerebellum.

Fink-Heimer/Nauta demonstration of regenerating axons in the rat spinal cord.

Six months after complete spinal cord transection, regenerated descending motor axons can be found by electrophysiologic testing and can also be demonstrated anatomically using the Fink-Heimer/Nauta technique. Regeneration was found in all animals, treated or control, but statistically significant increased regeneration as measured by the Fink-Heimer/Nauta technique was found in animals treated with a single injection of 75 mg/kg of cyclophosphamide 24 hours after the original spinal cord transection. This result is similar to those of another study using the orthograde axonal transport of tritiated proline as a measure of axonal regeneration. The mode of action of cyclophosphamide may be by its immunosuppressive properties because this drug is most effective when administered 24 hours after cord transection, a time when its effects as an immunosuppressant would be maximal.

A mask for the artificial respiration of rats.

A simple artificial respiration mask for rats was constructed from the drip chamber of an intravenous solution administration set. The mask was held in place by means of straps and a hole through which the maximillary incisors protruded. This mask permitted artificial ventilation during drug-induced respiratory paralysis, was easily and inexpensively constructed, and may be used with a variety of positive pressure respirators.