Allelic losses on chromosomes 14, 10, and 1 in atypical and malignant meningiomas: a genetic model of meningioma progression.

To investigate chromosomal events that underlie formation and progression of meningiomas, we have examined a set of 18 benign (WHO grade I), 15 atypical (grade II), and 13 anaplastic/malignant (grade III) meningiomas for loss of heterozygosity (LOH) on chromosomes 1p, 6p, 9q, 10q, and 14q. Frequent loss of loci on these chromosomes was seen in grade II and grade III tumors, specifically, 14q (II and III, 47 and 55%), 1p (40 and 70%), and 10q (27 and 40%). In contrast, LOH for these loci was infrequent in benign meningiomas, specifically, 14q (0%), 1p (11%), and 10q (12%). The smallest common regions of deletion that could be defined were 14q24-q32, 1p32-pter, and 10q24-qter. These observations indicate the likely presence of tumor suppressor genes in these regions that are involved in the development of WHO grade II and grade III meningiomas. Because LOH for loci on chromosomes 1p and 10q was found in tumors of all grades and because the frequency of LOH in all three regions increased with tumor grade, these results would support a model for the formation of aggressive meningiomas through tumor progression.

Cerebral arterial innervation: II. Development of calcitonin-gene-related peptide and norepinephrine in the rat.

The pre- and postnatal development of trigeminal calcitonin-gene-related peptide (CGRP)- and sympathetic norepinephrine (NE)-containing nerves supplying the cerebral arteries was studied with immunohistochemistry in rats. At 18-19 days in utero (E 18-19), CGRP fibers were present only as one or two longitudinal bundles zigzagging along the anterior cerebral artery and anterior communicating artery. Growth-cone-like swellings were found at the terminals of individual fibers. In contrast, at this same prenatal age NE fibers were present as a meshwork on all cerebral arteries. The density of NE fibers was higher in the rostral than in the caudal parts of the circle of Willis; growth cones were present on individual fibers at the middle segment of the basilar artery and distal parts of major cerebral arteries. At postnatal day 1-2 (PND 1-2; date of birth = PND 1), the outgrowth of CGRP axons extended along the walls of the middle cerebral and internal carotid arteries. These axons were relatively straight and unbranched. At the same time, NE fibers increased in number and density and continued to form the meshwork pattern on all cerebral arteries. At the end of the first postnatal week, all the longitudinal NE bundles on the rostral part of the circle of Willis began to form circular arborizations. At the end of the second postnatal week, the pattern of NE innervation had completely changed, consisting almost entirely of circumferential rather than tangential fibers. Beginning in the first postnatal week, CGRP fibers increased greatly in number and density and began to form a meshwork pattern. At the second postnatal week, the pattern of CGRP innervation, compared to the pattern at fetal and neonatal stages, had changed significantly, consisting predominantly of a meshwork pattern. By 4 weeks after birth, both the NE and CGRP fiber systems achieved adult densities and patterns. The present results demonstrate the following: 1) Both sympathetic-NE and trigeminal-CGRP innervation of cerebral arteries begin in utero; the NE system innervates corresponding parts of the vessels earlier than the CGRP system. 2) Both NE and CGRP fibers are more dense in the rostral than in the caudal segments of the circle of Willis; this rostrocaudal gradient is expressed in both density and pattern by the earliest fibers of both neurochemical systems and is maintained throughout all developmental stages.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebral arterial innervation by nerve fibers containing calcitonin gene-related peptide (CGRP): I. Distribution and origin of CGRP perivascular innervation in the rat.

The origin, density and distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in cerebral perivascular nerves and the trigeminal ganglion of rats were examined in this study. CGRP immunoreactive axons were abundant on the walls of the rostral circulation of the major cerebral arteries in the circle of Willis. The fibers form a grid- or meshwork of longitudinal and circumferential axons studded with numerous varicose swellings. The density of CGRP fibers was particularly high at the bifurcation of major arteries. A few CGRP fibers cross the midline to innervate arteries on the contralateral side of the arterial tree. The arteries of the caudal circulation were sparsely innervated by CGRP fibers. In the trigeminal ganglion, about 30% of the ganglion cells had CGRP immunoreactivity. The cell size of most (75%) of CGRP neurons was less than 30 micron in diameter. There was no significant difference in staining density between small and large CGRP neurons. Unilateral transection of the maxillary and mandibular divisions of the trigeminal nerve caused a substantial decrease of CGRP immunoreactivity in the ipsilateral dorsal two-thirds of the trigeminal nucleus and cervical spinal cord but did not noticeably change the diameter of the vascular lumen or the densities of CGRP fibers in the walls of the cerebral arteries. In contrast, unilateral transection that included the ophthalmic division eliminated CGRP fibers on the ipsilateral cerebral arteries and eliminated CGRP immunoreactivity throughout the trigeminal nucleus in the brainstem and rostral cervical cord. In addition, these lesions caused a significant reduction in the diameter of the denervated arteries. The present study demonstrates that CGRP, a putative neurotransmitter/neuromodulator, is especially abundant in the rostral cerebral circulation and is derived from the ipsilateral ophthalmic division of the trigeminal nerve. In addition, the loss of CGRP perivascular nerves is associated with a reduction of the arterial lumen. This suggests that CGRP is a strong candidate as a nerve-derived trophic factor at trigeminal terminals and provides additional evidence that CGRP is a component in the trigeminovascular system influencing vascular diameter.

Hemorrhage and epilepsy in cryptic cerebrovascular malformations.

A series of 15 angiographically cryptic, histologically proved, cerebrovascular malformations occurred. Nine patients were admitted to the hospital with evidence of recent neurological deterioration or onset of headache. Six patients had convulsions. Computed tomographic scan and surgical exploration disclosed a substantial cerebral hematoma in eight instances. The pathological diagnosis was arteriovenous malformation in 11 cases, cavernous angioma in three, and venous angioma in one. Histological evidence of previous microhemorrhage was present in the majority of the specimens, including the patients who had seizures. A change in neurological status or onset of seizures probably indicates recent hemorrhage in cryptic cerebrovascular malformations.

Tic convulsif, the combination of geniculate neuralgia and hemifacial spasm relieved by vascular decompression.

A patient had combined otalgia and intractable unilateral facial spasm, relieved by microsurgical vascular decompression of the seventh and eighth cranial nerve complex in the cerebellopontine angle without section of the intermediate nerve. A dolicho-ectatic anterior inferior cerebellar artery compressed the seventh and eighth cranial nerves complex, suggesting that vascular compression of the intermediate nerve or of the sensory portion of the facial nerve may cause geniculate neuralgia. "Tic convulsif" seems to be a combination of geniculate neuralgia and hemifacial spasm. This combination could be due to vascular compression of the sensory and motor components of the facial nerve at their junction with the brainstem.

Treatment of trigeminal neuralgia in the aged by a simplified surgical approach (percutaneous electrocoagulation).

Trigeminal neuralgia can be excruciatingly painful. For aged patients, among whom trigeminal neuralgia most commonly occurs, medical therapy may often afford relief of pain. However, since this disorder is likely to become worse with increasing age, medical therapy eventually may fail because of increasing drug requirements and intolerable side effects. Major forms of surgical treatment requiring craniotomy may afford longstanding relief but are associated with significant side effects in 3-5 per cent of cases. For these reasons the authors began to test a new surgical approach, i.e., stereotaxic percutaneous electrocoagulation of the trigeminal nerve. More than 300 patients have been treated by this technique in the past five years. Successive radiofrequency lesions allow the production of a graded sensory deficit sufficient to relieve pain while preserving touch and motor function in the face. Unnecessary suffering from the severe pain of trigeminal neuralgia need not occur because of age or a debilitated condition which might ordinarily preclude surgical treatment. More than 100 patients over 65 years of age (4 of them older than 90) have been treated. Of this group, 93 per cent reported good to excellent results. Seven per cent have had some recurrent pain during the follow-up period; however, recoagulation has been required in only 5 per cent of these patients. Recoagulation may be readily performed in any patient who shows evidence of fading of the sensory deficit. The electrocoagulation technique and the results in elderly patients are discussed.

Surgical management of the totally occluded internal carotid artery: a ten-year study.

Although surgical treatment of the stenotic and ulcerative internal carotid artery has been accepted as an effective approach to the management of cerebrovascular insufficiency, uncertainty and controversy have prevailed over the past two decades regarding the optimal management of the totally occluded artery. Over a 10-year period, 47 thromboendarterectomies were performed for recent total occlusion of the internal carotid artery. The patients were categorized and selected for surgery according to their neurologic manifestations and clinical status. Postoperative patency was studied by angiography and noninvasive laboratory tests, including oculoplethysmography, carotid phonoangiography, Doppler ultrasound, and ultrasonography. The patency rate achieved appeared to be related to the duration of carotid occlusion (100% within 7 days and 50% at 1 month). The overall patency rate was 68%. There were no operative deaths or morbidity. Dramatic improvement occurred in three patients who underwent surgery immediately after the onset of a major neurologic deficit. The results of this study indicate that surgical treatment for internal carotid occlusion should be considered in selected circumstances. Careful case selection and judicious timing of operation are mandatory.

Identification of motoneurons innervating the tensor tympani and tensor veli palatini muscles in the cat.

The somatotopic arrangement of the motoneurons associated with the two non-masticatory muscles innervated by the trigeminal motor nerve, tensor tympani (TT) and tensor veli palatini (TVP), was determined in the cat using retrograde transport of horseradish peroxidase. The motoneurons of the TT are distinct and separate, ventral and ventral-lateral to the rostral two-thirds of the trigeminal motor nucleus. The cells are smaller than those of the motor nucleus and constitute a parvocellular division. Based on functional and morphological criteria, TT motoneurons may be considered as an accessory trigeminal nucleus. The somatotopic arrangement of TVP motoneurons has been described for the first time. These motoneurons are located in the rostral two-thirds of the ventromedial division of the cat trigeminal motor nucleus. The location of motoneurons associated with TT and TVP does not fit the parcellation of the cat trigeminal motor nucleus as described by previous investigators. The motoneurons of these muscles can now be assigned to areas either within (TVP) or adjacent to (TT) the rostral two-thirds of the motor nucleus.

Development of cerebral arterial innervation: synchronous development of neuropeptide Y (NPY)- and vasoactive intestinal polypeptide (VIP)-containing fibers and some observations on growth cones.

The pre- and postnatal development of sympathetic fibers containing neuropeptide Y (NPY) and parasympathetic fibers containing vasoactive intestinal polypeptide (VIP) supplying the cerebral arteries were studied with immunohistochemistry in rats. The innervation patterns and densities of NPY and VIP fibers were similar at all stages of development and similar to that previously reported for norepinephrine (NE). There was a striking reorganization of the innervation pattern of all three fiber systems between the first and second postnatal weeks. At all stages of development prior to the first postnatal week, growth cones were present on individual fibers at the distal part of major cerebral arteries and the middle segment of the basilar artery. The growth cones had a range of shapes from blunt to stellate, lanceolate or filiform. NPY and VIP immunoreactive granules were commonly present. The present results taken with our earlier developmental study of NE fibers (J. Comp. Neurol., 271 (1988) 435-444), demonstrate that: (1) both sympathetic and parasympathetic perivascular nerves on immature cerebral vessels develop with similar sequences: first longitudinal fibers and fiber bundles are present; these transform to a meshwork pattern and finally transform again into the mature, predominantly circumferential pattern; (2) both the classical (NE) and peptidergic transmitters (NPY) within the sympathetic system appear to develop identically in terms of time of appearance, innervation patterns, densities and reorganization.(ABSTRACT TRUNCATED AT 250 WORDS)

The sensory representation of the dura mater in the trigeminal ganglion of the cat.

The representation of the dura mater in the trigeminal ganglion was examined in the cat using the horseradish peroxidase (HRP) method. Following craniotomy a 50% solution of HRP was applied to various areas of the cranial dura and after a survival time of 48 h the trigeminal ganglion was processed. Cells in the first division gave rise to fibers innervating the medial aspect of the anterior fossa as well as the tentorium cerebelli. Labeled cells associated with the orbital roof were located predominantly in the dorsal and intermediate layers of the second division while the middle fossa was found to be represented mainly in the more dorsal strata of the third division. Labeled cells were smaller than the average ganglion cell.

Utility, safety, and accuracy of intraoperative angiography in the surgical treatment of aneurysms and arteriovenous malformations.

BACKGROUND AND PURPOSE: The role of intraoperative angiography in the treatment of neurovascular lesions has remained extremely controversial. We retrospectively reviewed the utility, safety, and accuracy of intraoperative angiography to ascertain its effect on the treatment of patients with neurovascular lesions. METHODS: We reviewed the results of intraoperative angiography in 91 patients treated surgically for intracranial aneurysms and in 98 patients treated surgically for arteriovenous malformations (AVMs). All treatments were completed at two major teaching hospitals between October 1987 and March 1995. RESULTS: The initial angiographic findings caused the surgical procedure to be modified in 24 (26%) of the patients with aneurysms and in 28 (29%) of the patients with AVMs. Analysis of the final angiographic sequence showed residual lesions in nine (10%) of the aneurysm cases and in eight (8%) of the AVM cases. The imperfect angiographic results were deemed acceptable because there was either evidence of collateral flow when the parent vessel was occluded or the risk of further surgical modification was considered more dangerous than the abnormality itself. Seven patients suffered complications, of which only one had permanent neurologic sequelae: a CNS complication rate of 0.5%. Comparison of the intraoperative angiographic findings with those of postoperative studies revealed four false-negative results (5.2%). CONCLUSION: Intraoperative angiography is an important component in the treatment of patients with intracranial vascular lesions. It is effective and can be carried out with low risk in this patient population.

Adult choroidal vein of Galen malformation.

We report staged embolization and stereotactic radiation in a true adult choroidal vein of Galen malformation. Management dilemmas and their resolutions are also discussed.

Aneurysm formation after carotid occlusion.

We present two cases of subarachnoid hemorrhage caused by aneurysm development and enlargement in the anterior communicating artery complex. The cases occurred in a series of 58 balloon occlusions for unclippable giant aneurysms of the internal carotid artery.

Cervical myelopathy associated with intracranial dural arteriovenous fistula: MR findings before and after treatment.

The MR findings in three patients with intracranial dural arteriovenous fistula associated with cervical myelopathy are described. The MR appearance of an enlarged cord with associated abnormal signal and enhancement is nonspecific and can simulate tumor, demyelination, and inflammation. Enlarged perimedullary vessels may not always be identifiable, but if present, should suggest the presence of an arteriovenous fistula.

M. Gazi Yasargil: Neurosurgery's man of the century.

Dissatisfied with the available macrosurgical techniques and encouraged by colleagues such as Donaghy and Krayenbühl, M. Gazi Yasargil possessed the ingenuity to take advantage of and further improve emerging technologies such as angiography to develop microsurgery. To enable the advancement of microsurgical techniques, Yasargil created innovative instrumentation, such as the floating microscope, the self-retaining adjustable retractor, microsurgical instruments, and ergonomic aneurysm clips and appliers. His genius in developing microsurgical techniques for use in cerebrovascular neurosurgery has transformed the outcomes of patients with conditions that were previously inoperable.

Long-term results of surgical treatment of idiopathic neuralgias of the glossopharyngeal and vagal nerves.

Physicians disagree about the best surgical treatment for patients with idiopathic neuralgias of the glossopharyngeal and vagal nerves after medical treatment has failed. Some favor percutaneous thermal rhizotomy, and other prefer extracranial section of the glossopharyngeal or branches of the vagal nerve, intracranial section of the glossopharyngeal and upper vagal rootlets, or microvascular decompression. However, the results of these procedures are limited to series with follow-up periods of less than 5 years or to series with longer follow-ups that were performed before the microneurosurgical era. We reviewed the long-term results of 14 patients with vagoglossopharyngeal neuralgia treated surgically at our center between 1976 and 1987 to determine the best treatment. Sixteen procedures were performed: 2 percutaneous thermal rhizotomies; 2 extracranial sections of the superior laryngeal nerve; and 12 intracranial glossopharyngeal and upper vagal rhizotomies, 4 with and 8 without microvascular decompression. The follow-ups ranged from 4 to 17 years (mean, 10 yr). All 14 patients who underwent percutaneous or intracranial rhizotomies were pain free. Two patients who underwent percutaneous rhizotomies developed persistent dysphagia and hoarseness. Both patients who underwent extracranial nerve section experienced pain recurrence 2 and 4 years later. Of 12 patients who underwent intracranial section of the glossopharyngeal and upper vagal rootlets, 2 developed dysphagia, which resolved completely in 1 patient and persisted mildly in the other; 1 had transient hoarseness; and 2 developed frequent coughing episodes, which persisted in 1 patient and resolved completely in the other. Side effects due to motor vagal deficits may be eliminated by intraoperative monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Foreign body embolization of the middle cerebral artery: review of the literature and guidelines for management.

Two cases of traumatic middle cerebral artery occlusion secondary to migratory intravascular metallic pellets are presented. Surgical removal of the occlusive pellet was achieved in one patient, and vessel patency was restored. One patient recovered from his neurological deficit without surgical intervention. Factors such as the availability of a microvascular surgeon, the status of the neurological deficit resulting from the embolus, the time interval from injury to the proposed operation, and the extent of ancillary injuries sustained concurrently all bear weight on the decision to explore surgically or treat by medical measures. We believe that in cases of trauma an attempt to remove intravascular emboli is warranted to prevent migration of the embolus and distal propagation of thrombus, to avoid chronic sepsis, to prevent arterial erosion, and to restore the integrity of the vascular tree.

Comparison of surgical treatments for trigeminal neuralgia: reevaluation of radiofrequency rhizotomy.

In this study, we reevaluate the results of radiofrequency rhizotomy and review the effectiveness of other surgical procedures for the treatment of trigeminal neuralgia. Five hundred patients with trigeminal neuralgia underwent radiofrequency rhizotomy at the University of Cincinnati Medical Center, Cincinnati, OH, between 1981 and 1986. Their results are compared with those of patients reported in the literature who underwent radiofrequency rhizotomy (6205 patients), glycerol rhizotomy (1217 patients), balloon compression (759 patients), microvascular decompression (MVD) (1417 patients), and partial trigeminal rhizotomy (250 patients). Comparisons were based on the following outcome parameters: technical success, pain relief and recurrence, facial numbness, dysesthesia, corneal anesthesia, keratitis, trigeminal motor dysfunction, permanent cranial nerve deficit, intracranial hemorrhage or infarction, perioperative morbidity, and perioperative mortality. We found that MVD had the lowest rate of technical success. Radiofrequency rhizotomy and MVD had the highest rates of initial pain relief and the lowest rates of pain recurrence. Glycerol rhizotomy had the highest rate of pain recurrence. Balloon compression had the highest rate of trigeminal motor dysfunction. Balloon compression and MVD had the lowest rates of corneal anesthesia or keratitis. MVD had the lowest rates of facial numbness and dysesthesia. All percutaneous procedures had similar rates of dysesthesia. Posterior fossa exploration had the highest rates of permanent cranial nerve deficit, intracranial hemorrhage or infarction, and perioperative morbidity and mortality. On the basis of our experience and a review of the literature, we conclude the following: 1) percutaneous techniques and posterior fossa exploration offer advantages and disadvantages, 2) radiofrequency rhizotomy is the procedure of choice for most patients undergoing first surgical treatments, and 3) MVD is recommended for healthy patients who have isolated pain in the first ophthalmic trigeminal division or in all three trigeminal divisions and patients who desire no sensory deficit.

Recurrence of hemifacial spasm after microvascular decompression.

The success of medical and surgical treatment for hemifacial spasm, and involuntary paroxysmal unilateral contraction of the facial muscles, has been mixed. Although microvascular decompression has the greatest reported success, symptom recurrence affects many patients in whom treatment was initially successful. In this study, we report the results of 34 patients who underwent microvascular decompression of the facial nerve from 1976 to 1989 as well as review the literature concerning the incidence and timing of recurrence in more than 600 patients who underwent microvascular decompression. In this series, 94% of 34 patients had continuous relief of spasm after surgical treatment (mean duration, > 6 yr). Of those patients whose spasms were completely initially relieved, 10.3% developed some degree of recurrent spasm; however, no patient developed a recurrence after 24 months without spasm. Our review of the literature discloses that 86% of all recurrences occurred within 2 years of surgery. Patients who have no recurrence of symptoms 2 years after surgical treatment have only a 1% chance of developing recurrent hemifacial spasm. We also comment on possible causes of treatment failure and recurrence of hemifacial spasm after surgical treatment.

Successful laser-assisted excision of a metastatic midbrain tumor.

Metastatic lesions to the midbrain are rare. They are found in 1 to 3% of autopsy series of solitary brain metastases. The consensus of opinion in the current literature is that they are inoperable lesions and should be treated by radiation therapy alone. This is the first case report of a completely excised metastatic adenocarcinoma to the midbrain. The patient's clinical course has been stable, and there is no computed tomographic evidence of recurrence at 18 months follow-up.